Mindie H. Nguyen, MD, MAS, AGAF, FAASLD
Professor of Medicine (Gastroenterology and Hepatology) and, by courtesy, of Epidemiology and Population Health
Medicine - Gastroenterology & Hepatology
Web page: http://www.med.stanford.edu/fm/?/&faculty.html&gastrohep.stanford.edu
Bio
Dr. Nguyen is Professor of Medicine, a Stanford Cancer Institute member and specializes in the treatment and prevention of primary liver cancer such as hepatocellular carcinoma (HCC).
Dr. Nguyen is also a Professor of Epidemiology and Population Health by courtesy at Stanford. Her clinical and research focus has been liver cancer for the past 20+ years. She is a frequent lecturer for the management and prevention of liver cancer for care providers and researchers at national and international conferences. She has published several key research papers to inform clinicians of the care and treatment of patients with liver cancer.
Dr. Nguyen’s clinical and research focus also include patients with cirrhosis, viral hepatitis, nonalcoholic fatty liver disease (NAFLD/NASH). Her goal is to promote early detection of liver tumors and to prevent and treat complications from chronic liver diseases and liver cancer. She has extensive experience in performing clinical trials on liver cancer, fatty liver, cirrhosis, and viral hepatitis. She has lead several multi-center US and international studies.
Dr. Nguyen is clinically active, seeing patients three full days a week, with a large and comprehensive practice of general liver, liver cancer, and transplant patients at Stanford University Medical Center, as well as weekly outreach clinics in the San Jose area.
Dr. Nguyen has served as Director of the Hepatology Fellowship Program in the Division of Gastroenterology and Hepatology and the Liver Transplant Program . Currently, she is Director of the Hepatology Clerkship, a member of Stanford Bio-X, and Stanford Population Science, a member of the Appointments and Promotions Committee and a Diversity LENS Advocate for the Department of Medicine, assisting in the promotion of equity and diversity in the professoriate search process.
Dr. Nguyen has mentored over 150 trainees of diverse racial, ethnic, and economic backgrounds and levels of training. Her research lab includes trainees who are high school students, undergraduate students, medical students, graduate students in the Master’s in Epidemiology or Public Health, PhD students in Epidemiology, clinical interns and residents, clinical gastroenterology and hepatology fellows, postdoctoral research fellows, early and mid-career faculty, and international visiting scholars. She has also served as Pre-Major Academic Advisor for the undergraduate school. Her mentees are from Stanford as well as other institutions in the US and overseas.
Dr. Nguyen is a Fellow of the American Association for the Study of Liver Diseases (AASLD) and the American Gastroenterological Association (AGA), and a member of the American College of Gastroenterology (ACG), the European Association for the Study of Liver Diseases (EASL), and the Asia Pacific Association for the Study of Liver (APASL). She is also currently the President of the International Association for the Study of Liver Diseases (IASL).
Dr. Nguyen is active in national and international professional society service and community outreach efforts locally, including service as an executive board of director for nonprofit organizations. She is very active in AASLD, having served as Chair of the Hepatitis B Special Interest Group and in the Education and Hepatology Associate Committees, as member of the Steering Committee for the Hepatobiliary Neoplasia and Hepatitis B Special Interest Group, and as a member of the Practice Guideline Committee. She is a member of the Research Award Panel for the AGA, and a member of the Practice Management Committee for the ACG.
Dr. Nguyen has served in the editorial and advisory boards for several journals, including Gastroenterology, Hepatology, Lancet GI Hepatology, and as ad hoc reviewer for over thirty scientific journals including JAMA, AIM and the Lancet Group.
Clinical Focus
- Liver cancer and tumors
- Hepatocellular Carcinoma
- Cirrhosis
- Non-alcoholic fatty liver disease
- Chronic hepatitis B and C
- Hepatology and Liver Transplantation
- End-stage liver disease
- Evaluation of abnormal liver tests
- Community Outreach
- Liver tumors
- Transplant Hepatology
Academic Appointments
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Professor - University Medical Line, Medicine - Gastroenterology & Hepatology
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Professor - University Medical Line (By courtesy), Epidemiology and Population Health
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Member, Bio-X
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Member, Stanford Cancer Institute
Administrative Appointments
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Academic Editor, PLOS Medicine (2024 - Present)
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Member, Advisory Task Force SIG, American Association for the Study of Liver Disease (AASLD) (2023 - 2025)
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President, International Association for the Study of Liver Diseases (IASL) (2023 - 2025)
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Steering Committee, HBV Special Interest Group, American Association for the Study of Liver Disease (AASLD) (2023 - 2025)
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Steering Committee, Hepatobiliary Neoplasia Special Interest Group, American Association for the Study of Liver Disease (AASLD) (2023 - 2025)
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Chair, Abstract Review Committee, Liver and Biliary Carcinoma (Treatment, Diagnosis, Nat Hx), Digestive Disease Week (American Gastroenterological Association) (2022 - Present)
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Associate Editor, Portal Hypertension & Cirrhosis (2022 - 2024)
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Faculty Search Diversity Advisor, Department of Medicine, Stanford University (2019 - Present)
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Governing Council and Treasurer, International Association for the Study of Liver Diseases (IASL) (2019 - Present)
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Clinical Practice Guideline Committee, AASLD (2019 - 2022)
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Practice Management Committee, American College of Gastroenterology (ACG) (2019 - 2022)
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Research Award Panel, American Gastroenterological Association (AGA) (2019 - 2021)
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Chair, Hepatitis B SIG, American Association for the Study of Liver Disease (AASLD) (2019 - 2020)
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Chair, Global Outreach Subcommittee, Hepatitis B Special Interest Group, American Association for the Study of Liver Disease (AASLD) (2018 - Present)
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International Advisory Board, Lancet Gastroenterology and Hepatology (2018 - Present)
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Professoriate Appointments and Promotions Committee (DoM A&P Committee), Department of Medicine, Stanford University (2018 - Present)
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International Editorial Board, Alimentary Pharmacology and Therapeutics (2018 - 2023)
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Vice-Chair, Hepatitis B SIG, American Association for the Study of Liver Disease (AASLD) (2018 - 2019)
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Editorial Board, Hepatology (2017 - 2019)
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CIGH Faculty Fellow, Center for Innovation in Global Health (CIGH), Stanford University (2015 - Present)
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Steering Committee, HBV Special Interest Group, American Association for the Study of Liver Diseases (AASLD) (2015 - Present)
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Director of Hepatology Fellowship, http://med.stanford.edu/gastrohepfellows/, Stanford University Medical Center (2014 - 2023)
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Steering Committee, Hepatobiliary Neoplasia Special Interest Group, American Association for the Study of Liver Diseases (AASLD) (2014 - 2016)
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Director of Hepatology Clerkship, Stanford University School of Medicine (2013 - Present)
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Executive Board of Director, Asian Health Foundation (2013 - Present)
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Medical Advisory Board, American Liver Foundation (2013 - Present)
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Committee Chair, Abstract Review for Chronic Hepatitis B, American Association for the Study of Liver Diseases (AASLD) (2013 - 2019)
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Education Committee, American Association for the Study of Liver Diseases (AASLD) (2013 - 2016)
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Hepatology Associates Committee , MD Liaison, American Association for the Study of Liver Diseases (AASLD) (2013 - 2016)
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Liver Section Editor, Journal of Clinical Gastroenterology (2013 - 2016)
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Editorial Board, Gastroenterology (2011 - 2023)
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Abstract review member for the Hepatitis B : Epidemiology/Prevention/Control review group, American Association for the Study of Liver Diseases (AASLD) (2011 - 2016)
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Editorial Board, Digestive Diseases and Sciences (2008 - Present)
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Director of Continuing Medical Education, Pacific Health Foundation (2005 - 2012)
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Director of Clinical Research, Pacific Health Foundation (2004 - 2010)
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Training and Workforce Committee, Member, American Association for the Study of Liver Diseases (AASLD) (2002 - 2004)
Honors & Awards
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The Professor Mindie H. Nguyen Award for Excellent Clinical Research by Young Investigators, American Asso for the Study of Liver Diseases, www.aasldfoundation.org/named-travel-awards (2020-current)
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Senior Fellow at the Center for Innovation in Global Health, Center for Innovation in Global Helath, Stanford University, Stanford, CA (2015 Oct)
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Stanford Asian American Faculty Awards, The Asian American Activities Center, Stanford University, Stanford, CA (2015 May)
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2015 Divisional Teaching Award, Department of Medicine, Stanford University Medical Center, Palo Alto, CA (2015 Dec)
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Pacific Free Clinic Physician Service Award, Cardinal Free Clinics, Stanford University School of Medicine (2013 April)
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The Franklin Edbaugh Advising Award for Faculty, Stanford University School of Medicine (2013 May)
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Chief Fellow in Gastroenterology and Hepatology, Stanford University Medical Center (2002)
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Advanced Hepatology Research Fellow Award, American Association for the Study of Liver Diseases (2001)
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Chief Resident, University of California, San Diego Medical Center (1996)
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Excellence in Teaching Award, University of California, San Diego, School of Medicine (1996)
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Magna Cum Laude, University of California, Irvine (1988)
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Phi Beta Kappa, University of California, Irvine (1985)
Boards, Advisory Committees, Professional Organizations
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See Administrative Appointment Section above, See above (2013 - Present)
Professional Education
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Fellowship: Stanford University Division of Gastroenterology and Hepatology (2002) CA
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Board Certification: American Board of Internal Medicine, Gastroenterology (2020)
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Residency: UCSD Internal Medicine Residency (1995) CA
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Medical Education: University of California San Diego School of Medicine (1992) CA
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Board Certification, American Board of Internal Medicine, Gastroenterology (2018)
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Board Certification: American Board of Internal Medicine, Transplant Hepatology (2010)
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B.S., University of California, Irvine, Biological Sciences (1988)
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M.D., Univ. of California, San Diego, Medicine (1992)
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M.A.S., Univ. of Calif., San Francisco, Masters of Advanced Studies in Clinical Research (2004)
Community and International Work
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Governning Council
Partnering Organization(s)
International Association for the Study of Liver Diseases
Ongoing Project
Yes
Opportunities for Student Involvement
No
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Board of Directors
Partnering Organization(s)
Pacific Health Foundation
Location
Bay Area
Ongoing Project
No
Opportunities for Student Involvement
No
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Board of Directors
Partnering Organization(s)
Asian Health Foundation
Location
US
Ongoing Project
No
Opportunities for Student Involvement
No
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Scientific Chair, Myanmar Liver Symposium 2018, Yangon
Topic
Viral Hepatitis and Liver Cancer
Partnering Organization(s)
Myanmar Ministry of Health&Sports and BK Kee Foundation
Populations Served
Physicians and Public Health Workers
Location
International
Ongoing Project
Yes
Opportunities for Student Involvement
Yes
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Scientific Chair, Health Needs Assessment and Liver Symposium, Yangon
Topic
Updates in Viral Hepatitis and Liver Cancer
Partnering Organization(s)
Myanmar Ministry of Health Sports, BK Kee Fdn, Stanford Global Health
Populations Served
Burmese
Location
International
Ongoing Project
Yes
Opportunities for Student Involvement
Yes
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Scientific Chair, Viral Hepatitis and Liver Cancer 2015: Mongolia National Training Workshop
Partnering Organization(s)
Mongolian Ministry of Health
Populations Served
Physicians
Location
International
Ongoing Project
No
Opportunities for Student Involvement
No
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Linkage to care, epidmiology of hepatitis B, hepatitis C, and/or liver cancer in Asia Pacific region, Mainland China, South Korea, Taiwan, Hong Kong, Japan, New Zealand, Myanmar
Location
International
Ongoing Project
Yes
Opportunities for Student Involvement
Yes
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Pacific Free Clinic
Topic
Hepatology Clinic
Location
Bay Area
Ongoing Project
No
Opportunities for Student Involvement
No
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Outreach Liver Clinics, San Jose and San Francisco, San Jose, 231 O'Connor Drive and 200 Jose Figueres Avenue; San Francisco and Daly city
Populations Served
Patients with liver disease
Location
International
Ongoing Project
Yes
Opportunities for Student Involvement
No
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Epidemiology and treatment outcomes of Asian patients with chronic hepatitis B and C, San Jose, CA and Dallas, Texas
Topic
Ethnic differences of disease activities, treatment, and outcomes in Asian Americans
Partnering Organization(s)
Pacific Health Foundation
Populations Served
Asian Americans
Location
International
Ongoing Project
Yes
Opportunities for Student Involvement
Yes
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Colon cancer screening in Asian Americans, San Jose
Partnering Organization(s)
Pacific Health Foundation
Populations Served
Asian Americans
Location
Bay Area
Ongoing Project
Yes
Opportunities for Student Involvement
Yes
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Updates in Hepatology, Vietnam
Partnering Organization(s)
University of Michigan and Vietnamese Association for the Study of Liver Diseases
Populations Served
Vietnamese Hepatologists
Location
International
Ongoing Project
No
Opportunities for Student Involvement
No
Current Research and Scholarly Interests
1. Clinical trials in fatty liver (NASH/NAFLD), liver cancer (HCC), hepatitis B and hepatitis C.
2. Epidemiology and population health of people with liver cancer, fatty liver, hepatitis B, hepatitis C, and liver cirrhosis.
3. Real-world studies of liver cancer, fatty liver, hepatitis B, hepatitis C,liver cirrhosis, and liver transplant.
4. Health disparities - sex differences, socioeconomic factors, and race/ethnicity-related issues
5. Translational studies of liver cancer, hepatitis B, and fatty liver.
6. Global health: medical education, public health, and research. Areas with current/prior work/collaboration: Spain, Romania,United Kingdom, Germany, Italy, Argentina, Brazil, Japan, Australia, New Zealand, Mainland China, Taiwan, Hong Kong, South Korea, Mongolia, Myanmar, Thailand, and Singapore.
7. Large databases used in prior published works: U.S. National Health and Nutrition Examination Survey (NHANES), Optum, Truven, Surveillance Epidemiology and End Results (SEER), UK Biobank, American Census Bureau, National Death Index (NDI), National Vital Statistic System (NVSS) from the CDC WONDER platform, National Inpatient Sample Database (NIS), United Network for Organ Sharing (UNOS), California inpatient database from the Office of Statewide Health Planning and Development (OSPHD), Taiwan National Health Insurance Research Database (NHIRD), Japan Medical Data Vision Database, Korea Health Insurance Review & Assessment Service Database (HIRA).
For more information, please contact my lab at 650-498-6084.
Clinical Trials
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ALTUS: Performance of a Multi- Target Hepatocellular Carcinoma (HCC) Test in Subjects With Increased Risk
Recruiting
The primary objective is to assess overall sensitivity and specificity of Oncoguard™ Liver for hepatocellular cancer (HCC) detection in a surveillance population.
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A Gilead Sequence Registry of Subjects Who Did Not Achieve Sustained Virologic Response
Not Recruiting
This Registry is designed to obtain long term data on participants who have failed to achieve sustained virologic response (SVR) while receiving at least one Gilead oral antiviral agent (OAV) in a previous Gilead-sponsored hepatitis C virus (HCV) study.
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H. Nguyen, MD, 650-498-7878.
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Case-Control Study of the Glycotest™ HCC Panel vs AFP for the Detection of Early-stage Hepatocellular Carcinoma
Not Recruiting
Clinical guidelines (AASLD) recommend the use of abdominal ultrasound (US) for surveillance testing for the early detection of Hepatocellular Carcinoma (HCC). The serum protein biomarker alpha-fetoprotein (AFP) is commonly used to augment US but its use alone is not recommended by clinical guidelines. Despite evidence that HCC surveillance improves early detection and reduces mortality from HCC, current HCC surveillance tests lack sensitivity, leaving a significant proportion of patients to present with late-stage disease. The Glycotest HCC Panel has shown better sensitivity than AFP, which is ineffective for the detection of early-stage HCC. This clinical study seeks to validate the Glycotest HCC Panel using a large multicenter cohort of cases and controls that includes patients diagnosed with early-stage HCC against a background of cirrhosis and cirrhotic patients without HCC (at risk) undergoing an established surveillance protocol.
Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.
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Clinical Trial Multi-analyte Blood Test
Not Recruiting
This is a clinical trial designed to evaluate the performance of a multi-analyte blood test alone to ultrasound alone for the detection of HCC within a population that is at high risk for HCC due to liver cirrhosis.
Stanford is currently not accepting patients for this trial.
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Comparative Efficacy of Fixed-dose Combination Sofosbuvir + Ledipasvir, 8 vs. 12 Weeks in Chronic Hepatitis C Genotype 6
Not Recruiting
The primary objectives of this study are to describe the efficacy of: 1. 8-week treatment of SOF/LED for treatment-naïve, non-cirrhotic, HCV genotype 6 2. 12-week treatment of SOF/LED for all other HCV-6 populations
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H Nguyen, MD, MAS, 650-498-5691.
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Efficacy & Safety of Tenofovir Disoproxil Fumarate (TDF) Plus Peginterferon α-2a (Peg-IFN) Versus TDF or Peg-IFN Monotherapy in Chronic Hepatitis B
Not Recruiting
The primary objective of this study is to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) plus peginterferon α-2a (Peg-IFN) combination therapy for 48 weeks versus standard of care TDF monotherapy or Peg-IFN monotherapy for 48 weeks in non-cirrhotic adults with chronic hepatitis B virus (HBV) as determined by loss of hepatitis B surface antigen (HBsAg). The study will consist of 2 phases for participants in the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups. Following an initial 48 weeks of treatment, participants in these groups will be monitored for 24 weeks for signs of worsening HBV, and those meeting TDF retreatment and flare management criteria will be eligible to receive TDF monotherapy during a retreatment phase, up to Week 120.
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie Nguyen, MD, 650-498-7878.
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Epidemiologic Study of Hepatocellular Carcinoma in the US
Not Recruiting
The purpose of this study is: * to investigate the risk factors of HCC among Americans with focus on lifestyle factors and energy balance. * to identify single nucleotide polymorphisms (SNPs) and haplotypes that are associated with HCC risk through a genome-wide search. * to assess if genetic susceptibility differs by hepatitis virus infection or lifestyle factors, and to explore if there are interplays or effect modifications between genetic factors and viral infection or lifestyle factors.
Stanford is currently not accepting patients for this trial.
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Evaluation of Stereotactic Radiosurgery For Liver Malignancies
Not Recruiting
This study is intended to establish the practicality of treating cancer in the liver with precisely administered single fractions of high-energy radiation using a radiosurgical (cross-firing) technique. A second purpose is to establish a safe dose for such therapy. Finally, the efficacy of radiosurgical ablation of liver tumors, in terms of radiographic response, will be measured.
Stanford is currently not accepting patients for this trial. For more information, please contact Jeff Kim, (650) 498 - 7703.
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Gilead Sustained Virologic Response (SVR) Registry
Not Recruiting
This Registry is designed to provide long term clinical and virologic follow up in participants who have achieved sustained virologic response (SVR) while participating in a previous Gilead sponsored hepatitis C virus (HCV) study. This long term follow up study is observational and no treatment is provided for HCV.
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H. Nguyen, MD, 650-498-7878.
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GS 5885 Administered Concomitantly With GS-9451, Tegobuvir and Ribavirin (RBV) in Chronic Genotype 1 Hepatitis C Virus (HCV) Infection
Not Recruiting
The purpose of this phase 2 study is to determine whether 30 mg or 90 mg of GS-5885 when given with GS-9451, Tegobuvir and Ribavirin (RBV) for 12 or 24 weeks is effective, safe and tolerable in the treatment of Chronic Genotype 1 HCV Infection.
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H Nguyen, MD, 650-498-7878.
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Hepatitis B Virus (HBV) Viral Suppression by Entecavir in Adefovir Partial Responders
Not Recruiting
We propose a largely retrospective study with short-term prospective follow-up in a subgroup of patients who have not yet been treated with 48 weeks of entecavir following partial response to adefovir. The aim of the study is to describe sequential virologic response to adefovir and entecavir.
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H. Nguyen, MD, 650-498-7878.
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Metabolic Interventions to Resolve Non-alcoholic Steatohepatitis (NASH) With Fibrosis (MIRNA)
Not Recruiting
The study aims to evaluate two, orally administered, investigational agents - PF-06865571 (DGAT2 inhibitor) and the coadministration of PF-06865571 with PF-05221304 (ACC inhibitor). This study is specifically designed to evaluate the effect of a range of doses of DGAT2i alone, and DGAT2i + ACCi, on resolution of NASH or improvement in liver fibrosis, as assessed histologically (via liver biopsy).
Stanford is currently not accepting patients for this trial. For more information, please contact SPECTRUM, (650) 722 - 4478.
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Registry Study for Patients With Chronic HBV Receiving Nucleotide Therapy
Not Recruiting
This registry will remain open for approximately 5 years (4 years of enrollment + 1 year of follow up). Subjects will be followed until Orthotopic Liver Transplant (OLT), resolution of liver decompensation, death, or conclusion of the registry.
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie Nguyen, 650-497-6474.
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Risk Factors and Molecular Genomics of U.S. Patients With Chronic Liver Disease and Hepatocellular Cancer
Not Recruiting
To identify risk factors for the development and diagnosis of hepatocellular CA in patients with chronic hepatitis C and to use the data to ultimately develop an effective screening program.
Stanford is currently not accepting patients for this trial. For more information, please contact Andrea Linder, (650) 725 - 4047.
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Safety and Efficacy of LDV/SOF Fixed-Dose Combination (FDC) ± Ribavirin in HCV Genotype 1 Subjects
Not Recruiting
This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV), administered for 8 or 12 weeks of treatment in participants with chronic genotype 1 hepatitis C virus (HCV) infection who are treatment-naive, and for 12 weeks in participants who had previously received a regimen containing a protease inhibitor for the treatment of HCV.
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H Nguyen, 650-498-7878.
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Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination (FDC) With and Without Ribavirin for the Treatment of HCV
Not Recruiting
The purpose of this study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir (LDV)/sofosbuvir (SOF) fixed-dose combination (FDC) tablets with or without ribavirin (RBV) administered for 12 and 24 weeks in treatment-naive subjects with chronic genotype 1 HCV infection.
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H. Nguyen, MD, 650-498-7878 .
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Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin in Treatment-Experienced Subjects With Genotype 1 HCV Infection
Not Recruiting
This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir fixed dose combination (FDC) with or without ribavirin (RBV) administered for 12 or 24 weeks in treatment-experienced subjects with chronic genotype 1 hepatitis C virus (HCV) infection.
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H. Nguyen, MD, 650-498-7878.
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Safety and Efficacy Study in Subjects With Chronic HCV and Underlying Hemophilia
Not Recruiting
The primary objective for this study is to evaluate the proportion of subjects who achieve SVR12 (HCV RNA \< LLOQ (target not detected) at post-treatment follow-up Week 12 in subjects with Genotype(GT)-1b, -4 and GT-2, -3
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H. Nguyen, MD, 650-498-7878.
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Safety, Tolerability, and Efficacy of 24 Weeks Simeprevir+Sofosbuvir for Chronic Hepatitis C Genotype 1
Not Recruiting
The goal of this pilot study is to examine both efficacy and tolerability in patients with HCV genotype 1 and mild decompensation with Child-Pugh-Turcott score of 6 or lower. The CPT score is used to assess the prognosis of chronic liver diseases, as well as the required strength and treatment and necessity of liver transplantation. A higher CPT score denotes higher necessity of liver transplantation.
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H Nguyen, MD, MAS, 650-498-5691.
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Samatasvir (IDX719) in Combinations With Simeprevir and/or TMC647055/Ritonavir With or Without Ribavirin for 12 Weeks in Participants With Chronic Hepatitis C Infection (MK-1894-005)
Not Recruiting
Parts A and B of this study are designed to evaluate the safety, tolerability, efficacy and pharmacokinetic profiles of samatasvir and simeprevir when administered in combination with ribavirin (RBV) for 12 weeks in treatment-naïve, Genotype (GT) 1b, 4 and 6 hepatitic C virus (HCV)-infected participants. Part C of this study is designed to evaluate the safety, tolerability, efficacy and pharmacokinetic profiles of samatasvir, simeprevir, TMC647055 and ritonavir (RTV) when administered in combination with or without RBV for 12 weeks in treatment-naïve or interferon/RBV-treatment relapsed, GT 1a and 1b HCV-infected participants.
Stanford is currently not accepting patients for this trial. For more information, please contact SPECTRUM, 650-497-6474.
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Study to Compare Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF) in Participants With Chronic Hepatitis B Infection Who Are Negative for Hepatitis B e Antigen
Not Recruiting
The primary objective of this study is to compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in treatment-naive and treatment-experienced adults with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection.
Stanford is currently not accepting patients for this trial. For more information, please contact SPECTRUM, 650-498-6084.
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Study to Compare Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF) in Participants With Chronic Hepatitis B Infection Who Are Positive for Hepatitis B e Antigen
Not Recruiting
The primary objective of this study is to compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in treatment-naive and treatment-experienced adults with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection.
Stanford is currently not accepting patients for this trial. For more information, please contact SPECTRUM, 650-498-6474.
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Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C
Not Recruiting
This study will assess the rates of Sustained Virological Response following anti-viral therapy with Peg-Interferon plus Ribavirin in patients that have been liver transplanted with recurrent Hepatitis C and treated with Neoral or tacrolimus.
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie Nguyen, MD, 650-498-7878.
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Transarterial Chemoembolization vs CyberKnife for Recurrent Hepatocellular Carcinoma
Not Recruiting
Primary Objective: To compare the efficacy of TACE vs. CyberKnife SBRT in the treatment of locally recurrent HCC after initial TACE. Secondary Objectives: 1. To determine the progression-free survival of TACE vs. CyberKnife SBRT 2. To determine the overall survival of TACE vs. CyberKnife SBRT for locally recurrent HCC 3. To determine the toxicities associated with TACE or CyberKnife SBRT for the treatment of recurrent HCC.
Stanford is currently not accepting patients for this trial. For more information, please contact Laurie Ann Columbo, (650) 736 - 0792.
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Treatment Outcomes in Chronic Hepatitis B Patients on Sequential Therapy With Tenofovir Alafenamide (TAF)
Not Recruiting
Primary Objective: To describe rate of persistence and/or improvement of viral suppression with TAF as with previous anti-HBV (hepatitis B virus) treatment
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H Nguyen, MD,MAS, 650-736-1731.
2024-25 Courses
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Independent Studies (9)
- Directed Reading in Epidemiology
EPI 299 (Aut, Win, Spr, Sum) - Directed Reading in Medicine
MED 299 (Aut, Win, Spr, Sum) - Early Clinical Experience in Medicine
MED 280 (Aut, Win, Spr, Sum) - Graduate Research
EPI 399 (Aut, Win, Spr, Sum) - Graduate Research
MED 399 (Aut, Win, Spr, Sum) - Medical Scholars Research
MED 370 (Aut, Win, Spr, Sum) - Out-of-Department Undergraduate Research
BIO 199X (Aut, Win, Spr) - Undergraduate Research
EPI 199 (Aut, Win, Spr, Sum) - Undergraduate Research
MED 199 (Aut, Win, Spr, Sum)
- Directed Reading in Epidemiology
Stanford Advisees
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Postdoctoral Faculty Sponsor
Hong Fan, Xinrong Zhang -
Master's Program Advisor
Patil Kavarian -
Postdoctoral Research Mentor
Xinrong Zhang
Graduate and Fellowship Programs
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Gastroenterology & Hepatology (Fellowship Program)
All Publications
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A Phase 3 Biomarker Validation of GALAD for the Detection of Hepatocellular Carcinoma in Cirrhosis.
Gastroenterology
2024
Abstract
Better surveillance tests for hepatocellular carcinoma (HCC) are needed. The GALAD score [Gender, Age, AFP-L3, AFP, and Des-carboxy-prothrombin] has been shown to have excellent sensitivity and specificity for HCC in phase two studies. We performed a phase three biomarker validation study to compare GALAD with AFP in detecting HCC.This is a prospective study of patients with cirrhosis enrolled at seven centers. Surveillance for HCC was performed every 6 months at each site, and HCC diagnosis was confirmed per AASLD guidelines. Blood for biomarker research was obtained at each follow-up visit and stored in a biorepository. Measurements of AFP, AFP-L3, and DCP (des-gamma carboxyprothrombin) were performed in a FujiFilm laboratory by staff blinded to clinical data. The performance of GALAD in detecting HCC was retrospectively evaluated within 12 months prior to the clinical diagnosis. All analyses were conducted by an unblinded statistician in the EDRN data management and coordinating center.A total of 1,558 patients with cirrhosis were enrolled and followed for a median of 2.2 years. A total of 109 patients developed HCC (76 very early or early stage) with an annual incident rate of 2.4%. The AUC for AFP and GALAD within 12 months prior to HCC 0.66 and 0.78 (p<0.001), respectively. Using cutoff for GALAD of -1.36, the specificity was 82% and sensitivity at 12 months prior to HCC diagnosis was 62%. For comparison, performance of AFP at 82% specificity showed 41% sensitivity at 12 months prior to HCC diagnosis (p=0.001).GALAD score, compared to AFP, improves the detection of HCC within 12 months prior to the actual diagnosis.
View details for DOI 10.1053/j.gastro.2024.09.008
View details for PubMedID 39293548
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Trends of chronic liver diseases by income level and socioeconomic factors in the United States: A population-based study.
Alimentary pharmacology & therapeutics
2024
Abstract
With polarizing income disparities, this study investigated the prevalence and trends of liver disease in a U.S. population-based sample based on income-to-poverty ratio (IPR).This cross-sectional study analysed survey data from the 1999-2018 National Health and Nutrition Examination Survey with highest (HIG), middle-income (MIG), and lowest income (LIG) groups defined as IPR ≤ 1, 1 < IPR <5, and IPR ≥ 5, respectively.We analysed 59,204 adult participants with 48.2% male, 39.7% aged 18-39, 36.2% 40-59, and 24.1% ≥60 years. The weighted prevalence of hepatitis C (HCV), B (HBV) infection, non-alcoholic fatty liver disease (NAFLD), alcohol-associated liver disease (ALD), and advanced fibrosis in LIG were 3.9% (n = 276), 7.4% (n = 527), 33.2% (n = 714), 5.2% (n = 401), and 9.0% (n = 694), respectively, compared to lower rates for HIG: 1.0% (n = 82), 3.2% (n = 263), 29.6% (n = 798), 3.9% (n = 354), and 5.0% (n = 638). After adjusting for age, sex, race and ethnicity, education, and birthplace, HIG had the lowest odds of having any liver disease [adjusted odds ratio (aOR) 0.67, p < 0.0001], with similar findings for specific conditions including HCV, HBV, and advanced fibrosis (aOR 0.24, 0.52, and 0.64, all p < 0.0001, respectively). While viraemic HCV prevalence decreased over time for HIG, there were no changes for MIG nor LIG. Similarly, NAFLD prevalence was stable for HIG but increased for MIG and LIG.LIG and MIG in the United States have higher liver disease burdens than HIG, with increasing NAFLD prevalence and lack of decline in current HCV infection prevalence over time as opposed to declining or stable trend in HIG.
View details for DOI 10.1111/apt.18242
View details for PubMedID 39238267
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Synergistic association of sodium-glucose cotransporter-2 inhibitor and metformin on liver and non-liver complications in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease.
Gut
2024
Abstract
Type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (diabetic MASLD) frequently coexist and worsen liver and non-liver outcomes, but effective pharmacological therapies are limited. We aimed to evaluate the long-term effect of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) on liver and non-liver outcomes among patients with diabetic MASLD.This population-based cohort study retrieved patients with diabetic MASLD from Merative Marketscan Research Databases (April 2013 and December 2021). The active comparator was other glucose-lowering drugs (oGLDs). Primary outcomes were liver complications including hepatocellular carcinoma (HCC) and liver cirrhosis, as well as non-liver complications including cardiovascular disease (CVD), chronic kidney disease (CKD) and non-liver cancer. Propensity score matching was applied and Cox regression models were conducted.Compared with oGLD, SGLT-2i users had significantly lower risk of HCC (HR 0.76, 95% CI 0.62 to 0.93), liver cirrhosis (HR 0.80, 95% CI 0.76 to 0.84), CVD (HR 0.82, 95% CI 0.79 to 0.85) and CKD (HR 0.66, 95% CI 0.62 to 0.70), non-liver cancer (HR 0.81, 95% CI 0.76 to 0.86). Compared with patients without metformin and SGLT-2i, a stepwise decreasing risk was observed in users of either metformin or SGLT-2i (HRs 0.76-0.97) and in users of both medications (HRs 0.58-0.79). The lower risk also was shown in liver decompensation, compensated cirrhosis, major CVD, end-stage renal disease and specific common cancers (HRs 0.61-0.84).In a nationwide cohort, SGLT-2i users were associated with a substantially lower risk of liver and non-liver complications than oGLD users among patients with diabetic MASLD. The risk was further reduced with concomitant metformin use.
View details for DOI 10.1136/gutjnl-2024-332481
View details for PubMedID 39122360
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Sex and ethnic disparities in hepatitis B evaluation and treatment across the world.
Journal of hepatology
2024; 81 (1): 33-41
Abstract
BACKGROUND & AIMS: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium.METHODS: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses.RESULTS: We analyzed 12,566 adult treatment-naive patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p=0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p<0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p<0.001).CONCLUSIONS: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.IMPACT AND IMPLICATIONS: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.
View details for DOI 10.1016/j.jhep.2024.02.033
View details for PubMedID 38906621
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MAFLD in adults: non-invasive tests for diagnosis and monitoring of MAFLD.
Hepatology international
2024
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the liver manifestation of a metabolic syndrome and is highly prevalent in the general population. There has been significant progress in non-invasive tests for MAFLD, from the diagnosis of fatty liver and monitoring of liver fat content in response to intervention, to evaluation of liver fibrosis and its change over time, and from risk stratification of patients within the context of clinical care pathways, to prognostication. Various non-invasive tests have also been developed to assess for fibrotic metabolic dysfunction-associated steatohepatitis, which has emerged as an important diagnostic goal, particularly in the context of clinical trials. Non-invasive tests can be used to diagnose clinically significant portal hypertension so that intervention can be administered to reduce the risk of decompensation. Furthermore, the use of risk stratification algorithms can identify at-risk patients for hepatocellular carcinoma surveillance. Beyond the liver, various tests that evaluate cardiovascular disease risk, assess sarcopenia and measure patient reported outcomes, can be utilized to improve the care of patients with MAFLD. This review provides an up-to-date overview of these non-invasive tests and the limitations of liver biopsy in the management of patients with MAFLD.
View details for DOI 10.1007/s12072-024-10661-x
View details for PubMedID 38913148
View details for PubMedCentralID 7154715
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Updates in characteristics and survival rates of cirrhosis in a nationwide cohort of real-world U.S. patients, 2003-2021.
Alimentary pharmacology & therapeutics
2024
Abstract
BACKGROUND: Adverse outcomes of cirrhosis remain a top priority.AIMS: We examined the distribution of cirrhosis causes, HCC incidence and mortality and related changes over time in a nationwide U.S.COHORT:METHODS: A retrospective study of a national sample of commercially insured patients with cirrhosis from Optum's de-identified Clinformatics Data Mart Database (CDM).RESULTS: A total of 628,743 cirrhosis cases were identified with 45% having NAFLD, 19.5% HCV, and 16.3% ALD. African Americans had the highest rate of decompensation (60.6%), while Asians had the highest rate of HCC (2.4%), both p<0.001. African Americans more frequently had HCV (28.4%) while Hispanic/Latinos more frequently had NAFLD (49.2%, p<0.001). Patients in the 2014-2021 cohort were significantly older (63.0±12.8 vs. 57.0±14.3), less frequently decompensated (54.5% vs. 58.3%) but more frequently had HCC (1.7% vs. 0.6%) and NAFLD (46.5% vs. 44.2%), all p<0.001. The overall annual incidence of HCC was 0.76% (95% CI: 0.75-0.77) with a 5-year cumulative incidence of 4.03% (95% CI: 3.98-4.09), with significant variation by sex, race/ethnicity, and cirrhosis aetiology. The overall median years of survival were 11.4 (95% CI: 11.3-11.5) with a 5-year cumulative survival of 73.4% (95% CI: 73.3%-73.6%), also with significant disparities in similar subgroups (lowest in cryptogenic cirrhosis and worse in 2014-2021 vs. 2003-2013). The 2014-2021 period was independently associated with worse survival (aHR: 1.14, 95% CI: 1.08-1.20).CONCLUSIONS: HCC incidence and survival vary by aetiology among patients with cirrhosis, with cryptogenic cirrhosis having the lowest survival and lower survival in the more recent time period.
View details for DOI 10.1111/apt.18024
View details for PubMedID 38693757
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Genome-wide association study identifies high-impact susceptibility loci for hepatocellular carcinoma in North America.
Hepatology (Baltimore, Md.)
2024
Abstract
Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have increased risk for hepatocellular carcinoma (HCC). However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European-descent populations (EDP).We conducted a two-stage genome-wide association study (GWAS) on HCC not affected by hepatitis B virus infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted meta-analysis. All analyses were conducted in the presence and absence of hepatitis C virus (HCV). The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for non-viral HCC: 3p22.1, MOBP, rs9842969, [0.51, (0.40-0.65)]; 5p15.33, TERT, rs2242652, [0.70, (0.62-0.79)]; 19q13.11, TM6SF2, rs58542926, [1.49, (1.29-1.72)]; 19p13.11 MAU2, rs58489806, [1.53, (1.33-1.75)]; and 22q13.31, PNPLA3, rs738409, [1.66, (1.51-1.83)]. One region was identified for HCV-induced HCC: 6p21.31, HLA-DQB1, rs9275224, [0.79, (0.74-0.84)]. A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for non-viral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC.Our GWAS highlights novel genetic susceptibility of non-viral HCC among EDP from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.
View details for DOI 10.1097/HEP.0000000000000800
View details for PubMedID 38381705
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Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis.
Clinical and molecular hepatology
2024
Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events.We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events.19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and BMI 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of liver-related mortality (p=0.054), HCC (p=0.043), and liver-related events (p=0.050) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (p<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (p<0.05).People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.
View details for DOI 10.3350/cmh.2023.0485
View details for PubMedID 38281814
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Antiviral Therapy Utilization and 10-Year Outcomes in Resected Hepatitis B Virus- and Hepatitis C Virus-Related Hepatocellular Carcinoma.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
2024: JCO2300757
Abstract
There are limited data on antiviral treatment utilization and its impact on long-term outcomes of hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after hepatic resection. We aimed to determine the utilization and impact of antivirals in HBV- and HCV-related HCC.This cohort study included 1,906 participants (1,054 HBV-related HCC and 852 HCV-related HCC) from 12 international sites. All participants had HBV- or HCV-related HCC and underwent curative surgical resection. The primary outcome was the utilization of antiviral therapy, and the secondary outcome was long-term overall survival (OS).The mean (±standard deviation [SD]) age was 62.1 (±11.3) years, 74% were male, and 84% were Asian. A total of 47% of the total cohort received antiviral therapy during a mean (±SD) follow-up of 5.0 (±4.3) years. The overall antiviral utilization for participants with HBV-related HCC was 57% and declined over time, from 65% before 2010, to 60% from 2010 to 2015, to 47% beyond 2015, P < .0001. The overall utilization of antivirals for HCV-related HCC was 35% and increased over time, from 24% before 2015 to 74% from 2015 and beyond, P < .0001. The 10-year OS was lower in untreated participants for both HBV (58% v 61%) and HCV participants (38% v 82%; both P < .0001). On multivariable Cox regression analysis adjusted for relevant confounders, antiviral therapy initiated before or within 6 months of HCC diagnosis was independently associated with lower mortality in both HBV- (adjusted hazard ratio [aHR], 0.60 [95% CI, 0.43 to 0.83]; P = .002) and HCV-related HCC (aHR, 0.18 [95% CI, 0.11 to 0.31]; P < .0001).Antiviral therapy is associated with long-term survival in people with HBV- or HCV-related HCC who undergo curative resection but is severely underutilized.
View details for DOI 10.1200/JCO.23.00757
View details for PubMedID 38175991
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Incidence and predictors of hepatocellular carcinoma in NAFLD without diagnosed cirrhosis: a nationwide real-world U.S. study.
Hepatology international
2023
Abstract
A substantial proportion of patients with nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) do not have cirrhosis. Data regarding the incidence and predictors of HCC development in NAFLD without cirrhosis are limited. We conducted a large, national study of NAFLD patients without documented cirrhosis to examine the incidence and predictors for HCC development.This retrospective study included 751,603 NAFLD patients (54% female) without documented cirrhosis derived from the deidentified Optum Clinformatics® Data Mart Database. Patients with cirrhosis, platelets < 120,000/µL or FIB-4 values > 2.67 were excluded.The mean age was 53.7 ± 15.0 years, 45.9% were male, 39.5% had diabetes, 57.6% were White, 18.4% Hispanic, 8.2% Black and 4.9% were Asian. The mean platelet count was 264,000 ± 72,000/µL, and 96.3% of patients had a FIB-4 < 1.30. Over 1,686,607 person-years of follow-up, there were 76 incident cases of HCC, resulting in an HCC incidence rate of 0.05 per 1000 person-years. There was a higher HCC incidence rate among patients with platelets ≤ 150,000/µL, versus those with platelets > 150,000/µL (0.23 per 1000 person-years, vs. 0.04 per 1000 person-years, p = 0.02) but not in subgroup analyses for age, sex, race/ethnicity or diabetes. Using multivariable Cox proportional hazards model adjusted multiple confounders, platelet count ≤ 150,000/µL remained an independent predictor of HCC development (adjusted HR 5.80, 95% CI 1.67-20.1, p = 0.006).HCC incidence in NAFLD without documented cirrhosis was below the threshold for cost-effective HCC surveillance in overall and multiple subgroup analyses. Platelet count < 150,000/µL may be a useful predictor of HCC development in this population.
View details for DOI 10.1007/s12072-023-10616-8
View details for PubMedID 38079023
View details for PubMedCentralID 8215299
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Updates in Characteristics and Survival Rates of Hepatocellular Carcinoma in a Nationwide Cohort of Real-World US Patients, 2003-2021.
Journal of hepatocellular carcinoma
2023; 10: 2147-2158
Abstract
Causes of hepatocellular carcinoma (HCC) may change as treatments become available for some liver diseases. We examined the distribution of HCC cause and survival of a nationwide cohort of insured patients.Optum's de-identified Clinformatics® Data Mart Database (CDM), 2003-2021.A total of 34707 patients with HCC were included: mean age: 68.3±11.6 years, 61% male, 62% Caucasian, 74% cirrhosis. Non-alcoholic fatty liver disease (NAFLD) was the most common etiology (38.9%), then hepatitis C virus (HCV) (25.3%), cryptogenic (18.0%), alcohol-associated liver disease (9.4%), other liver diseases (5.8%) and hepatitis B virus (HBV) at 2.6%. NAFLD patients were the oldest (mean age 71.1±11.2) and had the highest Charlson Comorbidity Index (CCI) (mean 10.5±3.9), while HCV were the youngest (mean age 64.2±9.2 years) and HBV had the lowest CCI (mean 7.2±4.4) (both P<0.0001). The overall 5-year survival was 18.8% (95% CI 18.2-19.3) but was lower in the recent 2014-2021 period vs 2003-2013 (18.1% vs 19.5%, P=0.003). The 2014-2021 cohort (inclusive of HCV treatment advances) was significantly older, with more females, fewer Caucasians, more African Americans, more Hispanics, fewer Asians, more cirrhosis, more NAFLD, and higher CCI (all P<0.001). On multivariable analysis, males (aHR: 1.13), Caucasians (aHR: 1.46), African Americans (aHR: 1.53) and Hispanics (aHR: 1.28) vs Asians, 2014-2021 (vs 2003-2013) cohort (aHR: 1.12), NAFLD (aHR: 1.14) or cryptogenic liver disease (aHR: 1.45) were associated with increased mortality (all P<0.001).HCC patients in more recent time 2014-2021 were more likely to be older, more likely to have nonviral etiology, and had worse survival compared to those from 2003 to 2013.
View details for DOI 10.2147/JHC.S420603
View details for PubMedID 38076642
View details for PubMedCentralID PMC10700040
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Treatment rates and factors associated with direct-acting antiviral therapy for insured patients with hepatitis C-related hepatocellular carcinoma - A real-world nationwide study.
Alimentary pharmacology & therapeutics
2023
Abstract
Since the inception of the interferon-free direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection, guidelines as to who should receive this potentially curative treatment have evolved. Treatment with DAAs is now considered for all patients except for those considered moribund.To determine the DAA treatment rate for patients with HCV-related hepatocellular carcinoma (HCC).This was a retrospective study from January 2015 to March 2021 of a national sample of privately insured patients with HCV-related HCC using Optum's Clinformatics® Data Mart (CDM) Database - a large, de-identified, adjudicated claims database.We identified 3922 patients with HCV-related HCC: 922 (23.5%) received DAA. Compared to untreated patients, DAA-treated patients were younger (65.2 ± 7.5 vs. 66.4 ± 7.5 years, p < 0.001), more frequently saw a gastroenterology/infectious disease (GI/ID) physician (41.2% vs. 34.2%), and had decompensated cirrhosis (56% vs. 53%, p = 0.001). In multivariable analysis, younger age (HR: 0.98, 95% CI: 0.97-0.99, p < 0.001), GI/ID care (HR: 3.06, 95% CI: 2.13-4.51, p < 0.001), and having cirrhosis (compensated: HR: 1.60, 95% CI: 1.18-2.21, p = 0.003; decompensated: HR: 1.45, 95% CI: 1.07-1.98, p = 0.02) were associated with receiving DAA treatment, but not sex, race, or ethnicity. DAA-treated patients had significantly higher 5-year survival than untreated patients (47.2% vs. 35.2%, p < 0.001). Following adjustment for age, sex, race/ethnicity, Charlson Comorbidity Index, and HCC treatment, receiving DAA treatment was associated with lower mortality (aHR: 0.61, 95% CI: 0.53-0.69, p < 0.001).DAA treatment remains underutilised in insured patients with HCV-related HCC; fewer than one in four patients received treatment. Seeing a specialist and having decompensated cirrhosis were predictors for DAA treatment; additional efforts are needed to increase awareness of HCV treatment.
View details for DOI 10.1111/apt.17794
View details for PubMedID 37937485
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Increased spine bone density in patients with chronic hepatitis B switched to tenofovir alafenamide: A prospective, multinational study.
Alimentary pharmacology & therapeutics
2023
Abstract
Data on patients switched to tenofovir alafenamide (TAF) from nucleos(t)ide analogues (NUCs) other than tenofovir disoproxil fumarate are limited.To assess the treatment and renal/bone safety outcomes following the switch to TAF.We prospectively enrolled adult patients with chronic hepatitis B (CHB) who switched from any NUC to TAF at 14 centres in Japan, Korea, Taiwan and the U.S. Study outcomes were viral suppression (VR; HBV DNA < 20 IU/mL), biochemical response (BR; alanine aminotransferase normalisation), and changes in estimated glomerular filtration rate (eGFR) and T-scores (L-spine) by bone absorptiometry by 24 months after switch to TAF.We enrolled 270 eligible patients. Mean age was 58.1; 58.2% were male; 12.2% had cirrhosis and 73.3% previously received entecavir monotherapy. VR rate increased significantly from 95.2% to 98.8% by 24 months after the switch to TAF (p = 0.014). Between the switch and 24 months later, the mean spine T-score improved significantly from -1.43 ± 1.36 to -1.17 ± 1.38 (p < 0.0001), while there was no significant change in mean eGFR (88.4 ± 16.9-89.5 ± 16.3 mL/min/1.73 m2 , p = 0.13). On multivariable analysis adjusted for age, sex, baseline spine T-score and prior TDF or adefovir dipivoxil use, male sex was significantly associated with lower risk of worsening spine T-score (odds ratio: 0.29, p = 0.020), while age was significantly associated with a higher risk of worsening chronic kidney disease stage (OR: 1.07, p = 0.019).At 24 months after the switch to TAF, VR rates and spine bone density improved significantly while renal function remained stable.
View details for DOI 10.1111/apt.17785
View details for PubMedID 37882252
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Sex differences in treatment response to nucleos(t)ide therapy in chronic hepatitis B: a multicenter longitudinal study.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2023
Abstract
It is unclear if there may be sex differences in response to nucleos(t)ide analogs (NA) including viral suppression [VR], biochemical response [BR], complete response [CR], and HCC incidence among hepatitis B patients. We compared NA treatment outcomes by sex.A retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female; 2138 male) from the REAL-B consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, USA). We used propensity-score matching (PSM) to balance background characteristics of the male and female groups and competing risks analysis to estimate incidence and subdistribution hazard ratios (SHR) of VR, BR, CR, and HCC.Females (vs. males) were older (52.0 vs. 48.6 years), less likely overweight/obese (49.3% vs. 65.7%), diabetic (9.9% vs. 13.1%), or cirrhotic (27.9% vs. 33.0%), and with lower HBV DNA (5.9 vs. 6.0 log10 IU/mL) and ALT (91 vs. 102 IU/L) [all P<0.01]. However, following PSM, relevant background characteristics became balanced between the two groups. Females (vs. males) had similar 5-year cumulative VR (91.3% vs. 90.3%, P=0.40) and HCC incidence rates (5.1% vs. 4.4%, P=0.64), but lower BR (84.0% vs. 90.9%, P<0.001) and CR (78.8% vs. 83.4%, P=0.016). Males were more likely to achieve BR (SHR: 1.31, 95% CI: 1.17-1.46, P<0.001) and CR (SHR: 1.16, 95% CI: 1.03-1.31, P=0.016) but VR and HCC risks were similar.Sex differences exist for treatment outcomes among hepatitis B patients. Male sex associated with 16% higher likelihood of clinical remission and 31% higher likelihood of biochemical response than females, while viral suppression and HCC incidence were similar between the two groups.
View details for DOI 10.1016/j.cgh.2023.09.002
View details for PubMedID 37734582
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Hepatocellular carcinoma surveillance - utilization, barriers and the impact of changing aetiology.
Nature reviews. Gastroenterology & hepatology
2023
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Surveillance for HCC is critical for early detection and treatment, but fewer than one-quarter of individuals at risk of HCC undergo surveillance. Multiple failures across the screening process contribute to the underutilization of surveillance, including limited disease awareness among patients and health-care providers, knowledge gaps, and difficulty recognizing patients who are at risk. Non-alcoholic fatty liver disease and alcohol-associated liver disease are the fastest-rising causes of HCC-related death worldwide and are associated with unique barriers to surveillance. In particular, more than one-third of patients with HCC related to non-alcoholic fatty liver disease do not have cirrhosis and therefore lack a routine indication for HCC surveillance on the basis of current practice guidelines. Semi-annual abdominal ultrasound with measurement of α-fetoprotein levels is recommended for HCC surveillance, but the sensitivity of this approach for early HCC is limited, especially for patients with cirrhosis or obesity. In this Review, we discuss the current status of HCC surveillance and the remaining challenges, including the changing aetiology of liver disease. We also discuss strategies to improve the utilization and quality of surveillance for HCC.
View details for DOI 10.1038/s41575-023-00818-8
View details for PubMedID 37537332
View details for PubMedCentralID 9670241
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Diagnostic Performance of the Fibrosis-4 Index and Nonalcoholic Fatty Liver Disease Fibrosis Score in Lean Adults With Nonalcoholic Fatty Liver Disease.
JAMA network open
2023; 6 (8): e2329568
Abstract
The diagnostic performance of the fibrosis-4 index (FIB-4) and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) for advanced fibrosis in lean patients with NAFLD is limited.To evaluate the diagnostic performance of the FIB-4 and NFS in lean individuals with NAFLD.This diagnostic study included adults with biopsy-proven NAFLD from 6 referral centers in Asia from 1995 to 2019. Cohorts were matched by age and sex between the lean and nonlean groups. All statistical analyses were executed from October 2022 to March 2023.The diagnostic performance of the FIB-4 and NFS at the current cutoff for advanced hepatic fibrosis in lean (body mass index [BMI] below 23 [calculated as weight in kilograms divided by height in meters squared]) and nonlean (BMI above 23) patients were evaluated.A total of 1501 patients were included in analysis (mean [SD] age, 46.1 [16.4] years); 788 male (52.5%), 115 lean (7.7%), 472 (30.2%) Korean, 821 (48.7%) Japanese, and 341 (21.3%) Taiwanese. Among the age- and sex-matched cohort, the mean (SD) age was 52.3 (15.1) years and 41.2% (47 of 114) were male. The diagnostic performance and areas under the operating characteristic curve of the FIB-4 (lean, 0.807 vs nonlean, 0.743; P = .28) and NFS (lean, 0.790 vs nonlean, 0.755; P = .54) between the 2 groups were comparable in the age- and sex-matched cohort. The sensitivity and specificity of the NFS showed increasing and decreasing tendency according to the BMI quartiles (P for trend < .001), while those of the FIB-4 did not (P for trend = .05 and P = .20, respectively). Additionally, although the areas under the operating characteristic curve of the FIB-4 and NFS were not significantly different in the lean group (0.807 vs 0.790; P = .09), the sensitivity of the current NFS cutoff values was lower in the lean group than in that of FIB-4 (54.4% vs 81.8%; P = .03).In this cohort study, the performance of the FIB-4 and NFS in diagnosing advanced fibrosis did not differ significantly between the 2 groups overall. However, in lean NAFLD, while the sensitivity for diagnosing advanced hepatic fibrosis remained reasonable at the current cutoff level, the sensitivity of NFS at the current cutoff was too low to be an adequate screening tool.
View details for DOI 10.1001/jamanetworkopen.2023.29568
View details for PubMedID 37589973
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Real-world treatment outcome with protease inhibitor direct-acting antiviral in advanced hepatitis C cirrhosis: a REAL-C study.
Hepatology international
2023
Abstract
Current guidelines discourage the use of direct-acting antiviral (DAA) containing protease-inhibitor (PI) in advanced HCV cirrhosis. We aimed to compare the real-world tolerability of PI vs. non-PI DAA regimens in this population.We identified advanced cirrhosis patients treated with DAA from the REAL-C registry. The primary outcome was significant worsening or improvement in CPT or MELD scores following DAA treatment.From the REAL-C registry of 15,837 patients, we included 1077 advanced HCV cirrhosis patients from 27 sites. 42% received PI-based DAA. Compared to non-PI group, the PI group was older, had higher MELD and higher percentage with kidney disease. Inverse probability of treatment weighting (IPTW; matching on age, sex, history of clinical decompensation, MELD, platelet, albumin, Asia site, Asian ethnicity, hypertension, hemoglobin, genotype, liver cancer, ribavirin) was used to balance the two groups. In the IPTW-matched cohorts, the PI and non-PI groups had similar SVR12 (92.9% vs. 90.7%, p = 0.30), similar percentages of significant worsening in CTP or MELD scores at posttreatment week 12 and 24 (23.9% vs. 13.1%, p = 0.07 and 16.5% vs. 14.6%, p = 0.77), and similar frequency of new HCC, decompensating event, and death by posttreatment week 24. In multivariable analysis, PI-based DAA was not associated with significant worsening (adjusted odds ratio = 0.82, 95% CI 0.38-1.77).Tolerability and treatment outcomes were not significantly different in advanced HCV cirrhosis treated with PI-based (vs. non-PI) DAA up to CTP-B or MELD score of 15. Safety of PI-based DAA in those with CTP-C or MELD beyond 15 awaits further data.
View details for DOI 10.1007/s12072-023-10547-4
View details for PubMedID 37273170
View details for PubMedCentralID 6821220
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Antiviral therapy substantially reduces hepatocellular carcinoma risk in chronic Hepatitis B patients in the indeterminate phase.
Hepatology (Baltimore, Md.)
2023
Abstract
BACKGROUND AIMS: Hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared to the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase.APPROACH RESULTS: We analyzed 855 adult (59% male), treatment-naive CHB patients without advanced fibrosis in the indeterminate phase at 14 centers (U.S., Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46 ± 13 years, the median ALT was 38 (IQR, 24 - 52) U/L, the mean HBV DNA was 4.5 ± 2.1 log10 IU/mL and 20% were HBeAg positive. The two groups were similar after IPTW. After IPTW (n = 819), the 5-, 10- and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients(n = 425), respectively (p = 0.02), with consistent findings in subgroup analyses for age > 35 years, males, HBeAg positive, HBV DNA > 1,000IU/mL, and ALT < upper limit of normal. In multivariable Cox proportional hazards analysis adjusted for age, sex, HBeAg, HBV DNA, ALT, diabetes, and platelets, antiviral therapy remained an independent predictor of reduced HCC risk (adjusted HR 0.3, 95%CI 0.1 - 0.6, p = 0.001).CONCLUSION: Antiviral therapy reduces HCC risk by 70% among indeterminate phase CHB patients. These data have important implications for the potential expansion of CHB treatment criteria.
View details for DOI 10.1097/HEP.0000000000000459
View details for PubMedID 37184202
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Utilization of Antiviral Therapy for Patients With Hepatitis B-Related Hepatocellular Carcinoma: A Nationwide Real-World US Study.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2023
Abstract
Although oral antiviral therapy (OAV) is reported to improve outcomes in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), it is underutilized. We determined the rate and factors associated with OAV utilization among patients with HBV-related HCC in a US population with health insurance.Patients with HBV-related HCC were identified from the de-identified administrative health claims database for patients with private insurance, Optum Clinformatics (2003-2021).We identified 2129 patients with HBV-related HCC: 71% male, mean age 62.7 ± 12.5 years, 40% Asian individuals, 72% with cirrhosis, and 37% received OAV. The treatment rate improved over time (40.5% after 2010 vs 26.3% earlier; P < .001). Significantly lower treatment rates were noted for females, non-Asian patients, noncirrhotic patients, and patients without gastroenterologist/hepatologist or infectious disease (GI/ID) specialist care (P < .0001). OAV treatment predictors included Asian race and ethnicity (adjusted odds ratio [aOR], 3.6; 95% CI, 2.8-4.5; P < .001), male sex (aOR, 1.6; 95% CI, 1.3-2.0; P < .001), seeing a GI/ID specialist (aOR, 1.5; 95% CI, 1.10-1.99; P = .0091), having compensated cirrhosis (aOR, 2.2; 95% CI, 1.7-2.8; P < .001), and being treated from 2011 to 2021 (aOR, 2.3; 95% CI, 1.8-3.0; P < .001); being younger (aOR, 0.98; 95% CI, 0.98-0.99; P < .001) was less likely for treatment. OAV initiated at or before HCC diagnosis was associated independently with improved survival (adjusted hazard ratio, 0.84; 95% CI, 0.72-0.99; P = .037).Among patients with HBV-related HCC, only 1 in 3 received OAV despite having insurance coverage. Efforts must continue to develop ways to improve HBV OAV treatment, especially among females, non-Asian patients, and patients without cirrhosis or not seen by specialists.
View details for DOI 10.1016/j.cgh.2023.04.020
View details for PubMedID 37805836
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Development and validation of a REcurrent Liver cAncer Prediction ScorE (RELAPSE) following liver transplantation in patients with hepatocellular carcinoma: analysis of the us multicenter hcc transplant consortium.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
2023
Abstract
Hepatocellular carcinoma (HCC) recurrence following liver transplantation (LT) is highly morbid and occurs despite strict patient selection criteria. Individualized prediction of post-LT HCC recurrence risk remains an important need.Clinico-radiologic and pathologic data of 4981 patients with HCC undergoing LT from the United States Multicenter HCC Transplant Consortium (UMHTC) were analyzed to develop a REcurrent Liver cAncer Prediction ScorE (RELAPSE). Multivariable Fine and Gray competing risk analysis and machine learning algorithms (MLA; Random Survival Forest [RSF] and Classification and Regression Tree (CART) models) identified variables to model HCC recurrence. RELAPSE was externally validated in 1160 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant (EurHeCaLT) study group.Of 4981 UMHTC patients with HCC undergoing LT, 71.9% were within Milan criteria (MC), 16.1% were initially beyond MC with 9.4% downstaged prior to LT, and 12.0% had incidental HCC on explant pathology. Overall and recurrence-free survival at 1-, 3-, and 5-years was 89.7%, 78.6%, 69.8% and 86.8%, 74.9%, 66.7%, respectively, with a 5-year incidence of HCC recurrence of 12.5% (median 16 mo) and non-HCC mortality of 20.8%. A multivariable model identified maximum AFP (HR = 1.35 per-log SD, 95%-CI:1.22-1.50,p < 0.001), neutrophil-lymphocyte ratio (HR = 1.16 per-log SD, 95%-CI:1.04-1.28,p < 0.006), pathologic maximum tumor diameter (HR = 1.53 per-log SD, 95%-CI 1.35-1.73,p < 0.001), microvascular (HR = 2.37, 95%-CI:1.87-2.99,p < 0.001) and macrovascular (HR = 3.38, 95%-CI:2.41-4.75,p < 0.001) invasion, and tumor differentiation (moderate HR = 1.75, 95%-CI:1.29-2.37,p < 0.001; poor HR = 2.62, 95%-CI:1.54-3.32,p < 0.001) as independent variables predicting post-LT HCC recurrence (C-statistic = 0.78). MLAs incorporating additional covariates improved prediction of recurrence (RSF C-statistic = 0.81). Despite significant differences in EurHeCaLT recipient radiologic, treatment, and pathologic characteristics, external validation of RELAPSE demonstrated consistent 2 and 5-year recurrence risk discrimination (AUC 0.77 and 0.75, respectively).We develop and externally validate a RELAPSE score which accurately discriminates post-LT HCC recurrence risk, and may allow for individualized post-LT surveillance, immunosuppression modification, and selection of high-risk patients for adjuvant therapies.
View details for DOI 10.1097/LVT.0000000000000145
View details for PubMedID 37029083
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Global incidence of non-alcoholic fatty liver disease: a systematic review and meta-analysis of 63 studies and 1,201,807 persons.
Journal of hepatology
2023
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. We aimed to estimate the pooled global NAFLD incidence.We performed a systematic review and meta-analysis of cohort studies of adults without NAFLD at baseline to evaluate the global incidence of ultrasound-diagnosed NAFLD.A total of 63 eligible studies (1,201,807 persons) were analyzed. Studies were from Mainland China/Hong Kong (n=26), South Korea (n=22), Japan (n=14), other (n=2, Sri Lanka, Israel); 63.8% were clinical center studies; median study year 2000 to 2016; 87% were good quality. Among the 1,201,807 persons at risk, 242,568 persons developed NAFLD with incidence rate of 4,612.8 (95% CI 3,931.5-5,294.2) per 100,000 person-years; no statistically significant differences by study sample size (P=0.90) or study setting (P=0.055). Males had higher incidence versus females (5,943.8 vs. 3,671.7, P=0.0013). Both the obese (vs. nonobese) and the overweight/obese groups (vs. normal weight) were about 3 times more likely to develop NAFLD (8,669.6 vs. 2,963.9 and 8,416.6 vs. 3,358.2, respectively) (both P<0.0001). Smokers had higher incidence than nonsmokers (8,043.2 vs. 4,689.7, P=0.046). By meta-regression, adjusting for study year, study setting, and study location, study period of 2010 or after and study setting were associated with increased incidence (P=0.010 and P=0.055, respectively). By country, China had a higher NAFLD incidence compared to non-China regions (P=0.012) and Japan a lower incidence compared to non-Japan regions (P=0.005).NAFLD incidence is increasing with a current estimate of 4,613 new cases per 100,000 years. Males and overweight/obese had significantly higher incidence rates compared to females and those of normal weight. Public health interventions for prevention of NAFLD are needed with a special emphasis on males, overweight/obese persons, and higher risk region. Impact and Implications; Non-alcoholic fatty liver disease (NAFLD) affects approximately 30% of people worldwide and appears to be increasing but data to estimate the incidence rate are limited. In this meta-analytic study of over 1.2 million people, we estimated the incidence rate of NAFLD was 46.13 per 1000 person years with significant differences by sex, BMI, geography, and time-period. As treatment options for NAFLD remain limited, prevention of NAFLD should remain the focus of public health. Studies such as these can help policy makers in determining which and whether their prevention interventions are impactful.
View details for DOI 10.1016/j.jhep.2023.03.040
View details for PubMedID 37040843
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Global burden of hepatitis B virus: current status, missed opportunities and a call for action.
Nature reviews. Gastroenterology & hepatology
2023
Abstract
Chronic hepatitis B virus (HBV) infection affects about 296 million people worldwide and is the leading aetiology of cirrhosis and liver cancer globally. Major medical complications also include acute flares and extrahepatic manifestations. In addition, people living with HBV infection also experience stigma. HBV-related cirrhosis resulted in an estimated 331,000 deaths in 2019, and it is estimated that the number of deaths from HBV-related liver cancer in 2019 was 192,000, an increase from 156,000 in 2010. Meanwhile, HBV remains severely underdiagnosed and effective measures that can prevent infection and disease progression are underutilized. Birth dose coverage for HBV vaccines remains low, particularly in low-income countries or regions where HBV burden is high. Patients with HBV infection are inadequately evaluated and linked to care and are undertreated worldwide, even in high-income countries or regions. Despite the goal of the World Health Organization to eliminate viral hepatitis as a public health problem by 2030, the annual global deaths from HBV are projected to increase by 39% from 2015 to 2030 if the status quo remains. In this Review, we discuss the current status and future projections of the global burden of HBV infection. We also discuss gaps in the current care cascade and propose future directions.
View details for DOI 10.1038/s41575-023-00760-9
View details for PubMedID 37024566
View details for PubMedCentralID 6096795
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Perspectives on the Underlying Etiology of HCC and Its Effects on Treatment Outcomes.
Journal of hepatocellular carcinoma
2023; 10: 413-428
Abstract
Hepatocellular carcinoma (HCC) continues to be a serious medical problem with poor prognosis worldwide. The distribution of the major etiologies of HCC is changing due to the progress of anti-viral treatments, including hepatitis B virus (HBV) suppression by nucleoside/nucleotide analogues (NAs) and increased sustained virologic response (SVR) rates by direct-acting antivirals (DAAs) for hepatitis C virus (HCV), as well as the rising trend of nonviral liver disease. Although viral hepatitis remains the most common cause of HCC, non-alcoholic liver disease (NAFLD) with metabolic syndrome and alcohol-associated liver disease (ALD) are increasing. Effective and well-tolerated NAs treatment can slow the disease progression of chronic HBV infection to cirrhosis, end-stage liver disease, and reduce HCC risk. Treatment with NAs is also associated with significant improvement in the long-term survival of patients with HBV infection who already have HCC. DAAs have achieved viral elimination in almost all patients with HCV without significant adverse events, even in patients with decompensated liver cirrhosis and HCC. Similarly, DAA therapy can reduce disease progression, liver and non-liver complications, and improve the long-term survival of patients with chronic HCV infection with or without HCC. Meanwhile, NAFLD is a rapidly increasing cause of HCC along with the epidemics of obesity and type 2 diabetes globally. NAFLD-related HCC can occur in patients without cirrhosis and is known to have a lower survival rate than viral hepatitis-related HCC. Since there is currently no specific pharmacotherapy effective for NAFLD, lifestyle modification and prevention of complications are important to improve prognosis. Additionally, ALD is the second fastest-growing cause of HCC-related deaths, especially with an accelerated trend since the COVID-19 pandemic. This review provides an overview of the epidemiologic trends in the etiologies of HCC, and the progress of treatments for each etiology and the impact on outcome in the patients with HCC.
View details for DOI 10.2147/JHC.S347959
View details for PubMedID 36926055
View details for PubMedCentralID PMC10013586
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Effectiveness and tolerability of camrelizumab combined with molecular targeted therapy for patients with unresectable or advanced HCC.
Cancer immunology, immunotherapy : CII
2023
Abstract
There is a lack of effective programmed cell death protein 1 (PD-1)-targeted immunotherapy with good tolerability in patients with advanced hepatocellular carcinoma (HCC) and severely compromised liver function. We assessed patient outcomes after combined camrelizumab and molecular targeted therapy in a multicenter cohort study in China. The study included 99 patients with advanced HCC (58 Child-Pugh A and 41 Child-Pugh B), 84 of them received camrelizumab combined with molecular targeted therapy from January 10, 2019, to March 31, 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were assessed. The median follow-up was 12.1 months. For patients with Child-Pugh B, the OS probability at 12-months, ORR and DCR were 49.7%, 31.7% and 65.9%, respectively, and the median PFS was 5.1 months [95% confidence interval (CI) 3.0-7.1], which were comparable with Child-Pugh A patients, although median OS was shorter in Child-Pugh B patients (20.5 vs.13.4 months, P = 0.12). In multivariate analysis, macrovascular infiltration (MVI), but not sex, age, hepatitis B virus etiology, extrahepatic metastasis, Child-Pugh B, or AFP > 400 ng/ml, was associated with 12-months OS [hazard ratio (HR) 2.970, 95% CI 1.276-6.917, P = 0.012] and ORR (HR 2.906, 95% CI 1.18-7.16, P = 0.020). Grade 3/4 immune-related AEs occurred in 26.8% of Child-Pugh B patients, including one potentially treatment-related death. In both groups, the most common AEs were immune thrombocytopenia and hepatotoxicity. Camrelizumab combined with targeted therapy showed favorable effectiveness and tolerability with manageable toxicities in Chinese HCC patients, regardless of Child-Pugh A/B liver function. MVI was associated with suboptimal immunotherapy response and poor prognosis.
View details for DOI 10.1007/s00262-023-03404-8
View details for PubMedID 36840762
View details for PubMedCentralID 6813818
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Global treatment rate and barriers to DAA therapy: A systematic review and meta-analysis of 146 studies and 1,760,352 HCV patients.
Liver international : official journal of the International Association for the Study of the Liver
2023
Abstract
Global data on the treatment rate with direct-acting antivirals (DAAs) for chronic hepatitis C (CHC) are sparse. We aimed to evaluate the CHC treatment rate and barriers to treatment in the DAA era.We searched PubMed, EMBASE, and Cochrane from inception to August 5, 2021, for relevant articles. Patients treated with DAAs without interferon (IFN) therapy were categorized as IFN-free DAAs. Patients receiving DAA with IFN or unclear IFN status were categorized as DAA/IFN.We identified and analyzed data from 146 studies (1,760,352 CHC patients). DAA/IFN treatment rate was 16.0% (95% CI: 9.9-23.3, 49 studies, 886,535 patients). IFN-free DAA treatment rate was 52.3% (95% CI: 46.2 - 58.4, 123 studies, 1,276,754 patients): 45.4% in North America, 64.2% in South America (1 study), 90.4% in Africa (most data from Egypt), 54.4% in Europe, 60.7% in Australia, and 60.5% in Asia, p < 0.0001); 49% with hepatitis B co-infection, and 32.3% with hepatocellular carcinoma (HCC). Treatment was not a priority in 22.8% of patients in Europe and 16.7% in Australia, compared to only 4.8% in North America and 2.1% in Asia (P<0.0001). Poor adherence to clinic follow-up was the cause of no treatment in 74.7% of patients in Australia, 37.0% in North America, 7.9% in Europe, and 14.3% in Asia (P<0.0001).Though a marked improvement from IFN/DAA, the treatment rate with IFN-free DAA remains suboptimal (52.3% overall, 32.3% in HCC patients). Non-adherence to clinical follow-up and lack of disease awareness were treatment barriers.
View details for DOI 10.1111/liv.15550
View details for PubMedID 36825358
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Racial and Ethnic Disparities in Characteristics and Care Patterns of Chronic Hepatitis B Patients in the United States.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2023
Abstract
CHB disproportionately impacts foreign-born patients and those of Asian or Black race. Given the paucity of data, we aimed to study the impact of race/ethnicity on chronic hepatitis B (CHB) patient characteristics and management.A retrospective analysis of adult CHB patients using data recorded in the deidentified Optum Clinformatics® Data Mart Database (1/2003‒3/2021) was performed. We characterized and examined the rates of receiving adequate treatment evaluation (measuring HBV DNA and alanine transaminase) and HBV treatment among the racial and ethnic groups.The study cohort included 42,140 patients: age 51.9±15.1 years, 56.1% male, 47% Asian, 26% White, 11% Black, and 7% Hispanic. 33% of White and 48% of Asian patients had annual household income >100,000 USD compared to 16% for Black and 25% for Hispanic patients (P<0.001), with similar disparities in educational levels. About one-third of White (29.3%), Black (35.1%), and Hispanic (35.4%) and half of Asian (49.9%) patients received adequate evaluation (P<0.001). Among patients who met AASLD treatment criteria, treatment rates were similar among White (60.8%, P=0.09) and Black (62.8%, P=0.48) but lower among Hispanic (54.7%, P=0.03) as compared to Asian patients (65.4%). On multivariable logistic regression adjusted for age, sex, provider type, viral co-infection, and fatty liver disease, Hispanic patients were less likely to receive treatment (adjusted hazards ratio: 0.69, 95%CI 0.53‒0.91, P=0.01) compared to Asian patients.Compared to Asian CHB patients, non-Asian patients were less likely to undergo adequate evaluation and Hispanic patients less likely to receive treatment for CHB. Additional efforts are needed to improve CHB management, especially for non-Asian patients.
View details for DOI 10.1016/j.cgh.2023.01.035
View details for PubMedID 36781005
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Racial and ethnic disparities in years of potential life loss among patients with cirrhosis during the COVID-19 pandemic in the United States.
The American journal of gastroenterology
2023
View details for DOI 10.14309/ajg.0000000000002191
View details for PubMedID 36728136
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Meta-analysis: Chemoprevention of hepatocellular carcinoma with statins, aspirin and metformin.
Alimentary pharmacology & therapeutics
2023
Abstract
BACKGROUND: Emerging data suggest that statins, aspirin and metformin may protect against hepatocellular carcinoma (HCC) development. However, prior meta-analyses were limited by heterogeneity and inclusion of studies without adequate adjustment for baseline risks.AIM: To examine by an updated meta-analysis the association between these medications and HCC risk.METHODS: Medline and Embase databases were searched from inception to March 2022 for studies that balanced baseline risks between study groups via propensity score matching or inverse probability of treatment weighting, that reported the impact of statins, aspirin or metformin on HCC risk. Multivariable-adjusted hazard ratios (HRs) for HCC were pooled using a random effects model.RESULTS: Statin use was associated with reduced HCC risk overall (HR: 0.52; 95% CI: 0.37-0.72) (10 studies, 1,774,476), and in subgroup analyses for cirrhosis, hepatitis B/C, non-alcoholic fatty liver disease, studies accounting for concurrent aspirin and metformin consumption and lipophilic statins. Aspirin use was associated with reduced HCC risk overall (HR: 0.48; 95% CI: 0.27-0.87) (11 studies, 2,190,285 patients) but not in studies accounting for concurrent statin and metformin use. Metformin use was not associated with reduced HCC risk overall (HR: 0.57; 95% CI: 0.31-1.06) (3 studies, 125,458 patients). Most analyses had moderate/substantial heterogeneity, except in follow-up <60months for aspirin (I2 =0%).CONCLUSION: Although statin and aspirin use were associated with reduced HCC risk, only statin use was significant in subgroup analyses accounting for concurrent medications. Metformin use was not associated with reduced HCC risk. These data have implications for future clinical trial design.
View details for DOI 10.1111/apt.17371
View details for PubMedID 36625733
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NAFLD and Non-Liver Comorbidities.
Clinical and molecular hepatology
2023
View details for DOI 10.3350/cmh.2022.0442
View details for PubMedID 36603574
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Liver-Related Mortality in Hepatitis B Virus Core Antibody+/Hepatitis B Virus Surface Antigen- Patients: Occult Hepatitis B Virus, Hepatitis B Virus Reactivation, and Hepatocellular Carcinoma Development.
The American journal of gastroenterology
2023; 118 (1): 24-25
Abstract
Although hepatitis B virus surface antigen (HBsAg) serum clearance is an important milestone in the natural history of chronic hepatitis B virus (HBV) infection, HBsAg-negative patients are at risk of liver cancer and liver-related death, especially when progressive fibrosis is present. HBsAg-negative/anti-HBV core antibody-positive patients should be carefully evaluated and managed accordingly for the presence of significant liver fibrosis, other viral coinfections, occult HBV infection, risk of HBV reactivation, and hepatocellular carcinoma. Antiviral prophylaxis should be initiated in isolated anti-HBV core antibody patients receiving high-risk chemotherapy or biologics. Hepatocellular carcinoma surveillance with liver ultrasound and serum alpha-fetoprotein should be considered for patients with risk factors.
View details for DOI 10.14309/ajg.0000000000002030
View details for PubMedID 36602834
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Impact of the COVID-19 pandemic on liver disease-related mortality rates in the United States
JOURNAL OF HEPATOLOGY
2023; 78 (1): 16-27
View details for DOI 10.1016/s0168-8278(22)03263-9
View details for Web of Science ID 000923633900004
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Outcomes in liver transplant recipients with nonalcoholic fatty liver disease-related HCC: results from the US multicenter HCC transplant consortium.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
2023; 29 (1): 34-47
Abstract
NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.
View details for DOI 10.1097/LVT.0000000000000007
View details for PubMedID 36630156
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Association of Direct-Acting Antiviral Therapy With Liver and Nonliver Complications and Long-term Mortality in Patients With Chronic Hepatitis C.
JAMA internal medicine
2022
Abstract
Chronic hepatitis C (CHC) and its complications are associated with high rates of morbidity and mortality. However, large-scale data analysis of the long-term liver and nonliver effects of direct-acting antiviral (DAA) treatment has been limited.To assess the association of hepatitis C virus elimination through DAA treatment with the risk of liver and nonliver morbidity and mortality during long-term follow-up among a large nationwide cohort of insured patients with CHC in the US.This was a retrospective cohort study of 245 596 adult patients with CHC using data from the Optum Clinformatics Data Mart database, 2010 to 2021. Of the total cohort, 40 654 patients had received 1 or more prescriptions for DAA medication (without interferon), and 204 942 patients were untreated.Treatment with a DAA.Incidence of hepatocellular carcinoma (HCC), liver decompensation, relevant nonliver events (nonliver cancer, diabetes, chronic kidney disease, cardiovascular disease), and overall mortality.The DAA-treated cohort (vs untreated) were older (mean [SD] age, 59.9 [10.8] vs 58.5 [13.0] years; P < .001); more likely to be male (25 060 [62%] vs 119 727 [58%] men; P < .001) and White (23 937 [59%] vs 115 973 [57%]; P < .001) individuals; and more likely to have diabetes (10 680 [26%] vs 52 091 [25%]; P < .001) or cirrhosis (17 971 [44%] vs 60 094 [29%]; P < .001). Comparing DAA-treated with untreated patients, the incidence (per 1000 person-years) of liver outcomes (eg, decompensation, 28.2 [95% CI, 27.0-29.4] vs 40.8 [95% CI, 40.1-41.5]; P < .001, and HCC in compensated cirrhosis, 20.1 [95% CI, 18.4-21.9] vs 41.8 [95% CI, 40.3-43.3]; P < .001) and nonliver outcomes (eg, diabetes, 30.2 [95% CI, 35.4-37.7] vs 37.2 [95% CI, 36.6-37.9]; P < .001; and chronic kidney disease, 31.1 [95% CI, 29.9-32.2] vs 34.1 [95% CI, 33.5-34.7]; P < .001) were significantly lower in treated patients. The all-cause mortality rates per 1000 person-years were also significantly lower in DAA-treated compared with untreated patients (mortality, 36.5 [95% CI, 35.4-37.7] vs 64.7 [95% CI, 63.9-65.4]; P < .001). In multivariable regression analysis, DAA treatment was independently associated with a significant decrease in the risk of liver (adjusted hazard ratio [aHR] for HCC, 0.73; decompensation, 0.36), nonliver (aHR for diabetes, 0.74; chronic kidney disease, 0.81; cardiovascular disease, 0.90; nonliver cancer, 0.89), and mortality outcomes (aHR, 0.43).The findings of this retrospective cohort study indicate that DAA treatment for insured patients with CHC was associated with improved liver- and nonliver outcomes, and ultimately, with long-term overall survival.
View details for DOI 10.1001/jamainternmed.2022.5699
View details for PubMedID 36508196
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Curing chronic hepatitis B virus infection.
The Lancet. Infectious diseases
2022
View details for DOI 10.1016/S1473-3099(22)00743-5
View details for PubMedID 36509099
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Characteristics and outcomes of hepatocellular carcinoma patients with macrovascular invasion following surgical resection: a meta-analysis of 40 studies and 8,218 patients.
Hepatobiliary surgery and nutrition
2022; 11 (6): 848-860
Abstract
Guidelines recommend that hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and/or hepatic vein tumor thrombosis (HVTT) should undergo systemic therapy. However, recent data suggest that surgical resection may be beneficial in selected cases, but outcomes are heterogenous. We aimed to estimate pooled overall survival (OS), recurrence free survival (RFS) and complication rates in HCC patients with macrovascular invasion (MVI) following surgical resection.In this systematic review and meta-analysis, two investigators independently searched PubMed, Embase, and Cochrane databases from inception to Nov 10, 2020, without language restrictions, for studies reporting outcomes of adult HCC patients with MVI who underwent liver resection with curative intent.We screened 8,598 articles and included 40 studies involving 8,218 patients. Among all patients with MVI, the pooled median OS was 14.39 months [95% confidence interval (CI): 10.99-18.84], 1-year OS was 54.47% (95% CI: 46.12-62.58%) and 3-year OS was 23.20% (95% CI: 16.61-31.42%). Overall, 1- and 3-year RFS were 27.70% (95% CI: 21.00-35.57%) and 10.06% (95% CI: 6.62-15.01%), respectively. Among patients with PVTT, median OS was 20.41 months in those with segmental/2nd order involvement compared to 12.91 months if 1st order branch was involved and 6.41 months if the main trunk was involved. The pooled rate of major complications was 6.17% (95% CI: 3.53-10.56%).Overall median survival was 14.39 months for HCC patients with MVI following resection. Median survival was higher in PVTT with segmental/2nd order involvement at 20.41 versus 6.41 months if the main trunk was involved.
View details for DOI 10.21037/hbsn-21-419
View details for PubMedID 36523924
View details for PubMedCentralID PMC9745615
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Characteristics and Treatment Rate of Patients With Hepatitis C Virus Infection in the Direct-Acting Antiviral Era and During the COVID-19 Pandemic in the United States.
JAMA network open
2022; 5 (12): e2245424
Abstract
Clinical data on hepatitis C virus (HCV) treatment rates in the United States are sparse.To evaluate HCV treatment rates in the era of direct-acting antivirals (DAAs).This retrospective cohort study used data from the deidentified Optum Cliniformatics Data Mart Database (2014-2021) on patients with HCV in the DAA and COVID-19 eras. The database includes patients with private health insurance in the US.The treatment rate and changes over time were assessed with adjusted log-binomial regression, and factors associated with treatment were examined using multivariable logistic regression.A total of 133 348 patients with HCV (79 567 [59.7%] men; mean [SD] age, 59.7 [12.3] years; 4448 [3.3%] Asian, 24 662 [18.5%] Black, and 74 750 [56.1%] White individuals) were included; 38 180 (26.8%) had HCV RNA data, and of those, 20 277 (53.1%) had positive HCV RNA. Overall, 13 214 patients with positive HCV RNA tests (65.2%) received DAA treatment; 6456 of 6634 patients treated with DAAs (97.3%) achieved sustained virologic response. After adjusting for age, sex, and race and ethnicity, the treatment rate in 2018 was 0.5 times greater than the rate in 2014 (adjusted prevalence ratio, 1.50; 95% CI, 1.42-1.59) but declined after 2018, decreasing from 64.8% to 61.2%, and especially after 2019, when it decreased to less than 60% (P < .001). The number of patients with viremic HCV identified in between April 2020 and March 2021 also decreased to 496 from 2761 and 3258 in the preceding 2 years. Receiving care from a gastroenterologist or infectious disease specialist with advanced care practitioner (ie, nurse practitioner, physician assistant, or clinical nurse specialist) was independently associated with greater odds of DAA treatment (adjusted odds ratio [aOR], 1.64; 95% CI, 1.07-1.50). Patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) were 31% less likely to receive treatment compared with those without (aOR, 0.69; 95% CI, 0.54-0.90).In this cohort study, less than two-thirds of insured patients with viremic HCV received DAA treatment, with declines in both the treatment rate and the number of viremic HCV diagnoses since 2019 and especially during the COVID-19 pandemic. Further efforts are needed to increase HCV diagnosis and treatment, especially for those with cirrhosis and HCC. An urgent call for nationwide actions to improve access to DAA treatment, community outreach programs, and specialists through referral pipelines is needed in the United States to stay on track to meet the World Health Organization goal of reducing the burden of viral hepatitis with the eventual goal to eliminate viral hepatitis.
View details for DOI 10.1001/jamanetworkopen.2022.45424
View details for PubMedID 36477481
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A Reappraisal of the Diagnostic Performance of B-Mode Ultrasonography for Mild Liver Steatosis.
The American journal of gastroenterology
2022
Abstract
Previous studies have shown that ultrasonography has high specificity (80%-100%) but low sensitivity (50%-70%) in diagnosing fatty liver; sensitivity is especially low for mild steatosis. In this study, we aimed to reappraise the diagnostic performance of B-mode ultrasonography (B-USG) for fatty liver disease.We performed a retrospective, multinational, multicenter, cross-sectional, observational study (6 referral centers from 3 nations). We included 5,056 participants who underwent both B-USG and magnetic resonance proton density fat fraction (MRI-PDFF) within a 6-month period. The diagnostic performance of B-USG was compared with that of MRI-PDFF as a reference standard for fatty liver diagnosis, using sensitivity, specificity, positive and negative predictive values, diagnostic accuracy, and area under the receiver operating characteristic curve (AUC).B-USG showed a sensitivity of 83.4%, specificity of 81.0%, and AUC of 0.822 in diagnosing mild liver steatosis (6.5% ≤MRI-PDFF ≤14%). The sensitivity, specificity, and AUC in diagnosing the presence of fatty liver disease (MRI-PDFF ≥6.5%) were 83.4%, 81.0%, and 0.822, respectively. The mean PDFF of B-USG-diagnosed nonfatty liver differed significantly from that of diagnosed mild liver steatosis (3.5% ± 2.8% vs 8.5% ± 5.0%, P < 0.001). The interinstitutional variability of B-USG in diagnosing fatty liver was similar in diagnostic accuracy among the 6 centers (range, 82.8%-88.6%, P = 0.416).B-USG was an effective, objective method to detect mild liver steatosis using MRI-PDFF as comparison, regardless of the etiologies and comorbidities.
View details for DOI 10.14309/ajg.0000000000002020
View details for PubMedID 36305695
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Prevalence, characteristics, and mortality outcomes of obese and nonobese MAFLD in the United States.
Hepatology international
2022
Abstract
BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) establishes new criteria for diagnosis of fatty liver disease independent of alcohol intake. We aimed to describe the prevalence and compare characteristics and mortality outcomes of persons with nonobese and obese MAFLD.METHODS: Using data from 13,640 participants from the third National Health and Nutrition Examination Survey (NHANES III) 1988-1994, we identified participants with fatty liver on ultrasound who had MAFLD and analyzed them by the presence of obesity.RESULTS: Overall prevalence of MAFLD was 19%; amongst those, 54% were obese and 46% were nonobese. Nonobese MAFLD was more common in participants older than 65 than in younger participants (56.8% vs. 43.2%, p<0.0001). Nonobese MAFLD was more common in males (63.2% vs. 48.3%, p<0.0001). Obese MAFLD was more common in females (51.7% vs. 48.3%, p<0.0001). After adjusting for several demographic factors and alcohol use, older age [adjusted odds ratio (aOR) 1.02, 95% CI 1.00-1.02, p=0.003] and being male (aOR: 1.65, 95% CI 1.25-2.17, p=0.001) were independent risk factors for nonobese MAFLD. Nonobese MAFLD participants had a higher 20-year cumulative incidence for all-cause mortality compared to obese MAFLD participants (33.2% vs. 28.8%, p=0.0137). However, nonobese MAFLD was not independently associated with mortality after adjusting for relevant confounders, while FIB-4>1.3 and cardiovascular disease were the strongest risk factors associated with increased mortality [adjusted hazard ratio (aHR) >2.7 for both, p<0.0001 for both].CONCLUSIONS: Nonobese MAFLD constitutes about half of the MAFLD in the United States, especially among males and the elderly. Notably, nonobese MAFLD carries higher mortality than obese MAFLD. Screening and diagnosis of MAFLD should be considered in nonobese populations.
View details for DOI 10.1007/s12072-022-10436-2
View details for PubMedID 36309601
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Gaps in hepatocellular carcinoma surveillance among insured patients with hepatitis B infection without cirrhosis in the United States.
Hepatology communications
2022
Abstract
Suboptimal adherence to guidelines for hepatocellular carcinoma (HCC) surveillance among high-risk patients is a persistent problem with substantial detriment to patient outcomes. While patients cite cost as a barrier to surveillance receipt, the financial burden they experience due to surveillance has not been examined. We conducted a retrospective administrative claims study to assess HCC surveillance use and associated costs in a US cohort of insured patients without cirrhosis but with hepatitis B virus (HBV) infection, monitored in routine clinical practice. Of 6831 patients (1122 on antiviral treatment, 5709 untreated), only 39.3% and 51.3% had received any abdominal imaging after 6 and 12 months, respectively, and patients were up to date with HCC surveillance guidelines for only 28% of the follow-up time. Completion of surveillance was substantially higher at 6 and 12 months among treated patients (51.7% and 69.6%, respectively) compared with untreated patients (36.9% and 47.6%, respectively) (p < 0.001). In adjusted models, treated patients were more likely than untreated patients to receive surveillance (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.53-2.01, p < 0.001), and the proportion of those up to date with surveillance was 9.7% higher (95% CI 6.26-13.07, p < 0.001). Mean total and patient-paid daily surveillance-related costs ranged from $99 (ultrasound) to $334 (magnetic resonance imaging), and mean annual patient costs due to lost productivity for surveillance-related outpatient visits ranged from $93 (using the federal minimum wage) to $321 (using the Bureau of Labor Statistics wage). Conclusion: Use of current HCC surveillance strategies was low across patients with HBV infection, and surveillance was associated with substantial patient financial burden. These data highlight an urgent need for accessible and easy-to-implement surveillance strategies with sufficient sensitivity and specificity for early HCC detection.
View details for DOI 10.1002/hep4.2087
View details for PubMedID 36178256
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Forecasted 2040 Global Prevalence of NAFLD using Hierarchical Bayesian Approach.
Clinical and molecular hepatology
2022
Abstract
Background: Due to increases in obesity and type 2 diabetes, nonalcoholic fatty liver disease (NAFLD) is increasing. Current forecast models may not include non-obese NAFLD. We used a Bayesian approach forecasting the prevalence of NAFLD through 2040.Methods: Prevalence data from 245 articles involving 2,699,627 persons were used with a hierarchical Bayesian approach to forecast the prevalence of NAFLD through 2040. Subgroup analyses were conducted for age, gender, presence of metabolic syndrome, region, and smoking. Sensitivity analysis was conducted for clinical setting and study quality.Results: Forecasted 2040 prevalence rate was 55.7%, a 3-times increase since 1990 and 43.2% increase from the 2020 prevalence of 38.9%. The estimated average yearly increase since 2020 was 2.16%. For those aged <50 years and ≥50 years old, the 2040 prevalence rates were not different (56.7% vs 61.5%, P=0.52). There was a significant difference in 2040 prevalence by sex (males- 60% vs.50%, P+) but trend is stepper for females (2.5% vs 1.5%, P=0.025). No difference in trends overtime by region (P=0.48). The rate of increase was significantly higher in those without metabolic syndrome (3.8% vs. 0.84%, P=0.003) and for smokers (1.4% vs. 1.1%, P=0.011). There was no difference by clinical/community setting (P=0.491) or the quality of the studies (P=0.85).Conclusion: By 2040, over half the adult population is forecasted to have NAFLD. The largest increases occur in women, smokers and those without metabolic syndrome. Intensification of efforts raising awareness and determining long term solutions addressing driving factors of NAFLD are needed.
View details for DOI 10.3350/cmh.2022.0239
View details for PubMedID 36117442
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Gaps in hepatocellular carcinoma surveillance in a United States cohort of insured patients with cirrhosis.
Current medical research and opinion
2022: 1-35
Abstract
Objective Surveillance for hepatocellular carcinoma (HCC) is known to be underutilized; however, neither the variation of surveillance adherence by cirrhosis etiology nor the patient-side economic burden of surveillance are well understood. To identify potential barriers to HCC surveillance, we assessed utilization patterns and costs among US patients with cirrhosis monitored in routine clinical practice. Methods: We conducted a retrospective study of insured adult patients with cirrhosis using national administrative claims data from January 2013 - June 2019. Time up-to-date with recommended surveillance, correlates of surveillance receipt, and surveillance-associated costs were assessed during a ≥6-month follow-up. Results: Among 15,543 patients with cirrhosis (mean [SD] age 64.0 [11.1] years, 50.7% male), 45.8% and 58.7% had received any abdominal imaging at 6 and 12 months, respectively. Patients were up-to-date with recommended surveillance for only 31% of a median 1.3-year follow-up. Those with viral hepatitis were more likely to receive surveillance than those with other etiologies (hazard ratio [HR] 1.55, 95% CI 1.11-2.17, p=0.010 for patients without a baseline gastroenterologist [GI] visit and 2.69, 95% CI 1.77-4.09, p<0.001 for patients with a GI visit, relative to those with nonalcoholic fatty liver disease and no GI visit). For all etiologies except NAFLD, the HR (95% CI) for surveillance receipt was higher among patients with vs without a baseline GI visit (alcohol-related, 1.164 [1.002-1.351] vs 0.880 [0.796-0.972]; viral hepatitis, 2.688 [1.765-4.093] vs 1.553 [1.111-2.171]; Other, 0.612 [0.519-0.722] vs 0.549 [0.470-0.641]). Mean total and patient-paid daily surveillance-related costs ranged from $540 and $113, respectively (ultrasound) to $1,580 and $300, respectively (magnetic resonance imaging), and mean estimated patient productivity costs were $730-$2,514 annually. Conclusion: HCC surveillance was underutilized and was lowest among patients with nonviral etiologies and those who had not seen a gastroenterologist. Surveillance-related out-of-pocket expenses and lost productivity were substantial. Development of surveillance strategies that reduce patient burden, such as those using blood-based biomarkers, may help improve surveillance adherence and effectiveness.
View details for DOI 10.1080/03007995.2022.2124070
View details for PubMedID 36111416
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Bulevirtide and tenofovir combination therapy for hepatitis D virus infection: longer treatment and more diverse trial populations are needed.
The Lancet. Infectious diseases
2022
View details for DOI 10.1016/S1473-3099(22)00412-1
View details for PubMedID 36113539
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Effectiveness of entecavir vs tenofovir disoproxil fumarate for functional cure of chronic hepatitis B in an international cohort.
Hepatology international
2022
Abstract
Both entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line therapies for chronic hepatitis B (CHB), but their comparative effectiveness with regards to hepatitis B surface antigen (HBsAg) seroclearance remains unclear.This international multicenter cohort study enrolled 7697 treatment-naïve CHB patients (median age 50 years; male 66.75%) initiated on either ETV (n = 5430) or TDF (n = 2267) without baseline malignancy or immunosuppression from 23 centers across 10 countries or regions. Patients were observed for HBsAg seroclearance until death, loss to follow-up, or treatment discontinuation or switching. The incidences of HBsAg seroclearance were adjusted for competing mortality and compared between ETV and TDF cohorts with inverse probability of treatment weighting (IPTW) and also by multivariable regression analysis.The study population was followed up for a median duration of 56.1 months with 36,929 11 person-years of observation. HBsAg seroclearance occurred in 70 ETV-treated and 21 TDF-treated patients, yielding 8-year cumulative incidence of 1.69% (95% confidence interval [CI] 1.32-2.17) for ETV and 1.34% (95% CI 0.85-2.10%), for TDF (p = 0.58). In the IPTW analysis with the two study cohorts more balanced in background covariates, the age-adjusted hazard ratio (HR) of TDF versus ETV for HBsAg seroclearance was 0.91 (95% CI 0.50-1.64; p = 0.75). Furthermore, there was no significant difference between the two medications in the multivariable competing risk regression model (adjusted sub-distributional HR 0.92 for TDF vs. ETV; 95% CI 0.56-1.53; p = 0.76).ETV and TDF did not differ significantly in the incidence of HBsAg seroclearance, which rarely occurred with either regimen.
View details for DOI 10.1007/s12072-022-10411-x
View details for PubMedID 36070123
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Most excess years of potential life loss among individuals with cirrhosis during the pandemic were not related to COVID-19
GUT
2022
View details for DOI 10.1136/gutjnl-2022-328188
View details for Web of Science ID 000850850100001
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Impact of the COVID-19 pandemic on liver disease-related mortality rates in the United States.
Journal of hepatology
2022
Abstract
The pandemic has resulted in an increase of deaths not directly related to COVID-19 infection. We aimed to use a national death dataset to determine the impact of the pandemic on people with liver disease in the U.S, focusing on alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD).Using data from the National Vital Statistic System from the CDC WONDER platform and ICD-10 codes, we identified deaths associated with liver disease. We evaluated observed versus predicted mortality for 2020-2021 based on trends from 2010-2019 with joinpoint and prediction modeling analysis.Among 626,090 chronic liver disease-related deaths between 2010 and 2021, Age-standardized mortality rates (ASMR) for ALD dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 3.5% to 17.6%, P<0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (15.67 vs.13.04) and 2021 (17.42 vs.13.41). ASMR for NAFLD also increased during the pandemic (APC:14.5%), while the rates for hepatitis B and C decreased. Notably, the ASMR rise for ALD was most pronounced in non-Hispanic Whites, Blacks, and Alaska Indians/Native Americans (APC: 11.7%, 10.8%, 18.0%, all P<0.05), with similar but less critical findings for NAFLD while rates were steady for non-Hispanic Asians throughout 2010-2021 (APC: 4.9%). The ASMR rise for ALD was particularly severe for the 25-44 age group (APC: 34.6%, versus 13.7% and 12.6% for 45-64 and ≥65, all P<0.01), which were also all higher than pre-COVID-19 rates (all P<0.01).ASMR for ALD and NAFLD increased at an alarming rate during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations.The impact of the pandemic on people with liver disease in the U.S remains unclear. This study indicated that age-standardized mortality rates for alcohol associated liver disease and non-alcohol fatty liver disease greatly accelerated during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations. Increasing awareness about the care importance of chronic liver disease in specific populations must be prioritized.
View details for DOI 10.1016/j.jhep.2022.07.028
View details for PubMedID 35988691
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Increased mortality of patients with alcohol-related liver diseases during the COVID-19 pandemic in the United States.
Journal of internal medicine
2022
View details for DOI 10.1111/joim.13545
View details for PubMedID 35869603
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Utilization and outcomes of hepatitis B-positive grafts in orthotopic liver transplantation in the United States, 1999-2021.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
2022
Abstract
The demand for orthotopic liver transplants (OLT) is projected to increase which indicates a need to expand the liver donor pool. We aimed to investigate the utilization of hepatitis B (HBV)-positive graft utilization and the outcomes of recipients undergoing orthotopic liver transplant (OLT) with HBV-positive grafts.We conducted a retrospective cohort study analyzing all deceased donors and OLT recipients in the Organ Procurement and Transplantation Network database from January 1999 through March 2021. Donor HBV status was positive if HBsAg was positive or HBV nucleic acid testing was detectable. Recipients of HBV-positive allografts were matched 1:5 to recipients of HBV-negative allografts based on recipient and donor age, transplant year, recipient gender, donation after circulatory death, recipient location, and MELD score at transplant.Among the 185,212 potential donors, 422(0.2%) were HBV-positive and 265(63%) of the HBV-positive grafts were transplanted (14 of 265[5.3%] in HBV-positive recipients). The overall discard rate for HBV-positive donors of 37.2% (157/422) remained significantly higher than the discard rate for HBV-negative donors of 26.5% (49,026/185,212) during the study period (p < 0.001). Recipients of HBV-positive (n = 209) had similar mortality (log-rank, p=0.47) and graft loss (log-rank, p=0.72) to matched recipients of HBV-negative allografts (n = 1,045). The 3-year graft survival was 77.9% for the HBV-positive group and 79.7% in the matched HBV-negative group.Based on this analysis, transplant recipients of HBV-positive liver allografts do not experience increased rates of mortality or graft loss. Utilizing these HBV-positive allografts is one strategy that may help expand the donor pool and lower the waiting-list mortality rate.
View details for DOI 10.1002/lt.26543
View details for PubMedID 35844046
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Cabozantinib plus atezolizumab in advanced hepatocellular carcinoma and the role of adjuvant antiviral therapy.
The Lancet. Oncology
2022
View details for DOI 10.1016/S1470-2045(22)00383-7
View details for PubMedID 35798015
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Meta-analysis: global prevalence, trend and forecasting of non-alcoholic fatty liver disease in children and adolescents, 2000-2021.
Alimentary pharmacology & therapeutics
2022
Abstract
BACKGROUND: NAFLD is increasing in children.AIMS: To determine the recent trend and forecast the future global prevalence of paediatric NAFLD METHODS: We searched PubMed, Embase, Web of Science and Cochrane library databases from inception to 1 May 2021 for studies of children and adolescents (≤21years) with NAFLD. Obesity was defined with weight at ≥95th percentile and overweight as 85th to <95th percentile as per the Center for Disease Control BMI-for-age percentile cut-offs.RESULTS: From 3350 titles and abstracts, we included 74 studies (276,091 participants) from 20 countries/regions. We included 14 studies in the general NAFLD prevalence analysis, yielding an overall prevalence of 7.40% (95% CI: 4.17-12.81) regardless of the diagnostic method, and 8.77% (95% CI: 3.86-18.72) by ultrasound. Among continents with more than one study, the prevalence of NAFLD was 8.53% (95% CI: 5.71-12.55) for North America, 7.01% (95% CI: 3.51-13.53) for Asia, and 1.65% (95% CI: 0.97-2.80) for Europe. NAFLD prevalence regardless of the diagnostic method was 52.49% (95% CI: 46.23-58.68, 9159 participants) and 39.17% (95% CI: 30.65-48.42, 5371 participants) among obese and overweight/obese participants, respectively. For the general population, trend analysis from 2000 to 2017 indicates an increasing global prevalence of paediatric NAFLD from 4.62% to 9.02% at a yearly increase of 0.26%, whereas forecast analysis predicts a prevalence of 30.7% by 2040.CONCLUSION: The prevalence of paediatric NAFLD varies by region and is 52.49% overall among the obese population and 7.40% in the general population. It is predicted to reach 30.7% by 2040.
View details for DOI 10.1111/apt.17096
View details for PubMedID 35736008
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Poor diagnostic efficacy of noninvasive tests for advanced fibrosis in obese or younger than 60 diabetic NAFLD patients.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2022
Abstract
Serum-based non-invasive tests (NITs) have been widely used to assess liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). However, the diagnostic efficacy of NITs across ranges of age, body mass index (BMI), and presence of type 2 diabetes (T2DM) may vary and have not been well characterized.background METHODS: We analyzed 1,489 patients with biopsy-proven NAFLD from 6 centers in Japan, Taiwan, and Korea. Using histology as the gold standard, we compared the AUROCs of fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and the new Hepamet fibrosis score (HFS) with a focus on performance in subgroups as stratified by age, BMI, and the presence of T2DM.By histology, 44.0% (655/1489) of the overall cohort had F2-4 and 20.6% (307/1489) had F3-4 fibrosis. FIB-4 had the highest AUROCs for both F2-4 (0.701 vs. NFS 0.676 and HFS 0.682, P=0.001) and F3-4 (0.767 vs. NFS 0.736 and HFS 0.752, P=0.002). However, for F3-4 fibrosis, the AUROCs of all 3 NITs were generally higher in older (>60 years), nonobese (BMI<25 kg/m2), and non-diabetic patients, though overall the best performance was observed with FIB-4 among nonobese (BMI<25) diabetic patients (AUROC 0.92). The worst performance was observed in younger patients with T2DM for all NITs including FIB-4 (AUROC 0.63-0.66).results CONCLUSION: FIB-4 had higher diagnostic efficacy for F3-4 than NFS or HFS, but this varied greatly by age, BMI and T2DM, with better performance in older, nonobese, and nondiabetic patients. However, all NITs including FIB-4 had unacceptably poor performance in young or obese diabetic patients.
View details for DOI 10.1016/j.cgh.2022.05.015
View details for PubMedID 35654298
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NAFLD versus MAFLD: Prevalence, Outcomes and Implications of a Change in Name.
Clinical and molecular hepatology
2022
Abstract
Non-alcoholic fatty liver disease (NAFLD) affects about a third of the world's adult population and is a major public health concern. NAFLD is defined by the presence of hepatic steatosis and the absence of other causes of liver disease. As NAFLD is closely associated with the presence of the metabolic syndrome, several experts have called for a change in nomenclature from NAFLD to metabolic-associated fatty liver disease (MAFLD) to better reflect the underlying pathophysiology of NAFLD as a metabolically driven disease and shift to a "positive" diagnostic criteria rather than one of exclusion. Recent studies have suggested that the global prevalence of MAFLD is higher than that of NAFLD, and patients with MAFLD have more metabolic comorbidities compared to those with NAFLD. Emerging data also suggest that all-cause and cardiovascular mortality may be higher in MAFLD compared with NAFLD. In this synopsis, we discuss differences in clinical features, prevalence and clinical outcomes between NAFLD and MAFLD. In addition, we highlight the advantages and disadvantages of a name change from NAFLD to MAFLD from the perspective of the scientific community, care providers and patients.
View details for DOI 10.3350/cmh.2022.0070
View details for PubMedID 35545437
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Characteristics and outcomes of hepatocellular carcinoma patients with macrovascular invasion following surgical resection: a meta-analysis of 40 studies and 8,218 patients
HEPATOBILIARY SURGERY AND NUTRITION
2022
View details for DOI 10.21037/hbsn-21-419
View details for Web of Science ID 000834075100001
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Global and regional long-term survival following resection for HCC in the recent decade: A meta-analysis of 110 studies.
Hepatology communications
2022
Abstract
Surgical resection for HCC remains a major curative treatment option, but it is unclear whether there are differences in outcomes by region and whether outcomes have improved over time. We aimed to estimate pooled overall survival (OS), recurrence-free survival (RFS), and complication rates in patients with hepatocellular carcinoma (HCC) following curative surgical resection and to compare outcomes by region and by time period. In this systematic review and meta-analysis, we searched Pubmed, Embase, and Cochrane databases from inception to May 15, 2020. We selected studies reporting OS, RFS, and complications in adult patients with HCC undergoing curative surgical resection. Two authors independently searched the literature and extracted the data. We screened 6983 articles and included 110 eligible studies with 82,392 patients, with study periods spanning from 1980-2017. The global pooled 1-year and 5-year survival rates were 88.9% (95% confidence interval [CI] 87.1-90.4) and 56.2% (95% CI 52.8-59.6) for OS and 71.1% (95% CI 67.6-74.3) and 35.2% (95% CI 32.5-38.0) for RFS, respectively. Five-year OS was higher in Asia (57.03%) than in other regions (Europe 48.3%; North America 48.0%; and South America 49.5%); p=0.002. Five-year RFS was higher in patients with hepatitis B virus versus patients with hepatitis C virus (34.8% vs. 24.1%; p=0.02). There was no significant improvement in 5-year OS and RFS over time. The pooled rate for complications was 27.6% (95% CI 23.4-32.3), with 9.7% (95% CI 6.3-14.7) classified as major. One-year OS after surgical resection for HCC is excellent (~90%). However, 5-year OS (~55%) and RFS (~35%) are still poor, suggesting that long-term care is suboptimal. Greater efforts are required to improve survival through enhanced surveillance and preventing recurrence through antiviral therapy.
View details for DOI 10.1002/hep4.1923
View details for PubMedID 35234371
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County-Level Variation in Cirrhosis-Related Mortality in the US, 1999-2019.
JAMA network open
2022; 5 (2): e2146427
View details for DOI 10.1001/jamanetworkopen.2021.46427
View details for PubMedID 35107576
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Global multi-stakeholder endorsement of the MAFLD definition.
The lancet. Gastroenterology & hepatology
2022
View details for DOI 10.1016/S2468-1253(22)00062-0
View details for PubMedID 35248211
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Is it safe to treat chronic hepatitis C patients with decompensated cirrhosis with PI-based DAA?
Journal of hepatology
2022
View details for DOI 10.1016/j.jhep.2021.12.037
View details for PubMedID 35074472
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Performance of noninvasive tests of fibrosis among Asians, Hispanic and non-Hispanic Whites in the STELLAR trials.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2022
Abstract
The effect of race on routinely available noninvasive tests of fibrosis is incompletely understood. This study evaluated the performance of noninvasive tests among White and Asian patients in the STELLAR trials (NCT03053050 and NCT03053063), which evaluated selonsertib in patients with advanced (F3-F4) fibrosis due to nonalcoholic steatohepatitis (NASH).Baseline liver biopsies were centrally read using the NASH Clinical Research Network system, and four noninvasive tests (Nonalcoholic fatty liver disease fibrosis score [NFS], Fibrosis-4 index [FIB-4], Enhanced Liver Fibrosis test [ELF] and liver stiffness [LS] by vibration-controlled transient elastography) were measured. The performance of these tests to discriminate advanced fibrosis was evaluated using areas under the receiver operating characteristics curves (AUROCs) with 5-fold cross-validation repeated 100 times.Among 3207 patients screened with evaluable liver histology, 2281 were Whites and 762 were Asians. 72% of Whites and 67% of Asians had advanced fibrosis. The AUROCs of the noninvasive tests for advanced fibrosis were similar in Whites and Asians: 0.73 and 0.75 for NFS, 0.78 and 0.80 for FIB-4, 0.79 and 0.81 for ELF, and 0.80 and 0.83 for LS, respectively. At the published cutoffs, the tests had similar sensitivities and specificities in the two groups. However, the sensitivities of NFS, FIB-4 and ELF were low in both White and Asian patients younger than 40 years.In the global phase 3 STELLAR trials, the diagnostic performance of routinely available noninvasive tests for the detection of advanced fibrosis due to NASH was acceptable and similar between White and Asian patients.
View details for DOI 10.1016/j.cgh.2022.01.015
View details for PubMedID 35074532
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Statin Use and Reduced Hepatocellular Carcinoma Risk in Patients with Non-alcoholic Fatty Liver Disease.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2022
Abstract
Recent evidence suggests potential clinical benefits of statin in cancer chemoprevention and treatment. Non-alcoholic fatty liver disease (NAFLD) is expected to become the leading cause of hepatocellular carcinoma (HCC). We aimed to investigate the association between statin initiation and the risk of HCC among patients with NAFLD.In this study using the Optum de-identified Clinformatics® database, cox proportional-hazards regression model was performed to determine the risk of HCC in statin initiators versus nonusers. We incorporated inverse probability of treatment weighting (IPTW) to minimize potential confounding.Among 272,431 adults with NAFLD diagnosis, IPTW model shows that statin initiators had a 53% less risk of developing HCC compared to nonusers (HR: 0.47, 95% confidence interval: 0.36-0.60). In the sub-cohort with FIB-4 data available, statin initiation was associated with a 56% hazard reduction of developing HCC in NAFLD after adjusting for FIB-4 score (HR: 0.44; 0.30-0.65). The association between statin initiation and lower risk of HCC development was observed for both lipophilic statin (HR: 0.49; 0.37-0.65) and hydrophilic statin (HR: 0.40; 0.21-0.76). Moreover, we observed a greater hazards reduction as the dose and duration of statin use increased. NAFLD patients with more than 600 cDDDs of statin had a 70% reduction in hazards of developing HCC (HR: 0.30; 0.20-0.43).Our study provides strong evidence for the association between statin initiation and reduced risk of HCC development in NAFLD patients. These findings imply that statin can be used as a protective medication for NAFLD patients to reduce the risk of HCC.
View details for DOI 10.1016/j.cgh.2022.01.057
View details for PubMedID 35158055
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Inhibition of Viral Replication Reduces Transcriptionally Active Distinct Hepatitis B Virus Integrations with Implications on Host Gene Dysregulation.
Gastroenterology
2022
Abstract
Hepatocellular carcinogenesis of hepatitis B virus (HBV) infection may arise from integration of viral DNA into the host genome. We aimed to gauge the effect of viral inhibition on transcriptionally active HBV-host integration events and explore the correlation of viral integrations with host gene dysregulation.We leveraged data and biospecimens from an interventional trial, in which patients with HBV viremia above 2,000 IU/mL and minimally raised serum liver enzyme were randomized to receive tenofovir disoproxil fumarate (TDF) or placebo for 3 years. Total RNA sequencing was performed on paired liver biopsies taken before and after the 3-year intervention in 119 patients. Virus-host chimeric reads were captured to quantify the number of distinct viral integrations. Dysregulation of a host gene disrupted by viral integration was defined by aberrant expression >2 standard deviations away from samples without viral integration.The TDF (n=64) and placebo groups (n=55) were comparable at baseline. Expressed viral integrations were detected in all pre- and post-treatment samples. The number of distinct viral integrations significantly correlated with circulatory biomarkers indicative of viral activities including HBV DNA, RNA, and viral antigens (p<0.0003 for all correlations). Moreover, TDF versus placebo achieved a significantly greater reduction in distinct viral integrations, with 3.28-fold and 1.81-fold decreases in the expressed integrations per million reads, respectively (ANCOVA, p=0.037). Besides, viral integrations significantly correlated with host gene dysregulation.Inhibition of viral replication reduces the number of transcriptionally active distinct HBV-host DNA integrations in patients with substantial viremia. Given the mutagenic potentials of viral integrations, such treatment effects should be considered in patient management.
View details for DOI 10.1053/j.gastro.2021.12.286
View details for PubMedID 34995536
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Clinical profiles of Asians with NAFLD: A systematic review and meta-analysis.
Digestive diseases (Basel, Switzerland)
2021
Abstract
NAFLD is increasingly prevalent in Asia, where people suffer more metabolic comorbidities at a lower body mass index (BMI), suggesting potential differences in their clinical profile. Therefore, we attempted to characterize the clinical profile of Asians with NAFLD via a meta-analytic approach.We searched Pubmed, EMBASE, and Cochrane databases from January 1, 2000 to January 17, 2019. Two authors independently reviewed and selected 104 articles (2,247,754 persons) that identified NAFLD in Asians and reported relevant data, especially BMI and ALT, and excluded individuals with other liver disease and excessive alcohol consumption. Individual patient-level data were obtained from seven cohorts in Asia to complement meta-analyzed data.Overall, the mean age was 52.07 (95%CI:51.28-52.85) years with those from Southeast Asia (42.66, 95%CI: 32.23-53.11) being significantly younger. The mean BMI was 26.2 kg/m2, higher in moderate-severe vs. mild hepatic steatosis (28.3 vs. 25.7) patients and NFS ≥-1.455 vs. <-1.455 (27.09 vs. 26.02), with 34% having non-obese NAFLD. The mean ALT was 31.74 U/L, higher in NFS <-1.455 vs. ≥-1.455 (33.74 vs. 27.83), though no differences were found by obesity or steatosis severity. The majority of males (85.7%) and females (60.7%) had normal to minimally elevated ALT (1-1.5x 95% ULN). Individual patient-level data analysis (N=7,668) demonstrated similar results.About one-third of Asians with NAFLD were non-obese and the majority did not have markedly elevated ALT. Therefore, abnormal ALT or BMI are not recommended as a criterion for NAFLD screening in this population. Additionally, there were significant differences in the clinical profiles of NAFLD among the different regions of Asia.
View details for DOI 10.1159/000521662
View details for PubMedID 34942625
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2019 global NAFLD prevalence - A systematic review and meta-analysis.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2021
Abstract
BACKGROUND & AIMS: The increasing rates of obesity and type 2 diabetes mellitus may lead to increased prevalence of NAFLD. We aimed to determine the current and recent trends on the global and regional prevalence of NAFLD.METHODS: Systematic search from inception to March 26, 2020 was performed without language restrictions. Two authors independently performed screening and data extraction. We performed meta-regression to determine trends in NAFLD prevalence.RESULTS: We identified 17,244 articles from literature search and included 245 eligible studies involving 5,399,254 individuals. The pooled global prevalence of NAFLD was 29.8% (95% CI 28.6-31.1); of these, 82.5% of included articles used ultrasound to diagnose NAFLD with prevalence of 30.6% (95% CI 29.2-32.0). South America (3 studies, 5,716 individuals) and North America (4 studies, 18,236 individuals) had the highest NAFLD prevalence at 35.7% (95% CI 34.0-37.5) and 35.3% (95% CI 25.4-45.9), respectively. From 1991-2019, trend analysis showed NAFLD increased from 21.9% to 37.3% [yearly increase of 0.7% (P<0.0001)], with South America showing the most rapid change of 2.7% per year followed by Europe at 1.1%.CONCLUSIONS: Despite regional variation, the global prevalence of NAFLD is increasing overall. Policy makers must work towards reversing the current trends by increasing awareness of NAFLD and promoting healthy lifestyle environments.
View details for DOI 10.1016/j.cgh.2021.12.002
View details for PubMedID 34890795
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Risk of hepatocellular carcinoma with tenofovir versus entecavir in chronic hepatitis B Reply
LANCET GASTROENTEROLOGY & HEPATOLOGY
2021; 6 (2): 87–88
View details for Web of Science ID 000608617700016
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Substantial gaps in evaluation and treatment of patients with hepatitis B in the US.
Journal of hepatology
2021
Abstract
HBV associated liver complication is reduced by antiviral therapy. Prior studies using local institutional cohorts have suggested suboptimal evaluation and treatment. We aimed to determine the proportion of patients with chronic HBV infection who received adequate evaluation, were treatment eligible, and received antiviral treatment using a large, nationwide cohort.This retrospective analysis utlized claims data of approximately 73 million enrollees across the US from Optum's de-identified Clinformatics® Data Mart Database, 2003-2019. Adults with chronic HBV infection observed for ≥ 6 months before and after index chronic HBV infection diagnosis were identified via ICD-9/ICD-10 codes and confirmed by positive HBsAg, HBeAg or HBV DNA PCR.We included 12,608 eligible patients in the study analysis (mean age 45.7 years, 52.1% male, 54.6% Asian, 18.1% Caucasian, 10.5% African American). About half of the cohort (n=6,559, 52.3%) did not have a complete laboratory evaluation (defined as having HBeAg, HBV DNA, and ALT tests) and only 72.4% (n=9,129) had an "adequate" evaluation (at least HBV DNA and ALT) during the entire study period. Of those with an adequate evaluation, 11.2% were treatment eligible by AASLD criteria and 13.9% by EASL criteria; and of these, 60.4% of AASLD eligible patients and 54.3% of EASL eligible patients received treatment within 12 months from becoming eligible.Half of chronic HBV infection patients in the US with private insurance did not have a complete laboratory assessment. Over one third of treatment-eligible patients did not receive antiviral therapy. Patients who visited a GI/ID specialist had a higher chance of receiving adequate evaluation and treatment. Urgent intervention is needed to identify and address the barriers for these care gaps.In this study, we used a national database that includes laboratory data in addition to medical and pharmacy claims data to assess the current real-world situation of chronic HBV infection care in the US. Among the 12,608 patients with chronic HBV infection included in our study, 52.3% never had a complete laboratory and only 73% had adequate evaluation. Among those who were treatment eligible by AASLD or EASL guidelines, only 60.4% and 54.3% received treatment within 12 months, respectively.
View details for DOI 10.1016/j.jhep.2021.08.019
View details for PubMedID 34474097
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Effect of sarcopenia on survival in patients with cirrhosis: A systematic review and meta-analysis.
Journal of hepatology
2021
Abstract
The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, by sex, underlying liver disease etiology, and severity of hepatic dysfunction.PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included.22 studies with 6965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), higher in male patients, patients with alcohol associated liver disease (ALD), patients with CTP grade C, and when sarcopenia was defined in patients by lumbar 3- skeletal muscle index (L3-SMI). Sarcopenia was associated with the increased risk of mortality in patients with cirrhosis (adjusted-hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in sensitivity analysis of cirrhosis patients without HCC (aHR 2.35, 95% CI 1.95-2.83) and in subgroup analysis by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the poor prognosis for patients with sarcopenia (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in all analyses.Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis.The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% in patients with ALD or Child's class C cirrhosis. Sarcopenia was independently associated with about 2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer period of having sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.
View details for DOI 10.1016/j.jhep.2021.11.006
View details for PubMedID 34785325
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Treatment Algorithm for Managing Chronic Hepatitis B Virus Infection in the United States: 2021 Update.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2021
Abstract
Chronic hepatitis B (CHB) infection remains the most frequent etiology of hepatocellular carcinoma globally as well as a major cause of cirrhosis. Despite vaccination, substantial numbers of persons have already been infected with hepatitis B virus and remain at risk of progressive liver disease.In 2004, a CHB management algorithm was developed by a panel of North American hepatologists which was subsequently updated in 2006, 2008, and 2015. Since the most recent version, several developments have altered the management of CHB. Tenofovir alafenamide, with a more favorable safety profile than tenofovir disoproxil fumarate, has been introduced as an initial antiviral choice as well as an alternative for long-term therapy. Quantitation of hepatitis B surface antigen (HBsAg) is becoming more widely available in clinical practice, with implications for monitoring response to treatment. Additionally, there has been a shift in how the natural history of CHB is perceived as newer evidence has challenged the concept that during the immunotolerant phase of infection disease progression is not a concern. Finally, recent analyses indicate that in the United States, the average age of CHB patients has increased implying that the presence of comorbidities including metabolic liver disease increasing use of biologics associated with aging will increasingly affect disease management.This updated algorithm is intended to serve as a guide to manage CHB while new antiviral strategies are developed.Recommendations have been based on evidence from the scientific literature, when possible, as well as clinical experience and consensus expert opinion. Points of continued debate and areas of research need are also described.
View details for DOI 10.1016/j.cgh.2021.07.036
View details for PubMedID 34329775
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Effects of Cirrhosis and Diagnosis Scenario in Metabolic-Associated Fatty Liver Disease-Related Hepatocellular Carcinoma.
Hepatology communications
2021; 5 (1): 122-132
Abstract
Metabolic-associated fatty liver disease (MAFLD) is a major cause of liver-related complications, including hepatocellular carcinoma (HCC). While MAFLD-related HCC is known to occur in the absence of cirrhosis, our understanding of MAFLD-related HCC in this setting is limited. Here, we characterize MAFLD-related HCC and the impact of cirrhosis and screening on survival. This was a multicenter, retrospective, cohort study of MAFLD-related HCC. MAFLD was defined based on the presence of race-adjusted overweight, diabetes, or both hypertension and dyslipidemia in the absence of excess alcohol use or other underlying cause of liver disease. The primary outcome of interest was overall survival, and the primary dependent variables were cirrhosis status and prior HCC screening. We used Kaplan-Meier methods to estimate overall survival and Cox proportional hazards models and random forest machine learning to determine factors associated with prognosis. This study included 1,382 patients from 11 centers in the United States and East/Southeast Asia. Cirrhosis was present in 62% of patients, but under half of these patients had undergone imaging within 12 months of HCC diagnosis. Patients with cirrhosis were more likely to have early stage disease but less often received curative therapy. After adjustment, cirrhosis was not associated with prognosis, but the presence of cancer-related symptoms at diagnosis was associated with poorer prognosis. Conclusion: Cirrhosis was not associated with overall survival in this cohort of MAFLD-related HCC, while diagnosis in the presence of symptoms was associated with poorer prognosis. The HCC surveillance rate in patients with MAFLD-related HCC was disappointingly low in a multicenter cohort.
View details for DOI 10.1002/hep4.1606
View details for PubMedID 33437906
View details for PubMedCentralID PMC7789832
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Risk of hepatocellular carcinoma with tenofovir versus entecavir in chronic hepatitis B - Authors' reply.
The lancet. Gastroenterology & hepatology
2021; 6 (2): 87–88
View details for DOI 10.1016/S2468-1253(20)30395-2
View details for PubMedID 33444533
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Incidences and Determinants of Functional Cure during Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B.
The Journal of infectious diseases
2021
Abstract
Long-term incidences and baseline determinants of functional cure (HBsAg seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood.This is an international multicenter cohort study of treatment-naïve chronic hepatitis B (CHB) patients who initiated on ETV or TDF without baseline malignancy. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression.The analysis included 4,769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26,614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% CI, 1.54 -- 2.88%) and an annual rate of 0.22% (95% CI, 0.17--0.28%). Baseline predictors included low-level viremia with HBV DNA <2,000 IU/mL (adjusted sub-distribution HR [aSHR], 3.14; 95% CI, 1.80--5.49), elevated serum alanine aminotransferase (ALT) >200 U/L (aSHR, 3.68; 95% CI, 2.07--6.53), serum bilirubin (aSHR, 1.11 per mg/dL; 95% CI, 1.06--1.17), and fatty liver (aSHR, 1.84; 95% CI, 1.03--3.29).HBsAg seroclearance rarely occurs in CHB patients treated with ETV or TDF and is associated with low-level viremia, ALT flare, bilirubin level, and fatty liver.
View details for DOI 10.1093/infdis/jiab241
View details for PubMedID 33999179
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Differential clinical characteristics and mortality outcomes in persons with NAFLD and/or MAFLD.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2021
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) establishes new criteria for diagnosing fatty liver disease independent of alcohol intake and concomitant viral hepatitis infection. However, the long-term outcomes of patients with MAFLD are sparse. We aimed to describe the characteristics and long-term survival of persons meeting criteria for NAFLD only (non-MAFLD NAFLD), for both NAFLD and MAFLD (NAFLD-MAFLD), and for MAFLD only (non-NAFLD MAFLD).Using data from the third National Health and Nutrition Examination Survey (NHANES III) 1988 - 1994, 2997 participants with fatty liver identified via ultrasound were categorized into three distinct groups: non-MAFLD NAFLD, NAFLD-MAFLD, and non-NAFLD MAFLD.Participants in the NAFLD-MAFLD and non-NAFLD MAFLD groups were older, had more metabolic traits and higher mean liver enzymes. Nearly 8% of participants in the non-NAFLD MAFLD group had advanced fibrosis (FIB-4 >2.67) while only 1.3% and 1.9% in the NAFLD-MAFLD and non-MAFLD NAFLD groups did, respectively (P <0.0001). Non-NAFLD MAFLD participants had the highest cumulative incidence of all-cause mortality (26.2%) followed by those with NAFLD-MAFLD then non-MAFLD NAFLD participants (21.1% and 10.6%, respectively, P <0.0001). Similar findings were observed for cardiovascular disease (CVD)-related and other-cause (non-CVD, non-cancer) mortality. Non-NAFLD MAFLD was independently associated with all-cause mortality compared to non-MAFLD NAFLD (adjusted hazard ratios: 2.4, 95% CI: 1.2 - 4.6, P = 0.01).MAFLD criteria identified a significant group of people with more comorbidities and worse prognosis compared to those with NAFLD only. These criteria should be considered in the general population to identify high-risk groups for early interventions.
View details for DOI 10.1016/j.cgh.2021.05.029
View details for PubMedID 34033923
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ALT levels in Treatment-Naïve, Chronic Hepatitis B Patients with Concurrent Fatty Liver Disease: A U.S. Nationwide Study.
Digestive diseases (Basel, Switzerland)
2021
View details for DOI 10.1159/000518645
View details for PubMedID 34348281
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Progression Rates by Age, Sex, Treatment, and Disease Activity by AASLD and EASL Criteria: Data for Precision Medicine.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2021
Abstract
Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status and disease activity based on the 2018 AASLD and 2017 EASL guidelines.We analyzed 18,338 patients (8914 treated; 9424 untreated) from 6 centers from the US and 27 centers from Asia Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years.The cohort was 63% male, with a mean age of 46.19 years, baseline cirrhosis of 14.3%, and median follow up of 9.60 years. By AASLD criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07%-3.94% for cirrhosis, from 0.04%-2.19% for HCC in patients without cirrhosis, and 0.40%-8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 and females younger than 50 had annual HCC risk near or exceeding 0.2%. Similar results were found using EASL criteria.There is great variability in CHB disease progression rates even among "lower risk" populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, disease activity, plus treatment status.
View details for DOI 10.1016/j.cgh.2021.05.062
View details for PubMedID 34089852
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Outcomes of Sequential Therapy With Tenofovir Alafenamide After Long-term Entecavir.
The American journal of gastroenterology
2021; 116 (6): 1264-1273
Abstract
Entecavir (ETV) and tenofovir alafenamide (TAF) are both first-line hepatitis B virus (HBV) therapies, but ETV-to-TAF switch outcome data are limited. We aimed to assess outcomes up to 96 weeks after ETV-to-TAF switch.ETV-treated (≥12 months) chronic hepatitis B patients switched to TAF in routine practice at 15 centers (United States, Korea, Japan, and Taiwan) were included. Primary outcome was complete viral suppression (CVS) rate (HBV DNA <20 IU/mL).We analyzed 425 eligible patients (mean age 60.7 ± 13.2 years, 60% men, 90.8% Asian, 20.7% with diabetes, 27% with hypertension, 14.8% with cirrhosis, 8.3% with hepatocellular carcinoma, and mean ETV duration before switch 6.16 ± 3.17 years). The mean baseline estimated glomerular filtration rate (eGFR) was 89 ± 19 (chronic kidney disease [CKD] stages: 55.6% stage 1, 35.7% stage 2, and 8.8% stages 3-5). CVS rate increased from 91.90% at switch (from 90.46% 24 weeks before switch) to 95.57% and 97.21% at 48 and 96 weeks after (P = 0.03 and 0.02, respectively). Over the 96 weeks after switch, mean HBV DNA (P < 0.001) but not alanine aminotransferase or CKD stage decreased. Between switch and 96-week follow-up, 11% (26/235) of CKD stage 1 patients migrated to stage 2 and 8% (12/151) of stage 2 patients to stages 3-5, whereas 18% (27/151) from stage 2 to 1, and 19% (7/37) from stages 3-5 to 2. On multivariable generalized estimated equation analysis adjusted for age, sex, hypertension, diabetes, and cirrhosis, baseline eGFR, age (P < 0.001), and CKD stages 2 and 3-5 (vs 1) (both P < 0.001) were associated with lower follow-up eGFR.After an average of 6 years on ETV, CVS increased from 91.9% at TAF switch to 97.2% at 96 weeks later.
View details for DOI 10.14309/ajg.0000000000001157
View details for PubMedID 34074829
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The Changing Epidemiology of Liver Disease Among US Children and Adolescents From 1999 to 2016.
The American journal of gastroenterology
2021
Abstract
Nonalcoholic fatty liver disease (NAFLD) and infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) are major causes of liver disease in adults. However, data for children and adolescents are limited. Our study aimed to characterize the prevalence, trend, and risk factors of infection of HBV and HCV and possible NAFLD for this population.We analyzed 6,647 children and adolescents (aged 6-21 years) from the 1999-2016 National Health and Nutrition Examination Survey.Among individuals aged 6-21 years, HBV prevalence decreased after 2011, from 0.72% in 1999-2004 and 0.85% in 2005-2010 to 0.27% in 2011-2016 (P < 0.001), whereas HCV prevalence increased to 0.26% in 2011-2016 after an initial decline from 0.15% in 1999-2004 to 0.02% in 2005-2010 (P = 0.01). Possible NAFLD prevalence also increased by approximately 40% in individuals aged 12-21 years, from 8.54% in 1999-2004 to 10.1% in 2005-2010 and then 11.8% in 2011-2016 (P = 0.033), with most possible NAFLD individuals being male, being obese, or having higher glucose, fasting insulin, hemoglobin A1c, homeostatic model assessment of insulin resistance, liver enzymes, lipids, and uric acid (all P < 0.01). On multivariate logistic regression, hypertension (odds ratio 4.79, 95% confidence interval 1.44-15.9) and dyslipidemia (odds ratio 11.6, 95% confidence interval 5.65-23.9) increased risk for possible NAFLD but not income:poverty ratio, hours spent on computer use, or added sugars.Although HBV prevalence has decreased in recent years among US children and adolescents, HCV and possible NAFLD have increased. Public health efforts must seek further understanding of the driving factors of this increase so that age-appropriate interventions can be developed and implemented.
View details for DOI 10.14309/ajg.0000000000001386
View details for PubMedID 34328446
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Fatty Liver Index and Development of Cardiovascular Disease: Findings from the UK Biobank.
Digestive diseases and sciences
2021
Abstract
Nonalcoholic fatty liver disease is common and is associated with rising morbidity and mortality in the UK. Cardiovascular disease is the main cause of death in people with nonalcoholic fatty liver disease.To determine the association between baseline cardiovascular risk factors with fatty liver index, and to investigate the association between fatty liver index and the incidence of cardiovascular disease in the UK.This study is a population-based retrospective cohort study using the UK Biobank database.The mean fatty liver index in the study cohort was 44.9, and 33.7% met the criteria for nonalcoholic fatty liver disease. Fatty liver index was significantly associated with a wide range of cardiovascular risk factors at baseline. During a mean follow-up of 7.86 years, the combined incidence of cardiovascular disease was 6.92 per 1000-person years at risk. We found significant association between fatty liver index and incident cardiovascular disease in the fully adjusted model. We found significant association between fatty liver index and incident cardiovascular disease in subgroups stratified by BMI as well as subgroups with fatty liver index < 30, < 60, and ≥ 60.Fatty liver index not only predicts NAFLD diagnosis, but also indicates baseline and future development of cardiovascular disease on long-term follow-up across weight categories and fatty liver index spectrum. These findings can inform clinicians and other stakeholders on cardiovascular disease management and preventive efforts. Patients with high fatty liver index should be counseled on the increased future risk of developing cardiovascular disease.
View details for DOI 10.1007/s10620-021-06954-y
View details for PubMedID 33782808
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Surveillance of patients with cirrhosis remains suboptimal in the United States.
Journal of hepatology
2021
Abstract
Regular monitoring/surveillance for liver complications is crucial in the management of patients with cirrhosis to reduce morbidity and mortality. Recommendations from professional societies are available but adherence is not well studied, especially outside of academic centers. We aimed to determine the frequencies and factors associated with laboratory monitoring, hepatocellular carcinoma (HCC) and esophageal varices (EV) surveillance in patients with cirrhosis.We identified 82,427 patients with cirrhosis (43,280 compensated and 39,147 decompensated) from the Truven Health MarketScan Research Database®, 2007-2016. We calculated the proportion of patients with cirrhosis with various frequencies of procedures/testing for laboratory (complete blood count, comprehensive metabolic panel, and prothrombin time), HCC and EV surveillance. We also used multivariable logistic regression to determine factors associated with having procedures.The proportions of patients undergoing HCC surveillance (8.78%), laboratory testing (29.72%) at least every 6-12 months, or EV surveillance (10.6%) at least every 1-2 years were suboptimal. The majority did not have HCC (45.4%) or EV (80.3%) surveillance during the entire study period. On multivariable regression, age 41-55 (vs. <41) years, PPO (vs. HMO) insurance plan, specialist care (vs. primary care and other specialties), diagnosis between 2013-2016 (vs. 2007-2009), decompensated (vs. compensated) cirrhosis, NAFLD (vs. viral hepatitis), and higher Charlson's comorbidity index were associated with significantly higher odds of undergoing procedures/testing every 6-12 months and EV surveillance every 1-2 years.Despite having modest improvement in the more recent years, routine monitoring and surveillance for patients with cirrhosis is suboptimal. Further efforts including provider awareness, patient education, and system/incentive-based quality improvement measures are urgently needed.Patients with cirrhosis should undergo health monitoring for liver complications to achieve early detection and treatment. In a large nationwide cohort of 82,427 patients with cirrhosis in the United States, we found a low rate of adherence (well less than half) to routine blood test monitoring and surveillance for liver cancer and esophageal varices (swollen blood vessels in the abdomen that could lead to fatal bleeding). Adherence has increased in the recent years, but much more improvement is needed.
View details for DOI 10.1016/j.jhep.2021.04.042
View details for PubMedID 33965477
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Optimizing Hepatitis B Virus Screening in the United States Using a Simple Demographics-Based Model.
Hepatology (Baltimore, Md.)
2021
Abstract
Chronic hepatitis B (CHB) affects over 290 million people globally and only 10% have been diagnosed, presenting a severe gap that must be addressed. We developed logistic regression and machine learning (random forest) models to accurately identify patients with HBV, using only easily-obtained demographic data from a population-based data set.We identified participants with data on hepatitis B surface antigen (HBsAg), birth year, sex, race/ethnicity, and birthplace from 10 cycles of the National Health and Nutrition Examination Survey (NHANES, 1999-2018) and divided them into two cohorts: training (cycles 2, 3, 5, 6, 8, 10; n = 39,119) and validation (cycles 1, 4, 7, 9; n = 21,569). We then developed and tested our two models. The overall cohort was 49.2% male, 39.7% White, 23.2% Black, 29.6% Hispanic, and 7.5% Asian/Other, with a median birth year of 1973. In multivariable logistic regression, the following factors were associated with HBV infection: birth year 1991 or after (adjusted OR [aOR] of 0.28, P < 0.001), male sex (aOR 1.49, P = 0.0080), Black and Asian/Other vs. White (aOR 5.23 and 9.13, P < 0.001 for both), and being United States-born (vs. foreign-born) (aOR 0.14, P < 0.001). We found that the machine learning model consistently outperformed the logistic regression model, with higher AUROC values (0.83 vs. 0.75 in validation cohort, P < 0.001) and better differentiation of high and low risk individuals.Our machine learning model provides a simple, targeted approach to HBV screening, using only easily-obtained demographic data.
View details for DOI 10.1002/hep.32142
View details for PubMedID 34496066
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Initial Evaluation, Long-Term Monitoring, and Hepatocellular Carcinoma Surveillance of Chronic Hepatitis B in Routine Practice: A Nationwide US Study.
The American journal of gastroenterology
2021
Abstract
Previous studies, mostly small and single center, have shown gaps in the evaluation and monitoring of patients with chronic hepatitis B (CHB) virus infection. We aimed to examine the rates and predictors of adherence to guidelines for CHB care in a large nationwide cohort.We identified adult patients with CHB infection from the Truven MarketScan databases of commercially insured and Medicare patients with private insurance supplement (2007-2014) using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The initial evaluation cohort had at least 6 months follow-up, whereas at least 12 months was required for the long-term monitoring cohort.We analyzed 55,317 eligible patients with CHB infection: mean age 46 ± 12 years, 58% men, and 14.8% with cirrhosis. Over a mean follow-up of 3.2 ± 2.3 years, 55.8% had specialist (gastroenterology or infectious diseases) visits. For initial evaluation, 59% of patients received both alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA tests, whereas only 33% had ALT, HBV DNA, and hepatitis B e antigen tests, with higher frequencies among patients with specialist visits. For long-term monitoring, only 25% had both ALT and HBV DNA tests performed annually. Among patients at higher risk of developing hepatocellular carcinoma (patients with cirrhosis, male patients without cirrhosis older than 40 years, and female patients without cirrhosis older than 50), less than 40% underwent annual hepatocellular carcinoma surveillance, with 25% never receiving surveillance during the study period. Predictors of optimal initial evaluation and long-term monitoring were compensated cirrhosis (odds ratio: 1.60 and 1.47, respectively) and specialist visits (odds ratio: 1.86 and 1.31, respectively) (both P < 0.001).In this large cohort of patients with CHB infection with private insurance or Medicare with private insurance supplement, we observed poor adherence to the recommended initial evaluation and long-term monitoring. Among the predictors of adherence were specialist visits. Further efforts are needed to identify barriers and improve access to care.
View details for DOI 10.14309/ajg.0000000000001271
View details for PubMedID 33927125
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Prevalence of hepatic steatosis, fibrosis and associated factors in chronic hepatitis B.
Alimentary pharmacology & therapeutics
2021
Abstract
As the prevalence of hepatitis steatosis (HS) increases, the prevalence of HS among those with chronic hepatitis B (CHB) may also be increasing but data on the effect of HS on CHB disease progression are lacking.To determine the prevalence of HS in CHB and associated factors, prevalence of fibrosis and its association with HS.Two researchers independently searched the literature and extracted data. We included full-length original articles of adults with CHB that evaluated. Prevalence estimates were pooled using a random-effects model. Associations between HS and fibrosis were assessed by pooled odds ratios (ORs) or mean differences (MD).Of the 2821 records screened, 54 eligible studies (28 648 patients) were analysed. The pooled prevalence of HS in CHB was 32.8% (95% CI, 28.9-37.0) with higher prevalence in men and obese patients. Older age, male sex and metabolic factors were associated with HS while an inverse association was observed between HS and HBeAg (OR 0.82, 95% CI, 0.75-0.91) and HBV DNA levels (MD -0.38, 95% CI -1.16--0.42). The pooled prevalence of significant fibrosis (≥F2 or ≥F3) was similar between patients with CHB with or without HS (40.1% vs 42.22%, P = 0.68). HS was not significantly associated with fibrosis (pooled OR 0.87, 95% CI 0.54-1.39, 20 studies, 6232 patients).Approximately 30% of patients with CHB had HS, which was positively associated with male sex, diabetes and metabolic factors, and was negatively associated with HBeAg and HBV DNA. HS was not significantly associated with increased fibrosis.
View details for DOI 10.1111/apt.16595
View details for PubMedID 34469587
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Treatment and renal outcomes up to 96 weeks after tenofovir alafenamide switch from tenofovir disoproxil fumarate in routine practice.
Hepatology (Baltimore, Md.)
2021
Abstract
Real-world data for treatment effectiveness and renal outcomes in chronic hepatitis B (CHB) patients who were switched to the new and safer pro-drug, tenofovir alafenamide (TAF) from tenofovir disoproxil fumarate (TDF) are limited. Therefore, we aimed to evaluate treatment and renal outcomes of this population.We analyzed 834 CHB patients previously treated with TDF for ≥12 months who were switched to TAF in routine practice at 13 U.S. and Asia centers for changes in viral (HBV DNA <20 IU/mL), biochemical (ALT <35/25 U/L for male/ female) and complete (viral+biochemical) response; as well as estimated glomerular filtration rate (eGFR, mL/min/1.73 m2 ) up to 96-weeks after switch. Viral suppression (P<0.001) and ALT normalization (P=0.003) rates increased significantly after switch, as well as trend for increasing complete response (Ptrend =0.004) while eGFR trend (Ptrend >0.44) or mean eGFR (P>0.83, adjusted for age, sex, baseline eGFR, and diabetes, hypertension or cirrhosis by generalized linear modeling) remained stable. However, among those with baseline eGFR <90 (CKD stage ≥2), mean eGFR decreased significantly while on TDF (P=0.029) but not after TAF switch (P=0.90). By week 96, 21% (55/267) of patients with CKD stage 2 at switch improved to stage 1, 35% (30/85) of CKD stage 3-5 patients improved to stage 2 and 1.2% (1/85) to stage 1.Overall, we observed continued improvement in virologic response, ALT normalization, and no significant changes in eGFR following switch to TAF from TDF.
View details for DOI 10.1002/hep.31793
View details for PubMedID 33706421
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Chronic hepatitis, osteoporosis, and men: under-recognised and underdiagnosed.
The lancet. Diabetes & endocrinology
2021; 9 (3): 141
View details for DOI 10.1016/S2213-8587(21)00020-6
View details for PubMedID 33607040
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Characteristics and healthcare costs in the aging hepatitis B population of Japan: A nationwide real-world analysis.
Digestive diseases (Basel, Switzerland)
2021
Abstract
Advancing age, comorbidity, and financial burden have been observed in chronic hepatitis B (CHB) patients globally. As Japan is leading the world in aging demographics, similar real-world data are urgently needed for its CHB population to inform all stakeholders.This cross-sectional study characterized the demographics, comorbidities, and healthcare costs of a large Japanese real-world adult (≥18 years) CHB patient (ICD-10: B18.1) population from the Medical Data Vision database from 01/01/2012 to 31/12/2016. Comorbidities were identified by ICD-10 codes and the annual point-prevalence and Charlson Comorbidity Index (CCI) score were calculated. Annual mean and median all-cause healthcare utilization and costs per-patient were calculated. Comparison tests were conducted for CCI scores, prevalence of comorbidities and healthcare resource utilization and costs.We identified 11,125 CHB patients. Between 2012 and 2016, the mean age increased from 62.0±13.3 to 65.2±13.2 years, and the percentage of those aged ≥65 years increased from 45.6% to 60.7%. The prevalence of cirrhosis remained similar (5.8% in 2012 and 5.6% in 2016, p=0.69) while hepatocellular carcinoma decreased from 6.3% to 4.5% (p<0.01). The prevalence of non-liver comorbidities increased (40.9% to 52.0% for cancer (p<0.01), 12.1% to 17.7% for osteoporosis (p<0.01), and 10.7% to 15.0% for renal impairment (p<0.01). Healthcare resource utilization and costs also increased, with a 119.3% increase in the median total healthcare costs from ¥229,143 in 2012 to ¥502,467 in 2016 (p<0.01).The CHB population of Japan is predominantly elderly and carry a high non-liver comorbidity burden, while incurring increasing healthcare costs.
View details for DOI 10.1159/000515854
View details for PubMedID 33721872
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The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995-2040.
Hepatology international
2021
Abstract
NAFLD is increasing in Asia including Japan, despite its lower obesity rate than the West. However, NAFLD can occur in lean people, but data are limited. We aimed to investigate the epidemiology of NAFLD in Japan with a focus on lean NAFLD.We searched PubMed, Cochrane Library, EMBASE, Web of Science, and the Japan Medical Abstracts Society (inception to 5/15/2019) and included 73 eligible full-text original research studies (n = 258,531). We used random-effects model for pooled estimates, Bayesian modeling for trend and forecasting, contacted authors for individual patient data and analyzed 14,887 (7752 NAFLD; 7135 non-NAFLD-8 studies) patients.The overall NAFLD prevalence was 25.5%, higher in males (p < 0.001), varied by regions (p < 0.001), and increased over time (p = 0.015), but not by per-person income or gross prefectural productivity, which increased by 0.64% per year (1983-2012) and is forecasted to reach 39.3% in 2030 and 44.8% in 2040. The incidence of NAFLD, HCC, and overall mortality were 23.5, 7.6 and 5.9 per 1000 person-years, respectively. Individual patient-level data showed a lean NAFLD prevalence of 20.7% among the NAFLD population, with lean NAFLD persons being older and with a higher all-cause mortality rate (8.3 vs. 5.6 per 1000 person-years for non-lean NAFLD, p = 0.02). Older age, male sex, diabetes, and FIB-4 were independent predictors of mortality, but not lean NAFLD.NAFLD prevalence has increased in Japan and may affect half of the population by 2040. Lean NAFLD individuals makeup 20% of the NAFLD population, were older, and had higher mortality.
View details for DOI 10.1007/s12072-021-10143-4
View details for PubMedID 33580453
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Transition rates to cirrhosis and liver cancer by age, gender, disease and treatment status in Asian chronic hepatitis B patients.
Hepatology international
2021
Abstract
Increasing hepatitis-related mortality has reignited interest to fulfill the World Health Organization's goal of viral hepatitis elimination by 2030. However, economic barriers have enabled only 28% of countries to implement countermeasures. Given the high disease burden among Asians, we aimed to present age, sex, disease activity and treatment-specific annual progression rates among Asian chronic hepatitis B (CHB) patients to inform health economic modeling efforts and cost-effective public health interventions.We analyzed 18,056 CHB patients from 36 centers across the U.S. and seven countries/regions of Asia Pacific (9530 treated; 8526 untreated). We used Kaplan-Meier methods to estimate annual incidence of cirrhosis and hepatocellular carcinoma (HCC). Active disease was defined by meeting the APASL treatment guideline criteria.Over a median follow-up of 8.55 years, there were 1178 incidences of cirrhosis and 1212 incidences of HCC (297 without cirrhosis, 915 with cirrhosis). Among the 8526 untreated patients (7977 inactive, 549 active), the annual cirrhosis and HCC incidence ranged from 0.26% to 1.30% and 0.04% to 3.80% in inactive patients, and 0.55 to 4.05% and 0.19 to 6.03% in active patients, respectively. Of the 9530 treated patients, the annual HCC rates ranged 0.03-1.57% among noncirrhotic males and 2.57-6.93% among cirrhotic males, with lower rates for females. Generally, transition rates increased with age, male sex, the presence of fibrosis/cirrhosis, and active disease and/or antiviral treatment.Using data from a large and diverse real-world cohort of Asian CHB patients, the study provided detailed annual transition rates to inform practice, research and public health planning.
View details for DOI 10.1007/s12072-020-10113-2
View details for PubMedID 33394321
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Natural History and Hepatocellular Carcinoma Risk in Untreated Chronic Hepatitis B Patients with Indeterminate Phase (117/120).
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2021
Abstract
Many patients with chronic hepatitis B (CHB) may not conform to any of the defined phases, hence classified as indeterminate. We aimed to characterize the baseline prevalence of indeterminate patients and their natural history, phase transition and hepatocellular carcinoma (HCC) risk.This is a retrospective cohort study of 3,366 adult untreated non-cirrhotic CHB patients seen at five U.S. clinics and seven Taiwanese townships who had at least one year of serial laboratory data prior to enrollment with a mean follow-up of 12.5 years. Patients' clinical phases were determined at baseline and through serial data during follow-up, based on the AASLD 2018 Guidance.At baseline, 1,303 (38.7%) patients were in the indeterminate phase. By up to year 10 of follow-up, 686 patients (52.7%) patients remained indeterminate, while 283 (21.7%) became immune active. Compared to patients who remained inactive, patients who remained indeterminate had higher 10-year cumulative HCC incidence (4.6% vs. 0.5%, P<0.0001) and adjusted hazard ratio (HR) for HCC of 14.1 (P=0.03). Among patients who remained indeterminate, age ≥ 45 years (adjusted HR 18.4, P=0.005) was independently associated with HCC development.Nearly 40% of patients had indeterminate CHB phase. Of these, half remained indeterminate and one-fifth transitioned to the immune active phase. HCC risk in persistently indeterminate CHB was 14 times higher than inactive CHB. Among persistently indeterminate CHB patients, age ≥ 45 years was associated with 18 times higher risk for HCC development. Further studies are needed to evaluate the potential benefit of antiviral therapy for indeterminate patients, especially in the older subgroup.
View details for DOI 10.1016/j.cgh.2021.01.019
View details for PubMedID 33465482
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Prevalence of Hepatitis B Vaccination Coverage and Serologic Evidence of Immunity Among US-Born Children and Adolescents From 1999 to 2016.
JAMA network open
2020; 3 (11): e2022388
Abstract
Importance: The World Health Assembly has called for the elimination of hepatitis B and C by 2030. As hepatitis B has no cure, the US strategy to eliminate hepatitis B has focused on prevention through vaccination. However, there are limited data on the trend in vaccine-associated immunity since the US implementation of universal infant hepatitis B vaccination.Objective: To compare self-reported hepatitis B vaccination coverage among children and adolescents with serologic evidence of immunity and infection in the US from 1999 to 2016.Design, Setting, and Participants: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016. US-born persons aged 2 to 18 years without missing hepatitis B serologic test results and with reported vaccination history were included. Data were analyzed from September 2017 to June 2018.Main Outcomes and Measures: The proportion of participants who reported complete vaccination for hepatitis B and who had positive serologic test results indicating immunity.Results: Of 21 873 children and adolescents, 51.2%% were male, and the mean (SD) age was 10.6 (4.6) years. The survey reported that hepatitis B vaccination coverage increased significantly from 1999 to 2016 (from 62.6% [95% CI, 58.6%-66.4%] to 86.3% [95% CI, 82.9%-89.2%]; P<.001). Vaccine-associated immunity also increased from 1999 to 2016 among children aged 2 to 5 years (from 60.7% [95% CI, 48.8%-71.4%] to 65.2% [95% CI, 57.4%-72.3%]; P=.001) but decreased among children aged 6 to 10 years (from 64.6% [95% CI, 57.7%-70.9%] to 46.5% [95% CI, 39.1%-54.0%]; P<.001), adolescents aged 11 to 13 years (from 68.8% [95% CI, 58.1%-77.8%] to 26.2% [95% CI, 18.6%-35.5%]; P<.001), and adolescents aged 14 to 18 years (from 68.5% [95% CI, 62.9%-73.6%] to 15.6% [95% CI, 12.2%-19.8%]; P<.001). By birth year, serologic evidence of vaccine-associated immunity significantly decreased in the 1994-2003 NHANES birth cohort but not among those born between 1988 and 1993. Non-US-born children and adolescents did not show the same decreasing trend in immunity.Conclusions and Relevance: In this cross-sectional study, decreasing hepatitis B immunity was observed among US-born children and adolescents in the 1994-2003 NHANES birth cohort despite increasing rates of hepatitis B vaccination coverage. These findings suggest a possible need for surveillance and a booster vaccine dose for hepatitis B as those without serologic evidence of immunity become young adults and may engage in behaviors associated with an increased risk for infection.
View details for DOI 10.1001/jamanetworkopen.2020.22388
View details for PubMedID 33175174
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Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients.
Clinical and translational gastroenterology
2020; 11 (9): e00196
Abstract
Spontaneous hepatitis B surface antigen (HBsAg) seroclearance, the functional cure of hepatitis B infection, occurs rarely. Prior original studies are limited by insufficient sample size and/or follow-up, and recent meta-analyses are limited by inclusion of only study-level data and lack of adjustment for confounders to investigate HBsAg seroclearance rates in most relevant subgroups. Using a cohort with detailed individual patient data, we estimated spontaneous HBsAg seroclearance rates through patient and virologic characteristics.We analyzed 11,264 untreated patients with chronic hepatitis B with serial HBsAg data from 4 North American and 8 Asian Pacific centers, with 1,393 patients with HBsAg seroclearance (≥2 undetectable HBsAg ≥6 months apart) during 106,192 person-years. The annual seroclearance rate with detailed categorization by infection phase, further stratified by hepatitis B e antigen (HBeAg) status, sex, age, and quantitative HBsAg (qHBsAg), was performed.The annual seroclearance rate was 1.31% (95% confidence interval: 1.25-1.38) and over 7% in immune inactive patients aged ≥55 years and with qHBsAg <100 IU/mL. The 5-, 10-, 15-, and 20-year cumulative rates were 4.74%, 10.72%, 18.80%, and 24.79%, respectively. On multivariable analysis, male (adjusted hazard ratio [aHR] = 1.66), older age (41-55 years: aHR = 1.16; >55 years: aHR = 1.21), negative HBeAg (aHR = 6.34), and genotype C (aHR = 1.82) predicted higher seroclearance rates, as did lower hepatitis B virus DNA and lower qHBsAg (P < 0.05 for all), and inactive carrier state.The spontaneous annual HBsAg seroclearance rate was 1.31%, but varied from close to zero to about 5% among most chronic hepatitis B subgroups, with older, male, HBeAg-negative, and genotype C patients with lower alanine aminotransferase and hepatitis B virus DNA, and qHBsAg independently associated with higher rates (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A367).
View details for DOI 10.14309/ctg.0000000000000196
View details for PubMedID 33094953
View details for PubMedCentralID PMC7494149
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Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients
CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY
2020; 11 (9)
View details for DOI 10.14309/ctg.0000000000000196
View details for Web of Science ID 000575994700002
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Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma Analysis From the US Multicenter HCC Transplant Consortium
ANNALS OF SURGERY
2020; 271 (4): 616–24
View details for DOI 10.1097/SLA.0000000000003253
View details for Web of Science ID 000544920700005
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Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis.
The lancet. Gastroenterology & hepatology
2020
Abstract
Although non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, it is increasingly being identified in non-obese individuals. We aimed to characterise the prevalence, incidence, and long-term outcomes of non-obese or lean NAFLD at a global level.For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Library from inception to May 1, 2019, for relevant original research articles without any language restrictions. The literature search and data extraction were done independently by two investigators. Primary outcomes were the prevalence of non-obese or lean people within the NAFLD group and the prevalence of non-obese or lean NAFLD in the general, non-obese, and lean populations; the incidence of NAFLD among non-obese and lean populations; and long-term outcomes of non-obese people with NAFLD. We also aimed to characterise the demographic, clinical, and histological characteristics of individuals with non-obese NAFLD.We identified 93 studies (n=10 576 383) from 24 countries or areas: 84 studies (n=10 530 308) were used for the prevalence analysis, five (n=9121) were used for the incidence analysis, and eight (n=36 954) were used for the outcomes analysis. Within the NAFLD population, 19·2% (95% CI 15·9-23·0) of people were lean and 40·8% (36·6-45·1) were non-obese. The prevalence of non-obese NAFLD in the general population varied from 25% or lower in some countries (eg, Malaysia and Pakistan) to higher than 50% in others (eg, Austria, Mexico, and Sweden). In the general population (comprising individuals with and without NAFLD), 12·1% (95% CI 9·3-15·6) of people had non-obese NAFLD and 5·1% (3·7-7·0) had lean NAFLD. The incidence of NAFLD in the non-obese population (without NAFLD at baseline) was 24·6 (95% CI 13·4-39·2) per 1000 person-years. Among people with non-obese or lean NALFD, 39·0% (95% CI 24·1-56·3) had non-alcoholic steatohepatitis, 29·2% (21·9-37·9) had significant fibrosis (stage ≥2), and 3·2% (1·5-5·7) had cirrhosis. Among the non-obese or lean NAFLD population, the incidence of all-cause mortality was 12·1 (95% CI 0·5-38·8) per 1000 person-years, that for liver-related mortality was 4·1 (1·9-7·1) per 1000 person-years, cardiovascular-related mortality was 4·0 (0·1-14·9) per 1000 person-years, new-onset diabetes was 12·6 (8·0-18·3) per 1000 person-years, new-onset cardiovascular disease was 18·7 (9·2-31·2) per 1000 person-years, and new-onset hypertension was 56·1 (38·5-77·0) per 1000 person-years. Most analyses were characterised by high heterogeneity.Overall, around 40% of the global NAFLD population was classified as non-obese and almost a fifth was lean. Both non-obese and lean groups had substantial long-term liver and non-liver comorbidities. These findings suggest that obesity should not be the sole criterion for NAFLD screening. Moreover, clinical trials of treatments for NAFLD should include participants across all body-mass index ranges.None.
View details for DOI 10.1016/S2468-1253(20)30077-7
View details for PubMedID 32413340
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Hepatitis B Virus Reactivation Potentiated by Biologics.
Infectious disease clinics of North America
2020
Abstract
Hepatitis B virus (HBV) reactivation can be a serious complication for patients with chronic or resolved HBV infection when treated with biologics. For HBsAg-positive patients receiving biologics, the risk of HBV reactivation is moderate to high. HBsAg-negative/anti-HBc positive patients are at lower risk of HBV reactivation than HBsAg-positive patients. However, patients taking anti-CD20 agents, such as rituximab, have high risk of HBV reactivation (>10%), so antiviral prophylactic therapies are required. This review provides the different classes of biologics associated with HBV reactivation, stratifies the various reactivation risk levels by HBV status and biologic agent, and discusses management strategies.
View details for DOI 10.1016/j.idc.2020.02.009
View details for PubMedID 32334985
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Ethnic influence on nonalcoholic fatty liver disease prevalence and lack of disease awareness in the United States, 2011-2016.
Journal of internal medicine
2020
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a rising global disease associated with clinical and economic burdens.We aimed to quantify NAFLD prevalence and awareness to provide stakeholders necessary information to combat NAFLD burden.This study utilizes data from the National Health and Nutrition Examination Survey 2011-2016 and included 4538 adult participants who did not have heavy drinking or viral hepatitis history. The US fatty liver index defined NAFLD and NAFLD fibrosis score defined fibrosis. NAFLD awareness was captured by questionnaire.Amongst the study population of 4538 persons, NAFLD prevalence was 32.5%, lowest in non-Hispanic Blacks (18.0%) and Asians (18.1%), highest amongst Mexican Americans (48.4%). Within the NAFLD group, advanced fibrosis was highest in non-Hispanic Blacks (28.5%) and lowest amongst non-Hispanic Asians (2.7%). Of the 1473 (97.5%) NAFLD participants who answered NAFLD awareness question, 90% visited a healthcare centre at least once in the past year, but only 5.1% were aware of having NAFLD. On weighted population estimates, 77.33 million persons had NAFLD, 17.63 million had advanced fibrosis, and 73.39 million NAFLD participants were not aware of having NAFLD.Of 77.33 million people in the United States have NAFLD with 17.63 million having advanced fibrosis, with lowest prevalence in non-Hispanic Asians and highest in Mexican Americans. A conundrum exists amongst non-Hispanic Blacks who have low NAFLD prevalence but highest prevalence of advanced fibrosis. Awareness of NAFLD was low across all ethnicities. Effort is needed to improve disease awareness whilst addressing NAFLD clinical burden across ethnicities.
View details for DOI 10.1111/joim.13035
View details for PubMedID 32128904
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Discrepancies between actual weight, weight perception and weight loss intention amongst persons with NAFLD.
Journal of internal medicine
2020
Abstract
Currently, weight loss remains the main management strategy for NAFLD, but the weight loss intention and methods remain poorly characterized.We analysed data about the perception of weight status, intention and methods to lose weight amongst 3,822 persons with NAFLD (United States Fatty Liver Index ≥ 30) from the National Health and Nutrition Examination Survey, 2001-2014.Only 53.9% of people with NAFLD intended to lose weight, 91.8% with perception of overweight and 8.2% with normal weight perception. Persons with perception of overweight or overweight/obese status were four times more likely to try to lose weight (adjusted odds ratios 3.9 and 4.2, respectively, both P < 0.0001). Younger age, women, higher educational level, Hispanic and blacks (versus whites) were significant independent factors associated with weight loss intention. Notably, ≤10% attended weight loss programme. Metabolic equivalent of task hours per week was significantly higher in whites who exercised to lose weight (vs. no exercise, P = 0.003) but not in other racial/ethnic groups. Interestingly, calorie intake was similar between those who dieted versus not (2056 vs. 1970 kcal/day, P = 0.11). About 30% reported ≥ 10-lb weight loss, with 50% higher odds of success for men but there was no difference by race/ethnicity.Overweight or obese perception was a key driver in weight loss activities but was inconsistent with actual weight status and varied by race/ethnicity and other sociodemographic factors. Weight loss programme is under-utilized and should take in account of weight perception training and culturally appropriate approach.
View details for DOI 10.1111/joim.13203
View details for PubMedID 33340186
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Racial and Socioeconomic Disparities in Hospitalization of Pediatrics with Liver Disease from 2005 to 2015.
Digestive diseases and sciences
2020
Abstract
Adult liver-related hospitalizations have recently increased in the USA, but data are limited for the pediatric population.Utilizing the Office of Statewide Health Planning and Development hospital claims database (covering > 98% of all California hospitalizations), we aimed to characterize the demographic, clinical, and socioeconomic factors of liver disease-associated admissions among children between 2005 and 2015.We used ICD-9 codes to identify admissions associated with liver disease in patients up to 21 years of age. Patient characteristics were described as percentages and evaluated using the χ2 test. We used linear regression to examine changes over time.We analyzed 37,372 eligible admissions. Overall, close to one-third (28%) and one-half (48.0%) of admissions occurred in the age group 0-5 years and 16-21 years, respectively, with the remaining 23.1% occurring in the age group between 5 and 15 years. Over half (54.9%) were in males. By race, blacks made up half of the admission (49.7%), while by ethnicity, Hispanic also accounted for half of the admission (49.7%). Medicaid and Medicare payors were also disproportionately represented (54.6%). The most common liver disease was Alagille syndrome (29.2%) in 2005. Between 2005 and 2015, both the number of pediatric liver-associated admissions and the proportion of pediatric liver admissions over total admissions increased from 3130 to 3429 and 1.2% to 1.6%, respectively (both p = 0.001). By 2015, while Alagille syndrome admissions decreased to 26.4% (p = 0.004), NAFLD admission increased to 19.7% (p < 0.001).Major disparities exist in inpatient liver disease burden for blacks and Hispanics with liver disease, while NAFLD emerged as a rapidly rising liver disease in pediatrics.
View details for DOI 10.1007/s10620-020-06530-w
View details for PubMedID 32797346
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Increasing comorbidities in a South Korea insured population-based cohort of patients with chronic hepatitis B.
Alimentary pharmacology & therapeutics
2020
Abstract
It is controversial whether chronic hepatitis B (CHB) patients have more non-liver comorbidities than non-CHB subjects.To characterise the demographics, comorbidity and health utilisation of CHB patients in South Korea and compare them to matched controls.Using the Health Insurance Review & Assessment Service (HIRA) 2007-2016 database, adult patients with claims for CHB analysed. CHB cases and non-CHB controls matched in a 1:4 ratio using propensity score matching method.The age of CHB patients significantly increased from a mean 46.9 years in 2007 to 52.3 years in 2016. The proportions of persons having both liver-related and non-liver related comorbidities were higher in CHB patients compared to matched controls (dyslipidaemia [37.23% vs 23.77%, P < 0.0001], hypertension [29.39% vs 25.27%, P < 0.0001] chronic kidney disease (CKD) [3.02% vs 1.14%, P < 0.0001] and osteoporosis/fracture [OF] [4.09% vs 3.23%, P < 0.0001]). Approximately 50% of CHB patients had more than one comorbidity among CKD, diabetes, DLP, and OF. The odds of CKD in CHB patients were 1.42 times higher, and the odds of OF in CHB patients were 1.09 times higher than matched controls after adjustment for confounders (P < 0.0001).Prevalence of liver as well as non-liver comorbidities in patients with CHB was higher than matched control group and increased over time.
View details for DOI 10.1111/apt.15867
View details for PubMedID 32542860
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The epidemiology of NAFLD in Mainland China with analysis by adjusted gross regional domestic product: a meta-analysis.
Hepatology international
2020
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. This study aimed to estimate the prevalence, incidence, and outcome of NAFLD in the large and diverse population of Mainland China.PubMed, Embase, and the Cochrane Library databases were searched to identify published studies with NAFLD epidemiology data in adult participants (≥ 18 years old) from Mainland China. Random effects models were used to determine pooled estimates.We screened 1,328 studies and included 167 eligible studies (participant n = 1,486,635): 149 studies (n = 1,350,819) for prevalence, 18 studies (n = 147,316) for incidence, 7 studies (n = 5446) for evolution of hepatic steatosis, and 2 studies (n = 647) for mortality analysis. The NAFLD prevalence of the overall populations was 29.88%, with higher rates in males, increasing age and increasing gross regional domestic product (GRDP) per capita (all p ≤ 0.010). The prevalence was the highest in North China (36.41%; higher in Uyghur and Hui Chinese 40.86% and 34.36% vs 28.11% in Han Chinese), higher in diabetics (51.83% vs. 30.76% in non-diabetics) and in obese participants (66.21% vs. 11.72% in lean). The NAFLD incidence was 56.7 (95% CI 47.4-66.8) per 1000 person-years, higher in males and with higher GRDP per capita. The overall mortality was 7.3 (3.3-12.7) per 1000 person-years.The overall prevalence of NAFLD in Mainland China is about 30%. The highest prevalences were found among regions with higher income, North China, the non-Han ethnic minorities, diabetics, and the obese. China's NAFLD prevalence is on par with Western countries.
View details for DOI 10.1007/s12072-020-10023-3
View details for PubMedID 32130675
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Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients with Hepatocellular Carcinoma Presenting Beyond Milan Criteria.
Hepatology (Baltimore, Md.)
2020
Abstract
The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are downstaged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of downstaging, and the impact of LRT in beyond-MC HCC patients from the US Multicenter HCC Transplant Consortium (20 centers, 2002-2013). Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n=3,570) and beyond MC (n=789) who were downstaged (DS, n=465), treated with LRT and not downstaged (LRT-NoDS, n=242), or untreated (NoLRT-NoDS, n=82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared to DS (64.3% and 59.5%), and lowest in NoDS (n=324; 60.2% and 53.8%; overall P<0.001). DS patients had superior RFS (60% vs 54%,P=0.043) and lower 5-year HCC-R (18% vs 32%,P<0.001) compared to NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/< 5cm and 39.1% in NoDS/>5cm,P<0.001). Multivariate predictors of downstaging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared to NoLRT-NoDS (34.1% vs 26.1%,P<0.001), even after controlling for clinicopathologic variables (HR=2.33,P<0.001) and inverse probability of treatment weighted propensity matching (HR=1.82,P<0.001). Conclusion In LT recipients with HCC presenting beyond MC, successful downstaging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden, and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared to NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.
View details for DOI 10.1002/hep.31210
View details for PubMedID 32124453
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Development and validation of a risk score for liver cirrhosis prediction in untreated and treated chronic hepatitis B.
The Journal of infectious diseases
2020
Abstract
Chronic hepatitis B (CHB) can progress to cirrhosis, but there are limited noninvasive tools available to estimate cirrhosis risk, including in patients receiving antiviral therapy. This study developed/validated a simple model to assess risk in CHB patients.The derivation cohort included 3,000 CHB patients from 6 centers in the US, with 52.60% receiving antiviral therapy. External validation was performed for 4,552 CHB individuals from similar cohorts in Taiwan, with 21.27% receiving therapy. Cox proportional hazards regression analyses were used to screen predictors and develop the risk score for cirrhosis. The areas under receiver operating characteristic (AUROCs) were calculated for predictive value.Sex, age, diabetes, antiviral treatment status/duration, hepatitis B e-antigen, and baseline alanine aminotransferase/aspartate aminotransferase levels were significantly associated with increased cirrhosis risk. A 13-point risk score was developed based on these predictors. The AUROCs for predicting cirrhosis risk were 0.82 at 3 years, 0.85 at 5 years, and 0.89 at 10 years in the derivation cohort, and 0.82, 0.79, and 0.77 in the validation cohort, respectively.We developed/validated a simple cirrhosis prediction model with an independent external cohort that can be applied to both treatment-naïve and treatment-experienced CHB patients in diverse settings and locations.
View details for DOI 10.1093/infdis/jiaa330
View details for PubMedID 32525978
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Diagnosis Rates of Chronic Hepatitis B in Privately Insured Patients in the United States.
JAMA network open
2020; 3 (4): e201844
Abstract
To achieve the World Health Organization goal of viral hepatitis elimination by 2030, it is important to estimate current rates of chronic hepatitis B (CHB) diagnosis and treatment.To provide an accurate accounting of the number of patients with CHB aged 6 years or older who have not yet been diagnosed in the United States.This cross-sectional study used the commercial US Truven Health MarketScan Database (138 634 154 privately insured individuals in January 2007 to December 2014) to identify patients with CHB diagnosis and the National Health and Nutrition Examination Survey to estimate the actual number of privately insured persons with CHB. Based on sex and age distribution derived from the US Census Bureau, we calculated the total population with CHB and the proportion of those who remained undiagnosed among the 198 073 302 privately insured individuals. Next, we identified diagnosed CHB patients who received 1 or more prescription for CHB medications to calculate the treatment rate for those with severe disease states, such as cirrhosis and hepatocellular carcinoma, that would warrant treatment. Analyses were performed from October 2017 to January 2020.The rate and number of patients with CHB who remained undiagnosed and treatment rates for patients with CHB who have cirrhosis or hepatocellular carcinoma.Among the 198 073 302 privately insured individuals (48.55% male; 15.52% aged 6-17 years; 84.48% aged ≥18 years), there were 511 029 (95% CI, 317 733-704 325) individuals with CHB, but only 95 075 of these had been diagnosed, yielding a diagnosis rate of only 18.60% (95% CI, 13.50%-29.92%), meaning that 81.40% (95% CI, 70.08%-86.50%) were undiagnosed. The treatment rates were 34.79% (95% CI, 33.31%-36.27%) for those with cirrhosis and 48.64% (95% CI, 45.59%-51.69%) for those with hepatocellular carcinoma.In this study, only approximately 1 in 5 privately insured patients with CHB had been diagnosed. Only one-third of patients with CHB who had cirrhosis and one-half who had hepatocellular carcinoma received antiviral therapy. Further efforts are needed to improve the current situation of poor connection to care for patients with CHB, especially for those with advanced liver disease.
View details for DOI 10.1001/jamanetworkopen.2020.1844
View details for PubMedID 32271388
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Hepatitis B Virus: Advances in Prevention, Diagnosis, and Therapy.
Clinical microbiology reviews
2020; 33 (2)
Abstract
SUMMARYCurrently, despite the use of a preventive vaccine for several decades as well as the use of effective and well-tolerated viral suppressive medications since 1998, approximately 250 million people remain infected with the virus that causes hepatitis B worldwide. Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the leading causes of liver cancer and overall mortality globally, surpassing malaria and tuberculosis. Linkage to care is estimated to be very poor both in developing countries and in high-income countries, such as the United States, countries in Western Europe, and Japan. In the United States, by CDC estimates, only one-third of HBV-infected patients or less are aware of their infection. Some reasons for these low rates of surveillance, diagnosis, and treatment include the asymptomatic nature of chronic hepatitis B until the very late stages, a lack of curative therapy with a finite treatment duration, a complex natural history, and a lack of knowledge about the disease by both care providers and patients. In the last 5 years, more attention has been focused on the important topics of HBV screening, diagnosis of HBV infection, and appropriate linkage to care. There have also been rapid clinical developments toward a functional cure of HBV infection, with novel compounds currently being in various phases of progress. Despite this knowledge, many of the professional organizations provide guidelines focused only on specific questions related to the treatment of HBV infection. This focus leaves a gap for care providers on the other HBV-related issues, which include HBV's epidemiological profile, its natural history, how it interacts with other viral hepatitis diseases, treatments, and the areas that still need to be addressed in order to achieve HBV elimination by 2030. Thus, to fill these gaps and provide a more comprehensive and relevant document to regions worldwide, we have taken a global approach by using the findings of global experts on HBV as well as citing major guidelines and their various approaches to addressing HBV and its disease burden.
View details for DOI 10.1128/CMR.00046-19
View details for PubMedID 32102898
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Prevalence, characteristics and mortality outcomes of obese, nonobese and lean NAFLD in the United States, 1999-2016.
Journal of internal medicine
2020
Abstract
Updated prevalence and outcome data for nonobese NAFLD for the multi-ethnic US population is limited.We aimed to investigate the prevalence, clinical characteristics and mortality of obese and nonobese individuals with NAFLD in the United Sates.A retrospective study was conducted using the 1999-2016 NHANES databases. We determined hazard ratio stratified by obesity status in NAFLD individuals using Cox regression and log-rank test.Overall NAFLD prevalence was 32.3%: 22.7% were obese and 9.6% were nonobese, with increasing trend over time for obese NAFLD, but not nonobese NAFLD. Amongst those with NAFLD, 29.7% (95% CI: 27.8%-31.7%) were nonobese, of which 13.6% had lean NAFLD. Nonobese NAFLD was more common in older (40.9% if ≥ 65 vs. 24.2% if < 65 years), male (34.0% vs. 24.2%) and foreign-born Asian people (39.8% vs. 11.4%) and uncommon in black (11.5% vs 30-35% in other ethnicities, P < 0.001). Metabolic comorbidities were common in nonobese NAFLD individuals who also had more advanced fibrosis. Nonobese NAFLD individuals had higher 15-year cumulative all-cause mortality (51.7%) than obese NAFLD (27.2%) and non-NAFLD (20.7%) (P < 0.001). However, DM and fibrosis, but neither obese nor nonobese NAFLD compared to non-NAFLD was independently associated with higher mortality.Nonobese NAFLD makes up about one-third of the NAFLD in the United States (even higher in older, male and foreign-born individuals) and carries higher mortality than obese NAFLD. Screening for NAFLD should be considered in high-risk groups even in the absence of obesity.
View details for DOI 10.1111/joim.13069
View details for PubMedID 32319718
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Prevalence of significant hepatic fibrosis using magnetic resonance elastography in a health check-up clinic population.
Alimentary pharmacology & therapeutics
2020; 51 (3): 388–96
Abstract
Significant hepatic fibrosis is associated with higher mortality. However, data on the estimated prevalence of liver fibrosis in the general population are scarce.To use magnetic resonance elastography (MRE) to investigate the prevalence of hepatic fibrosis in a Korean health check-up clinic cohort.We enrolled 2170 participants at our health check-up clinic between January 2015 and May 2018, all of whom had MR with chemical shift technique and MRE. The primary objective was to estimate the prevalence of liver fibrosis. For generalisation, sex- and age-standardised prevalence was calculated based on the Korean Statistical Information Service (KOSIS) during the period 2015-2018.The prevalence of F2 (≥3.0 kPa) and F3 (≥3.6 kPa) in the overall cohort was 5.1% and 1.3% respectively (sex- and age-adjusted prevalence of 3.8% and 1.3%). Non-alcoholic fatty liver disease (NAFLD) prevalence (>5% fat fraction) was 27.7% in the average risk population (after excluding alcohol use and viral hepatitis), and the prevalence of significant and advanced fibrosis in NAFLD participants was 8.0% and 1.5% respectively. In participants with diabetes, 12.5% had ≥F2 and 4.3% ≥F3. In participants with NAFLD plus diabetes, 24.1% had ≥F2 and 6.0% ≥F3. On multivariate analysis, only age, insulin, diabetes and fatty liver on MR were independently associated with significant fibrosis.In a Korean health check-up clinic setting, the prevalence of significant and advanced liver fibrosis was 5.1% and 1.3% (sex- and age-adjusted prevalence of 3.8% and 1.3%). The prevalence of advanced liver fibrosis was five times higher for diabetic participants with NAFLD.
View details for DOI 10.1111/apt.15626
View details for PubMedID 31943268
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Association between fatty liver and cirrhosis, hepatocellular carcinoma, and HBsAg seroclearance in chronic hepatitis B.
The Journal of infectious diseases
2020
Abstract
Chronic hepatitis B (CHB) and fatty liver (FL) are common, natural history data on concurrent FL and CHB (FL-CHB) are limited. This study aimed to evaluate the effect of FL on cirrhosis, hepatocellular carcinoma (HCC), and HBsAg seroclearance incidence in CHB patients.In a retrospective cohort study of 6,786 adult CHB patients, we used propensity score matching (PSM) to balance the FL-CHB and non-FL CHB groups. Kaplan-Meier methods were used to compare cumulative cirrhosis, HCC, and HBsAg seroclearance rates between subgroups.Before PSM, compared to non-FL CHB, FL-CHB patients had lower 10-year cumulative rates of cirrhosis, HCC, and a higher HBsAg seroclearance rate. Similar results were found in the matched FL-CHB and non-FL CHB patients, as well as in antiviral treated PSM cohort. Cox proportional hazards model indicated FL to remain significantly and strongly associated with lower risk of cirrhosis and HCC (HR: 0.19, 95% CI: 0.12-0.33, P<0.001, 0.21, 95% CI: 0.09-0.51, P=0.001, respectively) in antiviral treated patients, but not in untreated patients.FL was significantly associated with lower cirrhosis and HCC risk and higher HBsAg seroclearance. Further studies are needed to confirm our funding and investigate the mechanisms underlying the impact of FL on CHB.
View details for DOI 10.1093/infdis/jiaa739
View details for PubMedID 33249474
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HCC risk post-SVR with DAAs in East Asians: findings from the REAL-C cohort.
Hepatology international
2020
Abstract
Despite HCV cure, patients remain at risk for HCC, but risk factor data for HCC following SVR are limited for Asian patients.To address this gap, we analyzed 5814 patients (5646 SVR, 168 non-SVR) from the Real-World Evidence from the Asia Liver Consortium for HCV (REAL-C) who did not have HCC or a history of HCC at baseline (pre-DAA treatment) and did not develop HCC within 6 months of baseline. To assess the effect of SVR on HCC incidence, we used 1:4 propensity score matching [(PSM), age, sex, baseline cirrhosis, and baseline AFP] to balance the SVR and non-SVR groups.In the PSM cohort (160 non-SVR and 612 SVR), the HCC incidence rate per 100 person years was higher in the non-SVR compared to the SVR group (5.26 vs. 1.94, p < 0.001). Achieving SVR was independently associated with decreased HCC risk (adjusted HR [aHR]: 0.41, p = 0.002). Next, we stratified the SVR cohort of 5646 patients to cirrhotic and noncirrhotic subgroups. Among cirrhotic SVR patients, aged ≥ 60, having an albumin bilirubin grade (ALBI) of 2 or 3 (aHR: 2.5, p < 0.001), and baseline AFP ≥ 10 ng/mL (aHR: 1.6, p = 0.001) were associated with higher HCC risk, while among the non-cirrhotic SVR group, only baseline AFP ≥ 10 ng/mL was significant (aHR: 4.26, p = 0.005).Achieving SVR decreases HCC risk; however, among East Asians, patients with elevated pretreatment AFP remained at risk. Pretreatment AFP, an easily obtained serum marker, may provide both prognostic and surveillance value for HCC in East Asian patients who obtained SVR.
View details for DOI 10.1007/s12072-020-10105-2
View details for PubMedID 33277685
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Hepatocellular carcinoma incidence with tenofovir versus entecavir in chronic hepatitis B: a systematic review and meta-analysis.
The lancet. Gastroenterology & hepatology
2020
Abstract
It is unclear whether tenofovir disoproxil fumarate and entecavir differ in their association with risk of hepatocellular carcinoma in patients with chronic hepatitis B, and previous meta-analyses have shown conflicting conclusions with substantial heterogeneity. We aimed to analyse the updated data and elucidate the source of heterogeneity.We searched PubMed, Embase, Web of Science, and the Cochrane library for relevant studies with time-to-event data for incident hepatocellular carcinoma occurring in patients with chronic hepatitis B who received tenofovir disoproxil fumarate or entecavir monotherapy with follow-up of at least 1 year. Studies published between Jan 1, 2006, and April 17, 2020, and abstracts from international conferences in 2018 and 2019 were included. We pooled covariate adjusted hazard ratios (HRs) for hepatocellular carcinoma using a random-effects model, assessed heterogeneity among included studies using the I2 statistic and Cochran's Q test, and identified the source of heterogeneity using prespecified subgroup analyses. This study is registered with PROSPERO, ID CRD42020176513.31 studies involving 119 053 patients were analysed. The 5-year cumulative incidence of hepatocellular carcinoma was 5·97% (95% CI 5·81-6·13, 28 studies) for entecavir and 3·06% (2·86-3·26, 13 studies) for tenofovir disoproxil fumarate in studies with unmatched populations (p<0·0001). For all eight studies matched by propensity score, the 5-year cumulative incidence was 3·44% (95% CI 3·08-3·80) for entecavir and 3·39% (2·94-3·83) for tenofovir disoproxil fumarate (p=0·87). Analysis of 14 comparative studies with covariate adjustment found that tenofovir disoproxil fumarate and entecavir had similar risk of hepatocellular carcinoma (primary outcome); adjusted HR 0·88, 95% CI 0·73-1·07; p=0·20), although heterogeneity was significant (I2=56·4%, p=0·0038). In a subgroup analysis for hospital-based clinical cohorts, there was no difference in hepatocellular carcinoma incidence between the two regimens (adjusted HR 1·03, 95% CI 0·88-1·21; I2=0%). However, tenofovir disoproxil fumarate was associated with a lower risk of hepatocellular carcinoma compared with entecavir in administrative database research (adjusted HR 0·67, 0·59-0·76; I2=0%).Our study found no significant difference between tenofovir disoproxil fumarate and entecavir in their association with incident hepatocellular carcinoma. We suggest that treatment should be guided by patient tolerability and affordability rather than whether one drug is more effective than the other.Supported in part by E-DA Hospital (EDAHP 106008; EDAHP 103046).
View details for DOI 10.1016/S2468-1253(20)30249-1
View details for PubMedID 33007228
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Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis
JOURNAL OF HEPATOLOGY
2019; 71 (3): 473–85
View details for DOI 10.1016/j.jhep.2019.04.017
View details for Web of Science ID 000481571400005
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Chronic hepatitis B prevalence among foreign-born and US-born adults in the United States, 1999-2016.
Hepatology (Baltimore, Md.)
2019
Abstract
Hepatitis B virus (HBV) infection remains a major global health problem, exacerbated by poor linkage to care. We aimed to determine the prevalence of HBV infection, exposure, self-reported vaccination, vaccine-induced immunity, disease awareness, and treatment in the United States (U.S.) by birthplace and race/ethnicity during 1999-2016. 47,628 adult participants in the National Health and Nutrition Examination Survey completed HBV core antibody (anti-HBc) and surface antigen (HBsAg) tests and 47,618 adults completed HBV surface antibody (anti-HBs) and anti-HBc tests and were included in the analysis. HBV infection was defined by positive HBsAg and past exposure by positive anti-HBc. Vaccine-mediated immunity was defined by positive anti-HBs and negative anti-HBc. No significant change in the prevalence of HBV infection was observed between 1999-2016 (P=0.442), affecting 0.35% (95% CI: 0.28-0.45) or 0.84 million adults. In contrast, a significant decrease in HBV exposure and increase in vaccine-mediated immunity was observed. U.S. born had significantly lower prevalence of HBV infection and exposure as well as higher prevalence of vaccine-mediated immunity and self-reported vaccination than foreign born. Prevalence of HBV infection was highest in non-Hispanic Asians in both foreign- (3.85%, 95% CI: 2.97-4.97) and U.S.-born (0.79%, 95% CI: 0.17-3.59) persons during 2011-2016. Among infected persons, liver disease awareness was only 15.19%, and treatment rate was only 4.60%. CONCLUSION: This study revealed disparities of HBV infection among ethnic/racial groups and between U.S.-born and foreign-born persons. Awareness of liver disease and treatment rate among infected persons was dismal. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/hep.30831
View details for PubMedID 31228279
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Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999-2019: a systematic review and meta-analysis
LANCET GASTROENTEROLOGY & HEPATOLOGY
2019; 4 (5): 389–98
View details for DOI 10.1016/S2468-1253(19)30039-1
View details for Web of Science ID 000463786300024
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Poor Adherence to Guidelines for Treatment of Chronic Hepatitis B Virus Infection at Primary Care and Referral Practices
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
2019; 17 (5): 957-+
View details for DOI 10.1016/j.cgh.2018.10.012
View details for Web of Science ID 000461795700030
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Prevalence of Undetectable Vaccine-Induced Immunity Against Hepatitis B Virus in US Adults at High Risk for Infection
HEPATOLOGY
2019; 69 (4): 1385–97
View details for DOI 10.1002/hep.30285
View details for Web of Science ID 000462612400006
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Changes in Renal Function in Patients With Chronic HBV Infection Treated With Tenofovir Disoproxil Fumarate vs Entecavir
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
2019; 17 (5): 948-+
View details for DOI 10.1016/j.cgh.2018.08.037
View details for Web of Science ID 000461795700029
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Advancing Age and Comorbidity in a US Insured Population-Based Cohort of Patients With Chronic Hepatitis B
HEPATOLOGY
2019; 69 (3): 959–73
View details for DOI 10.1002/hep.30246
View details for Web of Science ID 000459816500006
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Factors Associated With Rates of HBsAg Seroclearance in Adults With Chronic HBV Infection: A Systematic Review and Meta-analysis
GASTROENTEROLOGY
2019; 156 (3): 635-+
View details for DOI 10.1053/j.gastro.2018.10.027
View details for Web of Science ID 000457714300026
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Direct-acting antivirals in East Asian hepatitis C patients: real-world experience from the REAL-C Consortium.
Hepatology international
2019
Abstract
One-third of the global hepatitis C virus (HCV) burden is found in Asia. Real-world data from diverse East Asian cohorts remain limited. This study addressed the real-world status of direct-acting antiviral (DAA) therapy among patients from East Asia.Chronic hepatitis C (CHC) patients from clinical sites in Japan, Taiwan, South Korea, and Hong Kong were recruited in the REAL-C registry, an observational chart review registry. The primary outcome was sustained virologic response (SVR12, HCV RNA PCR < 25 IU/mL 12 week post-therapy).A total of 6287 CHC patients were enrolled. Compared to other East Asian patients, patients from Japan were older (66.3 vs. 61.5 years, p < 0.0001), had lower body mass indices (22.9 kg/m2 vs. 24.6 kg/m2, p < 0.001), and were more likely to have non-liver malignancy history (12.2% vs. 5.0%, p < 0.001).The overall SVR12 rate was 96.4%, similar to patients both inside and outside Japan (96.6% vs. 96%, p = 0.21). The SVR12 rate ranged from 91.1 to 99.4% except treatment-experienced cirrhotic HCV genotype-1 patients who received daclatasvir/asunaprevir (85.9%) and the treatment-experienced cirrhotic HCV genotype-2 patients treated with sofosbuvir/ribavirin (87%). The overall rate of drug discontinuation was 1.9%, also similar across regions. On multivariate regression analyses, there was no significant association between geographic region and SVR outcomes.In this large multinational CHC cohort from the East Asia, oral DAAs were highly effective and well tolerated across the region. Policies should encourage treatment for all CHC patients with DAAs in Asia with its heavy burden of HCV.
View details for DOI 10.1007/s12072-019-09974-z
View details for PubMedID 31463665
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Tenofovir Versus Entecavir for Hepatocellular Carcinoma Prevention in an International Consortium of Chronic Hepatitis B.
The American journal of gastroenterology
2019
Abstract
It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).This retrospective cohort study analyzed an international consortium that encompassed 19 centers from 6 countries or regions composed of previously untreated CHB patients then treated with either ETV or TDF monotherapy. Those who developed HCC before antiviral treatment or within 1 year of therapy were excluded. The association between antiviral regimen and HCC risk was evaluated using competing-risk survival regression. We also applied propensity score matching (PSM) to 1:1 balance the 2 treatment cohorts. A total of 5,537 patients were eligible (n = 4,837 received ETV and n = 700 received TDF) and observed for HCC occurrence until December 23, 2018. Before PSM, the TDF cohort was significantly younger and had generally less advanced diseases.In the unadjusted analysis, TDF was associated with a lower risk of HCC (subdistribution hazard ratio [SHR], 0.45; 95% confidence interval [CI], 0.26-0.79; P = 0.005). The multivariable analysis, however, found that the association between TDF and HCC no longer existed (SHR, 0.81; 95% CI, 0.42-1.56; P = 0.52) after adjustment for age, sex, country, albumin, platelet, α-fetoprotein, cirrhosis, and diabetes mellitus. Furthermore, the PSM analysis (n = 1,040) found no between-cohort differences in HCC incidences (P = 0.51) and no association between regimens (TDF or ETV) and HCC risk in the multivariable-adjusted analysis (adjusted SHR, 0.89; 95% CI, 0.41-1.92; P = 0.77).TDF and ETV did not significantly differ in the prevention of HCC in patients with CHB.
View details for DOI 10.14309/ajg.0000000000000428
View details for PubMedID 31634265
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The Phosphatidylethanolamine Biosynthesis Pathway Provides a New Target for Cancer Chemotherapy.
Journal of hepatology
2019
Abstract
Since iPSC human develop into hepatic organoids through stages that resemble human embryonic liver development, they can be used to study developmental processes and disease pathology. Therefore, we examined the early stages of hepatic organoid formation to identify key pathways affecting early liver development.Single cell RNA-sequencing and metabolomic analysis was performed on developing organoid cultures at the iPSC, hepatoblast (day 9) and mature organoid stage. The importance of the phosphatidyl-ethanolamine biosynthesis pathway to early liver development was examined in developing organoid cultures using iPSC with a CRISPR-mediated gene knockout and an over the counter medication (meclizine) that inhibits the rate-limiting enzyme in this pathway. Meclizine's effect on the growth of a human hepatocarcinoma cell line in a xenotransplantation model and on the growth of acute myeloid leukemia cells in vitro was also examined.Transcriptomic and metabolomic analysis of organoid development indicated that the phosphatidyl-ethanolamine biosynthesis pathway is essential for early liver development. Unexpectedly, early hepatoblasts were selectively sensitive to the cytotoxic effect of meclizine. We demonstrate that meclizine could be repurposed for use in a new synergistic combination therapy for primary liver cancer: a glycolysis inhibitor reprograms cancer cell metabolism to make it susceptible to the cytotoxic effect of meclizine. This combination inhibited the growth of a human liver carcinoma cell line in vitro; and in a xenotransplantation model without causing significant side effets. This drug combination was also highly active against acute myeloid leukemic cells.Our data indicates that the phosphatidyl-ethanolamine biosynthesis is a targetable pathway for cancer; and that meclizine may have clinical efficacy as a repurposed anti-cancer drug when used as part of a new combination therapy.
View details for DOI 10.1016/j.jhep.2019.11.007
View details for PubMedID 31760071
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Prevalence of viremic HCV infection by age, race/ethnicity, birthplace and disease awareness among viremic persons in the U.S., 1999-2016.
The Journal of infectious diseases
2019
Abstract
Though curative therapy is now available for hepatitis C virus (HCV) infection in the United States, it is not clear if all affected persons have been diagnosed and/or linked to care.This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (1999-2016) and included 46,465 non-incarcerated and non-institutionalized participants.Viremic HCV prevalence decreased from 1.32% in 1999-2004 to 0.80% in 2011-2016, though most of the decrease occurred in U.S.-born whites and blacks but not the foreign-born or those born after 1985. In 2011-2016, approximately 1.90 million U.S. adults remained viremic with HCV, and 0.33 million were at higher risk for advanced fibrosis, but only 49.8% were aware of their HCV infection, with higher disease awareness in those with health insurance coverage and US-born persons.The prevalence of viremic HCV has decreased in recent years among U.S. born whites and blacks but not in other race/ethnicities and foreign-born persons and birth cohort born after 1985. Less than half of the viremic population was aware of having HCV infection. Improved HCV screening and linkage to care are needed, especially for the uninsured, foreign-born, birth cohort after 1985 and certain ethnic minorities.
View details for DOI 10.1093/infdis/jiz479
View details for PubMedID 31560391
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REAL-B (Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for HBV) Risk Score for the Prediction of Hepatocellular Carcinoma in Chronic Hepatitis B Patients Treated with Oral Antiviral Therapy.
The Journal of infectious diseases
2019
Abstract
Patients on oral antiviral (OAV) therapy remain at HCC risk. Risk prediction tools distinguishing treated patients with residual HCC risk are limited. Aim: Develop an accurate, precise, simple-to-use HCC risk score using routine clinical variables among a treated Asian cohort.Routine practice adult Asian CHB patients on OAV were recruited from 25 centers in the US and Asia-Pacific region. Excluded persons were co-infected with hepatitis C, D, or HIV, had HCC prior to or within 1 year of study entry or their follow-up was <1 year. Patients were randomized to derivation and validation cohorts on a 2:1 ratio. Statistically significant predictors from multivariate modeling formed the REAL-B score.A total of 8,048 patients were randomized to the derivation (n=5,365) or validation group (n=2,683).The REAL-B model included 7 variables (male gender, age, alcohol use, diabetes, baseline cirrhosis, platelet count, and AFP) scores were categorized as: 0-3 low risk, 4-7 moderate risk, and 8-13 high risk. AUROCs were >0.80 for HCC risk at 3, 5, and 10 years, and were significantly higher than other risk models (p<0·001).The REAL-B score provides three distinct risk categories for HCC development in Asian CHB patients on OAV guiding HCC surveillance strategy.
View details for DOI 10.1093/infdis/jiz477
View details for PubMedID 31550363
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Reduced Incidence of Hepatocellular Carcinoma in Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis B Treated With Tenofovir-A Propensity Score-Matched Study
JOURNAL OF INFECTIOUS DISEASES
2019; 219 (1): 10–18
View details for DOI 10.1093/infdis/jiy391
View details for Web of Science ID 000458610200004
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HCV Cure Rates are Reduced in Patients with Active but not Inactive Hepatocellular Carcinoma- A Practice Implication.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
2019
Abstract
The cure rate of hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) for patients with active and inactive hepatocellular carcinoma (HCC) may differ, but well-controlled studies are limited. We aimed to evaluate DAA outcomes in a large East Asian HCV/HCC population compared to HCV/non-HCC patients.Using data from the REAL-C registry (Hong Kong, Japan, South Korea, and Taiwan), we used propensity score matching (PSM) to match HCC and non-HCC (1:1) groups for age, sex, cirrhosis, prior treatment, HCV genotype, treatment regimen, baseline platelet count, HCV RNA, total bilirubin, alanine aminotransferase, and albumin level to evaluate DAA treatment outcomes in a large population of HCV/HCC compared to HCV/non-HCC patients.We included 6,081 patients (HCC, n=465; non-HCC, n=5,616) treated with interferon-free DAAs. PSM of the entire study population yielded 436 matched pairs with similar baseline characteristics. There was no statistically significant difference in the overall SVR rate of the HCC (92.7%) and non-HCC (95.0%) groups. Rates of treatment discontinuation, adverse effects, and death were also similar between the HCC and non-HCC groups. Among patients with HCC, those with active HCC had a lower SVR than inactive HCC cases (85.5% vs. 93.7%, P=0.03). On multivariable analysis, active HCC, but not inactive HCC, was significantly associated with lower SVR (OR 0.28, P=0.01) when compared to non-HCC.Active HCC but not inactive HCC was independently associated with lower SVR compared to non-HCC patients undergoing DAA therapy, though cure rate was still relatively high (85%) in active HCC patients.
View details for DOI 10.1093/cid/ciz1160
View details for PubMedID 31777940
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Cure with Interferon Free DAA is Associated with Increased Survival in Patients with HCV related HCC from both East and West.
Hepatology (Baltimore, Md.)
2019
Abstract
Survival data among patients with HCV-related HCC after achieving sustained virologic response (SVR) with interferon (IFN)-free direct acting antivirals (DAAs) in both Asian and western countries are limited. Survival rates were compared between HCV-related HCC patients who were untreated for HCV and those who achieved SVR. Using data from two U.S. and six Asian centers from 2005-2017, we categorized 1676 mono-infected HCV-related HCC patients into patients untreated for HCV (untreated group) and DAA-treated patients with SVR (SVR group) and matched by propensity score-matching (PSM); multivariable Cox regression with HCV treatment status as a time-varying covariate was used to determine mortality risk and landmark analysis to avoid immortal time bias. There were 1,239 untreated and 437 SVR patients. After PSM, background risks of the 321 pairs of matched patients were balanced (all P>0.05). After time-varying adjustment for HCV treatment initiation compared to untreated patients, SVR patients had significantly higher 5-year overall survival (87.78% vs. 66.05%, P<0.001). Multivariable Cox regression showed that SVR was independently associated with a 63% lower risk of 5-year all-cause mortality (HR=0.37; 95% CI: 0.16-0.83, P=0.016) and 66% lower risk of 5-year liver-related mortality (HR=0.34; 95% CI: 0.13-0.88, P=0.026) with similar trends after removing liver transplanted patients. Landmark analysis at 90, 180, and 360 days showed consistent results (HRs ranged 0.22 to 0.44, all P<0.05). CONCLUSION: In this multinational consortium, HCV-related HCC patients who obtained SVR achieved a 60-70% improvement in 5-year survival (both all-cause and liver-related) compared to patients untreated for HCV. Patients eligible for HCC therapy should also be considered for DAA therapy.
View details for DOI 10.1002/hep.30988
View details for PubMedID 31610027
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Healthcare Resource Utilization and Costs by Disease Severity in an Insured National Sample of US Patients with Chronic Hepatitis B.
Journal of hepatology
2018
Abstract
BACKGROUND/AIM: Chronic hepatitis B (CHB) affects over 2 million people in the United States (US), with little reported on healthcare utilization and cost. We aimed to quantify annual CHB utilization and costs by disease severity and payer type.METHODS: Using Commercial, Medicare, and Medicaid databases from 2004 to 2015 and ICD9 codes, we retrospectively identified CHB adults analyzing all-cause inpatient, outpatient, and pharmaceutical utilization and costs by disease severity. We compared healthcare utilization and costs between CHB patients without advanced liver disease to matched non-CHB patients. All-cause inpatient, outpatient, and pharmaceutical utilization and costs were reported for each year and adjusted to 2015 dollars.RESULTS: Our sample consisted of 33,904 CHB cases and 86,072 non-CHB controls. All-cause inpatient admissions (average stay 6-10 days) were more frequent in advanced liver disease states. Across all payers, patients with decompensated cirrhosis had the highest emergency department utilization (1.6-2.8 annual visits) and highest mean annual costs. The largest all-cause cost components for Commercial and Medicaid were inpatient costs for all advanced liver disease groups (Commercial: 62%, 47%, 68%; Medicaid: 81%, 72%, 74%, respectively), and decompensated cirrhosis and hepatocellular carcinoma groups for Medicare (Medicare 49% and 48%). In addition, compensated liver disease patients had three times the cost of non-CHB controls.CONCLUSION: CHB patients, regardless of payer, who experienced decompensated cirrhosis, HCC, or a liver transplant incurred the highest annual costs and utilization of healthcare resources but even patients with CHB compensated liver disease incurred higher costs compared to those without CHB. All stakeholders in disease management need to combine efforts to prevent infection and advanced liver disease through improved vaccination rates, earlier diagnosis, and treatment.LAY SUMMARY: Hepatitis B virus can be a progressive disease leading to cirrhosis, hepatocellular carcinoma, liver transplant, and death. These progressive disease states are associated with a higher rate of hospitalizations, emergency room visits, outpatient visits, and costs compared to similar patients without hepatitis B. The most ill patients have the highest costs, but even less sick patients experience high costs compared to patients without hepatitis B.
View details for PubMedID 30287341
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The prevalence of undetectable vaccine-induced immunity against hepatitis B virus in US adults at high risk for infection.
Hepatology (Baltimore, Md.)
2018
Abstract
In 2015, the Centers for Disease Control and Prevention (CDC) reported a substantial increase in the number of acute hepatitis B virus (HBV) infections in the United States (US). Although national guidelines recommend vaccination of adults at high risk for HBV infection, the prevalence of undetectable immunity (i.e., susceptibility) in this population remains unknown. In this study, we analyzed a nationally representative sample using the National Health and Nutrition Examination Survey (NHANES) to evaluate the prevalence, trend, and predictors of undetectable vaccine-induced antibodies against HBV surface antigen (anti-HBs <10 mIU/mL) among high-risk adults from 2003-2014. Among adults at high risk for HBV infection, the prevalence of undetectable immunity decreased from 83.2% in 2003-2004 (95% confidence interval [CI]: 81.3-85.0) to 69.4% (about 64 million) in 2013-2014 (95% CI: 66.0-72.6). The prevalence decreased significantly in individuals with multiple sex partners or sexually transmitted disease and in pregnant women. However, there were no significant changes in men who have sex with men (MSMs), injection drug users (IDUs), hepatitis C virus (HCV)-infected and diabetes mellitus (DM)-patients, and those with elevated aspartate aminotransferase/ alanine aminotransferase (AST/ALT). Mexican Americans had the highest prevalence of undetectable immunity (77.6%, 95% CI: 72.6-81.9%), followed by non-Hispanic whites (70.1%, 95% CI: 66.9-73.1%). Older age, lower socioeconomic status, and having ≥1 high-risk factor(s) were associated with a higher risk of undetectable immunity, whereas an increased risk among the foreign-born disappeared after multivariable adjustment. In conclusion, around 64 million high-risk adults in the US remain susceptible to HBV infection, especially MSMs, IDUs, diabetics, HCV patients, and populations with elevated AST/ALT. To eliminate HBV, efforts should be made to increase screening and vaccination in high-risk adults. This article is protected by copyright. All rights reserved.
View details for PubMedID 30246260
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Advancing age and comorbidity in a United States insured population-based cohort of patients with chronic hepatitis B.
Hepatology (Baltimore, Md.)
2018
Abstract
Chronic hepatitis B (CHB) comorbidity data are limited. Using insurance claims databases, our aims were to determine the prevalence and incidence of non-liver comorbidities in CHB patients over time and the predictors of select comorbidities in CHB patients. Patients were adults with continuous coverage (Commercial/Medicare or Medicaid) 6 months prior to and after the first CHB diagnosis and matched non-CHB patients. Deyo-Charlson comorbidity index (DCCI) and comorbidities were analyzed (cardiovascular disease [CVD], carcinoma, diabetes [DM], obesity, hypertension [HTN], hyperlipidemia [HPL], alcohol use, renal impairment [RI], chronic kidney disease and [CKD]osteoporosis/fracture [OF]). Study population included 44,026 CHB cases and 121,568 matched controls. CHB patient mean age increased from 48.1±11.9 in 2006 to 51.8±12.4 years in 2015 for Commercial/Medicare and 44.1±11.1 to 50.2±10.2 years for Medicaid (P<0.001 for both). The Medicaid CHB cohort was the sickest (DCCI=2.6, P<0.001). The Commercial/Medicare 2006 CKD prevalence rate was 36.1/1000 in CHB and 10.2/1000 in controls, increasing to 97.6 and 38.8 in 2015, respectively. The 2006 CKD incidence (per 1,000 person-years) was 10.3 and 4.8; 15.2 and 11.3 by 2015, respectively (P<0.05 for all). Strongest predictors for CKD were: DM (HR: 2.48), HTN (HR: 3.29), and CVD (HR: 2.61) (all P<0.0001). Similar prevalence and incidence changes were observed for OF. Strongest predictors for OF were female (HR: 2.22), alcohol use (HR: 2.02), and viral coinfection (HR: 1.37) (all P<0.0001).CONCLUSION: Insured CHB patients were older with more comorbidities and experienced higher incidence and prevalence of CKD and OF than controls. This article is protected by copyright. All rights reserved.
View details for PubMedID 30175482
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Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study.
The lancet. Gastroenterology & hepatology
2018; 3 (6): 383–403
Abstract
The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment.In this modelling study, we used a Delphi process that included a literature review in PubMed and Embase, followed by interviews with experts, to quantify the historical epidemiology of HBV infection. We then used a dynamic HBV transmission and progression model to estimate the country-level and regional-level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on disease burden.We developed models for 120 countries, 78 of which were populated with data approved by experts. Using these models, we estimated that the global prevalence of HBsAg in 2016 was 3·9% (95% uncertainty interval [UI] 3·4-4·6), corresponding to 291 992 000 (251 513 000-341 114 000) infections. Of these infections, around 29 million (10%) were diagnosed, and only 4·8 million (5%) of 94 million individuals eligible for treatment actually received antiviral therapy. Around 1·8 (1·6-2·2) million infections were in children aged 5 years, with a prevalence of 1·4% (1·2-1·6). We estimated that 87% of infants had received the three-dose HBV vaccination in the first year of life, 46% had received timely birth-dose vaccination, and 13% had received hepatitis B immunoglobulin along with the full vaccination regimen. Less than 1% of mothers with a high viral load had received antiviral therapy to reduce mother-to-child transmission.Our estimate of HBV prevalence in 2016 differs from previous studies, potentially because we took into account the effect of infant prophylaxis and early childhood vaccination, as well as changing prevalence over time. Although some regions are well on their way to meeting prophylaxis and prevalence targets, all regions must substantially scale-up access to diagnosis and treatment to meet the global targets.John C Martin Foundation.
View details for DOI 10.1016/S2468-1253(18)30056-6
View details for PubMedID 29599078
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Clinical Features Associated with Survival Outcome in African-American Patients with Hepatocellular Carcinoma.
The American journal of gastroenterology
2018
Abstract
African-Americans (AA) have a higher incidence of hepatocellular carcinoma (HCC) and lower survival. We characterized survival rates and clinical features associated with survival in AA vs. Caucasians with HCC over the past two decades.HCC patients from three US medical centers were matched by year of diagnosis (1991-2016): AA (n = 578)/Caucasian (n = 578) and placed in one of two groups-HCC diagnosed prior to 2010 or 2010 and after. Data were obtained from chart review and the National Death Index. Multivariate and survival analysis controlling for key predictors were conducted.Prior to 2010, there was no difference in survival between Caucasians and AA (p = 0.61). After 2010, AA patients had poorer survival compared to Caucasians (35% vs. 44%, respectively, p = 0.044). Over time, survival improved for Caucasians (32% before 2010 vs. 44% after 2010, p = 0.003), but not AA (36% vs. 35%, p = 0.50). AA on presentation (in the after 2010 cohort) were more likely to have BCLC (Barcelona Clinic Liver Cancer) stage C (24% vs. 15%, p = 0.010) and less likely to receive treatment (85% vs. 93%, p = 0.002) compared to matched Caucasians. BCLC beyond stage A (aHR: 1.75, 95% CI: 1.26-2.43, p = 0.001) and child's class C (aHR 2.05, 95% CI: 1.23-3.41, p = 0.006) were the strongest predictors of mortality, while race was not.African-Americans presented with more advanced HCC and had poorer survival compared to Caucasians after 2010. Tumor stage was an independent predictor of mortality, but ethnicity was not. Further efforts are needed to improve early HCC diagnosis for AA.
View details for PubMedID 30333542
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Changing Landscape of Liver Cancer in California: A Glimpse Into the Future of Liver Cancer in the United States.
Journal of the National Cancer Institute
2018
Abstract
Asians and Hispanics currently have the highest incidence rates of hepatocellular carcinoma (HCC) in the United States. The numbers of these minority populations are rapidly increasing, reshaping the demographic in the United States and particularly California, where approximately one-third of US Asians and Hispanics reside. With the changing demographic and rising incidence of HCC that has tripled during the past three decades, it is important to forecast the future burden of HCC by age, sex, and race/ethnicity to plan prevention and control strategies for HCC.We used four Surveillance, Epidemiology, and End Results Program registries to obtain incidence data for California during 2000 to 2013, and 14 registries to represent non-California states. We applied age-period-cohort models to estimate future HCC incidence rates, and estimated HCC burden by multiplying incidence forecasts by corresponding US Census population projections.Our forecasts for California suggest that in 2030 Hispanics and blacks will have the highest HCC incidence rates and Asians the lowest. While incidence among whites, blacks, and Hispanics in California increased successively for each birth year cohort from 1915 through 1955, incidence among Asians in California decreased for each successive birth year cohort from 1915 through 1975. In contrast, consistent declines were not seen among Asians in the rest of the United States. In California, the estimated burden of HCC is 6482 new cases in 2030, where 80.0% of these patients are older than 65 years (vs 44.5% in 2014). The relative increase of burden in 2030 vs 2014 for this 65 years and older age group is especially high among Hispanics (318.3%), whereas it is the lowest among Asians (53.2%) in California.Prevention efforts in California should target persons currently ages 50 to 64 years who will make up the older age group (>65 years) in 2030, especially among Hispanics with the most rapid increase of HCC burden through 2030.
View details for PubMedID 30544184
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Factors Associated with Rates of HBsAg Seroclearance in Adults with Chronic HBV Infection: A systematic review and meta-analysis.
Gastroenterology
2018
Abstract
Seroclearance of hepatitis B surface antigen (HBsAg) is a marker for clearance of chronic hepatitis B virus (HBV) infection but reported annual incidence rates of HBsAg seroclearance vary. We performed a systematic review and meta-analysis to provide more precise estimates of HBsAg seroclearance rates among subgroups and populations.We searched PubMed, Embase, and Cochrane library for cohort studies that reported HBsAg seroclearance in adults with chronic HBV infection with more than 1 year of follow up and at least 1 repeat test for HBsAg. Annual and 5-, 10-, and 15-year cumulative incidence rates were pooled using a random effects model.We analyzed 34 published studies (with 42,588 patients; 303,754 person-years of follow-up; and 3194 HBsAg seroclearance events), including additional and updated aggregated data from 19 studies. The pooled annual rate of HBsAg seroclearance was 1.02% (95% CI, 0.79-1.27). Cumulative incidence rates were 4.03% at 5 years (95% CI, 2.49-5.93), 8.16% at 10 years (95% CI, 5.24-11.72), and 17.99% at 15 years (95% CI, 6.18-23.24). There were no significant differences between sexes. A higher proportion of patients negative for HBeAg at baseline had seroclearance (1.33%; 95% CI, 0.76-2.05) than patients positive for HBeAg (0.40%; 95% CI, 0.25-0.59) (P<.01). HBsAg seroclearance was also associated with a lower baseline HBV DNA (6.61 log10IU/mL; 95% CI, 5.94-7.27) than in patients without HBsAg seroclearance (7.71 log10IU/mL; 95% CI, 7.41-8.02) (P<.01) and lower level of HBsAg at baseline (2.74 log10IU/mL; 95% CI, 1.88-3.60) than in patients without HBsAg seroclearance (3.90 log10IU/mL, 95% CI, 3.73-4.06) (P<.01). HBsAg seroclearance was not associated with HBV genotype or treatment history. Heterogeneity was substantial across the studies (I2=97.49%).In a systematic review and meta-analysis, we found a low rate of HBsAg seroclearance in untreated and treated patients (pooled annual rate approximately 1%). Seroclearance occurred mainly in patients with less active disease. Patients with chronic HBV infection should therefore be counseled on the need for lifelong treatment, and curative therapies are needed.
View details for PubMedID 30342034
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HCV Genotype 6 Increased the Risk for Hepatocellular Carcinoma Among Asian Patients With Liver Cirrhosis.
American journal of gastroenterology
2017
Abstract
Hepatitis C virus (HCV) infection is a well-documented risk factor for hepatocellular carcinoma (HCC). Seven HCV genotypes have been classified, and the genotypes show a great variety of geographic distribution. HCV genotype 6 is prevalent in Southeast Asia and has been less studied than the other genotypes.This follow-up study was designed to evaluate the natural history of HCV genotype 6. The cohort enrolled 851 Asian patients consisting of 222 with HCV genotype 6 and 629 with other genotypes. The incidence of HCC per 1,000 person-years of various HCV genotypes was estimated by dividing the new HCC cases to the person-years of follow-up. The adjusted hazards ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox's proportional hazards models.After 4072 person-years of follow-up, there were 96 newly-developed HCC cases, confirming an incidence of 23.6 per 1000 person-years. By stratifying cirrhosis at study entry, the cumulative risk of HCC among HCV genotype 6 vs. non-6 was 2.9 vs. 2.2% for those without cirrhosis (P=0.45) and 76.2% (95% CI: 55.6-96.8%) vs. 36.2% (95% CI: 28.7-39.1%) for those with cirrhosis (P<0.05), respectively. Among patients with cirrhosis, HCV genotype 6 was significantly associated with HCC compared to patients with non-6 genotypes, with the adjusted HR=2.12 (1.33-3.39), P<0.05. In a model treating patients with genotypes other than 1 or 6 as the reference, the adjusted HR for HCC for HCV genotypes 1 and 6 were 1.13 (0.56-2.27) and 2.34 (1.12-4.86), respectively.Among patients with cirrhosis, those with HCV genotype 6 infection should be given high priority for antiviral therapy to decrease HCC risk and for vigilant adherence to HCC surveillance.Am J Gastroenterol advance online publication, 25 April 2017; doi:10.1038/ajg.2017.123.
View details for DOI 10.1038/ajg.2017.123
View details for PubMedID 28440303
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Impact of Pretransplant Bridging Locoregional Therapy for Patients With Hepatocellular Carcinoma Within Milan Criteria Undergoing Liver Transplantation: Analysis of 3601 Patients from the US Multicenter HCC Transplant Consortium.
Annals of surgery
2017
Abstract
To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC).Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited.Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013).Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P < 0.001; 4+ LRTs: HR 2.5, P < 0.001), and unfavorable waitlist alphafetorotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P < 0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044).Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.
View details for PubMedID 28654545
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Hepatocellular carcinoma decreases the effectiveness of hepatitis C antiviral treatment: does direct-acting antiviral regimens matter?
Hepatology (Baltimore, Md.)
2017
View details for PubMedID 29194694
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Open Label Study of 8 vs. 12 Weeks of Ledipasvir/Sofosbuvir in Genotype 6 Treatment Naïve or Experienced Patients.
The American journal of gastroenterology
2017
Abstract
Hepatitis C genotype 6 (HCV-GT6) is one of the most prevalent genotypes in Southeast Asia. Ledipasvir and sofosbuvir fixed-dose combination (LDV/SOF FDC) for 12 weeks has been shown to be effective for multiple HCV genotypes including treatment-naïve HCV-6. Our goal was to examine treatment outcomes in a diverse HCV-6 population.We prospectively enrolled 60 HCV-GT6 patients at four US centers. Treatment -naïve without cirrhosis patients received open-labeled LDV/SOF FDC orally once a day for 8 weeks; All cirrhotic and/or treatment-experienced patients received LDV/SOF FDC for 12 weeks. The primary outcome was sustained virological response 12 weeks after therapy (SVR12). Secondary outcomes were adverse events (AEs) and/or serious adverse events (SAEs). All patients gave written consent.Overall mean age was 58±10 and 58% were male. All patients were Asian and foreign born. The 8-week group included 20 patients (33.3%) and the 12-week included 40 patients (66.7%). There were 2 (5%) patients with decompensation, 3 with liver cancer (7.5%), and 14 with prior treatment (35%) in the 12-week group. SVR12 was 95.0% for the 8-week group (19/20) and 95.0% for the 12-week group (38/40). AEs included fatigue (5%), insomnia (3.3%), headache (1.7%), and nausea (1.7%); however, all patients completed the intended treatment duration. There were two treatment-unrelated SAEs.LDV/SOF FDC for 8 or 12 weeks was safe and effective for patients without cirrhosis or prior treatment failure as well as for patients with cirrhosis and/or prior treatment failure, respectively.Am J Gastroenterol advance online publication, 31 October 2017; doi:10.1038/ajg.2017.399.
View details for PubMedID 29087397
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Serum Alanine Aminotransferase and Hepatitis B DNA Flares in Pregnant and Postpartum Women with Chronic Hepatitis B.
American journal of gastroenterology
2016; 111 (10): 1410-1415
Abstract
Alterations in the immune system during pregnancy have been associated with reactivation of hepatitis B virus (HBV) in chronic hepatitis B (CHB) women. However, the effects of pregnancy on CHB remain not well understood. The goal of this study was to examine flares in HBV DNA and serum alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women untreated prior to pregnancy.This was a multicenter retrospective study of 113 pregnancies in 101 CHB women who presented during pregnancy at two community gastroenterology clinics and two tertiary medical centers in the United States during 1997-2015. Outcomes analyzed included onset, severity, and resolution of flares in HBV and ALT that occurred prior to starting antiviral therapy, if antiviral therapy was subsequently initiated. Women who initiated antiviral therapy during pregnancy were not included in the analysis of postpartum flares.HBV DNA flares were observed in 9% (8/90) of women during pregnancy and 4% (2/48) of women during postpartum. Flares in ALT (99-2522 U/l) were observed in 6% (7/112) of women during pregnancy and 10% (5/51) of women within the first 3 months of delivery. Age, HBeAg positivity, baseline HBV DNA, baseline ALT, gravida, and parity were not found to be significant predictors of flare.Flares in HBV DNA and ALT can occur during late pregnancy and early postpartum in CHB women, and can be severe. Women with CHB should therefore be closely monitored during pregnancy and early postpartum.Am J Gastroenterol advance online publication, 26 July 2016; doi:10.1038/ajg.2016.296.
View details for DOI 10.1038/ajg.2016.296
View details for PubMedID 27456990
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Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients With Hepatitis C Virus Genotype 2, 3, 4, or 6 Infections in an Open-label, Phase 2 Trial.
Gastroenterology
2016
Abstract
Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections who have failed by a prior course of antiviral therapy, and the feasibility of further shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients.We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand, from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naïve and treatment-experienced patients (1 with HCV genotype 1b, 33 with HCV genotype 2, 74 with HCV genotype 3, 17 with genotype HCV 4, and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6-12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12).Following 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naïve patients without cirrhosis (29/33; 95% CI, 72%-97%). Following 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naïve patients with cirrhosis (28/30; 95% CI, 78%-99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36/36; 95% CI, 90%-100%) and 97% of treatment-experienced patients with cirrhosis (28/29; 95% CI, 82%-100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events.In a phase 2 open-label trial, we found sofosbuvir-velpatasvir plus GS-9857 (8 weeks in treatment-naïve patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov no: NCT02378961.
View details for DOI 10.1053/j.gastro.2016.07.038
View details for PubMedID 27486033
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Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis.
The New England journal of medicine
2014; 370 (20): 1879-88
Abstract
High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen.In this phase 3, open-label study, we randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive ledipasvir and sofosbuvir (ledipasvir-sofosbuvir) for 8 weeks, ledipasvir-sofosbuvir plus ribavirin for 8 weeks, or ledipasvir-sofosbuvir for 12 weeks. The primary end point was sustained virologic response at 12 weeks after the end of therapy.The rate of sustained virologic response was 94% (95% confidence interval [CI], 90 to 97) with 8 weeks of ledipasvir-sofosbuvir, 93% (95% CI, 89 to 96) with 8 weeks of ledipasvir-sofosbuvir plus ribavirin, and 95% (95% CI, 92 to 98) with 12 weeks of ledipasvir-sofosbuvir. As compared with the rate of sustained virologic response in the group that received 8 weeks of ledipasvir-sofosbuvir, the rate in the 12-week group was 1 percentage point higher (97.5% CI, -4 to 6) and the rate in the group that received 8 weeks of ledipasvir-sofosbuvir with ribavirin was 1 percentage point lower (95% CI, -6 to 4); these results indicated noninferiority of the 8-week ledipasvir-sofosbuvir regimen, on the basis of a noninferiority margin of 12 percentage points. Adverse events were more common in the group that received ribavirin than in the other two groups. No patient who received 8 weeks of only ledipasvir-sofosbuvir discontinued treatment owing to adverse events.Ledipasvir-sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis. No additional benefit was associated with the inclusion of ribavirin in the regimen or with extension of the duration of treatment to 12 weeks. (Funded by Gilead Sciences; ION-3 ClinicalTrials.gov number, NCT01851330.).
View details for DOI 10.1056/NEJMoa1402355
View details for PubMedID 24720702
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Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.
The New England journal of medicine
2014; 370 (20): 1889-98
Abstract
In phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus (HCV) genotype 1 infection.We conducted a phase 3, open-label study involving previously untreated patients with chronic HCV genotype 1 infection. Patients were randomly assigned in a 1:1:1:1 ratio to receive ledipasvir and sofosbuvir in a fixed-dose combination tablet once daily for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.Of the 865 patients who underwent randomization and were treated, 16% had cirrhosis, 12% were black, and 67% had HCV genotype 1a infection. The rates of sustained virologic response were 99% (95% confidence interval [CI], 96 to 100) in the group that received 12 weeks of ledipasvir-sofosbuvir; 97% (95% CI, 94 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir plus ribavirin; 98% (95% CI, 95 to 99) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 97 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir plus ribavirin. No patient in either 12-week group discontinued ledipasvir-sofosbuvir owing to an adverse event. The most common adverse events were fatigue, headache, insomnia, and nausea.Once-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection. (Funded by Gilead Sciences; ION-1 ClinicalTrials.gov number NCT01701401.).
View details for DOI 10.1056/NEJMoa1402454
View details for PubMedID 24725239
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Treating hepatitis C in lower-income countries.
New England journal of medicine
2014; 370 (20): 1869-1871
View details for DOI 10.1056/NEJMp1400160
View details for PubMedID 24720680
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Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.
New England journal of medicine
2014; 370 (16): 1483-1493
Abstract
Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need.We conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor. Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.Among the 440 patients who underwent randomization and were treated, 20% had cirrhosis and 79% had HCV genotype 1a infection. The rates of sustained virologic response were high in all treatment groups: 94% (95% confidence interval [CI], 87 to 97) in the group that received 12 weeks of ledipasvir-sofosbuvir; 96% (95% CI, 91 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin; 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin. No patient discontinued treatment owing to an adverse event. The most common adverse events were fatigue, headache, and nausea.Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment. (Funded by Gilead Sciences; ION-2 ClinicalTrials.gov number, NCT01768286.).
View details for DOI 10.1056/NEJMoa1316366
View details for PubMedID 24725238
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Ethnic Differences in Viral Dominance Patterns in Patients with Hepatitis B Virus and Hepatitis C Virus Dual Infection
HEPATOLOGY
2011; 53 (6): 1839-1845
Abstract
Studies of hepatitis B virus (HBV)/hepatitis C virus (HCV) dual infection are limited. Most are small, conducted outside the United States, and compare dual infection with HCV monoinfection. The goal of this study was to characterize HBV/HCV dual infection in a large multiethnic, matched, case-control study of dual-infected and HBV-monoinfected patients at two United States centers. Using an International Classification of Disease Version 9 electronic query and chart review, we identified 115 HBV/HCV dual-infected patients with serial HBV DNA, HCV RNA, and alanine aminotransferase (ALT) levels. As a control, 115 HBV-monoinfected patients were chosen randomly and matched with cases by age ±10 years, sex, Asian versus non-Asian ethnicity, and study site. Both groups had similar sex, ethnic, and age distributions (68% male, 83% Asian, age 52 ± 14 years). The median follow-up times were 33 and 38 months for the dual-infected and monoinfected groups, respectively. More monoinfected patients received HBV antiviral therapy than dual-infected patients (43% versus 24%; P = 0.002). No significant difference was detected between the proportion of monoinfected versus dual-infected patients with ALT above 40 U/L at presentation or during follow-up. Dual infection patients exhibited very little HBV/HCV codominance at baseline and throughout follow-up: patients had either HBV viremia with low or absent HCV RNA or detectable HCV RNA with low or absent HBV DNA. Asian ethnicity was predictive of HBV dominance after adjusting for sex, age, and baseline ALT elevation (odds ratio 7.35; P = 0.01).HBV/HCV dual-infected and HBV-monoinfected patients had similar clinical characteristics. Asian ethnicity is a major independent predictor of HBV-dominant disease, and HCV dominance with undetectable HBV DNA is more common in non-Asian individuals. Larger studies are needed to further characterize the natural history of HBV/HCV dual infection in Asian and non-Asian individuals.
View details for DOI 10.1002/hep.24308
View details for Web of Science ID 000291307300009
View details for PubMedID 21425314
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Randomized Controlled Trial of Pegylated Interferon-Alfa 2a and Ribavirin in Treatment-Naive Chronic Hepatitis C Genotype 6
HEPATOLOGY
2010; 52 (5): 1573-1580
Abstract
Hepatitis C virus (HCV) genotype is an important criteria in determining duration of therapy and predictor of sustained virologic response (SVR) to pegylated interferon (PEG IFN) and ribavirin (RBV) therapy. Optimal duration of therapy for patients with HCV genotype 6 is not known. We conducted a multicenter, open-label randomized controlled trial of patients with HCV genotype 6 at five gastroenterology clinics in the western U.S. Patients were stratified by viral load and histologic stage and assigned to receive PEG IFN-α2a 180 μg subcutaneously weekly and weight-based oral RBV 800 to 1,200 mg daily for 24 or 48 weeks. Primary outcome measurement was SVR rate by intention-to-treat analysis. From February 2005 to October 2007 a total of 60 patients (age 51 ± 10 years, 47% male, log HCVRNA 6.3 ± 1.1 IU/mL) were enrolled: 27 patients to 24 weeks and 33 patients to 48 weeks of therapy. In the 24-week and 48-week groups, 96% and 97% achieved early virologic response (P = 0.90); 89% versus 94% achieved end of therapy virologic response (P = 0.48). SVR was achieved in 70% versus 79% of patients assigned to 24 weeks versus 48 weeks (P = 0.45). Rapid virologic response (RVR) was a significant predictor of SVR in the 48-week group and trending towards significance in the 24-week group: 82% and 83% of those with RVR achieved SVR versus 33% and 29% for the 24-week and 48-week groups, respectively (P = 0.07 and P = 0.02).There was no significant difference in SVR rates in patients with HCV genotype 6 treated with PEG IFN-α2a and RBV for 24 versus 48 weeks.
View details for DOI 10.1002/hep.23889
View details for Web of Science ID 000283764800007
View details for PubMedID 21038410
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Histological Disease in Asian-Americans With Chronic Hepatitis B, High Hepatitis B Virus DNA, and Normal Alanine Aminotransferase Levels
AMERICAN JOURNAL OF GASTROENTEROLOGY
2009; 104 (9): 2206-2213
Abstract
At present there is no clear consensus on how patients with chronic hepatitis B (CHB), high serum hepatitis B virus (HBV) DNA, and normal alanine aminotransferase (NLALT) levels should be managed. This study hypothesizes that a significant proportion of such patients may have histological disease.We carried out a retrospective study of 101 consecutive treatment-naive patients with CHB who underwent liver biopsies at a community gastroenterology clinic and had high HBV DNA and NLALT (< or = 40 U/l) levels at the time of biopsy. All patients were Asians. ALT levels were observed for a period of time before liver biopsy and were used to classify patients into two groups, namely those with only NLALT levels and those with fluctuating ALT (FLALT) levels. All patients had at least two ALT measurements during this period of time. Significant histology was defined as stage > or = 2 fibrosis or stage 1 fibrosis plus grade > or = 2 inflammation using the Batts-Ludwig scoring system.In patients with NLALT levels, the proportions of those with significant histology were 0, 22, and 45% for age < or = 35, 36-50, and >50 years, respectively (n=11, n=27, n=19; P=0.033). In patients who had FLALT levels, the corresponding proportions were 22, 42, and 69% (n=9, n=22, n=13; P=0.091). After adjustments for gender, hepatitis B e antigen (HBeAg) status, and mean pre-biopsy HBV DNA levels, significant predictors of histological disease were older age (odds ratio (OR)=6.2 for age 36-50 years and OR=17.6 for age >50 years compared with age < or = 35 years, P=0.041 and P=0.003, respectively) and FLALT levels (OR=3.6, P=0.008). Sub-analysis of patients with NLALT levels using lower cutoffs (30 U/l for men and 19 U/l for women) showed similar trends.Patients with CHB, high HBV DNA, and NLALT levels and aged more than 35 years or those with FLALT levels may have significant histological disease (22-70%).
View details for DOI 10.1038/ajg.2009.248
View details for PubMedID 19491836
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Renal Dysfunction in Chronic Hepatitis B Patients Treated with Adefovir Dipivoxil
HEPATOLOGY
2009; 50 (3): 727-734
Abstract
Renal dysfunction has been reported in patients treated with adefovir dipivoxil (ADV); however, its incidence and clinical importance may be underappreciated given the lack of long-term follow-up and data outside of a clinical trial setting. Our goal was to examine the severity and incidence of renal dysfunction in a real-life setting for patients treated with ADV and whose baseline estimated glomerular filtration rate (eGFR) was >50 mL/minute. We performed a cohort study of 290 chronic hepatitis B patients: 145 patients treated with 10 mg ADV and 145 patients unexposed to ADV at two community clinics, who were matched for age (+/-10 years), sex, and baseline eGFR. The exposed and unexposed populations were well-matched with a similar mean age (46-47 years), proportion of male patients (76.5%), baseline serum creatinine (0.97-0.99 mg/dL), and baseline creatinine clearance (85.0-85.4 mL/minute). The incidence density for renal dysfunction defined by treatment termination and/or development of eGFR < or =50 mL/minute was five cases per 100 patient-years in the exposed group compared with 1.36 cases per 100 patient-years in the unexposed group (P = 0.02). The relative risk of exposed to unexposed was 3.68 (95% confidence interval 1.1-19.3). On Cox proportional hazard analysis also inclusive of sex, ADV was a significant predictor of significant renal dysfunction (hazard ratio [HR] 3.94, P = 0.03). There were also significant trends for age >50 years (HR 3.49, P = 0.087), mild renal impairment at baseline (HR 4.49, P = 0.073), and hypertension and/or diabetes mellitus (HR 2.36, P = 0.074).ADV is an independent predictor for significant deterioration of renal function. Patients on ADV should be monitored, especially patients who are older, have baseline renal insufficiency, or have hypertension and/or diabetes mellitus.
View details for DOI 10.1002/hep.23044
View details for Web of Science ID 000269551100011
View details for PubMedID 19517525
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Transarterial Chemoinfusion for Hepatocellular Carcinoma as Downstaging Therapy and a Bridge toward Liver Transplantation
AMERICAN JOURNAL OF TRANSPLANTATION
2009; 9 (5): 1158-1168
Abstract
Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n = 95) and those with more advanced disease (n = 27). With TACI treatment, 87% of the Milan criteria group remained within the Milan criteria and 63% of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90% patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria.
View details for DOI 10.1111/j.1600-6143.2009.02576.x
View details for Web of Science ID 000265222200023
View details for PubMedID 19344435
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Higher rate of sustained virologic response in chronic hepatitis C genotype 6 treated with 48 weeks versus 24 weeks of peginterferon plus ribavirin
AMERICAN JOURNAL OF GASTROENTEROLOGY
2008; 103 (5): 1131-1135
Abstract
Infection with hepatitis C virus (HCV) genotype 6 is common in patients from parts of China and Southeast Asia. No study to date has examined the treatment response to peginterferon and ribavirin (PEG IFN + RBV) in these patients, or the effects of treatment duration on sustained virologic response (SVR) rates.We performed a retrospective study of 190 consecutive Asian-American patients who were diagnosed with HCV genotype 6 at a gastroenterology clinic in northern California between 2001 and 2004, 66 of whom were treatment-naïve and subsequently completed 24 wk of IFN + RBV or PEG IFN + RBV or 48 wk of PEG IFN + RBV therapy. The primary outcome was SVR.There was no statistical difference in SVR of 31 patients treated with 24 wk of IFN + RBV and in 23 patients treated with 24 wk of PEG IFN + RBV (51.6%vs 39%, P= 0.363). The SVR in 12 patients treated with 48 wk of PEG IFN + RBV was significantly higher than that in those treated for only 24 wk (75%vs 39%, P= 0.044).Treatment-eligible patients with HCV genotype 6 should be treated with a full course of 48 wk as tolerated. Larger prospective studies of patients with HCV genotype 6 are needed to confirm the optimal treatment duration with PEG IFN + RBV.
View details for DOI 10.1111/j.1572-0241.2008.01793.x
View details for Web of Science ID 000255750000010
View details for PubMedID 18477343
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Racial differences in effectiveness of alpha-fetoprotein for diagnosis of hepatocellular carcinoma in hepatitis C virus cirrhosis
HEPATOLOGY
2002; 36 (2): 410-417
Abstract
alpha-Fetoprotein (AFP) is frequently used as a diagnostic marker for hepatocellular carcinoma (HCC). Most available data concerning AFP come from studies of patients with chronic hepatitis B or other chronic liver diseases of mixed etiologies. Limited data concerning the diagnostic value of AFP for hepatitis C virus (HCV)-related HCC have to date come only from Asian and European studies, and results are conflicting. There may be significant differences in AFP levels depending on racial backgrounds and etiologies of primary liver disease. We conducted a multicenter, retrospective, case-control study of 163 HCC patients with HCV infection and 149 control patients with HCV-related cirrhosis. The positive likelihood ratios for AFP at 0 to 20, 21 to 50, 51 to 100, and 101 to 200 ng/mL were 0.46, 1.31, 1.15, and 6.90, respectively. No controls had AFP greater than 200 ng/mL. The sensitivity of AFP for the diagnosis of HCC in African Americans with HCV infection was lower than that of patients of all other ethnic groups combined (57.1% vs. 81.6% for AFP > 10 ng/mL, P =.02, and 42.9% vs. 66.0% for AFP > 20 ng/mL, P =.05). The area under the receiver operating characteristics curve was 0.81 for non-African Americans but only 0.56 for African Americans. In conclusion, AFP greater than 200 ng/mL can be used to confirm HCC in patients with HCV-related cirrhosis and a hepatic mass. However, AFP is insensitive for the diagnosis of HCC in African Americans.
View details for DOI 10.1053/jhep.2002.34744
View details for Web of Science ID 000177085100018
View details for PubMedID 12143050
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ASO Author Reflections: Hepatic Resection as the Primary Treatment Modality for Hepatocellular Carcinoma After Orthotopic Liver Transplantation.
Annals of surgical oncology
2024
View details for DOI 10.1245/s10434-024-16237-1
View details for PubMedID 39277547
View details for PubMedCentralID 7698397
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Letter: Enhancing cirrhosis management-The critical role of social workers in supporting NAFLD surveillance: Authors' reply.
Alimentary pharmacology & therapeutics
2024
View details for DOI 10.1111/apt.18265
View details for PubMedID 39252386
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Integrating Strategic, Equity, and Socioeconomic Perspectives: A Holistic Approach to Advancing Hepatitis B Management and Outcomes.
Journal of hepatology
2024
View details for DOI 10.1016/j.jhep.2024.08.013
View details for PubMedID 39218225
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Hepatic Resection as the Primary Treatment Method for Hepatocellular Carcinoma After Orthotopic Liver Transplantation.
Annals of surgical oncology
2024
Abstract
Liver transplantation (LT) is the treatment of choice for end-stage liver disease and certain malignancies such as hepatocellular carcinoma (HCC). Data on the surgical management of de novo or recurrent tumors that develop in the transplanted allograft are limited. This study aimed to investigate the perioperative and long-term outcomes for patients undergoing hepatic resection for de novo or recurrent tumors after liver transplantation.The study enrolled adult and pediatric patients from 12 centers across North America who underwent hepatic resection for the treatment of a solid tumor after LT. Perioperative outcomes were assessed as well as recurrence free survival (RFS) and overall survival (OS) for those undergoing resection for HCC.Between 2003 and 2023, 54 patients underwent hepatic resection of solid tumors after LT. For 50 patients (92.6 %), resection of malignant lesions was performed. The most common lesion was HCC (n = 35, 64.8 %), followed by cholangiocarcinoma (n = 6, 11.1 %) and colorectal liver metastases (n = 6, 11.1 %). The majority of the 35 patients underwent resection of HCC did not receive any preoperative therapy (82.9 %) or adjuvant therapy (71.4 %), with resection their only treatment method for HCC. During a median follow-up period of 50.7 months, the median RFS was 21.5 months, and the median OS was 49.6 months.Hepatic resection following OLT is safe and associated with morbidity and mortality rates that are comparable to those reported for patients undergoing resection in native livers. Hepatic resection as the primary and often only treatment modality for HCC following LT is associated with acceptable RFS and OS and should be considered in well selected patients.
View details for DOI 10.1245/s10434-024-16085-z
View details for PubMedID 39172301
View details for PubMedCentralID 7698397
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Changes in the epidemiological trends of primary liver cancer in the Asia-Pacific region.
Scientific reports
2024; 14 (1): 19544
Abstract
Primary liver cancer is the third leading cause of cancer-related mortality. The increasing prevalence of metabolic syndrome and alcohol consumption, along with the existing burden of viral hepatitis, could significantly heighten the impact of primary liver cancer. However, the specific effects of these factors in the Asia-Pacific region, which comprises more than half of the global population, remain largely unexplored. This study aims to analyze the epidemiology of primary liver cancer in the Asia-Pacific region. We evaluated regional and national data from the Global Burden of Disease study spanning 2010 to 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years associated with primary liver cancer in the Asia-Pacific region. During the study period, there were an estimated 364,700 new cases of primary liver cancer and 324,100 deaths, accounting for 68 and 67% of the global totals, respectively. Upward trends were observed in the age-standardized incidence rates of primary liver cancer due to metabolic dysfunction-associated fatty liver disease (MASLD) and alcohol-associated liver disease (ALD) in the Asia-Pacific region, as well as an increase in primary liver cancer from Hepatitis B virus infection in the Western Pacific region. Notably, approximately 17% of new cases occurred in individuals aged 15-49 years. Despite an overall decline in the burden of primary liver cancer in the Asia-Pacific region over the past decade, increases in incidence were noted for several etiologies, including MASLD and ALD. However, viral hepatitis remains the leading cause, responsible for over 60% of the total burden. These findings underscore the urgent need for comprehensive strategies to address the rising burden of primary liver cancer in the Asia-Pacific region.
View details for DOI 10.1038/s41598-024-70526-z
View details for PubMedID 39174722
View details for PubMedCentralID 5328612
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Correspondence to editorial on "Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal real-world study".
Clinical and molecular hepatology
2024
View details for DOI 10.3350/cmh.2024.0611
View details for PubMedID 39103996
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Global epidemiology, natural history, maternal-to-child transmission, and treatment with DAA of pregnant women with HCV: a systematic review and meta-analysis.
EClinicalMedicine
2024; 74: 102727
Abstract
Pregnant women with hepatitis C virus (HCV) infection represent a special population in which treatment access remains limited despite its increasing prevalence. A reliable estimate of the burden and clinical outcomes of pregnant women with HCV infection is crucial for HCV elimination. We aimed to determine the prevalence, maternal-to-child transmission (MTCT), maternal and fetal complication rates, and direct acting antivirals (DAA) treatment outcomes of chronic HCV infection in pregnant women.We searched PubMed, EMBASE, Scopus, Web of Science from inception until March 1, 2024, for studies reporting on the prevalence, MTCT, complications of HCV infection, and treatment outcomes of DAA in pregnant women. Study quality was assessed using the Newcastle-Ottawa Scale. We performed subgroup analysis based on 9 variables to explore the source of heterogeneity in HCV prevalence. The PROSPERO registration number is CRD42024500023.From a total of 311,905,738 pregnant women from 333 studies, the pooled global seroprevalence of HCV in pregnant women was 2.6% (95% CI: 2.0-3.2, I 2 = 100%) which increased in patients with intravenous drug use and HIV. Majority of the HCV cases in pregnant women (75%) are diagnosed through universal screening. The pooled MTCT rate was 9.0% (95% CI: 6.6-11.7, I 2 = 79%), which was higher with HIV co-infection (OR: 3.1, 95% CI: 2.1-4.6, I 2 = 10%), but was not influenced by the mode of delivery or breastfeeding. Pregnant women with HCV infection had more maternal complications, including intrahepatic cholestasis, preterm delivery, and antepartum hemorrhage. Neonates of mothers with HCV had higher odds of being small for gestational age. The pooled rate of sustained virologic response (SVR12) among the 74 women treated with DAA during pregnancy was 98.4%, with no serious adverse events reported.HCV prevalence in pregnant women varies by geographic region and patient population, while MTCT occurs in almost one in ten viremic mothers. The incidence of both maternal and neonatal complications is significantly higher in patients with HCV infection. Limited data suggest that DAA are safe in pregnant women with HCV infection.None.
View details for DOI 10.1016/j.eclinm.2024.102727
View details for PubMedID 39109190
View details for PubMedCentralID PMC11301193
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Global epidemiology, natural history, maternal-to-child transmission, and treatment with DAA of pregnant women with HCV: a systematic review and meta-analysis
ECLINICALMEDICINE
2024; 74
View details for DOI 10.1016/j.eclinm.2024.102727
View details for Web of Science ID 001268491100001
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Real-world Effectiveness and Tolerability of Interferon-free Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C: A Multinational Cohort Study.
Journal of clinical and translational hepatology
2024; 12 (7): 646-658
Abstract
As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6.We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021.The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12.In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).
View details for DOI 10.14218/JCTH.2024.00089
View details for PubMedID 38993510
View details for PubMedCentralID PMC11233980
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Impact of Income-to-Poverty Ratio on Long-Term Mortality of Persons with Chronic Liver Disease in the USA, 1999-2018.
Digestive diseases (Basel, Switzerland)
2024: 1-13
Abstract
Chronic liver disease (CLD) is associated with increased morbidity and mortality. Understanding health disparities can inform appropriate interventions. We aimed to study mortality outcomes of those with CLD by the income level (income-to-poverty ratio <5 as lower income and ≥5 as higher income).In this retrospective cohort study, we analyzed data of adults from the National Health and Nutrition Examination Survey, 1999-2018. CLD included viral hepatitis, nonalcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD).We analyzed 59,204 adults: 47,224 without CLD and 11,980 with CLD. The CLD group was older, more likely male, racial/ethnic minority groups or foreign-born, and had lower educational and income levels (p < 0.001). Most (80.02%) CLD participants did not have college degrees and had lower income (79.18%). Among CLD participants, similar differences were observed between lower and higher income groups. Lower income participants with CLD had significantly higher 10-year cumulative mortality compared to higher income CLD participants (15.26 vs. 8.00%, p < 0.001), with consistent findings in viral hepatitis and NAFLD subgroups (p < 0.001) but not ALD (p = 0.71). Adjusting for age, sex, race, birthplace, lower income CLD participants were 2.01 (hazard ratio [HR]: 2.01; 95% CI: 1.79-2.26) times more likely to die overall and in viral hepatitis (HR: 2.05; 95% CI: 1.31-3.24) and NAFLD subgroups (HR: 2.32; 95% CI: 1.69-3.18) but not ALD (HR: 1.17; 95% CI: 0.55-2.51).Lower income, foreign-born, and racial/ethnic minority groups were disproportionately represented among those with CLD, with lower income and CLD individuals having double the mortality risk compared to their higher income counterparts. Interventions should be culturally appropriate and address socioeconomic barriers.
View details for DOI 10.1159/000539858
View details for PubMedID 38885622
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Editorial: Redefining liver health-Personalised approach to assessment of serum ALT in clinical practice. Authors' reply.
Alimentary pharmacology & therapeutics
2024
View details for DOI 10.1111/apt.18112
View details for PubMedID 38877677
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Editorial: Revisit the causes and long-term outcomes in cirrhosis patients-Authors' reply.
Alimentary pharmacology & therapeutics
2024
View details for DOI 10.1111/apt.18065
View details for PubMedID 38779938
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An international multidisciplinary consensus on pediatric metabolic dysfunction-associated fatty liver disease.
Med (New York, N.Y.)
2024
Abstract
Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts.A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management.In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD.The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD.This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).
View details for DOI 10.1016/j.medj.2024.03.017
View details for PubMedID 38677287
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Antiviral therapy response in patients with chronic hepatitis B and fatty liver: A systematic review and meta-analysis.
Journal of viral hepatitis
2024
Abstract
The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to systematically review and analyse antiviral treatment response in CHB patients with and without FL. We searched PubMed, Embase, Web of Science and the Cochrane Library databases from inception to 31 May 2023 for relevant studies. Biochemical response (BR), complete viral suppression (CVS) and hepatitis B e antigen (HBeAg) seroconversion in CHB patients with FL (CHB-FL) and without FL (non-FL CHB) were compared. In an initial pool of 2101 citations, a total of 10 studies involving 2108 patients were included. After 12 weeks of treatment, CHB-FL patients as compared with non-FL CHB patients had lower BR rate (48.37% [108/227] vs. 72.98% [126/174], p = .04) but similar trend for CVS (36.86% [80/227] vs. 68.81% [114/174], p = .05) and similar rates of HBeAg seroconversion (6.59% [7/103] vs. 7.40% [7/110], p = .89). However, at week 48, there were no statistically significant differences between CHB-FL and non-FL CHB patients in any of the outcomes, including BR (60.03% [213/471] vs. 69.37% [314/717], p = .67), CVS (65.63% [459/746] vs. 73.81% [743/1132], p = .27) and HBeAg seroconversion (10.01% [30/275] vs. 14.06% [65/453], p = .58) with similar findings for week 96. BR rate was lower in CHB-FL patients after 12 weeks of antiviral treatment. However, after a longer follow-up of either 48 or 96 weeks, no statistically significant differences were observed in BR, CVS or HBeAg seroconversion rates between CHB patients with and without FL.
View details for DOI 10.1111/jvh.13942
View details for PubMedID 38590002
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Mortality in patients with chronic hepatitis B treated with tenofovir or entecavir: A multinational study.
Journal of gastroenterology and hepatology
2024
Abstract
The benefits of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in reducing the development of chronic hepatitis B (CHB)-related hepatocellular carcinoma remain controversial. Whether mortality rates differ between patients with CHB treated with ETV and those treated with TDF is unclear.A total of 2542 patients with CHB treated with either ETV or TDF were recruited from a multinational cohort. A 1:1 propensity score matching was performed to balance the differences in baseline characteristics between the two patient groups. We aimed to compare the all-cause, liver-related, and non-liver-related mortality between patients receiving ETV and those receiving TDF.The annual incidence of all-cause mortality in the entire cohort was 1.0/100 person-years (follow-up, 15 757.5 person-years). Patients who received TDF were younger and had a higher body mass index, platelet count, hepatitis B virus deoxyribonucleic acid levels, and proportion of hepatitis B e-antigen seropositivity than those who received ETV. The factors associated with all-cause mortality were fibrosis-4 index > 6.5 (hazard ratio [HR]/confidence interval [CI]: 3.13/2.15-4.54, P < 0.001), age per year increase (HR/CI: 1.05/1.04-1.07, P < 0.001), alanine aminotransferase level per U/L increase (HR/CI: 0.997/0.996-0.999, P = 0.003), and γ-glutamyl transferase level per U/L increase (HR/CI: 1.002/1.001-1.003, P < 0.001). No significant difference in all-cause mortality was observed between the ETV and TDF groups (log-rank test, P = 0.69). After propensity score matching, no significant differences in all-cause, liver-related, or non-liver-related mortality were observed between the two groups.Long-term outcomes of all-cause mortality and liver-related and non-liver-related mortality did not differ between patients treated with ETV and those receiving TDF.
View details for DOI 10.1111/jgh.16537
View details for PubMedID 38480009
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Upper limit of normal ALT levels in health and metabolic diseases: Pooled analysis of 423,355 individuals with bootstrap modelling.
Alimentary pharmacology & therapeutics
2024
Abstract
Given the global rise in obesity-related metabolic diseases, the upper limit of normal (ULN) alanine aminotransferase (ALT) in individuals with and without metabolic diseases may have changed. We performed a meta-analysis combined with bootstrap modelling to estimate the ALT ULN levels for individuals with and without metabolic diseases.Two separate searches of the PubMed, Embase and Cochrane databases were performed, one to identify healthy individuals which yielded 12 articles (349,367 individuals); another to include those with potential metabolic diseases but without known liver disease which yielded 35 articles (232,388 individuals). We estimated the mean ALT using a random-effects mixed model and the ULN level (95th-percentile value) via a bootstrap model with 10,000 resamples. In individuals without metabolic diseases and known liver disease, the ALT ULN levels were 32 U/L overall; 36 U/L in males and 28 U/L in females. In analyses that included individuals with metabolic diseases, the ALT ULN levels were 40 U/L among the overweight/obese (29 U/L if normal weight) and 36 U/L among those with type 2 diabetes mellitus (T2DM) (33 U/L if no T2DM). On meta-regression of study-level factors, body mass index (coefficient 1.49, 95% CI 0.11-2.86, p = 0.03), high-density lipoprotein (coefficient -0.47, 95% CI -0.85-(-0.08), p = 0.02) and triglycerides (coefficient 0.19, 95% CI 0.12-0.25, p < 0.0001) correlated with ALT.We provide expected ranges of ALT ULN levels for individuals without known liver disease without metabolic diseases and those with or without T2DM and/or are normal weight or overweight/obese. These data may have implications for clinical care and screening.
View details for DOI 10.1111/apt.17914
View details for PubMedID 38372477
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Reply to Letter to the Editor: Is the evidence convincing for the expansion of CHB treatment criteria to reduce the risk of HCC.
Hepatology (Baltimore, Md.)
2024
View details for DOI 10.1097/HEP.0000000000000802
View details for PubMedID 38373117
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In Response to: Steatotic Liver Disease-Know Your Enemies.
Clinical and molecular hepatology
2024
View details for DOI 10.3350/cmh.2024.0108
View details for PubMedID 38373421
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Racial and ethnic disparities in untreated patients with hepatitis C virus-related hepatocellular carcinoma but not in those with sustained virologic response.
Alimentary pharmacology & therapeutics
2024
Abstract
Racial and ethnic disparities exist for hepatitis C virus (HCV) treatment and hepatocellular carcinoma (HCC) survival.To evaluate the impact of HCV treatment on such disparities.In a retrospective cohort study, we analysed 6069 patients with HCV-related HCC (54.2% Asian, 30.1% White, 8.5% Black, and 7.3% Hispanic) from centres in the United States and Asia.The mean age was 61, 60, 59 and 68, respectively, for White, Black, Hispanic and Asian patients. Black patients were most likely to have Barcelona Clinic Liver Cancer stage D, vascular invasion and distant metastasis (23% vs. 5%-15%, 20% vs. 10%-17% and 10% vs. 5%-7%, respectively; all p < 0.0001). Treatment rate with direct-acting antiviral agents (DAA) was 35.9% for Asian, 34.9% for White, 30.3% for Hispanic (30.3%), and 18.7% for Black patients (p < 0.0001). Among those untreated or without sustained virologic response (SVR), 10-year survival rates were 35.4, 27.5, 19.3 and 14.0, respectively, for Asian, Hispanic, White and Black patients (p < 0.0001). There were no statistically significant differences among those with SVR (p = 0.44). On multivariable analysis adjusted for relevant confounders, there was no statistically significant association between survival and being Hispanic (aHR: 0.68, p = 0.26) or Black (aHR: 1.18, p = 0.60) versus White. There was a significant association between being Asian American and survival (aHR: 0.24, p = 0.001; non-U.S. Asian: aHR: 0.66, p = 0.05), and for SVR (aHR: 0.30, p < 0.0001).DAA treatment rates were suboptimal. Racial and ethnic disparities resolved with HCV cure. Early diagnosis and improved access to HCV treatment is needed for all patients with HCV infection.
View details for DOI 10.1111/apt.17863
View details for PubMedID 38173278
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Thick Data Analytics (TDA): An Iterative and Inductive Framework for Algorithmic Improvement
The American Statistician
2024
View details for DOI 10.1080/00031305.2024.2327535
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Differential Mortality Outcomes in Real-world Patients with Lean, Nonobese, and Obese Nonalcoholic Fatty Liver Disease.
Journal of clinical and translational hepatology
2023; 11 (7): 1448-1454
Abstract
Nonalcoholic fatty liver disease (NAFLD) is commonly associated with obesity but can develop in normal-weight people (lean NAFLD). We compared outcomes in lean, overweight, and obese NAFLD.This retrospective chart review included patients at Stanford University Medical Center with NAFLD confirmed by imaging between March 1995 and December 2021. Lean, overweight, and obese patients had body mass index of <25.0, >25.0 and <29.9, and ≥30.0 kg/m2 for non-Asian and >23.0 and ≥27.5 for overweight and obese Asian patients.A total of 9061 lean (10.2%), overweight (31.7%), and obese (58.1%) patients were included. Lean patients were 5 years older than obese patients (53±17.4 vs. 48.7±15.1 years), more were female (59.6% vs. 55.2%), white (49.1% vs. 46.5%), had NASH (29.2% vs. 22.5%), cirrhosis (25.3% vs.19.2%), or nonliver cancer (25.3% vs. 18.3%). Fewer had diabetes (21.7% vs. 35.8%) or metabolic comorbidities (all p<0.0001). Lean NAFLD patients had liver-related mortality similar to other groups but higher overall (p=0.01) and nonliver-related (p=0.02) mortality. After multivariable model adjustment for covariates, differences between lean and obese NAFLD in liver-related, nonliver-related, and overall mortality (adjusted hazard ratios of 1.34, 1.00, and 1.32; p=0.66, 0.99, and 0.20, respectively) were not significant.Lean NAFLD had fewer metabolic comorbidities but similar adverse or worse outcomes, suggesting that it is not benign. Healthcare providers should provide the same level of care and intervention as for overweight and obese NAFLD.
View details for DOI 10.14218/JCTH.2023.00016
View details for PubMedID 38161493
View details for PubMedCentralID PMC10752812
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Hepatitis B Core-Related Antigen Dynamics and Risk of Subsequent Clinical Relapses after Nucleos(t)ide Analog Cessation.
Clinical and molecular hepatology
2023
Abstract
Background: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR).Methods: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase (ALT) > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR.Results: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.1% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5-40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7-67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1% - 62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12-2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg < 1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21-0.81).Conclusions: Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.
View details for DOI 10.3350/cmh.2023.0194
View details for PubMedID 38092551
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Chronic Hepatitis B and Steatotic Liver Disease: a Blessing in Disguise?
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2023
View details for DOI 10.1016/j.cgh.2023.11.039
View details for PubMedID 38070630
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Collaborating with AI in literature search-An important frontier.
Hepatology communications
2023; 7 (12)
View details for DOI 10.1097/HC9.0000000000000336
View details for PubMedID 38055656
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Differential Mortality Outcomes in Real-world Patients with Lean, Nonobese, and Obese Nonalcoholic Fatty Liver Disease
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
2023
View details for DOI 10.14218/JCTH.2023.00016
View details for Web of Science ID 001119285500001
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Use and Outcomes of Hepatitis B Virus-Positive Grafts for Kidney or Heart Transplantation in the United States From 1999 to 2021.
Transplantation
2023
Abstract
The gap between demand and supply for solid organ transplants requires strategies to expand the donor pool. Successful use of hepatitis B virus (HBV)-positive grafts has been reported in liver transplantation.In this United Network for Organ Sharing database (January 1999 to June 2021) retrospective cohort study, outcomes of kidney transplant (KT) or heart transplant (HT) recipients with HBV donor grafts (hepatitis B surface antigen and/or for HBV nucleic acid test-positive) were examined. Propensity score matching was performed for HBV-positive to negative graft recipients (1:5 for renal transplantation and 1:10 for HT).Of 448 HBV-positive donors with 896 kidneys, 352 kidneys (39.3%) and 56 hearts (12.5%) were transplanted. Of these, 312 kidneys (88.6%) and 45 hearts (80.3%) were transplanted in hepatitis B surface antigen-negative recipients. Ten-year graft survival was 47.1% and 49% (log-rank P = 0.353), and patient survival was 58% and 59% (P = 0.999) for KT recipients. Similar figures among HT recipients were 41.9% and 38.9% for graft survival (P = 0.471), and 54.3% and 61.2% for patient survival (P = 0.277). Subgroup analyses in recipients with HBV nucleic acid test-positive grafts irrespective of antibodies to HBV core antigen-positive status, and recipients negative for anti-HBs (548 renal transplantation and 209 HT) were similar.Although we are limited by lack of available data on posttransplant anti-HBV treatment, the study observations suggest that using HBV-positive grafts is a reasonable strategy to expand the donor pool among candidates waiting for KT or HT.
View details for DOI 10.1097/TP.0000000000004759
View details for PubMedID 37953470
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Pretreatment gamma-glutamyl transferase predicts mortality in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs.
The Kaohsiung journal of medical sciences
2023
Abstract
Elevated serum gamma-glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma. However, their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive. Altogether, 2843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6months (Month-6) after initiating NAs were measured to explore their association with all-cause, liver-related, and non-liver-related mortality. The annual incidence of all-cause mortality was 0.9/100 person-years over a follow-up period of 17,436.3 person-years. Compared with patients who survived, those who died had a significantly higher pretreatment (89.3 vs. 67.4U/L, p=0.002) and Month-6-GGT levels (62.1 vs. 38.4U/L, p<0.001). The factors associated with all-cause mortality included cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 2.66/1.92-3.70, p<0.001), pretreatment GGT levels (HR/CI: 1.004/1.003-1.006, p<0.001), alanine aminotransferase level (HR/CI: 0.996/0.994-0.998, p=0.001), and age (HR/CI: 1.06/1.04-1.07, p<0.001). Regarding liver-related mortality, the independent factors included cirrhosis (HR/CI: 4.36/2.79-6.89, p<0.001), pretreatment GGT levels (HR/CI: 1.006/1.004-1.008, p<0.001), alanine aminotransferase level (HR/CI: 0.993/0.990-0.997, p=0.001), age (HR/CI: 1.03/1.01-1.05, p<0.001), and fatty liver disease (HR/CI: 0.30/0.15-0.59, p=0.001). Pretreatment GGT levels were also independently predictive of non-liver-related mortality (HR/CI: 1.003/1.000-1.005, p=0.03). The results remained consistent after excluding the patients with a history of alcohol use. A dose-dependent manner of <25, 25-75, and >75 percentile of pretreatment GGT levels was observed with respect to the all-cause mortality (trend p<0.001). Pretreatment serum GGT levels predicted all-cause, liver-related, and non-liver-related mortality in patients with CHB treated with NAs.
View details for DOI 10.1002/kjm2.12771
View details for PubMedID 37885338
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UPPER LIMIT OF NORMAL ALT LEVELS IN HEALTH AND METABOLIC DISEASES: POOLED ANALYSIS OF 484,177 INDIVIDUALS WITH BOOTSTRAP MODELLING
LIPPINCOTT WILLIAMS & WILKINS. 2023: S1676-S1677
View details for Web of Science ID 001094865404119
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Letter: Safety after cessation of nucleos(t)ide analogue therapy in patients with chronic hepatitis B infection-Authors' reply.
Alimentary pharmacology & therapeutics
2023; 58 (7): 733-734
View details for DOI 10.1111/apt.17681
View details for PubMedID 37702029
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DIABETES MELLITUS IS AN INDEPENDENT PREDICTOR OF SIGNIFICANT INFLAMMATION AND FIBROSIS IN CHRONIC HEPATITIS B PATIENTS CONCURRENT WITH HEPATIC STEATOSIS
LIPPINCOTT WILLIAMS & WILKINS. 2023: S424-S425
View details for Web of Science ID 001094865401039
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ACUTE HEPATITIS FLARES AFTER CESSATION OF NUCLEOS( T) IDE ANALOGUES ARE ASSOCIATED WITH LOWER RATES OF HBsAg SEROCLEARANCE IN PATIENTS WITH CHRONIC HEPATITIS
LIPPINCOTT WILLIAMS & WILKINS. 2023: S501-S502
View details for Web of Science ID 001094865401130
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INCIDENCE OF NAFLDRELATED HEPATOCELLULAR CARCINOMA WITH DETAILED STRATIFICATION BY RISK FACTORS: A NATIONWIDE UNITED STATES COHORT STUDY
LIPPINCOTT WILLIAMS & WILKINS. 2023: S984
View details for Web of Science ID 001094865402167
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LOW ANTIVIRAL TREATMENT RATE FOR PATIENTS WITH HEPATITIS C (HCV)-RELATED HEPATOCELLULAR CARCINOMA (HCC)-A REAL-WORLD NATIONWIDE U. S. STUDY
LIPPINCOTT WILLIAMS & WILKINS. 2023: S62
View details for Web of Science ID 001094865400059
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DIFFERENCES BETWEEN BIOPSY-PROVEN NASH PATIENTS WITH AND WITHOUT DIABETES MELLITUS
LIPPINCOTT WILLIAMS & WILKINS. 2023: S947-S948
View details for Web of Science ID 001094865402133
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DISPARITIES IN SURVIVAL OF PATIENTS WITH HEPATOCELLULAR CARCINOMA ( HCC) BY LIVER DISEASE ETIOLOGY AND TIME PERIODS: A U. S. POPULATION- BASED STUDY FROM 2000 TO 2017
LIPPINCOTT WILLIAMS & WILKINS. 2023: S1829-S1830
View details for Web of Science ID 001094865404305
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IMPACT OF SEX AND DIABETES ON LONG- TERM OUTCOMES OF PATIENTS WITH NAFLD
LIPPINCOTT WILLIAMS & WILKINS. 2023: S978-S979
View details for Web of Science ID 001094865402162
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IMPACT OF FATTY LIVER ( FL) ON VIROLOGIC ( VR), BIOCHEMICAL ( BR), AND COMPLETE RESPONSE ( CR) AMONG PATIENTS WITH CHRONIC HEPATITIS B ( CHB) TREATED WITH NUCLEOS( T) IDE ANALOGS ( NA): A REAL- B STUDY
LIPPINCOTT WILLIAMS & WILKINS. 2023: S471-S472
View details for Web of Science ID 001094865401092
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LONG- TERM ALLCAUSE AND LIVER- RELATED MORTALITY OF PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE ( NAFLD)- RELATED LIVER CIRRHOSIS WHO UNDERWENT BARIATRIC SURGERY: A POPULATION- BASED STUDY
LIPPINCOTT WILLIAMS & WILKINS. 2023: S1237-S1238
View details for Web of Science ID 001094865403044
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DIFFERENCES IN INCIDENCE OF ADVERSE CLINICAL EVENTS AMONG NAFLD PARTICIPANTS WITH LIVER BIOPSY PROVEN NAFLD STRATIFIED BY NASH: A SYSTEMATIC REVIEW AND META-ANALYSIS
LIPPINCOTT WILLIAMS & WILKINS. 2023: S949-S950
View details for Web of Science ID 001094865402135
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INCIDENCE OF ADVERSE CLINICAL EVENTS IN PERSONS WITH NAFLD: A SYSTEMATIC REVIEW AND META- ANALYSIS
LIPPINCOTT WILLIAMS & WILKINS. 2023: S983
View details for Web of Science ID 001094865402166
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TRENDS OF CHRONIC LIVER DISEASES BY INCOME LEVEL AND SOCIOECONOMIC FACTORS IN THE US NATIONAL POPULATION
LIPPINCOTT WILLIAMS & WILKINS. 2023: S1303-S1304
View details for Web of Science ID 001094865403129
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DEVELOPMENT AND VALIDATION OF A RISK SCORE FOR FIBROSIS STAGE 2 OR HIGHER: A REAL-NAFLD STUDY OF 1902 REAL-WORLD PATIENTS WITH BIOPSY
LIPPINCOTT WILLIAMS & WILKINS. 2023: S943-S944
View details for Web of Science ID 001094865402128
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REGIONAL AND SEX DIFFERENCES IN INCIDENCE OF ADVERSE CLINICAL EVENTS IN PERSONS WITH NAFLD: A SYSTEMATIC REVIEW AND META-ANALYSIS
LIPPINCOTT WILLIAMS & WILKINS. 2023: S1039
View details for Web of Science ID 001094865402218
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IMPACT OF FAMILY INCOME-TO-POVERTY RATIO ON LONG-TERM MORTALITY OF PERSONS WITH CHRONIC LIVER DISEASE IN THE UNITED STATES, 1999-2018
LIPPINCOTT WILLIAMS & WILKINS. 2023: S1286-S1287
View details for Web of Science ID 001094865403112
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DIAGNOSIS IS DELAYED: PERICOMPLICATION DIAGNOSIS OF NONALCOHOLIC FATTY LIVER DISEASE
LIPPINCOTT WILLIAMS & WILKINS. 2023: S945-S946
View details for Web of Science ID 001094865402130
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GLOBAL DIFFERENCES IN THE EVALUATION AND TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS B: A REAL- B STUDY
LIPPINCOTT WILLIAMS & WILKINS. 2023: S464-S466
View details for Web of Science ID 001094865401086
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COMPARISON OF CHARACTERISTICS AND OUTCOMES IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE WHO DID OR DIDN'T RECEIVE LIVER BIOPSY
LIPPINCOTT WILLIAMS & WILKINS. 2023: S931
View details for Web of Science ID 001094865402121
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Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: a longitudinal real-world study.
Clinical and molecular hepatology
2023
Abstract
Understanding of nonalcoholic fatty liver disease (NAFLD) continues to expand, but the relationship between race and ethnicity and NAFLD outside the use of cross-sectional data is lacking. Using longitudinal data, we investigated the role of race and ethnicity in adverse outcomes in NAFLD patients.Patients with NAFLD confirmed by imaging via manual chart review from any clinics at Stanford University Medical Center (1995-2021) were included. Primary study outcomes were incidence of liver events and mortality (overall and non-liver related).The study included 9,340 NAFLD patients: White (44.1%), Black (2.29%), Hispanic (27.9%), and Asian (25.7%) patients. For liver events, the cumulative 5-year incidence was highest among White (19.1%) patients, lowest among Black (7.9%) patients, and similar among Asian and Hispanic patients (~15%). The 5-year and 10-year cumulative overall mortality was highest for Black patients (9.2% and 15.0%, respectively, vs. 2.5-3.5% and 4.3-7.3% in other groups) as well as for non-liver mortality. On multivariable regression analysis, compared to White patients, only Asian group was associated with lower liver-related outcomes (aHR: 0.83, P=0.027), while Black patients were at more than two times higher risk of both non-liver related (aHR: 2.35, P=0.010) and overall mortality (aHR: 2.13, P=0.022) as well as Hispanic patients (overall mortality: aHR: 1.44, P=0.022).Compared to White patients, Black patients with NAFLD were at the highest risk for overall and non-liver-related mortality, followed by Hispanic patients with Asian patients at the lowest risk for all adverse outcomes. Culturally sensitive and appropriate programs may be needed for more successful interventions.
View details for DOI 10.3350/cmh.2023.0205
View details for PubMedID 37691484
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Incidence and Risk Factors for Hepatocellular Carcinoma in Cirrhosis: the Multi-center Hepatocellular Carcinoma Early Detection Strategy (HEDS) Study.
Gastroenterology
2023
Abstract
BACKGROUND AND AIMS: Worldwide, hepatocellular carcinoma (HCC) is a common malignancy. We aimed to prospectively determine the incidence and risk factors of HCC in a United States cohort.METHODS: The multi-center Hepatocellular Carcinoma Early Detection Strategy study of the National Institutes of Health prospectively enrolled patients with cirrhosis who underwent standard surveillance for HCC. Demographics, medical and family history, etiology of liver disease, and clinical features were evaluated for associations with HCC.RESULTS: Between 4/10/2013 and 12/31/2021, 1,723 patients were enrolled and confirmed eligible. During median follow up of 2.2 years (range: 0-8.7 years), there were 109 incident cases of HCC for an incidence rate of 2.4 per 100 person-years; 88 (81%) patients with very early/early BCLC stage (0, A), 20 (18%) intermediate stage (B), 1 (1%) unknown stage. Risk factor analyses were restricted to 1,325 patients, including 95 incident HCC, with at least 6 months of follow up. The majority were men (53.2%), obese or severely obese (median body mass index [BMI] 30.2 kg/m2), and white (86.3%); 42.0% had history of HCV infection, 20.7% had alcoholic liver disease (ALD), and 24.9% had nonalcoholic fatty liver disease (NAFLD). Fourteen risk factors for HCC were significant (p<0.05) in univariate analyses, and a multivariate subset was selected by stepwise logistic regression. The multivariate subset contained gender (p<0.001, male, OR=2.47, 95% C.I. 1.54-4.07), years with cirrhosis (p=0.004, OR=1.06, 95% C.I. 1.02-1.1), family history of liver cancer (p=0.02, yes, OR=2.69, 95% C.I. 1.11-5.86), age (per 5-years, p=0.02, OR=1.17, 95% C.I. 1.03-1.33), obesity (p=0.02, yes, OR=1.7, 95% C.I. 1.08-2.73), aspartate aminotransferase (log(1+AST), p=0.06, OR=1.54 95% C.I. 0.97-2.42), alpha-fetoprotein (log(1+AFP), p=0.07, OR=1.32, 95% C.I. 0.97-1.77), and albumin (p=0.10, OR=0.7, 95% C.I. 0.46-1.07).CONCLUSIONS: Thus far, this is the largest prospective and geographically diverse study of a United States cohort of patients with cirrhosis that validates known risk factors for HCC (gender, age, obesity, years with cirrhosis, family history of liver cancer, baseline AFP, albumin, and AST). The incidence of HCC was 2.4 % per 100 person years.
View details for DOI 10.1053/j.gastro.2023.06.027
View details for PubMedID 37429366
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Trends of Cirrhosis-related Mortality in the USA during the COVID-19 Pandemic.
Journal of clinical and translational hepatology
2023; 11 (3): 751-756
Abstract
Immunocompromised status and interrupted routine care may render patients with cirrhosis vulnerable to the coronavirus disease 2019 (COVID-19) pandemic. A nationwide dataset that includes more than 99% of the decedents in the U.S. between April 2012 and September 2021 was used. Projected age-standardized mortality during the pandemic were estimated according to prepandemic mortality rates, stratified by season. Excess deaths were determined by estimating the difference between observed and projected mortality rates. A temporal trend analysis of observed mortality rates was also performed in 0.83 million decedents with cirrhosis between April 2012 and September 2021 was included. Following an increasing trend of cirrhosis-related mortality before the pandemic, with a semiannual percentage change (SAPC) of 0.54% [95% confidence interval (CI): (0.0-1.0%), p=0.036], a precipitous increase with seasonal variation occurred during the pandemic (SAPC 5.35, 95% CI: 1.9-8.9, p=0.005). Significantly increased mortality rates were observed in those with alcohol-associated liver disease (ALD), with a SAPC of 8.44 (95% CI: 4.3-12.8, p=0.001) during the pandemic. All-cause mortality of nonalcoholic fatty liver disease rose steadily across the entire study period with a SAPC of 6.79 (95% CI: 6.3-7.3, p<0.001). The decreasing trend of HCV-related mortality was reversed during the pandemic, while there was no significant change in HBV-related deaths. While there was significant increase in COVID-19-related deaths, more than 55% of the excess deaths were the indirect impact of the pandemic. We observed an alarming increase in cirrhosis-related deaths during the pandemic especially for ALD, with evidence in both direct and indirect impact. Our findings have implications on formulating policies for patients with cirrhosis.
View details for DOI 10.14218/JCTH.2022.00313
View details for PubMedID 36969898
View details for PubMedCentralID PMC10037514
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Reply: Proper monitoring instead of expanding treatment for improving prognosis of indeterminate phase hepatitis B patients.
Hepatology (Baltimore, Md.)
2023
View details for DOI 10.1097/HEP.0000000000000525
View details for PubMedID 37368997
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Severe hepatitis B flares with hepatic decompensation after withdrawal of nucleos(t)ide analogues: A population-based cohort study.
Alimentary pharmacology & therapeutics
2023
Abstract
Finite nucleos(t)ide analogue (NUC) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB).To quantify the incidence of severe hepatitis flares following NUC cessation in everyday clinical practice.This population-based cohort study enrolled 10,192 patients (male 71.7%, median age 50.9 years, cirrhosis 10.7%) who had received first-line NUCs for at least 1 year before discontinuing treatment. The primary outcome was severe flare with hepatic decompensation. We used competing risk analyses to assess event incidences and associated risk factors.During a median follow-up of 2.2 years, 132 patients developed severe flares with hepatic decompensation, yielding a 4-year cumulative incidence of 1.8% (95% confidence interval [CI], 1.5%-2.2%). Significant risk factors were cirrhosis (adjusted sub-distributional hazard ratio [aSHR], 2.74; 95% CI, 1.82-4.12), manifestations of portal hypertension (aSHR, 2.46; 95% CI, 1.45-4.18), age (aSHR, 1.21 per 10 years; 95% CI, 1.03-1.42) and male sex (aSHR, 1.58; 95% CI, 1.04-2.38). In patients without cirrhosis or portal hypertension (n = 8863), the 4-year cumulative incidence of severe withdrawal flares stood at 1.3% (95% CI, 1.0%-1.7%). For those patients with available data confirming adherence to the standard stopping rules (n = 1274), the incidence was 1.1% (95% CI, 0.6%-2.0%).Severe flares with hepatic decompensation were observed in 1%-2% of patients with CHB after stopping NUC therapy in daily practice. Risk factors included older age, cirrhosis, portal hypertension and male sex. Our findings argue against NUC cessation as part of routine clinical care.
View details for DOI 10.1111/apt.17614
View details for PubMedID 37341016
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An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease.
Hepatobiliary surgery and nutrition
2023; 12 (3): 386-403
Abstract
With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no appropriate guidance on CKD in individuals with MAFLD. Furthermore, there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Using a Delphi-based approach, a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.This Delphi-based consensus statement provided guidance on the epidemiology, mechanisms, management and treatment of MAFLD and CKD, as well as the relationship between the severity of MAFLD and risk of CKD, which establish a framework for the early prevention and management of these two common and interconnected diseases.
View details for DOI 10.21037/hbsn-22-421
View details for PubMedID 37351121
View details for PubMedCentralID PMC10282675
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Diabetes mellitus (DM) is the strongest risk factor of significant inflammation or fibrosis in chronic hepatitis B (CHB) combined with non-alcoholic fatty liver disease (NAFLD)
ELSEVIER. 2023: S638-S639
View details for Web of Science ID 001037135102257
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Use and outcomes of hepatitis B virus positive grafts for renal or heart transplantation in the US (1999-2021)
ELSEVIER. 2023: S468
View details for Web of Science ID 001037135101301
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Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis
ELSEVIER. 2023: S1096-S1097
View details for Web of Science ID 001037135105029
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Effectiveness of HCC surveillance programs using multitarget blood test: A modeling study.
Hepatology communications
2023; 7 (6)
Abstract
The effectiveness of ultrasound-based surveillance for HCC in patients with cirrhosis is limited by suboptimal sensitivity for early tumor detection and poor adherence. Emerging blood-based biomarkers have been proposed as an alternative surveillance strategy. We aimed to evaluate the comparative effectiveness of a multitarget HCC blood test (mt-HBT)-with and without improved adherence-against ultrasound-based HCC surveillance.We developed a Markov-based mathematical model that simulated a virtual trial in patients with compensated cirrhosis comparing potential surveillance strategies: biannual surveillance using ultrasound, ultrasound plus AFP, and mt-HBT with or without improved adherence (+10% increase). We used published data to inform underlying liver disease progression rates, HCC tumor growth patterns, performance characteristics of surveillance modalities, and efficacy of treatments. Primary outcomes of interest were the number of early-stage HCCs detected and life years gained.Per 100,000 patients with cirrhosis, mt-HBT detected 1680 more early-stage HCCs than ultrasound alone and 350 more early-stage HCCs than ultrasound + AFP, yielding an additional 5720 and 1000 life years, respectively. mt-HBT with improved adherence detected 2200 more early-stage HCCs than ultrasound and 880 more early-stage HCCs than ultrasound + AFP, yielding an additional 8140 and 3420 life years, respectively. The number of screening tests needed to detect one HCC case was 139 with ultrasound, 122 with ultrasound + AFP, 119 with mt-HBT, and 124 with mt-HBT with improved adherence.mt-HBT is a promising alternative to ultrasound-based HCC surveillance, particularly given anticipated improved adherence with blood-based biomarkers could increase HCC surveillance effectiveness.
View details for DOI 10.1097/HC9.0000000000000146
View details for PubMedID 37204402
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COST OF LIVER CANCER SCREENING IN PATIENTS WITH CIRRHOSIS
ELSEVIER SCIENCE INC. 2023: S152
View details for Web of Science ID 001031473301045
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An international multidisciplinary consensus statement on MAFLD and the risk of CVD.
Hepatology international
2023
Abstract
Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists.A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management.The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.
View details for DOI 10.1007/s12072-023-10543-8
View details for PubMedID 37204656
View details for PubMedCentralID 7546877
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Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis.
Clinical and molecular hepatology
2023
Abstract
Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random-effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88%-95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27-0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all P≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, P<0.0001). On Cox regression, CHB-FL was associated with lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (hazard ratio=0.68, 0.61, 0.38, 1.35, respectively, all P≤0.004).IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.
View details for DOI 10.3350/cmh.2023.0004
View details for PubMedID 37157776
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Letter: grouping traditional biomarkers that are within reach has great utility - further validation is needed.
Alimentary pharmacology & therapeutics
2023; 57 (9): 1050-1051
View details for DOI 10.1111/apt.17459
View details for PubMedID 37053486
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Sarcopenia in cirrhosis: epidemiology, diagnosis, management and prognosis.
Current opinion in gastroenterology
2023; 39 (3): 131-139
Abstract
With the development of many international guidelines, research on sarcopenia has increased rapidly, showing that sarcopenia is predictive of adverse outcomes, including increased mortality and impaired mobility, in patients with cirrhosis. The purpose of this article is to review the current evidence concerning the epidemiology, diagnosis, management and predictive value of sarcopenia on the prognosis of patients with cirrhosis.Sarcopenia is a frequent and lethal complication of cirrhosis. Currently, abdominal computed tomography imaging is the most commonly used method to diagnose sarcopenia. In clinical practice, assessing muscle strength and physical performance, such as by measuring handgrip strength and gait speed, is of increasing interest. In addition to the necessary pharmacological therapy, adequate intake of protein, energy and micronutrients, as well as regular moderate-intensity exercise, can help to minimize sarcopenia. Sarcopenia has been shown to be a strong predictor of prognosis in patients with severe liver disease.A global consensus is needed on the definition and operational parameters for the diagnosis of sarcopenia. Further research should focus on developing standardized screening, management and treatment protocols for sarcopenia. Adding sarcopenia to existing models may better exploit the effect of sarcopenia on prognosis in patients with cirrhosis, which should be investigated further.
View details for DOI 10.1097/MOG.0000000000000922
View details for PubMedID 37144530
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Immortal Time and Selection Biases in Study of Direct-Acting Antiviral Treatment and Hepatitis C Outcomes-Reply.
JAMA internal medicine
2023
View details for DOI 10.1001/jamainternmed.2023.0557
View details for PubMedID 37067818
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Nonalcoholic fatty liver disease (NAFLD) detection and deep learning in a Chinese community-based population.
European radiology
2023
Abstract
We aimed to develop and validate a deep learning system (DLS) by using an auxiliary section that extracts and outputs specific ultrasound diagnostic features to improve the explainable, clinical relevant utility of using DLS for detecting NAFLD.In a community-based study of 4144 participants with abdominal ultrasound scan in Hangzhou, China, we sampled 928 (617 [66.5%] females, mean age: 56 years ± 13 [standard deviation]) participants (2 images per participant) to develop and validate DLS, a two-section neural network (2S-NNet). Radiologists' consensus diagnosis classified hepatic steatosis as none steatosis, mild, moderate, and severe. We also explored the NAFLD detection performance of six one-section neural network models and five fatty liver indices on our data set. We further evaluated the influence of participants' characteristics on the correctness of 2S-NNet by logistic regression.Area under the curve (AUROC) of 2S-NNet for hepatic steatosis was 0.90 for ≥ mild, 0.85 for ≥ moderate, and 0.93 for severe steatosis, and was 0.90 for NAFLD presence, 0.84 for moderate to severe NAFLD, and 0.93 for severe NAFLD. The AUROC of NAFLD severity was 0.88 for 2S-NNet, and 0.79-0.86 for one-section models. The AUROC of NAFLD presence was 0.90 for 2S-NNet, and 0.54-0.82 for fatty liver indices. Age, sex, body mass index, diabetes, fibrosis-4 index, android fat ratio, and skeletal muscle via dual-energy X-ray absorptiometry had no significant impact on the correctness of 2S-NNet (p > 0.05).By using two-section design, 2S-NNet had improved the performance for detecting NAFLD with more explainable, clinical relevant utility than using one-section design.• Based on the consensus review derived from radiologists, our DLS (2S-NNet) had an AUROC of 0.88 by using two-section design and yielded better performance for detecting NAFLD than using one-section design with more explainable, clinical relevant utility. • The 2S-NNet outperformed five fatty liver indices with the highest AUROCs (0.84-0.93 vs. 0.54-0.82) for different NAFLD severity screening, indicating screening utility of deep learning-based radiology may perform better than blood biomarker panels in epidemiology. • The correctness of 2S-NNet was not significantly influenced by individual's characteristics, including age, sex, body mass index, diabetes, fibrosis-4 index, android fat ratio, and skeletal muscle via dual-energy X-ray absorptiometry.
View details for DOI 10.1007/s00330-023-09515-1
View details for PubMedID 36892645
View details for PubMedCentralID 6770992
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Letter to the Editor: Risk Stratification for Sarcopenic Obesity in Nonalcoholic Fatty Liver Disease.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2023
View details for DOI 10.1016/j.cgh.2023.02.012
View details for PubMedID 36842631
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An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease
HEPATOBILIARY SURGERY AND NUTRITION
2023
View details for DOI 10.21037/hbsn-22-421
View details for Web of Science ID 000989425000001
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A prospective clinical trial to evaluate the performance of a multi-analyte blood test for early detection of hepatocellular carcinoma among at-risk patients with liver cirrhosis: The CLiMB study.
LIPPINCOTT WILLIAMS & WILKINS. 2023: TPS617
View details for Web of Science ID 001093994600049
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Letter: rising incidence and poor survival in patients with nonviral HCC-better HCC surveillance and treatment for alcohol-associated and non-alcohol fatty liver diseases are needed.
Alimentary pharmacology & therapeutics
2023; 57 (3): 361-362
View details for DOI 10.1111/apt.17334
View details for PubMedID 36641791
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Serious adverse events after cessation of nucleos(t)ide analogues in individuals with chronic hepatitis B: A systematic review and meta-analysis.
JHEP reports : innovation in hepatology
2023; 5 (1): 100617
Abstract
The risk of serious clinical outcomes following cessation of nucleos(t)ide analogues (NUCs) in individuals with chronic hepatitis B remains poorly characterized. This systematic review and meta-analysis aimed to evaluate current literature on this issue.We searched PubMed, Embase, and Web of Science for NUC stop studies that noted clinical outcomes published between January 1, 2006 and August 18, 2022. We performed meta-research analyses to examine the relationships of reported outcomes with study designs and characteristics and also pooled studies with non-overlapping populations to provide risk estimates for the proportions of (1) severe hepatitis flares or hepatic decompensation or (2) hepatitis flare-related death or liver transplantation.The meta-research analysis included 50 studies of highly heterogeneous designs and characteristics. We found that reporting of safety outcomes varied widely according to outcome definition, follow-up duration, and sample size. Only ten studies prespecified safety events as the study outcome, and only four had an outcome definition to include hepatic insufficiency, a follow-up duration >12 months, and a sample size >100 patients. We further pooled 15 studies with 4,525 individuals and estimated that severe hepatitis flares or decompensation would occur in 1.21% (95% CI 0.70-2.08%), with significant heterogeneity (I 2 = 54%, p <0.01), while hepatitis flare-related death or liver transplantation would occur in 0.37% (95% CI 0.20-0.67%), without significant heterogeneity (I 2 = 0.00%, p = 1.00).Current literature on the risk of serious clinical outcomes following NUC cessation is very limited and highly heterogeneous. Pooled analyses of available data found approximately 1% of patients who stopped NUCs developed severe flares or hepatic decompensation.Current literature regarding the safety concerns surrounding NUC cessation for individuals with chronic hepatitis B is limited and heterogeneous in designs and characteristics, and thus should be interpreted with great caution. Based on currently available data, the proportion of patients that develop severe hepatitis flares or hepatic decompensation was estimated at 1.21% and that of flare-related death or liver transplantation at 0.37%. Our findings are important for individuals receiving nucleos(t)ide analogues for hepatitis B virus infection because we not only pooled currently available data to estimate the risk of serious clinical adverse events following treatment cessation but also uncovered critical limitations of existing literature regarding the safety of finite therapy.
View details for DOI 10.1016/j.jhepr.2022.100617
View details for PubMedID 36466989
View details for PubMedCentralID PMC9708915
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Recognizing skin conditions in patients with cirrhosis: a narrative review.
Annals of medicine
2022; 54 (1): 3017-3029
Abstract
Background: The skin is a major target organ for extrahepatic manifestations of liver diseases, and dermatologic abnormalities are common in patients with hepatic disorders. Clinical examination of the skin, nails and hair can allow for appropriate recognition, early diagnosis and treatment of liver diseases, and improvement in the quality of life and life expectancy of affected patients.Methods: We searched 3 databases (Pubmed,Medline and Embase) and selected studies about cirrhosis related skin manifestations and their pathophysiology.Results: A total of 73 articles were included in the review. Studies displayed the spectrum of cutaneous manifestations related to hormonal and vascular changes as well as nail and hair changes in patients with cirrhosis and/or portal hypertension.Conclusion: Cutaneous alterations are important clues or potential indications in the diagnosis of liver cirrhosis. Familiarity with skin conditions can be promptly diagnosed and appropriate management initiated.KEY MESSAGESManifestations of the liver and skin disorders are interrelated in various ways. Cutaneous changes may be the first clue that a patient has liver disease.The skin is a major target organ for extrahepatic manifestations of liver diseases. A broad range of cutaneous alterations can be present in patients with cirrhosis, such as vascular, nail, hair, hormonal changes, etc.Recognizing these signs is crucial so that potential underlying diseases including liver disease can be promptly diagnosed and appropriate management timely initiated.
View details for DOI 10.1080/07853890.2022.2138961
View details for PubMedID 36308406
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Impact of advanced practice providers on characteristics and quality of care of patients with chronic hepatitis B.
Alimentary pharmacology & therapeutics
2022
Abstract
Advanced practice providers (APP) may be able to play a role in improving the linkage to care in chronic hepatitis B (CHB), but data are limited.To compare management of CHB patients under APP-assisted versus physician-only care.This retrospective analysis identified patients with CHB infection from Optum's de-identified Clinformatics® Data Mart Database (2003-2021) using ICD-9/ICD-10 codes. We compared the proportion of patients with CHB who had adequate evaluation for treatment (defined as ALT, HBV DNA, ± HBeAg), and the proportion of treatment-eligible patients with CHB who received treatment between APP versus physician-only care.We included 42,140 eligible patients (mean age: 51.9 ± 15.1, 56.1% male). Overall, 34.3% received APP care with increasing utilisation over time. Compared to physician-only care, patients who also received APP care were more likely to have viral co-infection, and more likely to have been seen by a specialist (72.1%). Overall, 62.8% and 56.2% of treatment-eligible patients based on AASLD and EASL guidelines, respectively, received treatment; APP care patients were more likely to be treated (AASLD adjusted HR: 1.18, 95%CI: 1.03-1.34; EASL adjusted HR:1.24, 95%CI: 1.09-1.41) after adjustment for age, sex, race/ethnicity, viral dual infection, baseline cirrhosis/liver cancer, number of HBV DNA and alanine aminotransferase measurements, and physician provider type.Treatment-eligible patients with CHB receiving APP care were more likely to receive antiviral therapy. APP care may help to expand the pool of providers for patients with CHB, and to improve current suboptimal treatment rates.
View details for DOI 10.1111/apt.17254
View details for PubMedID 36266768
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ANTIVIRAL THERAPY IS SEVERELY UNDERUTILIZED IN HEPATITIS B-AND HEPATITIS C-ASSOCIATED HEPATOCELLULAR CARCINOMA AFTER LIVER RESECTION: A REAL-HCC STUDY
WILEY. 2022: S1423-S1424
View details for Web of Science ID 000870796604289
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GLOBAL TREATMENT RATE AND BARRIERS TO DIRECT ACTING ANTIVIRAL (DAA) TREATMENT OF CHRONIC HEPATITIS C (CHC): A SYSTEMATIC REVIEW AND META-ANALYSIS OF 179 STUDIES AND 2,421,347 CHC PATIENTS
WILEY. 2022: S371-S372
View details for Web of Science ID 000870796601103
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CIRRHOSIS INCIDENCE AND LONG-TERM MORTALITY RATE AMONG LEAN, OVERWEIGHT, AND OBESE PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IN THE UNITED STATES
WILEY. 2022: S742-S743
View details for Web of Science ID 000870796602191
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RACIAL AND ETHNIC DISPARITIES IN YEARS OF POTENTIAL LIFE LOST ASSOCIATED WITH CIRRHOSIS IN THE UNITED STATES BEFORE AND DURING THE COVID-19 PANDEMIC
WILEY. 2022: S1074-S1075
View details for Web of Science ID 000870796603231
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IMPACT OF THE COVID-19 PANDEMIC ON MORTALITY RATE OF LIVER DISEASE IN THE UNITED STATES: A POPULATION-BASED STUDY, 2010-2021
WILEY. 2022: S117
View details for Web of Science ID 000870796600131
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RACIAL AND ETHNIC DISPARITIES IN CLINICAL PRESENTATION AND OUTCOMES AMONG PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE IN THE UNITED STATES: A REAL-WORLD STUDY OF 10,135 PATIENTS
WILEY. 2022: S707-S708
View details for Web of Science ID 000870796602147
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GLOBAL INCIDENCE OF NON-ALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
WILEY. 2022: S850
View details for Web of Science ID 000870796602332
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SERIOUS ADVERSE CLINICAL EVENTS AFTER CESSATION OF NUCLEOS(T) IDE ANALOGUES IN PATIENTS WITH CHRONIC HEPATITIS B: A SYSTEMATIC REVIEW AND META-ANALYSIS
WILEY. 2022: S237-S238
View details for Web of Science ID 000870796600275
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EXCESS CIRRHOSIS-RELATED MORTALITY AND RELEVANT DISPARITIES DURING THE COVID-19 PANDEMIC
WILEY. 2022: S129-S130
View details for Web of Science ID 000870796600145
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INCIDENCE AND PREDICTORS OF OFF-THERAPY RELAPSES AFTER CESSATION OF TENOFOVIR ALAFENAMIDE IN PATIENTS WITH CHRONIC HEPATITIS B
WILEY. 2022: S280
View details for Web of Science ID 000870796600332
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PREDICTION OF CLINICAL RELAPSE AFTER DISCONTINUATION OF NUCLEOS( T) IDE ANALOGS FOR CHRONIC HEPATITIS B USING DYNAMIC HBV CORE-RELATED ANTIGEN MEASUREMENTS
WILEY. 2022: S295
View details for Web of Science ID 000870796601001
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THE TREND OF YEARS OF POTENTIAL LIFE LOST ASSOCIATED WITH CIRRHOSIS BEFORE AND DURING THE COVID-19 PANDEMIC: A POPULATION-BASED STUDY
WILEY. 2022: S74-S75
View details for Web of Science ID 000870796600084
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RACIAL AND ETHNIC DISPARITIES IN CLINICAL PRESENTATION, TREATMENT, AND OVERALL SURVIVAL IN PATIENTS WITH HEPATITIS C-RELATED HEPATOCELLULAR CARCINOMA (HCV-HCC): A REAL-WORLD EXPERIENCE FROM THE REAL-HCC REGISTRY
WILEY. 2022: S403-S405
View details for Web of Science ID 000870796601142
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HIGHER HEPATOCELLULAR CARCINOMA (HCC) INCIDENCE IN CHRONIC HEPATITIS C (CHC) PATIENTS AFTER HEPATITIS C VIRUS (HCV) CURE COMPARED TO TREATED CHRONIC HEPATITIS B (CHB): RESULTS FROM A MULTINATIONAL REAL-WORLD COHORT OF PATIENTS WITH CIRRHOSIS
WILEY. 2022: S377-S379
View details for Web of Science ID 000870796601110
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SEX DIFFERENCES IN CLINICAL PRESENTATION AND SURVIVAL IN PATIENTS WITH CIRRHOSIS
WILEY. 2022: S1174-S1175
View details for Web of Science ID 000870796603355
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DIFFERENTIAL CHARACTERISTICS AND SURVIVAL BY CHRONIC LIVER DISEASE (CLD) ETIOLOGY IN A NATIONWIDE REAL-WORLD COHORT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC), 2003-2021
WILEY. 2022: S1422-S1423
View details for Web of Science ID 000870796604288
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PREDICTING HEPATOCELLULAR CARCINOMA DEVELOPMENT IN NAFLD PATIENTS WITHOUT CIRRHOSIS
WILEY. 2022: S1430
View details for Web of Science ID 000870796604298
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REAL-WORLD TREATMENT OUTCOME WITH PROTEASE INHIBITOR (PI) VERSUS NON-PI DIRECT ACTING ANTIVIRAL (DAA) IN DECOMPENSATED HEPATITIS C (HCV) CIRRHOSIS: A REAL-C STUDY WITH INVERSE PROBABILITY OF TREATMENT WEIGHTING (IPTW) ANALYSIS
WILEY. 2022: S45-S47
View details for Web of Science ID 000870796600049
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UTILIZATION OF ANTIVIRAL THERAPY AND ITS IMPACT ON SURVIVAL RATES IN PATIENTS WITH CHRONIC HEPATITIS B VIRUS-RELATED HEPATOCELLULAR CARCINOMA (HBV-HCC) IN THE UNITED STATES
WILEY. 2022: S282-S283
View details for Web of Science ID 000870796600334
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DIFFERENTIAL HEPATOCELLULAR CARCINOMA (HCC) INCIDENCE AND SURVIVAL RATES BY ETIOLOGY OF CHRONIC LIVER DISEASE (CLD) IN A NATIONWIDE REAL-WORLD COHORT OF UNITED STATES PATIENTS WITH CIRRHOSIS, 2003-2021
WILEY. 2022: S1222-S1223
View details for Web of Science ID 000870796604016
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NATIONWIDE POPULATION-LEVEL REAL-WORLD EVIDENCE OF LONG-TERM MORTALITY, LIVER AND NON-LIVER BENEFITS OF DAA THERAPY IN PATIENTS WITH CHRONIC HEPATITIS (CHC) TREATED WITH DIRECT-ACTING ANTIVIRALS (DAA)
WILEY. 2022: S373-S374
View details for Web of Science ID 000870796601105
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ANTIVIRAL THERAPY REDUCES HEPATOCELLULAR CARCINOMA RISK AMONG HBV PATIENTS IN THE INDETERMINATE PHASE
WILEY. 2022: S34-S35
View details for Web of Science ID 000870796600037
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CHARACTERISTICS AND TREATMENT RATE OF PATIENTS WITH HEPATITIS C VIRUS INFECTION IN THE DAA AND COVID-19 ERAS IN THE UNITED STATES
WILEY. 2022: S370-S371
View details for Web of Science ID 000870796601102
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INCREASED TREATMENT RESPONSE AND BONE DENSITY IN PATIENTS WITH CHRONIC HEPATITIS B SWITCHED TO TENOFOVIR ALAFENAMIDE FROM OTHER NUCLEOS(T) IDE ANALOGUE: 96-WEEK RESULTS FROM A PROSPECTIVE MULTINATIONAL STUDY
WILEY. 2022: S281-S282
View details for Web of Science ID 000870796600333
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RACIAL AND ETHNIC DISPARITIES IN CHARACTERISTICS AND CARE PATTERNS OF CHRONIC HEPATITIS B (CHB) PATIENTS IN THE UNITED STATES (US): RESULTS OF A NATIONWIDE COHORT
WILEY. 2022: S292
View details for Web of Science ID 000870796600347
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A NOVEL EDUCATIONAL PROGRAM TO ADDRESS MISUNDERSTANDINGS IN APPLYING AASLD HBV TREATMENT GUIDELINES
WILEY. 2022: S296-S297
View details for Web of Science ID 000870796601003
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CHARACTERISTICS AND CARE OF CHRONIC HEPATITIS B PATIENTS WITH ADVANCED PRACTICE PROVIDERS
WILEY. 2022: S279-S280
View details for Web of Science ID 000870796600331
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Trends of Cirrhosis-related Mortality in the USA during the COVID-19 Pandemic
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
2022
View details for DOI 10.14218/JCTH.2022.00313
View details for Web of Science ID 000875656600001
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Liver complications in untreated treatment-ineligible versus treated treatment-eligible patients with hepatitis B.
Digestive diseases (Basel, Switzerland)
2022
Abstract
A substantial number of patients who do not meet treatment criteria for chronic hepatitis B later develop adverse outcomes such as cirrhosis and hepatocellular carcinoma (HCC). Our aim was to determine whether current practice guidelines adequately identify chronic hepatitis B (CHB) patients who will benefit from antiviral therapy.We performed a retrospective cohort study comparing the incidence of adverse liver outcomes (cirrhosis and/or HCC) in untreated treatment-ineligible (at baseline and throughout follow-up) versus treated treatment-eligible patients according to standard AASLD 2018 guidance (ALT [U/L] > 70/50 for men/women plus HBV DNA [IU/mL] > 20,000/2,000 for HBeAg+/-) and with a sensitivity analyses using a lower threshold (ALT > 40 U/L and HBV DNA > 2,000 IU/mL).We reviewed records of 5,840 patients from 5 clinics in California and identified 2,987 treatment-naïve non-HCC CHB patients. Of those, 271 patients remained untreated treatment-ineligible, 514 patients were treatment-eligible and initiated treatment, with 5-year cumulative adverse liver incidences of 12.5% vs 7.2%, P=0.074. On multivariable analysis adjusting for age, sex, diabetes, albumin, platelet count and HBV DNA, compared to treated treatment-eligible patients, untreated treatment-ineligible patients had a significantly higher risk of adverse liver outcomes (adjusted HR: 2.38, 95% CI 1.03-5.48, P=0.04) in main analysis by AASLD 2018 criteria, but not in sensitivity analysis using the lower treatment threshold (P=0.09).Patients never meeting standard AASLD 2018 criteria for antiviral therapy and never treated had twice the risk of developing cirrhosis and/or HCC when compared to eligible and treated patients.
View details for DOI 10.1159/000526933
View details for PubMedID 36070707
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Clinical characteristics and outcomes in those with primary extrahepatic malignancy and malignant ascites.
BMC gastroenterology
2022; 22 (1): 410
Abstract
BACKGROUND: Malignancy-related ascites accounts for approximately 10% of causes of ascites. Our AIM was to characterize the ascites fluid and correlate clinical outcomes in those with extrahepatic malignancy and ascites.METHODS: 241 subjects with extrahepatic solid tumors and ascites were reviewed from 1/1/2000 to 12/31/2019, 119 without liver metastasis and 122 with liver metastasis.RESULTS: Ascites fluid consistent with peritoneal carcinomatosis (PC) was most common, 150/241 (62%), followed by fluid reflecting the presence of portal hypertension (PH), 69/241 (29%). 22/241 (9%) had low SAAG and low ascites fluid total protein, with evidence of PC on cytology and or imaging in 20/22. Lung cancer was the most common malignancy in subjects with ascites due to PC at 36/150 (24%), pancreatic cancer was the most common in subjects with ascites with features of PH at 16/69 (23%). Chemotherapy or immunotherapy alone was the most common management approach. Significantly higher 5-year, 3-year and 1-year mortality rate were noted in subjects with evidence of PC on cytology/imaging versus subjects with no evidence of PC, and in subjects with liver metastasis compared to subjects without liver metastasis. Subjects with pancreatic cancer and evidence of PC on cytology/imaging had higher 1 and 5-year mortality rates compared to subjects without PC.CONCLUSIONS: Ascites in solid tumor malignancy is most commonly due to PC. We also observed ascites fluid with characteristics of PH in 29% of subjects. Higher mortality rates in subjects with peritoneal carcinomatosis and liver metastasis were noted. These findings may help inform prognosis and treatment strategies.
View details for DOI 10.1186/s12876-022-02487-4
View details for PubMedID 36064324
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Incidence of hepatocellular carcinoma in chronic hepatitis B virus infection in those not meeting criteria for antiviral therapy.
Hepatology communications
2022
Abstract
Chronic hepatitis B virus (HBV) infection is the leading risk factor for hepatocellular carcinoma (HCC). The aim of this study was to explore the incidence of HCC in a cohort of subjects with HBV and correlate with HBV treatment current guidance. We identified 2846 subjects with HBV over the study period. HCC was diagnosed in 386 of 2846 (14%) subjects; 209 of 386 (54%) were on nucleos(t)ide analogue (NA) therapy at time of HCC diagnosis, and 177 of 386 (46%) were not on NA therapy. Of the 177 subjects not on NAs who developed HCC during follow-up, 153 of 177 (86%) had cirrhosis. Within the 177 subjects not on NAs, 158 of 177 (89%) had undetectable HBV DNA, 10 of 177 (6%) had detectable HBV DNA < 2000 IU/L, and 9 of 177 (5%) had HBV DNA > 2000 IU/L. Of those with cirrhosis and undetectable HBV DNA, 115 of 141 had compensated cirrhosis, and 26 of 141 had decompensated cirrhosis. Significant predictors of HCC on time to event analysis included cirrhosis (hazard ratio [HR] 10, 95% confidence interval [CI] 5.8-17.5; p < 0.001), alanine aminotransferase level (HR 1.004, 95% CI 1.002-1.006; p < 0.001), age (HR 1.04, 95% CI 1.03-1.06; p < 0.001), (HR 1.9, 95% CI 1.2-3.1; p 0.007), and nonalcoholic fatty liver disease (HR 1.7, 95% CI 1.1-2.8; p 0.02). Kaplan-Meier analysis demonstrated the cumulative incidence of HCC in subjects with compensated cirrhosis receiving NA therapy was significantly lower compared to subjects with compensated cirrhosis outside current HBV treatment practice guidance (undetectable HBV DNA) (32% vs. 51%; p < 0.001). Conclusion: Those with untreated compensated cirrhosis with undetectable HBV DNA who do not meet current guidance for treatment had higher rates of HCC than those with compensated cirrhosis and suppressed HBV DNA by NA therapy. This study highlights the need for earlier diagnosis and treatment of HBV.
View details for DOI 10.1002/hep4.2064
View details for PubMedID 36004713
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Transient Elastography and Serum-based Tests for Diagnosis of Fatty Liver and Advanced Fibrosis in a Community Cohort- a Cross Sectional Analysis.
Digestive diseases (Basel, Switzerland)
2022
Abstract
Non-invasive tests (NITs) are necessary for knowing the true prevalence of fatty liver (FL) and advanced fibrosis (AF). Noninvasive tests (NITs) for diagnosis of FL and fibrosis were compared.Data were obtained from the National Health and Examination Survey (NHANES; 2017-2018). Participants were excluded with other liver diseases, missing data for NIT calculation and/or excessive alcohol use. Area under the receiver operating characteristic (AUROC) compared the accuracy of 4 FL NITs (CAP, HIS, FLI, USFLI) among themselves and to CAP value of 285 dB/m and 5 fibrosis NITs (transient elastography, APRI, NFS, FIB-4, HEPAmet) among themselves and to LSM ≥ 8.7 kPa.Among 2051 participants (average age 47 (±17.7), 48% males, 62% white, 73% overweight/obese, 39% metabolic syndrome), demographics were similar among NIT groups (CAP=812; HSI=1,234; FLI=935; USFLI-824). FL prevalence by NIT: 39% CAP, 58% HSI, 47% FLI, 37% USFLI. AF prevalence by test- LSM (≥ 8.7 kPa) 10%-14%; FIB-4 (≥2.67) and APRI (≥0.7) 1.3%- 2.7%; HEPAmet (>0.47) 14%-21%. Compared to CAP ≥285, FLI (AUROC= 0.823) and USFLI (AUROC=0.833) performed better than HSI (AUROC: 0.798). Compared to LSM ≥8.7kPa, only NFS (AUROC= 0.722) performed well (Fib-4 AUROC=0.606; APRI=0.647; HEPAmet=0.629). Among the CAP cohort, the strongest FL predictor was obesity (OR 15.2, 95%CI 7.97-28.9, P<0.001); the only fibrosis predictor was elevated AST (OR: 1.06, 95%CI 1.00-1.12, P=0.04). The addition of CAP or LSM as a second NIT reduced the number of indeterminate patients especially for FL.Regardless of diagnostic method in 2017-2018, the prevalence of NAFLD was >35%. NITs for FL performed well but not for AF. CAP and LSM as a second NIT reduced those considered indeterminate.
View details for DOI 10.1159/000526503
View details for PubMedID 35973400
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Letter to the editor: Screening for fatty liver disease and fibrosis in the elderly population: A call for action.
Hepatology (Baltimore, Md.)
2022
View details for DOI 10.1002/hep.32727
View details for PubMedID 36057133
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Improved treatment response and bone density in patients with chronic hepatitis B (CHB) switched to tenofovir alafenamide (TAF) from other nucleos (t)ide analogue: 96-week results from a prospective multinational study
ELSEVIER. 2022: S875-S876
View details for Web of Science ID 000826275104286
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Could a multi-target blood test make hepatocellular carcinoma surveillance programs more effective? A modelling-based virtual trial
ELSEVIER. 2022: S214-S215
View details for Web of Science ID 000826275101181
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The effect of sarcopenia on survival of patients with cirrhosis: a systematic review and meta-analysis
ELSEVIER. 2022: S883-S884
View details for Web of Science ID 000826275104300
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Risk of Hepatocellular Carcinoma With Tenofovir vs Entecavir Treatment for Chronic Hepatitis B Virus: A Reconstructed Individual Patient Data Meta-analysis.
JAMA network open
2022; 5 (6): e2219407
Abstract
Conventional meta-analyses with aggregated study-level data have yielded conflicting results for the comparative effectiveness of tenofovir disoproxil fumarate vs entecavir in reducing hepatocellular carcinoma (HCC) risk among patients with chronic hepatitis B virus. Within-study heterogeneity, between-study heterogeneity, and the inability of conventional meta-analyses to capture time-to-event data were associated with these results.To perform a reconstructed individual patient data meta-analysis of high-quality propensity score-matched studies to provide robust estimates for comparative HCC risk between groups receiving tenofovir or entecavir.Medline and Embase databases were searched from inception to October 6, 2021.The initial search yielded 3435 articles. Fourteen studies that used propensity score matching to balance baseline characteristics were included in the final analysis.The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Individual patient data were reconstructed from Kaplan-Meier curves. Risk of HCC was evaluated using random-effects hazard ratios (HRs) via a shared-frailty model and a Cox proportional hazards model stratified by study group. Restricted mean survival time (RMST) analysis was conducted to account for varying estimated treatment effect across time.The comparative risk of HCC with tenofovir vs entecavir treatment.From analysis of 14 studes with 24 269 patients (10 534 receiving tenofovir and 13 735 receiving entecavir; mean age, 49.86 [95% CI, 48.35-51.36] years; 65.05% [95% CI, 58.60%-71.00%] men), tenofovir was associated with decreased HCC incidence compared with entecavir (stratified Cox HR, 0.85 [95% CI, 0.76-0.94] at 5 years; P = .002). However, there was no significant difference in subanalysis of clinical cohort studies (stratified Cox HR, 0.92 [95% CI, 0.80-1.06] at 5 years; P = .24). Among administrative database studies, proportionality was violated, and HRs could not be obtained via Cox proporational hazards-based models. The mean time to HCC development in RMST analysis was 2.8 (95% CI, 1.8-3.7) weeks longer (P < .001) for tenofovir vs entecavir at 5 years. The RMST analyses for other subgroups revealed either insignificant or minimal differences (<3 weeks) in the mean time to HCC at 5 years.In this meta-analysis, there was no clinically meaningful difference in the risk of HCC between patients who received entecavir and patients who received tenofovir. There was no difference between tenofovir and entecavir among clinical cohort studies, whereas the mean time to HCC development was less than 3 weeks longer for patients who received tenofovir vs those who received entecavir at year 5 among administrative database studies. The choice between tenofovir or entecavir should be decided based on patient convenience and tolerability.
View details for DOI 10.1001/jamanetworkopen.2022.19407
View details for PubMedID 35767258
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Machine Learning Can Predict Recurrence Patterns After Liver Transplantation in Hepatocellular Carcinoma Patients: Analysis from the US Multicenter HCC Transplant Consortium
SPRINGER. 2022: 348-349
View details for Web of Science ID 000789811800036
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Response to "Does NAFLD prevalence data expire?"
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2022
View details for DOI 10.1016/j.cgh.2022.03.039
View details for PubMedID 35398567
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Metabolic abnormalities play a crucial role in non-obese people suffering from non-alcoholic fatty liver disease (NAFLD).
Hepatobiliary surgery and nutrition
2022; 11 (2): 333-334
View details for DOI 10.21037/hbsn-22-26
View details for PubMedID 35464275
View details for PubMedCentralID PMC9023836
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Defining Age-Related Thresholds for ALT and the Risk of Confounders
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
2022; 20 (3): 715-716
View details for Web of Science ID 000754719700034
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Renal outcomes with tenofovir alafenamide in liver transplant recipients.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2022
View details for DOI 10.1016/j.cgh.2022.01.035
View details for PubMedID 35123081
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Multi-target blood test to improve the performance of hepatocellular carcinoma surveillance programs: A modeling-based virtual trial
LIPPINCOTT WILLIAMS & WILKINS. 2022
View details for DOI 10.1200/JCO.2022.40.4_suppl.405
View details for Web of Science ID 000770995900391
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Increased risk of liver-related outcomes in chronic hepatitis B patients with metabolic syndrome: A systematic review and meta-analysis.
Digestive diseases (Basel, Switzerland)
2022
Abstract
Chronic hepatitis B (CHB) patients with metabolic syndrome (MetS) may present increased risk of liver-related outcomes (LROs) but prior studies were limited by small sample size and/or conflicting results. Using a systematic review and meta-analytic approach, we aimed to determine the association between MetS and LROs in CHB.Two researchers independently screened studies from the PubMed, Embase, Web of Science, and Cochrane Library databases from inception to January 21, 2020 and extracted the data. Estimates were pooled using a random-effects model.We screened 2,228 articles and included 10 eligible studies (18,360 CHB patients, 2,557 with MetS). MetS was significantly associated with LROs overall (OR=2.45, 95%CI=1.39-4.32) but not the individual LRO components but subgroup analyses were limited by small study numbers.MetS is associated with almost 3 folds higher risk of LROs in CHB and should be considered in management decisions. However, additional studies are needed.
View details for DOI 10.1159/000521768
View details for PubMedID 34986486
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Serum soluble programmed cell death 1 levels predict spontaneous functional cure in inactive carriers with chronic hepatitis B.
Alimentary pharmacology & therapeutics
2022
Abstract
Hepatitis B surface antigen (HBsAg) seroclearance is the most important milestone indicating favourable clinical outcomes in patients with chronic hepatitis B (CHB). However, it is difficult to achieve due to the impaired HBV-specific immunity, such as programmed cell death 1 (PD-1)-associated T cell exhaustion. We assessed soluble PD-1 (sPD-1) as a novel seromarker for predicting spontaneous HBsAg loss.Serial serum levels of sPD-1 were evaluated in 1046 untreated hepatitis B e antigen (HBeAg)-seronegative individuals who had achieved undetectable serum HBV DNA. Multiple regression analyses were applied to assess associations among baseline and subsequent sPD-1 levels, HBsAg decline during follow-up, and spontaneous HBsAg seroclearance.A total of 390 individuals achieved spontaneous HBsAg seroclearance during 6464.4 person-years of follow-up. Baseline sPD-1 levels were inversely associated with baseline HBsAg levels (qHBsAg) as well as a greater decline in qHBsAg during follow-up. Incidence rates of HBsAg seroclearance were 11.5, 61.7, 96.7 and 151.0 per 1000 person-years for sPD-1 levels of ≥4000, 536-3999, 125-535 and <125 pg/mL, respectively (Ptrend < 0.0001). Compared with baseline sPD-1 levels ≥4000 pg/mL, the rate ratio (95% CI) of HBsAg seroclearance was 2.1 (1.1-3.9), 3.0 (1.6-5.5) and 5.1 (2.8-9.5), for baseline sPD-1 levels of 536-3999, 125-535 and <125 pg/mL, respectively, after adjustment for sex, age and serum alanine aminotransferase and HBsAg levels.sPD-1 level is a novel marker which independently predicts spontaneous HBsAg seroclearance of HBeAg-negative inactive CHB patients with undetectable HBV DNA. (word count: 234, <250).
View details for DOI 10.1111/apt.16752
View details for PubMedID 35032052
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Chronic hepatitis B and fatty liver -weal or woe?
The American journal of gastroenterology
2022
View details for DOI 10.14309/ajg.0000000000001644
View details for PubMedID 35108223
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MAFLD and pregnancy- What are the consequences?
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2022
View details for DOI 10.1016/j.cgh.2022.01.008
View details for PubMedID 35051647
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Is it safe to treat chronic hepatitis C patients with decompensated cirrhosis with PI-based DAA?
Liver international : official journal of the International Association for the Study of the Liver
2022
View details for DOI 10.1111/liv.15214
View details for PubMedID 35220647
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Letter: hepatic steatosis and fibrosis in chronic hepatitis B-the chicken-and-egg conundrum. Authors' reply.
Alimentary pharmacology & therapeutics
2022; 55 (1): 145-146
View details for DOI 10.1111/apt.16698
View details for PubMedID 34907551
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Letter: hepatic steatosis in chronic hepatitis B-viral, metabolic or treatment-related? Authors' reply.
Alimentary pharmacology & therapeutics
2022; 55 (1): 149
View details for DOI 10.1111/apt.16715
View details for PubMedID 34907560
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A multi-analyte cell-free DNA-based blood test for early detection of hepatocellular carcinoma.
Hepatology communications
2022
Abstract
The limited performance of guideline-recommended abdominal ultrasound and serum alpha-fetoprotein (AFP) highlights the urgent, unmet need for new biomarkers for more accurate detection of early hepatocellular carcinoma (HCC). To this end, we have conducted a prospective clinical validation study to evaluate the performance of the HelioLiver Test, a multi-analyte blood test combining cell-free DNA methylation patterns, clinical variables, and protein tumor markers. A blinded, multicenter validation study was performed with 247 subjects, including 122 subjects with HCC and 125 control subjects with chronic liver disease. The performance of the HelioLiver Test was compared with AFP and the GALAD score as established HCC surveillance blood tests. The performance of the HelioLiver Test (area under the receiver operating characteristic curve [AUROC] = 0.944) was superior to both AFP (AUROC = 0.851; p < 0.0001) and GALAD (AUROC = 0.899; p < 0.0001). Using a prespecified diagnostic algorithm, the HelioLiver Test showed sensitivities of 85% (95% confidence interval [CI], 78%-90%) for HCC of any stage and 76% (95% CI, 60%-87%) for early stage (American Joint Committee on Cancer [AJCC] I and II) HCC. In contrast, AFP (≥20 ng/mL) alone and the GALAD score (≥-0.63) showed lower sensitivities of 62% (95% CI, 54%-70%) and 75% (95% CI, 67%-82%) for HCC overall, and 57% (95% CI, 40%-71%) and 65% (95% CI, 49%-79%) for early stage (AJCC I and II) HCC, respectively. The specificities of the HelioLiver Test (91%; 95% CI, 85%-95%), AFP (97%; 95% CI, 92%-99%), and the GALAD score (94%; 95% CI, 88%-97%) were similar for control subjects. The HelioLiver Test showed superior performance for HCC detection compared to with both AFP and the GALAD score and warrants further evaluation in HCC surveillance settings.
View details for DOI 10.1002/hep4.1918
View details for PubMedID 35244350
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Hepatitis B screening-Universal or simplified semi-targeted but not the status quo.
Hepatology (Baltimore, Md.)
1800
View details for DOI 10.1002/hep.32303
View details for PubMedID 34951716
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A MULTI-ANALYTE BLOOD TEST FOR ACCURATE AND EARLY DETECTION OF HEPATOCELLULAR CARCINOMA
WILEY. 2021: 1418A
View details for Web of Science ID 000727360100124
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Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study.
JGH open : an open access journal of gastroenterology and hepatology
2021; 5 (12): 1363-1372
Abstract
Chronic hepatitis C virus (HCV) infection, long-term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene-environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome-wide association study (GWAS).Two case-control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and 1455 population controls for their associations with HCC and verified our findings in additional studies.In this GWAS, we found that two SNPs were associated with HCC at P < 5E-8 and six SNPs at P < 5E-6 after adjusting for age, sex, and the top three principal components (PCs). Five of the SNPs in chromosome 22q13.31, three in PNPLA3 (rs2281135, rs2896019, and rs4823173) and two in SAMM50 (rs3761472, rs3827385), were replicated in a small US case-control study and a cohort study in Singapore. The associations remained significant after adjusting for body mass index and HCV infection. Meta-analysis of multiple datasets indicated that these SNPs were significantly associated with HCC.SNPs in PNPLA3 and SAMM50 are known risk loci for nonalcoholic fatty liver disease (NAFLD) and are suspected to be associated with HCC. Our GWAS demonstrated the associations of these SNPs with HCC in a US population. Biological mechanisms underlying the relationship remain to be elucidated.
View details for DOI 10.1002/jgh3.12682
View details for PubMedID 34950780
View details for PubMedCentralID PMC8674550
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Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study
JGH OPEN
2021
View details for DOI 10.1002/jgh3.12682
View details for Web of Science ID 000722929300001
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On-treatment gamma-glutamyl transferase predicts the development of hepatocellular carcinoma in chronic hepatitis B patients.
Liver international : official journal of the International Association for the Study of the Liver
2021
Abstract
BACKGROUND &AIMS: Gamma-glutamyl transferase (GGT) has been predictive of chronic hepatitis C-related hepatocellular carcinoma (HCC) development. Its role in the risk of HCC in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs) is elusive.METHODS: A total of 2,172 CHB patients from East Asia were randomized into development and validation groups in a 1:2 ratio. Serum GGT levels before and 6 months (M6) after initiating NAs and the potential risk factors were measured. The primary endpoint was HCC development 12 months after NA initiation.RESULTS: The annual incidence of HCC was 1.4/100 person-years in a follow-up period of 11370.7 person-years. The strongest factor associated with HCC development was high M6-GGT levels (>25 U/L; hazard ratio [HR]/95% confidence interval [CI]:3.31/2.02-5.42, P<0.001), followed by cirrhosis (HR/CI: 2.06/1.39-3.06, P<0.001), male sex (HR/CI: 2.01/1.29-3.13, P=0.002), and age (HR/CI: 1.05/1.03-1.17, P<0.001). Among cirrhotic patients, the incidence of HCC did not differ between those with high or low M6-GGT levels (P=0.09). In contrast, among non-cirrhotic patients, the incidence of HCC was significantly higher for those with M6-GGT level >25 U/L than for their counterparts (P<0.001). Cox regression analysis revealed that the strongest factor associated with HCC development in non-cirrhotic patients was high M6-GGT levels (HR/CI: 5.05/2.52-10.16, P<0.001), followed by age (HR/CI: 1.07/1.04-1.09, P<0.001). Non-cirrhotic elderly patients with high M6-GGT levels had a similarly high HCC risk as cirrhotic patients did (P=0.29).CONCLUSIONS: On-treatment serum GGT levels strongly predicted HCC development in CHB patients, particularly non-cirrhotic patients, treated with NAs.
View details for DOI 10.1111/liv.15085
View details for PubMedID 34687130
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Lurking in acute hepatitis B flares following treatment cessation were inescapable uncertainty and potential irreversibility.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2021
View details for DOI 10.1016/j.cgh.2021.10.026
View details for PubMedID 34678514
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Nationwide Data on the Characteristics of Linked-to-Care Chronic Hepatitis B in Korea.
Journal of clinical medicine
2021; 10 (20)
Abstract
Linkage-to-care rate of chronic hepatitis B (CHB) is less well characterized. We aimed to evaluate the proportion, characteristics of CHB patients who are linked to care. We retrospectively analyzed insurance reimbursement claims data provided by the Korean National Health Insurance Service. CHB patients who had at least two clinic or hospital visits that were associated with a CHB diagnostic code during 2002-2006 were included. Those without a history of malignancy at baseline were followed up until 2018. Mean follow-up period was 14.5 ± 2.9 years. Among the participants, 553,085 patients (35.8%) were found to be linked to care. The rates were lower in men than women (35.7% vs. 36.0%, p = 0.006). By age, it was highest for the 40's age group at 44.8% and lowest at 29.4% for the 20's age group (All p < 0.0001). The linkage-to-care rate was higher in rural area than metropolitan area (p < 0.0001). The 15-year cumulative incidence of hepatocellular carcinoma and overall survival rates among linked-to-care CHB patients were 18.2% and 93.8%, respectively. Two thirds of CHB patients were not linked to care. Those who are male, dwelling in metropolitan areas, and not in life transition periods need to be targeted to improve the linkage-to-care rate in Korea.
View details for DOI 10.3390/jcm10204633
View details for PubMedID 34682760
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META-ANALYSIS: REGIONAL DIFFERENCES IN OUTCOMES OF SURGICAL RESECTION FOR HEPATOCELLULAR CARCINOMA
WILEY. 2021: 859A
View details for Web of Science ID 000707188004151
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ANTIVIRAL TREATMENT WITH TENOFOVIR DISOPROXIL FUMARATE DECREASES SERUM LEVELS OF HEPATITIS B CORE-RELATED ANTIGEN AND VIRAL RNA IN CHRONIC HEPATITIS B PATIENTS
WILEY. 2021: 428A-429A
View details for Web of Science ID 000707188002114
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GLOBAL PREVALENCE OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IN CHILDREN AND ADOLESCENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
WILEY. 2021: 1012A
View details for Web of Science ID 000707188005049
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GALAD SCORE IMPROVES EARLY DETECTION OF HCC PRIOR TO THE DIAGNOSIS OF HCC: A PHASE 3 BIOMARKER VALIDATION STUDY
WILEY. 2021: 92A-93A
View details for Web of Science ID 000707188000139
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OPTIMIZING HEPATITIS B VIRUS SCREENING IN THE UNITED STATES USING A SIMPLE DEMOGRAPHICS-BASED MODEL
WILEY. 2021: 461A-462A
View details for Web of Science ID 000707188002166
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ON-TREATMENT GAMMA-GLUTAMYL TRANSFERASE PREDICTS THE DEVELOPMENT OF HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B PATIENTS
WILEY. 2021: 440A-441A
View details for Web of Science ID 000707188002131
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RENAL OUTCOMES IN POST-LIVER TRANSPLANT RECIPIENTS TREATED WITH TENOFOVIR ALAFENAMIDE COMPARED WITH TENOFOVIR DISOPROXIL FUMARATE AND ENTECAVIR
WILEY. 2021: 492A-493A
View details for Web of Science ID 000707188002212
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THE INCIDENCE OF HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B VIRUS INFECTION SUBJECTS WITH CIRRHOSIS NOT MEETING CURRENT TREATMENT GUIDANCE
WILEY. 2021: 500A-501A
View details for Web of Science ID 000707188002225
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SEVERE HEPATITIS FLARE AND RELATED MORTALITY AFTER DISCONTINUATION OF ORAL ANTIVIRAL TREATMENT IN PATIENTS WITH CHRONIC HEPATITIS B: A POPULATION-BASED STUDY
WILEY. 2021: 18A
View details for Web of Science ID 000707188000024
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REDUCED HEPATOCELLULAR CARCINOMA RISK IN STATIN USERS WITH NON-ALCOHOLIC FATTY LIVER DISEASE: A NATIONWIDE US STUDY
WILEY. 2021: 666A
View details for Web of Science ID 000707188003167
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SEVERE ACUTE EXACERBATION AFTER CESSATION OF NUCLEOS(T)IDE ANALOGS FOR CHRONIC HEPATITIS B: A REAL-WORLD STUDY OF ROUTINE PRACTICE
WILEY. 2021: 495A
View details for Web of Science ID 000707188002216
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CHANGES IN SERUM LEVEL OF RHEUMATOID FACTOR FOLLOWING ERADICATION OF HEPATITIS C VIRUS INFECTION BY INTERFERON-BASED OR INTERFERON-FREE REGIMENS
WILEY. 2021: 563A-564A
View details for Web of Science ID 000707188002333
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REAL-WORLD EFFECTIVENESS AND SAFETY OF INTERFERON-FREE DAAS FOR 14,676 HEPATITIS C (CHC) PATIENTS WITH GENOTYPES 1, 2, 3, 4 AND 6: A MULTINATIONAL STUDY
WILEY. 2021: 579A-581A
View details for Web of Science ID 000707188003019
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GLOBAL NAFLD PREVALENCE NOW AND IN THE FUTURE- A META-ANALYSIS WITH TREND AND FORECASTING
WILEY. 2021: 1011A-1012A
View details for Web of Science ID 000707188005048
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ENTECAVIR VERSUS TENOFOVIR DISOPROXIL FUMARATE FOR SEROCLEARANCE OF HEPATITIS B SURFACE ANTIGEN IN AN INTERNATIONAL REAL-WORLD COHORT
WILEY. 2021: 434A-436A
View details for Web of Science ID 000707188002124
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DECLINING HBV IMMUNITY FOLLOWING HBV VACCINATION DURING CHILDHOOD/ADOLESCENCE AND AMNESTIC RESPONSE RATES TO BOOSTER: A SYSTEMATIC REVIEW AND META-ANALYSIS.
WILEY. 2021: 451A
View details for Web of Science ID 000707188002148
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CHANGE OF PREDICTIVE ABILITY IN NON-INVASIVE FIBROSIS MARKERS AMONG ASIAN NON-ALCOHOLIC FATTY LIVER DISEASE BY AGE, OBESITY, AND A PRESENCE OF TYPE 2 DIABETES
WILEY. 2021: 936A-937A
View details for Web of Science ID 000707188004278
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ALT LEVELS IN HEPATITIS B PATIENTS WITH CONCURRENT FATTY LIVER DISEASE: A US NATIONWIDE STUDY
WILEY. 2021: 444A
View details for Web of Science ID 000707188002137
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TREATMENT EVALUATION, TREATMENT ELIGIBILITY, AND ANTIVIRAL THERAPY AMONG ASIAN AND NON-ASIAN PATIENTS WITH CHRONIC HEPATITIS B (CHB)
WILEY. 2021: 467A-468A
View details for Web of Science ID 000707188002177
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COMPARATIVE DIAGNOSTIC PERFORMANCE OF NONINVASIVE TESTS FOR NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AND ADVANCED FIBROSIS: A UNITED STATES POPULATION-BASED STUDY IN 2017-2018
WILEY. 2021: 942A-943A
View details for Web of Science ID 000707188004285
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DISPARITIES IN CIRRHOSIS-RELATED MORTALITY AMONG URBAN AND RURAL AREAS IN THE UNITED STATES: A POPULATION-BASED STUDY FROM 1999-2019
WILEY. 2021: 117A-118A
View details for Web of Science ID 000707188000176
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LONG-TERM OVERALL AND RECURRENCE-FREE SURVIVAL FOLLOWING CURATIVE SURGICAL RESECTION FOR HEPATOCELLULAR CARCINOMA IN THE RECENT DECADE: A META-ANALYSIS OF 110 STUDIES AND 82,392 PATIENTS
WILEY. 2021: 655A-656A
View details for Web of Science ID 000707188003148
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UTILIZATION AND OUTCOMES OF HEPATITIS B-POSITIVE GRAFTS IN ORTHOTOPIC LIVER TRANSPLANTATION (OLT) IN THE UNITED STATES, 1987-2020
WILEY. 2021: 919A-920A
View details for Web of Science ID 000707188004251
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OVERALL (OS) AND RECURRENCE-FREE SURVIVAL (RFS) FOLLOWING SURGICAL RESECTION FOR HEPATOCELLULAR CARCINOMA (HCC) WITH MACROVASCULAR INVASION (MVI): A META-ANALYSIS OF 40 STUDIES AND 8,218 PATIENTS
WILEY. 2021: 861A
View details for Web of Science ID 000707188004154
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Provider Perspectives on HCC Surveillance in Patients With Cirrhosis: Community Provider Perspectives Matter
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
2021; 19 (9): 1991
View details for Web of Science ID 000685953000044
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Impact of non-alcoholic steatohepatitis (NASH) case definition on population characteristics identified in a US claims database
WILEY. 2021: 30-31
View details for Web of Science ID 000687807300062
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Characteristics and Survival Outcomes of Hepatocellular Carcinoma Developed After HCV SVR
WILEY. 2021: 66
View details for Web of Science ID 000688499100098
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The incidence rates of hepatobiliary diseases among non-alcoholic steatohepatitis patients stratified by fibrosis-4 (FIB-4) index for liver fibrosis
WILEY. 2021: 360-361
View details for Web of Science ID 000687807300733
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Characteristics and Survival Outcomes of Hepatocellular Carcinoma Developed after HCV SVR.
Cancers
2021; 13 (14)
Abstract
The clinical presentation and survival of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) eradication as compared to HCC in viremic patients are not well characterized. We aimed to investigate the characteristics and survival between HCV patients with and without viremia at HCC diagnosis.: We retrospectively analyzed overall survival outcomes in 1389 HCV-related HCC patients, including 301 with HCC developed after HCV eradication (post-SVR HCC) and 1088 with HCV viremia at HCC diagnosis (viremic HCC). We also evaluated overall survival in the two groups using propensity score-matching methods.: At HCC diagnosis, post-SVR HCC patients were older, less obese, less likely cirrhotic, with better liver function, lower alfa-fetoprotein levels, earlier BCLC stages, and higher rate of treatment with surgery. Overall, post-SVR HCC patients had higher median survival than viremic patients (153.3 vs. 55.6 months, p < 0.01), but post-SVR HCC was not independently associated with survival on multivariate analysis (adjusted HR: 1.05, 95% CI: 0.76-1.47). However, on sub-analysis, viremic HCC patients who subsequently received anti-viral treatment and achieved SVR had higher median survival than post-SVR HCC patients (p < 0.01). Viremic HCC with subsequent SVR was also significantly associated with lower mortality as compared to post-SVR HCC (adjusted HR: 0.18, 95% CI: 0.11-0.29). In addition, we observed similar findings in our analysis of the propensity score-matched cohorts.: The advantages in clinical and tumor characters at HCC diagnosis determined the better overall survival of post-SVR HCC patients; however, HCV eradication after HCC development was also associated with improved survival.
View details for DOI 10.3390/cancers13143455
View details for PubMedID 34298669
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Incidence of hepatic outcomes in patients with cirrhosis due to primary biliary cholangitis: A population-based epidemiology study
ELSEVIER. 2021: S434
View details for Web of Science ID 000667753800386
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Comorbidity and healthcare utilization burden of patients diagnosed with non-alcoholic steatohepatitis based on fibrosis-4 score severity
ELSEVIER. 2021: S577
View details for Web of Science ID 000667753801155
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Proportion, characteristics, and outcome of chronic hepatitis B who are 'linked to care' in Korea: A nationwide retrospective longitudinal study
ELSEVIER. 2021: S675
View details for Web of Science ID 000667753801316
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Characteristics and Survival Outcomes of Hepatocellular Carcinoma Developed After HCV SVR
ELSEVIER. 2021: S780-S781
View details for Web of Science ID 000667753802144
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Incidence rates of hepatobiliary outcomes among patients with non-alcoholic steatohepatitis based on fibrosis-4 score severity at baseline
ELSEVIER. 2021: S566-S567
View details for Web of Science ID 000667753801141
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A population-based US study of hepatitis C diagnosis rate.
European journal of gastroenterology & hepatology
2021
Abstract
BACKGROUND: Underdiagnosis of HCV infection may hinder the obtainment of 2030 elimination goal.OBJECTIVE: To estimate the pre-DAA HCV diagnosis rate to inform future public health effort.METHODS: Data were obtained from three nationwide databases (Truven Health MarketScan Research Database 2007-2014, US Census Bureau 2012-2016 and NHANES 2007-2014). HCV diagnosis was defined with either one inpatient or two outpatient HCV International Classification of Disease 9 codes, providing the number of patients with diagnosed HCV (Truven). US Census Bureau data were used for age- and sex-standardization. We derived the total (diagnosed and undiagnosed) HCV infection using the NHANES database. To determine the rate and number of undiagnosed HCV, we subtracted diagnosed HCV burden (Truven) from the total HCV burden (NHANES).RESULTS: Of the 198 073 302 privately insured Americans, 1.49% (2 951 490 persons) had HCV infection. However, only 362 672 (12.29%) persons were diagnosed with HCV, leaving 2 588 818 (87.71%) undiagnosed. About two-third (68.04%) and one-third (33.04%) of diagnosed HCV patients had HCV RNA or genotype tests overall, with even lower rates for the ≥65 age group, respectively.CONCLUSION: In the pre-DAA era, only 12% of insured Americans with HCV were diagnosed. While this grim statistic is expected to rise, much more effort is needed to enhance the HCV care cascade.
View details for DOI 10.1097/MEG.0000000000002149
View details for PubMedID 33867444
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Predictors of Outcomes of Patients Referred to a Transplant Center for Urgent Liver Transplantation Evaluation.
Hepatology communications
2021; 5 (3): 516-525
Abstract
Liver transplantation (LT) is definitive treatment for end-stage liver disease. This study evaluated factors predicting successful evaluation in patients transferred for urgent inpatient LT evaluation. Eighty-two patients with cirrhosis were transferred for urgent LT evaluation from January 2016 to December 2018. Alcohol-associated liver disease was the common etiology of liver disease (42/82). Of these 82 patients, 35 (43%) were declined for LT, 27 (33%) were wait-listed for LT, 5 (6%) improved, and 15 (18%) died. Psychosocial factors were the most common reasons for being declined for LT (49%). Predictors for listing and receiving LT on multivariate analysis included Hispanic race (odds ratio [OR], 1.89; P = 0.003), Asian race (OR, 1.52; P = 0.02), non-Hispanic ethnicity (OR, 1.49; P = 0.04), hyponatremia (OR, 1.38; P = 0.04), serum albumin (OR, 1.13; P = 0.01), and Model for End-Stage Liver Disease (MELD)-Na (OR, 1.02; P = 0.003). Public insurance (i.e., Medicaid) was a predictor of not being listed for LT on multivariate analysis (OR, 0.77; P = 0.02). Excluding patients declined for psychosocial reasons, predictors of being declined for LT on multivariate analysis included Chronic Liver Failure Consortium (CLIF-C) score >51.5 (OR, 1.26; P = 0.03), acute-on-chronic liver failure (ACLF) grade 3 (OR, 1.41; P = 0.01), hepatorenal syndrome (HRS) (OR, 1.38; P = 0.01), and respiratory failure (OR, 1.51; P = 0.01). Predictors of 3-month mortality included CLIF-C score >51.5 (hazard ratio [HR], 2.52; P = 0.04) and intensive care unit (HR, 8.25; P < 0.001). Conclusion: MELD-Na, albumin, hyponatremia, ACLF grade 3, HRS, respiratory failure, public insurance, Hispanic race, Asian race, and non-Hispanic ethnicity predicted liver transplant outcome. Lack of psychosocial support was a major reason for being declined for LT. The CLIF-C score predicted being declined for LT and mortality.
View details for DOI 10.1002/hep4.1644
View details for PubMedID 33681683
View details for PubMedCentralID PMC7917272
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Treatment eligibility in hepatitis B: a call for better linkage to optimal care
LANCET GASTROENTEROLOGY & HEPATOLOGY
2021; 6 (3): 160
View details for Web of Science ID 000632023300009
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Chronic hepatitis, osteoporosis, and men: under-recognised and underdiagnosed
LANCET DIABETES & ENDOCRINOLOGY
2021; 9 (3): 141
View details for Web of Science ID 000629808100010
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Differential Characteristics and Outcomes of Asian and non-Asian Patients with HBV-related Hepatocellular Carcinoma.
Liver international : official journal of the International Association for the Study of the Liver
2021
Abstract
The epidemiology of hepatitis B virus (HBV) infection differs between Asians and non-Asians, but little is known regarding the effect of ethnicity on outcomes of HBV-related hepatocellular carcinoma (HCC). We aim to characterize the presentation and survival outcomes in Asian and non-Asian patients with HBV-related HCC.We analyzed the baseline characteristics and long-term survival of 613 Asian and 410 non-Asian patients with HBV-related HCC from three U.S. and one Spanish center.Overall, non-Asian patients were more likely to have HIV or hepatitis C co-infection, cirrhosis, decompensated liver disease and advanced BCLC stage (all P≤0.04). Compared with Asians, non-Asians were more likely to be listed for transplantation (P<0.0001) and undergo HCC treatment with curative intent (P=0.003). Propensity-score matching on HCC diagnosis year, sex, and age was performed to balance the two groups for survival analysis and yielded 370 pairs of patients. There was no significant difference in survival overall (P=0.43) and among patients with cirrhosis (P=0.57). Among patients without cirrhosis, non-Asians had poorer 5-year survival compared with Asians (37.6% versus 53.7%, P=0.01), and was associated with poorer survival after adjusting for age, gender, diabetes, alcohol, co-infections, diagnosis date, antiviral therapy, BCLC stage and HCC treatment (adjusted HR 2.01 [95% CI 1.07-3.74], P=0.03).Among HBV-related HCC patients, non-Asians presented with more advanced BCLC stage compared to Asians. Non-Asian ethnicity was independently associated with twice the risk of mortality among patients without cirrhosis, but not among those with cirrhosis. Additional studies are needed to clarify this disparity.
View details for DOI 10.1111/liv.14877
View details for PubMedID 33713386
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Cost-effectiveness of HCC Surveillance among HCV patients after Sustained Virological Response with Direct-acting Antivirals.
Liver international : official journal of the International Association for the Study of the Liver
2021
Abstract
We read with interest the study "Hepatocellular carcinoma risk in hepatitis C stage-3 fibrosis after sustained virological response with direct-acting antivirals" by Dr Sánchez-Azofra and colleagues (1). The authors studied 506 hepatitis C virus (HCV) patients with sustained virological response (SVR) after direct-acting antivirals, all included patients had stage 3 fibrosis. Dr Sánchez-Azofra and colleagues found that the annual incidence of primary liver tumors in this cohort was 0.47%. Based on these findings, the authors concluded that the incidence of primary liver tumors among F3 fibrosis patients with HCV who had achieved SVR was lower than the 1.5% annual cut-off considered cost effective for hepatocellular carcinoma (HCC) surveillance (2). We congratulate the authors on studying this clinically relevant topic. However, we have several concerns regarding their conclusions.
View details for DOI 10.1111/liv.15072
View details for PubMedID 34587343
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Quantify the Risk of Severe Hepatitis B Flare in a Real World Where Cessation of Nucleos(t)ide Analog is Routinely Practiced.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2021
View details for DOI 10.1016/j.cgh.2021.09.032
View details for PubMedID 34587550
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Letter: hepatocellular carcinoma risk in patients with non-selective beta blockers.
Alimentary pharmacology & therapeutics
2021; 54 (8): 1093-1094
View details for DOI 10.1111/apt.16576
View details for PubMedID 34564887
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HBV-related Hepatocellular Carcinoma: A Call to Improve Surveillance and Linkage to Care.
Liver international : official journal of the International Association for the Study of the Liver
2021
Abstract
In our recent multi-center study, we found that non-Asians with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) were more likely to present with decompensated and advanced disease compared with Asians 1 . However, non-Asians were more likely to undergo curative HCC treatment versus Asians. Among patients without cirrhosis, non-Asians had a poorer 5-year survival versus Asians (38% versus 54%). The letter from Dr Jia and colleagues raises some points that merit discussion 2 .
View details for DOI 10.1111/liv.15023
View details for PubMedID 34309185
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Body weight changes in treated hepatitis B patients switching to tenofovir alafenamide☆.
Journal of the Formosan Medical Association = Taiwan yi zhi
2021
Abstract
Switching to a tenofovir alafenamide (TAF)-containing regimen has been reported to be associated with body weight gain in human immunodeficiency virus-infected subjects. We aimed to investigate the body weight change and virological, hepatic, and renal outcomes of TAF switching among chronic hepatitis B (CHB) patients.This retrospective study included 121 CHB patients who were switched to TAF after >12 months of treatment with another nucleot(s)ide analog (NUC). All patients were monitored for 12 months.The cohort was mostly Asian (96.7%) with a mean age of 55 years, 72% male, 14% cirrhosis, 21% HBeAg positive, and 75% with prior use of tenofovir disoproxil fumarate. At 12 months after TAF switching, their body weight significantly increased from 66.4 ± 11.8 to 67.8 ± 12.3 kg (p < 0.001), and 21.1% of the subjects had a ≥5% weight gain. Patients without diabetes or hypertension were more likely to have a body weight gain. Meanwhile, the complete viral suppression rate increased significantly from 89.3% to 96.2% (p = 0.016). The rate of alanine aminotransferase normalization also increased significantly from 71.1% to 87.6% (p < 0.001) by local criteria and from 58.7% to 70.2% (p = 0.029) by AASLD criteria. The mean eGFR (mL/min/1.73 m2) did not change (88.2 ± 18.8 vs. 87.2 ± 17.5, p = 0.28). However, for the subgroup with GFR <90 at TAF switching, there was a significant improvement in eGFR (72.9 ± 12.0 vs. 75.7 ± 14.2, p = 0.027).In real-world NUC-experienced CHB patients, unexpected body weight gain was observed after TAF switching. The mechanism needs to be investigated in the future.
View details for DOI 10.1016/j.jfma.2021.09.009
View details for PubMedID 34625346
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Antiviral kinetics of tenofovir alafenamide and tenofovir disoproxil fumarate over 24 weeks in women of childbearing potential with chronic HBV.
PloS one
2021; 16 (5): e0251552
Abstract
Use of tenofovir disoproxil fumarate (TDF) improves patient outcomes in preventing mother-to-child transmission (pMTCT) of the hepatitis B virus (HBV) in mothers with chronic HBV and high viral loads. Given the lack of data for tenofovir alafenamide (TAF) in pMTCT, rates of early viral suppression with TAF and TDF were evaluated in women of childbearing potential (WOCBP) participating in 2 randomized, double-blind, Phase 3 studies in chronic HBV.In a patient subset meeting WOCBP criteria and with baseline HBV DNA >200,000 IU/mL, rates of viral suppression with TAF or TDF in achieving the target of HBV DNA <200,000 IU/mL at weeks 12 and 24 were assessed. Multivariate logistic regression was used to identify factors predictive of failure to suppress HBV DNA to the target level.In 275 of 1298 (21%) patients meeting WOCBP criteria with high viral load, 93% and 96% had HBV DNA <200,000 IU/mL at weeks 12 and 24, respectively. Results for TAF (n = 194) vs TDF (n = 81) treatment were similar at weeks 12 and 24 (94% vs. 90% and 97% vs. 93%), respectively. High baseline HBV DNA level, genotype D infection, and prior interferon (week 24 only) were predictive of failure to achieve the target level. Both treatments were well tolerated with TAF showing less impact on renal and bone parameters.In WOCBP with high VL, no differences were found between TAF and TDF in reducing HBV DNA to levels associated with lower transmission risk. These data support ongoing studies of TAF for pMTCT.
View details for DOI 10.1371/journal.pone.0251552
View details for PubMedID 33984038
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Pooling data to assess risks and benefits of discontinuing nucleos(t)ide analogs in patients with chronic hepatitis B: challenges and opportunities.
Gut
2021
View details for DOI 10.1136/gutjnl-2021-326232
View details for PubMedID 34670810
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One-year Fibrosis-4 index helps identify minimal HCC risk in non-cirrhotic chronic hepatitis B patients with antiviral treatment.
Hepatology international
2021
Abstract
Fibrosis-4 (FIB-4) index is a HCC predictor in chronic hepatitis B (CHB) patients. However, little is known about whether FIB-4 helps identify non-cirrhotic CHB patients with minimal HCC risk after prolonged nucleos(t)ide analogue (NA) therapy.A total of 1936 ethnically diverse, non-cirrhotic CHB patients were enrolled in this retrospective multi-national study. All patients received prolonged NA treatment, including entecavir and tenofovir disoproxil fumarate. We explored whether FIB-4 cutoff of 1.30, a marker indicative of mild fibrosis severity, could stratify HCC risks in these patients.A total of 48 patients developed HCC after a mean follow-up of 6.98 years. FIB-4 level at 1 year after treatment (1-year FIB-4) was shown to be associated with HCC development and was superior to pre-treatment FIB-4 value. When patients were stratified by 1-year FIB-4 of 1.30, the high FIB-4 group was at an increased HCC risk compared to the low FIB-4 group, with a hazard ratio of 4.87 (95% confidence interval: 2.48-9.55). Multivariable analysis showed that sex and 1-year FIB-4 were independent predictors, with none of the 314 female patients with low 1-year FIB-4 developing HCC. Finally, 1-year FIB-4 of 1.30 consistently stratified HCC risks in patients with low PAGE-B score, a score composed of baseline age, sex and platelet count, and the annual incidence rate of HCC was 0.11% in those with PAGE-B < 10 + 1-year FIB-4 < 1.30.In non-cirrhotic CHB patients receiving prolonged NA therapy, 1-year FIB-4 < 1.30 is useful for identifying those with minimal HCC risk by combining with female sex or low PAGE-B score.
View details for DOI 10.1007/s12072-020-10124-z
View details for PubMedID 33547557
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Severe Acute Exacerbation after Cessation of Nucleos(t)ide Analog for Chronic Hepatitis B: a Real-world Study of Routine Practice.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2021
View details for DOI 10.1016/j.cgh.2021.08.037
View details for PubMedID 34464721
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Treatment eligibility in hepatitis B: a call for better linkage to optimal care.
The lancet. Gastroenterology & hepatology
2021; 6 (3): 160
View details for DOI 10.1016/S2468-1253(20)30391-5
View details for PubMedID 33581753
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Sarcopenic Obesity in Non-Alcoholic Fatty Liver Disease-The Union of Two Culprits.
Life (Basel, Switzerland)
2021; 11 (2)
Abstract
Non-alcoholic fatty liver disease (NAFLD) continues to rise and has become the most common cause of chronic liver disease among all ages and ethnicities. Metabolic disorders, such as obesity and insulin resistance, are closely associated with sarcopenia and NAFLD. Sarcopenic obesity is a clinical disorder characterized by the simultaneous loss of skeletal muscle and gain of adipose tissue. It is associated with worse outcomes in individuals with NAFLD. It is projected that NAFLD and sarcopenia will rise as the prevalence of obesity continues to increase at an unparallel rate. Recently, sarcopenia and sarcopenic obesity have gained considerable interest, but we still lack a well-defined definition and a management approach. Therefore, it is imperative to continue shining the light on this topic and better understand the underlying mechanism as well as treatment options. In this review article, we aimed to address the pathophysiology, impact, and outcomes of sarcopenic obesity on NAFLD.
View details for DOI 10.3390/life11020119
View details for PubMedID 33557355
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Improved survival and high sustained virologic response with DAA therapy in patients with HCV-related HCC: A call for expanded use.
Journal of gastroenterology and hepatology
2021
View details for DOI 10.1111/jgh.15420
View details for PubMedID 33528034
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Defining age related thresholds for ALT and the risk of confounders.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2021
View details for DOI 10.1016/j.cgh.2021.02.029
View details for PubMedID 33618026
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Letter to the Editor: HCC surveillance in cirrhosis patients: Is the real-world situation even worse than reported?
Hepatology (Baltimore, Md.)
2021
Abstract
We read with interest the recent systematic review and meta-analysis by Wolf and colleagues, which reported a pooled estimate for hepatocellular carcinoma (HCC) surveillance of 24.0% for patients with cirrhosis (1). We applaud the authors for performing this comprehensive study on a topic that is not only relevant clinically but also timely, especially with the increasing burden of cirrhosis in recent decades.
View details for DOI 10.1002/hep.31760
View details for PubMedID 33617661
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Epidemiology, pathogenesis, diagnosis, surveillance, and management of hepatocellular carcinoma associated with vascular liver disease.
The Kaohsiung journal of medical sciences
2021
Abstract
Vascular liver disease (VLD) presents special challenges in the diagnosis, surveillance, and treatment of hepatocellular carcinoma (HCC). HCC arising in the setting of vascular liver disease is often thought to be due to elevated hepatic arterial blood flow, rather than progressive fibrosis from chronic inflammation as with other chronic liver conditions such as viral hepatitis, autoimmune, and metabolic liver diseases. Vascular alteration inherent in VLD often impedes HCC non-invasive diagnosis and loco-regional treatment that depend on vascular properties found in typical liver environment. Benign and pre-malignant liver nodules such as focal nodular hyperplasia and hepatocellular adenoma are also more common in certain VLDs, further adding to surveillance and diagnostic challenges. In this synopsis, we aimed to review available literature on the epidemiology, surveillance, diagnosis, and management of HCC in patients with VLD and specifically Budd-Chiari syndrome, congenital porto-systemic shunts, Fontan-associated liver disease, hereditary hemorrhagic telangiectasia.
View details for DOI 10.1002/kjm2.12368
View details for PubMedID 33655707
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Evaluation of ethnic influence in the application of a hepatocellular carcinoma predictive model for chronic hepatitis C.
Journal of medical virology
2021
Abstract
Currently, there is no well-established algorithm predicting HCC development in untreated HCV patients. We aimed to validate an algorithm (REVEAL-HCV: age, AST, ALT, HCV RNA, HCV genotype, and cirrhosis) developed in Taiwanese patients.We analyzed 1,381 (50.1% White, 14.7% Hispanic, 13.8% Asian of diverse origin, and 7.8% African-American) adult treatment-naïve HCV patients (no viral co-infection, no HCC within 6 months) at 4 U.S. and one Hong Kong centers (11/1994-10/2017).Compared to the non-Asian cohort, the Asian cohort had higher percentage of patients in the low-risk group (46.1% vs. 26.1%) and lower percentage in the high-risk group (12.0% vs. 20.3%, p<0.01). Overall, 5-year HCC incidence were 1.75%, 4.71%, and 24.4% for low, medium and high-risk patients, respectively (p<0.0001). For the overall cohort, AUROC for HCC prediction were 0.83 (95% CI: 0.72-0.93), 0.82 (95% CI: 0.75-0.88), and 0.84 (95% CI: 0.77-0.89) for 1-year, 3-year and 5-year HCC risk, respectively. There was slightly lower AUROC for Asian compared to the non-Asian cohort at 3 years (0.75 vs. 0.83) and 5 years (0.78 vs. 0.84), though this was not statistically significant. In multivariable analysis, we found male sex, presence of metabolic syndrome as well as the risk score categories to be independently associated with HCC but not ethnicity.The REVEAL-HCV risk score has good validity for both Asian and non-Asian populations. Further studies should consider additional factors such as sex, metabolic syndrome and treatment status. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/jmv.27168
View details for PubMedID 34219250
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Resubclassification and clinical management for Barcelona Clinic Liver Cancer Stage C hepatocellular carcinoma.
Hepatology international
2021
Abstract
Patients with Barcelona Clinic Liver Cancer Stage C (BCLC-C) hepatocellular carcinoma (HCC) can be markedly heterogeneous with varying prognosis. This study aims to establish a new subclassification system for BCLC-C HCC to better predict overall survival (OS) and to tailor therapy.We retrospectively studied 1856 BCLC-C HCC patients between 2006 and 2017 from E-Da Hospital, Taiwan (n = 622, training cohort), Kaohsiung Medical University Hospital, Taiwan (n = 774, Taiwan validation cohort), and Stanford University Medical Center and Mayo Clinic (United States), Hanyang University Hospital (South Korea), and Ogaki Municipal Hospital (Japan) to make up the international validation cohort (n = 460).In the training cohort, significant factors associated with OS were largest tumor size ≥ 10 cm, extrahepatic spread, macrovascular invasion, and Child-Pugh class, which provided the basis, together with aged ≥ 75 years, for the substaging, through C0 to C4, of BCLC-C HCC patients. The median OS for substages C0, C1, C2, C3, and C4 were 43.8 months (95% confidence interval [CI] 32.2-53.7), 20.6 months (CI 14.1-25.9), 11.5 months (CI 8.02-14.1), 5.7 months (CI 4.02-5.98), and 3.2 months (CI 2.41-3.59), respectively, (p < 0.05). OS remained distinct among the proposed substages in the Taiwan validation cohort as well as the international validation cohort. The distinction between the substages persisted in subgroup analysis by substage combined with treatment modality. In substage C0-C3, patients receiving HCC curative therapy had a significantly better median OS than those receiving sorafenib or palliative therapy.Our new substaging system provides more precise prognosis to better tailor therapy for BCLC-C HCC patients.
View details for DOI 10.1007/s12072-021-10169-8
View details for PubMedID 34008091
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Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF: a REAL-B study.
Hepatology international
2021
Abstract
We aimed to compare the longitudinal changes in estimated glomerular filtration rate (eGFR) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF).This is a retrospective study of 6189 adult treatment-naïve CHB patients initiated therapy with TDF (n = 2482) or ETV (n = 3707) at 25 international centers using multivariable generalized linear modeling (GLM) to determine mean eGFR (mL/min/1.73 m2) and Kaplan-Meier method to estimate incidence of renal impairment (≥ 1 chronic kidney disease [CKD] stage worsening). We also examined above renal changes in matched ETV and TDF patients (via propensity score matching [PSM] on age, sex, diabetes mellitus [DM], hypertension [HTN], cirrhosis, baseline eGFR, and follow-up duration).In the overall cohort (mean age 49.7 years, 66.2% male), the baseline eGFR was higher for TDF vs. ETV group (75.9 vs. 74.0, p = 0.009). PSM yielded 1871 pairs of ETV or TDF patients with baseline eGFR ≥ 60 and 520 pairs for the eGFR < 60 group. GLM analysis of the overall (unmatched) cohort and PSM cohorts revealed lower adjusted mean eGFRs in TDF (vs. ETV) patients (all p < 0.01) during 10 years of follow-up. Among PSM eGFR ≥ 60 patients, the 5-year cumulative incidences of renal impairment were 42.64% for ETV and 48.03% for TDF (p = 0.0023). In multivariable Cox regression, TDF vs. ETV (adjusted HR 1.26, 95% CI 1.11-1.43) was associated with higher risk of worsening renal function.Over the 10-year study follow-up, compared to ETV, TDF was associated with a lower mean eGFR and higher incidence of renal impairment.
View details for DOI 10.1007/s12072-021-10271-x
View details for PubMedID 34822056
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Incorporating fatty liver disease in multidisciplinary care and novel clinical trial designs for patients with metabolic diseases.
The lancet. Gastroenterology & hepatology
2021
Abstract
With the global epidemics of obesity and associated conditions, including type 2 diabetes, metabolic dysfunction-associated fatty liver disease, chronic kidney disease, hypertension, stroke, cardiovascular disease, osteoporosis, cancer, and cognitive changes, the prevalence of multimorbidity is rapidly increasing worldwide. In this Review, a panel of international experts from across the spectrum of metabolic diseases come together to identify the challenges and provide perspectives on building a framework for a virtual primary care-driven, patient-centred, multidisciplinary model to deliver holistic care for patients with metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. We focus on clinical care and innovative trial design for metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. This work represents a call to action to promote collaboration and partnerships between stakeholders for improving the lives of people with, or at risk of, metabolic dysfunction-associated fatty liver disease and associated metabolic diseases.
View details for DOI 10.1016/S2468-1253(21)00132-1
View details for PubMedID 34265276
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Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.
Annals of surgery
2021; 274 (4): 613-620
Abstract
To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT).In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate.The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS).Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01).The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.
View details for DOI 10.1097/SLA.0000000000005070
View details for PubMedID 34506316
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Twelve-month post-treatment parameters are superior in predicting hepatocellular carcinoma in patients with chronic hepatitis B.
Liver international : official journal of the International Association for the Study of the Liver
2021
Abstract
There are currently several prediction models for hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) receiving oral antiviral therapy. However, most models are based on pre-treatment clinical parameters. The current study aimed to develop a novel and practical prediction model for HCC by using both pre- and post-treatment parameters in this population.We included two treatment-naïve CHB cohorts who were initiated on oral antiviral therapies: the derivation cohort (n=1,480, Korea prospective SAINT cohort) and the validation cohort (n=426, the US retrospective Stanford Bay cohort). We employed logistic regression, decision tree, lasso regression, support vector machine, and random forest algorithms to develop the HCC prediction model and selected the most optimal method.We evaluated both pre-treatment and the 12-month clinical parameters on-treatment and found the 12-month on-treatment values to have superior HCC prediction performance. The lasso logistic regression algorithm using the presence of cirrhosis at baseline and alpha-fetoprotein and platelet at 12 months showed the best performance (AUROC=0.843 in the derivation cohort. The model performed well in the external validation cohort (AUROC=0.844) and better than other existing prediction models including the APA, PAGE-B, and GAG models (AUROC=0.769 to 0.818).We provided a simple-to-use HCC prediction model based on presence of cirrhosis at baseline and two objective laboratory markers (AFP and platelets) measured 12 months after antiviral initiation. The model is highly accurate with excellent validation in an external cohort from a different country (AUROC 0.844). (Clinical trial number: KCT0003487).
View details for DOI 10.1111/liv.14820
View details for PubMedID 33550661
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NASH/liver fibrosis prevalence and incidence of non-liver comorbidities among people with NAFLD and incidence of NAFLD by metabolic comorbidites: Lessons from South Korea.
Digestive diseases (Basel, Switzerland)
2021
Abstract
NAFLD incidence, NASH prevalence, NAFLD fibrosis prevalence, incidence of metabolic comorbidities, as well as mortality data in the NAFLD population remain limited.We used a meta-analytic approach to "stage" NAFLD among the Korean population.We searched PubMed, Embase, Cochrane Library, and KoreaMed from inception until June 29, 2019 and calculated pooled estimates via random-effects model.We screened 1,485 studies and analyzed 191 eligible studies: 179 (3,556,579 participants) for NAFLD prevalence and outcome analysis and 32 (1,089,785 participants) for NAFLD incidence analysis. NAFLD prevalence was 31.46% overall and 50-60% in those with metabolic risks. The incidence (per 1,000 person-years) of NAFLD was 42.8 overall and 70-77% in those with metabolic risk. The incidence (per 1,000 person-years) of new onset T2DM, hypertension, cardiovascular disease, and chronic kidney disease were found to be 16.9, 47.9, 100.6, and 13.9, respectively. From biopsy data, 30.21% of the NAFLD population had moderate-to-severe steatosis (9 studies, 2,461 participants) and 52.27% had NASH (7 studies, 1,168 participants); 85.41% had fibrosis < stage 2 (8 studies, 1,995 participants). All-cause mortality was 2.6 (1.3 if without malignancy) per 1,000 person-years.The overall prevalence of NAFLD was 31.46% with an incidence rate of 42.8 per 1000 person-years. NASH prevalence was 52% but <15% had significant fibrosis. The prevalence and incidence of non-liver comorbidities was high especially for cardiovascular disease incidence. The burden of NAFLD is high in Korea. Health policy efforts need to be directed towards reversing the course of NAFLD disease.
View details for DOI 10.1159/000514953
View details for PubMedID 33535211
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Predictors of Outcomes of Patients Referred to a Transplant Center for Urgent Liver Transplantation Evaluation
HEPATOLOGY COMMUNICATIONS
2020
View details for DOI 10.1002/hep4.1644
View details for Web of Science ID 000602465100001
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ALT Levels for Asians With Metabolic Diseases: A Meta-analysis of 86 Studies With Individual Patient Data Validation.
Hepatology communications
2020; 4 (11): 1624-1636
Abstract
The current alanine aminotransferase (ALT) upper limit of normal was defined using selected healthy Caucasian blood donors. Given the global rise in obesity and different body habitus in Asians, we aimed to perform a systematic review and meta-analysis combined with bootstrap modeling and individual patient data validation to estimate the ALT upper threshold for Asians, including the overweight and diabetics. We included studies from PubMed, Embase, and Cochrane database searches that identified individuals without known liver diseases (i.e., viral hepatitis, alcohol, and ultrasound-detected nonalcoholic fatty liver disease). The mean ALT (U/L) was estimated using a random-effects mixed model and upper threshold (95th-percentile value, U/L) via a bootstrap model with 10,000 resamples. We screened 4,995 studies and identified 86 studies that reported ALT values for 526,641 individuals without excessive alcohol intake or known liver diseases, yielding a mean ALT of 19 and ALT upper threshold of 32. The ALT upper threshold was 37 in males versus 31 in females, 39 in overweight versus 28 in normal-weight individuals, and 36 for diabetics versus 33 for nondiabetics. We validated our study level data with individual patient level data in 6,058 individuals from five study centers in Japan. Consistent with our study-level data, we found that the ALT upper threshold in our individual patient data analysis was indeed higher in overweight versus normal-weight individuals (39 vs. 32) and in diabetics versus nondiabetics (42 vs. 33). Conclusion: We provide validated reference ranges for ALT upper threshold derived from Asians without known liver disease, including individuals with ultrasound-detected nonalcoholic fatty liver disease who are normal weight, overweight, nondiabetic, and diabetic, to inform practice.
View details for DOI 10.1002/hep4.1593
View details for PubMedID 33163833
View details for PubMedCentralID PMC7603525
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PRECISE MEDICINE USING A NEW SUBCLASSIFICATION AND CLINICAL MANAGEMENT FOR BARCELONA CLINIC LIVER CANCER STAGE C HEPATOCELLULAR CARCINOMA: A MULTICENTRE STUDY
WILEY. 2020: 96A–97A
View details for Web of Science ID 000574027000134
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INCIDENCE AND PREDICTIVE FACTORS OF HEPATOCELLULAR CARCINOMA (HCC) IN A PROSPECTIVELY FOLLOWED US COHORT OF PATIENTS AT RISK: HEPATOCELLULAR CARCINOMA EARLY DETECTION STRATEGY (HEDS) STUDY
WILEY. 2020: 643A
View details for Web of Science ID 000574027002193
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HCC RISK POST-SVR WITH DAAS IN EAST ASIANS: FINDINGS FROM THE REAL-C COHORT
WILEY. 2020: 34A–36A
View details for Web of Science ID 000574027000047
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VIROLOGIC, BIOCHEMICAL, AND RENAL OUTCOMES OF TREATMENT-NAIVE PATIENTS WITH SEQUENTIAL THERAPY FROM TENOFOVIR DISOPROXIL FUMARATE (TDF) TO TENOFOVIR ALAFENAMIDE (TAF) IN ROUTINE PRACTICE
WILEY. 2020: 498A–499A
View details for Web of Science ID 000574027001270
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DIFFERENTIAL CHARACTERISTICS AND OUTCOMES OF ASIAN AND NON-ASIAN PATIENTS WITH HBV-RELATED HEPATOCELLULAR CARCINOMA
WILEY. 2020: 457A–458A
View details for Web of Science ID 000574027001208
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THE EPIDEMIOLOGY OF NAFLD AND LEAN NAFLD IN JAPAN: A SYSTEMATIC REVIEW AND META-ANALYSIS WITH INDIVIDUAL PATIENT LEVEL DATA AND FORECASTING, 1995-2040
WILEY. 2020: 999
View details for Web of Science ID 000574027004096
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HEPATOCELLULAR CARCINOMA INCIDENCE WITH TENOFOVIR VS ENTECAVIR IN CHRONIC HEPATITIS B: A SYSTEMATIC REVIEW AND META-ANALYSIS
WILEY. 2020: 642A
View details for Web of Science ID 000574027002191
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INCREASED VIRAL SUPPRESSION RATE IN REAL-WORLD CHRONIC HEPATITIS B (CHB) PATIENTS AFTER SWITCH FROM LONG-TERN ENTECAVIR (ETV) THERAPY TO TENOFOVIR ALAFENAMIDE (TAF): A MULTICENTER STUDY
WILEY. 2020: 486A–487A
View details for Web of Science ID 000574027001252
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ELASTOGRAPHY AND LIVER BIOPSY DATA FOR NASH AND FIBROSIS PREVALENCE AMONG SOUTH KOREAN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD): A META-ANALYSIS OF 61 STUDIES AND 27,496 PARTICIPANTS
WILEY. 2020: 964–65
View details for Web of Science ID 000574027004040
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SEQUENTIAL THERAPY WITH TENOFOVIR ALAFENAMIDE (TAF) IN PATIENTS WITH CHRONIC HEPATITIS B (CHB): AN INTERIM ANALYSIS OF AN ONGOING MULTINATIONAL PROSPECTIVE STUDY
WILEY. 2020: 495A–496A
View details for Web of Science ID 000574027001265
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INCIDENCE AND FACTORS ASSOCIATED WITH FUNCTIONAL CURE (HBsAg SEROCLEARANCE) DURING ETV OR TDF THERAPY FOR CHRONIC HEPATITIS B (CHB): AN INTERNATIONAL REAL-WORLD STUDY WITH LONG-TERM FOLLOW-UP
WILEY. 2020: 463A–464A
View details for Web of Science ID 000574027001217
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LONGITUDINAL REAL-WORLD STUDY ON ESTIMATED GLOMERULAR FILTRATION RATE (EGFR) CHANGES IN ENTECAVIR (ETV) VERSUS TENOFOVIR DISOPROXIL FUMARATE (TDF)-TREATED CHRONIC HEPATITIS B (CHB) PATIENTS: A REAL-B STUDY
WILEY. 2020: 17A–18A
View details for Web of Science ID 000574027000022
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THE INCIDENCE OF HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B VIRUS INFECTION SUBJECTS NOT MEETING CRITERIA FOR ANTIVIRAL THERAPY
WILEY. 2020: 472A–473A
View details for Web of Science ID 000574027001230
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HIGH HCV CURE RATES WITH APPROVED INTERFERON-FREE DIRECT ACTING ANTIVIRALS AMONG DIVERSE MAINLAND CHINESE PATIENTS INCLUDING GENOTYPES 3a AND 3b
WILEY. 2020: 532A–533A
View details for Web of Science ID 000574027002011
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Clinical Response to Treatment for Acute Kidney Injury (AKI) in Patients With Cirrhosis
LIPPINCOTT WILLIAMS & WILKINS. 2020: S587–S588
View details for Web of Science ID 000607196703094
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Effects of Cirrhosis and Diagnosis Scenario in Metabolic-Associated Fatty Liver Disease-Related Hepatocellular Carcinoma
HEPATOLOGY COMMUNICATIONS
2020
View details for DOI 10.1002/hep4.1606
View details for Web of Science ID 000574610600001
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ALT Levels for Asians With Metabolic Diseases: A Meta-analysis of 86 Studies With Individual Patient Data Validation
HEPATOLOGY COMMUNICATIONS
2020
View details for DOI 10.1002/hep4.1593
View details for Web of Science ID 000570299500001
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High hepatitis C virus cure rates with approved interferon-free direct-acting antivirals among diverse mainland Chinese patients including genotypes 3a and 3b
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
2020
View details for DOI 10.1111/jgh.15192
View details for Web of Science ID 000555678900001
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Liver Care and Surveillance: The Global Impact of the COVID-19 Pandemic.
Hepatology communications
2020
Abstract
As social distancing and strict stay-at-home orders have been instituted to slow the spread of coronavirus disease 2019 (COVID-19), unintentional outcomes among those with chronic diseases including screening for the lethal hepatocellular carcinoma (HCC) may be occurring. We aimed to describe the changes in liver care before and after COVID-19 restricted access to health care. We obtained data on the number of liver clinic visits, abdominal ultrasound, computed tomography, and magnetic resonance imaging using electronic query or clinic registry at three medical centers in the United States, Japan, and Singapore for the following periods: February 1 to March 14, 2018, 2019, and 2020; and March 15 to May 1, 2018, 2019, and 2020. We performed trend analysis using logistic regression. In total, 14,403 visits were made to the liver clinics at the three centers: 5,900 in 2018, 5,270 in 2019, and 3,233 in 2020. Overall, there were no significant changes in the distribution of males and females between February 1 and May 1 from 2018 to 2020, but there was a lower proportion of seniors ages 65 years and older (P < 0.001). There were significant decreasing trends in the total number of liver clinic visits overall (p-trend = 0.038) and in the subanalysis for chronic hepatitis B, C, and other liver diseases. HCC/cirrhosis visits also dropped from 883 to 538 (39.07% decrease) overall and 665 to 355 (46.62% decrease) for the US site. In addition, there was a significant decreasing trend in the number of abdominal ultrasounds (P-trend = 0.004) and computed tomography/magnetic resonance imaging (P-trend = 0.007) performed overall. Conclusion: Liver clinic visits, hepatoma surveillance, and diagnostic abdominal imaging fell dramatically as social distancing measures were instituted. Care providers must find ways to recall patients for important care monitoring, including HCC surveillance.
View details for DOI 10.1002/hep4.1579
View details for PubMedID 32838107
View details for PubMedCentralID PMC7405084
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Liver Care and Surveillance: The Global Impact of the COVID-19 Pandemic
HEPATOLOGY COMMUNICATIONS
2020
View details for DOI 10.1002/hep4.1579
View details for Web of Science ID 000556933200001
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High hepatitis C virus cure rates with approved interferon-free direct-acting antivirals among diverse mainland Chinese patients including genotypes 3a and 3b.
Journal of gastroenterology and hepatology
2020
Abstract
Globally, China has the highest chronic hepatitis C (CHC) burden, but its real-world direct-acting antiviral (DAA) data are limited. Our aim is to investigate the real-world outcome of China Food and Drug Administration-approved DAA therapies across mainland China including those with genotype (GT) 3.The REAL-C is a multinational real-world interferon-free DAA-treated CHC registry of several mainland China and other Asian centers. We evaluated the sustained virological response rate 12 weeks after end of treatment (SVR12), adverse events, and treatment effect on liver function and fibrosis (fibrosis-4 index).We analyzed 859 DAA-treated CHC patients (6/1/2017-5/30/2019) from 12 mainland China centers (three municipalities and nine provinces): median age 52, 49.9% male, 33.1% cirrhosis, 95% treatment naïve, and 2.5% HBsAg+. The most common GT was GT1b (523, 62.2%), followed by GT2a (156, 18.5%), GT3b (74, 8.8%), GT3a (41, 4.9%), and GT6 (37, 4.4%). SVR12 rates were 98.0% overall (95% confidence interval 96.9-98.8%), 98.1% for GT1b, 96.8% GT2a, 100% GT3a, 97.3% GT3b, and 100% GT6. Baseline cirrhosis and male sex but not prior treatment history, renal dysfunction, age, and GTs were associated with SVR12. For both cirrhotic and non-cirrhotic patients, there were significant improvement in liver function tests, alpha fetoprotein, and fibrosis-4 index with SVR12. Serious adverse events were rare (1.1%) with only nine patients discontinuing therapy prematurely and anemia being the most common adverse event (13.1%, mostly with ribavirin).In real-world Chinese patients with diverse GTs, Chinese Food and Drug Administration-approved interferon-free DAAs were well tolerated, provided high cure rates (98.0% overall) including GT3a/3b, and led to improvement of liver function.
View details for DOI 10.1111/jgh.15192
View details for PubMedID 32840326
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Prevalence of Chronic Hepatitis B Virus Infection in the United States.
The American journal of gastroenterology
2020
Abstract
Chronic hepatitis B virus (HBV) infection represents a major global health problem, affecting an estimated 257-291 million persons worldwide and is associated with substantial morbidity and mortality because of clinical complications, such as liver cirrhosis and hepatocellular carcinoma. Despite existing resources for vaccination, screening, and treatment, the burden of chronic HBV remains significant within the United States (US). Both the World Health Organization (WHO) and US Department of Health and Human Services (DHHS) have articulated formal hepatitis elimination plans, although an updated assessment of the epidemiology and prevalence of chronic HBV is needed to inform these initiatives. The Chronic Liver Disease Foundation (CLDF), a nonprofit 501(c)(3) educational organization dedicated to raising awareness of liver disease, partnered with a panel of leading US hepatologists to conduct an updated literature review to develop a contemporary HBV prevalence range estimate. Panel members researched and evaluated the peer-reviewed literature on HBV prevalence and, in May 2019, discussed their findings during a live HBV epidemiology workshop. The panel proposed an overall estimated prevalence for chronic HBV infection in the US of 1.59 million persons (range 1.25-2.49 million). This review provides a summary of the workshop findings and conclusions, which may serve to inform future initiatives focused on HBV screening and prevention in the US.
View details for DOI 10.14309/ajg.0000000000000651
View details for PubMedID 32483003
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Fatty liver is not independently associated with rates of complete response to oral antiviral therapy in chronic hepatitis B patients.
Liver international : official journal of the International Association for the Study of the Liver
2020
Abstract
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB) are common liver diseases. Concurrent NAFLD may affect antiviral treatment outcomes in CHB patients. The aim of this study is to investigate the impact of NAFLD on complete viral suppression [(CVS), HBV DNA < 20-100 IU/mL] and/or biochemical response [(BR), ALT of ≤ 25 U/L for females; 35 U/L for males] in CHB patients who received oral antiviral therapy.METHODS: A retrospective study of 555 treated CHB patients (187 NAFLD; 368 non-NAFLD) from 2000 to 2016 at a USA medical center. NAFLD was diagnosed by imaging and/or histology after ruling out secondary causes of hepatic steatosis.RESULTS: The majority of patients were male (60.7%), Asian (87.56%), and HBeAg-negative (66.7%). NAFLD patients compared to non-NAFLD were more likely HBeAg negative (74.3% vs. 62.8%, P=0.02), hypertensive (33.2% vs. 22.8%, P=0.009), male (67.4% vs. 57.3%, P=0.02) with a higher mean BMI (25.4±4.3 vs. 23.8±4.0 kg/m2 , P<0.001). Both cohorts achieved similar rates of CVS (86% vs. 88%) and BR (38% vs. 41%) during follow-up of up to 60 months (P>0.05), but NAFLD had higher cumulative rates of CVS+BR, compared with non-NAFLD patients (32.5% vs. 22.8%, P=0.03). In multivariate analyses, NAFLD was not independently associated with CVS and/or BR outcomes. Receipt of entecavir or tenofovir (versus older therapies) and lower baseline HBV DNA or higher ALT were positively associated with achieving CVS or BR.CONCLUSION: Concomitant NAFLD had no impact on the long-term rates of CVS and/or BR in treated CHB patients.
View details for DOI 10.1111/liv.14415
View details for PubMedID 32086988
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Early multiplexed detection of cirrhosis by giant magnetoresistive biosensors with protein biomarkers.
ACS sensors
2020
Abstract
Liver cirrhosis is one of the leading causes of death in adults worldwide. It is highly prevalent in developing countries and is growing in prevalence in developed countries mostly due to chronic liver diseases, such as chronic hepatitis B and C, and alcoholic and nonalcoholic fatty liver disease. However, the prevalence of cirrhosis may be highly underestimated because early stages are asymptomatic and current early detection methods are inadequate. Here, we evaluate the potential of a set of novel cirrhotic protein biomarkers, including soluble intercellular adhesion molecule-1 (sICAM-1) and mac-2 binding protein glycosylation isomer (M2BPGi), for early detection of cirrhosis in a multiplexed assay using our giant magnetoresistive (GMR) sensor arrays. We evaluated the diagnostic performance of the biomarkers, individually and in combination, using multivariate logistic regression and random forest in a blinded proof-of-concept retrospective case-controlled study. The biomarkers in combination exhibited high diagnostic performance in both logistic regression and random forest models, with area under the curve (AUC) of 0.98 (0.94 - 1.00). In addition, the combination of biomarkers resulted in high sensitivity of 0.97 (0.95 - 1.00) and high specificity of 1.00. We showed that the diagnostic performance of our novel set of cirrhotic protein biomarkers on our multiplexed GMR sensor arrays is higher than the performance of currently used clinical biomarkers and factors (i.e. age, sex, alanine aminotransferase (ALT), aspartate aminotransferase (AST), etc.). With this combination of novel biomarkers and the GMR technology, we could potentially boost the diagnostic power of early cirrhosis detection.
View details for DOI 10.1021/acssensors.0c00232
View details for PubMedID 32896123
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Validity of International Classification of Diseases, 10th Revision, Codes for Cirrhosis.
Digestive diseases (Basel, Switzerland)
2020
Abstract
Accurate identification of patients with cirrhosis is important for research using administrative databases. We aimed to examine the accuracy of several major ICD-10 codes for cirrhosis diagnosis in a large and diverse patient cohort; there is little existing research on this topic.Using data from 3396 patients with chronic liver disease (hepatitis B, C or non-alcoholic fatty liver disease) from one university and several community medical centers, we calculated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUROC) for several major ICD-10 codes for cirrhosis, which was verified by individual chart review. We performed a secondary validation in a general cohort of 1560 randomly selected patients.While each of the individual study ICD-10 codes were specific (98.08 - 100%), none of the codes were sufficiently sensitive (0.27 - 55.70%). PPVs were high in the chronic liver disease cohort (88.41 - 100%) but lower in the general population (55.53 - 66.76%). The AUROC for having at least one code was higher (0.79) than any code alone (0.50 - 0.65).Individual ICD-10 codes are suboptimal for identifying patients with cirrhosis in the general patient population. We recommend conditioning ICD-10 code searches with a chronic liver disease diagnosis code and/or combining diagnostic codes to maximize performance.
View details for DOI 10.1159/000510981
View details for PubMedID 32814313
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Letter: a stepwise approach towards the screening of hepatic fibrosis in the general population-authors' reply.
Alimentary pharmacology & therapeutics
2020; 51 (6): 670–71
View details for DOI 10.1111/apt.15664
View details for PubMedID 32100344
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Editorial: choosing an appropriate risk stratification tool for nonalcoholic fatty liver disease-one size does not fit all. Authors' reply.
Alimentary pharmacology & therapeutics
2020; 51 (6): 662–63
View details for DOI 10.1111/apt.15651
View details for PubMedID 32100348
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Delayed Diagnosis and Disparity in Hepatitis C Virus-Infected Immigrants in North America: A Call for Action.
Liver international : official journal of the International Association for the Study of the Liver
2020
Abstract
We read with interest the recent paper by Lapointe-Shaw et al. (1) , which reported that peri-complication HCV diagnosis which occurred within +/- 6 months of developing decompensated cirrhosis, hepatocellular carcinoma (HCC), or undergoing a liver transplant occurred in 4.2 % of those with HCV diagnosis (1,645/39,515), which was 31.6 % of the total cases with end-stage complications (1,645/5,202). In addition, they found only 2.9% (n=133) of those with peri-complication diagnoses were immigrants and that immigrants were less likely to have been diagnosed with HCV as a result of presenting with end-stage liver complications.
View details for DOI 10.1111/liv.14709
View details for PubMedID 33091237
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Letter: substantial under-diagnosis of NAFLD - more efforts are needed globally.
Alimentary pharmacology & therapeutics
2020; 52 (10): 1624
View details for DOI 10.1111/apt.16110
View details for PubMedID 33085985
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Is tenofovir more effective than entecavir to prevent hepatocellular carcinoma? The controversy goes on.
Hepatology international
2020
View details for DOI 10.1007/s12072-020-10080-8
View details for PubMedID 32794049
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Baseline Mac-2 Binding Protein Glycosylation Isomer Level Stratifies Risks of Hepatocellular Carcinoma in Chronic Hepatitis B Patients with Oral Antiviral Therapy.
Liver cancer
2020; 9 (2): 207–20
Abstract
Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel biomarker correlating with liver fibrosis stages. However, little is known about how it predicts risks of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving long-term antiviral treatment.The study contained 2 parts. The first part was to explore whether M2BPGi could be an HCC predictor in 899 CHB patients receiving long-term entecavir therapy. The second part was to validate the findings in an independent cohort of 384 on-treatment CHB patients with more severe liver disease.In the discovery cohort, there were 64 patients developing HCC within an average follow-up of 7.01 years. Our data showed that M2BPGi level was positively associated with HCC development. When stratifying the patients by an M2BPGi level of 1.73 (the third quartile), the high M2BPGi group was shown to have an increased HCC risk compared to the low M2BPGi group with hazard ratio of 5.80 (95% CI 3.50-9.60). Furthermore, we found that the M2BPGi level complements PAGE-B score, a well-validated HCC prediction model, to predict HCC development. Lastly, the cutoff was validated in the independent cohort, especially those with an intermediate PAGE-B score.In CHB patients receiving long-term antiviral treatment, serum M2BPGi level not only serves as an independent HCC predictor but also complements PAGE-B in stratifying HCC risks.
View details for DOI 10.1159/000504650
View details for PubMedID 32399434
View details for PubMedCentralID PMC7206589
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Radiofrequency ablation versus repeat resection for recurrent hepatocellular carcinoma (≤ 5 cm) after initial curative resection.
European radiology
2020
Abstract
Recurrence rate is up to 70% at 5 years for hepatocellular carcinoma (HCC) after initial resection, but the management of recurrent HCC remains unclear. To compare the efficacy and safety of radiofrequency ablation (RFA) and repeat resection as the first-line treatment in recurrent HCC.This multicenter retrospective study analyzed 290 patients who underwent RFA (n = 199) or repeat resection (n = 91) between January 2006 and December 2016 for locally recurrent HCC (≤ 5 cm) following primary resection. We compared the overall survival (OS), progression-free survival (PFS), and complications between the two treatment groups for the total cohort and the propensity score matched (PSM) cohort.The 1-, 3-, and 5-year OS (90.7%, 69.04%, 55.6% vs. 87.7%, 62.9%, 38.1%, p = 0.11) and PFS (56.5%, 27.9%, 14.6% vs. 50.2%, 21.9%, 19.2%, p = 0.80) were similar in the RFA group and the repeat resection group. However, RFA was superior to repeat resection in complication rate and hospital stay (p ≤ 0.001). We observed similar findings in the PSM cohort of 48 pairs of patients and when OS and PFS were measured from the time of the primary resection. The OS of the RFA group was significantly better than repeat resection group among those with 2 or 3 recurrent tumor nodules in both the total cohort (p = 0.009) and the PSM cohort (p = 0.018).RFA has the same efficacy as repeat resection in recurrent HCC patients, but with fewer complications. RFA is more efficient and safer than repeat resection in patients with 2 or 3 recurrent tumor nodules.• Recurrence rate is up to 70% at 5 years for hepatocellular carcinoma (HCC) after initial resection. • RFA has the same efficacy as repeat resection in recurrent HCC patients, but with fewer complications. • RFA may be preferred for those with 2 or 3 recurrent HCC nodules.
View details for DOI 10.1007/s00330-020-06990-8
View details for PubMedID 32529568
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Genomic analysis of Vascular Invasion in Hepatocellular Carcinoma (HCC) Reveals Molecular Drivers and Predictive Biomarkers.
Hepatology (Baltimore, Md.)
2020
Abstract
Vascular invasion is a critical risk factor for hepatocellular carcinoma (HCC) recurrence and poor survival. The molecular drivers of vascular invasion in HCC are largely unknown. Deciphering the molecular landscape of invasive HCC will help identify novel therapeutic targets and noninvasive biomarkers. To this end, we undertook this study to evaluate the genomic, transcriptomic, and proteomic profile of tumors with vascular invasion using the multi-platform cancer genome atlas (TCGA) data (n=373). In the TCGA liver hepatocellular carcinoma (LIHC) cohort, macrovascular invasion was present in 5% (n=17) of tumors and microvascular invasion in 25% (n=94) of tumors. Functional pathway analysis revealed that the MYC oncogene was a common upstream regulator of the mRNA, miRNA and proteomic changes in vascular invasion. We performed comparative proteomic analyses of invasive human HCC and MYC driven murine HCC and identified fibronectin to be proteomic biomarker of invasive HCC (mouse Fn1 p= 1.7 X 10-11 ; human FN1 p=1.5 X 10-4 ) conserved across the two species. Mechanistically, we show that FN1 promotes the migratory and invasive phenotype of HCC cancer cells. We demonstrate tissue overexpression of fibronectin in human HCC using a large independent cohort of human HCC tissue microarray (n=153; p<0.001). Lastly, we showed that plasma fibronectin levels were significantly elevated in patients with HCC (n=35, mean=307.7 μg/ml, SEM=35.9) when compared to cirrhosis (n=10, mean=41.8 μg/ml, SEM=13.3; p<0.0001). CONCLUSION: Our study evaluates the molecular landscape of tumors with vascular invasion, identifying distinct transcriptional, epigenetic and proteomic changes driven by the MYC oncogene. We show that MYC upregulates fibronectin expression which promotes HCC invasiveness. In addition, we identify fibronectin to be a promising non-invasive proteomic biomarker of vascular invasion in HCC.
View details for DOI 10.1002/hep.31614
View details for PubMedID 33140851
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Proton pump inhibitors and risk of liver cancer and mortality in patients with chronic liver disease: a systematic review and meta-analysis.
European journal of clinical pharmacology
2020
Abstract
Epidemiological studies investigating the use of proton pump inhibitors (PPI) on the risk of liver cancer and/or mortality among persons with chronic liver disease (CLD) have reported conflicting results. We conducted a systematic review and meta-analysis to determine the impact of PPI use on liver cancer and/or death among patients with CLD.The core databases including MEDLINE, EMBASE, and Cochrane library were searched through January 2020. We included studies, evaluating the association between PPIs and liver cancer or mortality among patients with CLD including randomized controlled, nonrandomized controlled, and observational studies. We used inverse-variance random-effects models to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for liver cancer or mortality.Eleven studies including 173,894 patients were selected. In three studies, individuals with CLD who used PPIs had a 67% greater risk of developing hepatocellular carcinoma (HCC) compared to nonusers (RR, 1.67; 95% CI, 1.12-2.50; I2 = 92%). Combining data from the eight studies relating PPI to overall mortality, we observed a 57% increased risk of mortality in PPI users with CLD compared to CLD nonusers (RR: 1.57; 95% CI, 1.24-1.99; I2 = 69%).PPI use was associated with an increased risk of HCC and mortality in patients with CLD suggesting that PPI prescriptions in patients with CLD should be considered carefully.
View details for DOI 10.1007/s00228-020-02854-8
View details for PubMedID 32172363
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Provider Perspectives on HCC Surveillance in Patients With Cirrhosis: Community Provider Perspectives Matter.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2020
View details for DOI 10.1016/j.cgh.2020.10.050
View details for PubMedID 33248098
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Review article: current gaps and opportunities in HBV prevention, testing and linkage to care in the United States-a call for action.
Alimentary pharmacology & therapeutics
2020
Abstract
The World Health Organization (WHO) has set an elimination goal for hepatitis B virus (HBV) by 2030, so a comprehensive review of current HBV testing and care gaps are needed to help formulate solutions and opportunities for action.To summarise current gaps and barriers, and to propose solutions for HBV prevention, testing and linkage to care in the United States METHODS: Relevant guidelines and studies were reviewed including a systematic review of HCC surveillance adherence.A total of 64.5 million (95% CI, 61.3-67.5) high-risk US adults had no evidence of HBV immunity. Only 18.6% (95% CI, 13.5-29.9) of privately insured patients with HBV infection have been diagnosed. Among those with known HBV infection, linkage to care rate (33.3%-57%) was poor and the adherence to guidelines regarding anti-viral therapy (30.66% [95% CI, 30.28-31.03]) and HCC surveillance (8%-87%, from a systematic review) were poor with even more concerning data for care and treatment retention. The causes are complex and include lack of access to medical care, lack of physician knowledge, lack of patient health literacy and awareness, linguistic and cultural barriers and fear of stigma.A 'scale-up' effort is needed to optimise the care continuum to achieve the WHO 2030 targets. As targeted screening policy has leftover 80% of patients undiagnosed, we advocate for universal screening which can help to remove barriers regarding stigma. More active and system level interventions are also needed to improve linkage to care for patients with HBV infection.
View details for DOI 10.1111/apt.16125
View details for PubMedID 33222252
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Post-Transplant Outcomes in Older Patients with Hepatocellular Carcinoma (HCC) are Driven by non-HCC Factors.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
2020
Abstract
The incidence of hepatocellular carcinoma (HCC) is growing in the US, especially among the elderly. Older patients are increasingly getting transplanted for HCC, but the impact of advancing age on long-term post-transplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium (UMHTC) of 4980 patients. We divided the patients into 4 groups by age at transplantation- 18-64 (n = 4001), 65-69 (n = 683), 70-74 (n = 252) and ≥ 75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age over 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (p = 0.004), and not HCC-related death (p = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients transplanted for HCC (n = 302). Patients older than 65 years had a higher incidence of de-novo cancer (18.1% vs 7.6%, p = 0.006) after transplantation and higher overall cancer-related mortality (14.3% vs 6.6%, p = 0.03). CONCLUSION: Even carefully selected elderly patients with HCC have significantly worse post-transplant survival, which are mostly driven by non-HCC related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve outcomes in elderly patients transplanted for HCC.
View details for DOI 10.1002/lt.25974
View details for PubMedID 33306254
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Epidemiology of COVID-19: A Systematic Review and Meta-analysis of Clinical Characteristics, Risk factors and Outcomes.
Journal of medical virology
2020
Abstract
COVID-19 has become a pandemic, but its reported characteristics and outcomes vary greatly amongst studies.We determined pooled estimates for clinical characteristics and outcomes in COVID-19 patients including subgroups by disease severity (based on WHO Interim Guidance Report or IDSA/ATS criteria) and by country/region.We searched Pubmed, Embase, Scopus, Cochrane, Chinese Medical Journal, and preprint databases from January 1, 2020 to April 6, 2020. Studies of laboratory confirmed COVID-19 patients with relevant data were included. Two reviewers independently performed study selection and data extraction.From 6,007 articles, 212 studies from 11 countries/regions involving 281,461 individuals were analyzed. Overall, mean age was 46.7 years, 51.8% were male, 22.9% had severe disease, and mortality was 5.6%. Underlying immunosuppression, diabetes, and malignancy were most strongly associated with severe COVID-19 (coefficient=53.9, 23.4, 23.4, respectively, all p<0.0007), while older age, male gender, diabetes, and hypertension were also associated with higher mortality (coefficient=0.05 per year, 5.1, 8.2, 6.99, respectively, p=0.006 to 0.0002). Gastrointestinal (nausea, vomiting, abdominal pain) and respiratory symptoms (shortness of breath, chest pain) were associated with severe COVID-19, while pneumonia and end organ failure were associated with mortality.COVID-19 is associated with a severe disease course in about 23% and mortality in about 6% of infected persons. Individuals with comorbidities and clinical features associated with severity should be monitored closely, and preventive efforts should especially target those with diabetes, malignancy and immunosuppression. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/jmv.26424
View details for PubMedID 32790106
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Editorial: comorbidities in patients with chronic hepatitis B-authors' reply.
Alimentary pharmacology & therapeutics
2020; 52 (5): 893–94
View details for DOI 10.1111/apt.15979
View details for PubMedID 32852828
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Non-alcoholic fatty liver disease (NAFLD) in Asia - More efforts are needed.
Liver international : official journal of the International Association for the Study of the Liver
2020
Abstract
We read with interest the study by Zhang et al1 where they explored the association between lifestyle habits and the severity of non-alcoholic fatty liver disease (NAFLD) in different Asian regions. The authors found that unhealthy lifestyles and physical inactivity were common across all the regions and that patients with a liver stiffness <10 kPa were more likely to report participating in some vigorous activity. The focus on physical activity besides weight control is also timely as up to 40% of the NAFLD population are not obese.2.
View details for DOI 10.1111/liv.14657
View details for PubMedID 32891071
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Increasing age and non-liver comorbidities in patients with chronic hepatitis B in Taiwan: A nationwide population-based analysis.
Digestive diseases (Basel, Switzerland)
2020
Abstract
Data from the US suggest that chronic hepatitis B (CHB) patients have aged in the past decade. However, the burden of non-liver comorbidities have not been well characterized in Taiwan, where CHB is very prevalent.Our study examined this issue as it presented between 2001 and 2011in Taiwan.This study identified adult patients (≥18 years) who were diagnosed with CHB in 2001, 2006, and 2011, from the Taiwan National Health Insurance Research Database (NHIRD). Changes in demographic characteristics, prevalence of non-liver comorbidities, and medication usage over the decade were examined. Non-CHB controls were adults without CHB diagnosis from the Longitudinal Health Insurance Database 2000 (LHID2000).A total of 102,158, 252,809, and 338,200 eligible patients were identified in 2001, 2006, and 2011, respectively. The mean age significantly advanced from 45.4 to 52.3 years over the decade (P<0.001). The prevalence of comorbidities, including diabetes mellitus, hypertension, stroke, chronic kidney disease, and bone fracture all significantly increased between 2001 and 2011 (all P<0.001), as so were medication usage (all P<0.001). Moreover, within each study period, compared to non-CHB controls, CHB patients were also older and more likely to have metabolic and cardiovascular comorbidities (all P<0.001). In addition, the annual non-liver mortality in the CHB population significantly increased from 2001 to 2011.Over a decade, the CHB population in Taiwan has aged with a higher non-liver comorbidity burden and increasing non-liver mortality. These findings may provide information to care providers in the monitoring and management of CHB patients.
View details for DOI 10.1159/000511585
View details for PubMedID 32932249
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Inhibitory Effect of Nucleos(t)ide Analogs on Telomerase Activity and Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.
The American journal of gastroenterology
2020
View details for DOI 10.14309/ajg.0000000000000507
View details for PubMedID 31913195
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Noninvasive diagnosis methods are needed in paediatric non-alcoholic fatty liver disease (NAFLD).
Liver international : official journal of the International Association for the Study of the Liver
2020
Abstract
We read with interest the study by Li et al1 which proposed the "healthy" range of transient elastography (TE)-derived liver stiffness of 2.45 to 5.56 kPa and its association with hepatic steatosisfor children.
View details for DOI 10.1111/liv.14748
View details for PubMedID 33253448
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A Nationwide Study of Inpatient Admissions, Mortality, and Costs for Patients with Cirrhosis from 2005 to 2015 in the USA.
Digestive diseases and sciences
2019
Abstract
BACKGROUND AND AIMS: Liver cirrhosis is a substantial health burden in the USA, but population-based data regarding the trend and medical expenditure are limited and outdated. We investigated the trends of inpatient admissions, costs, and inpatient mortality from 2005 to 2015 among cirrhotic patients.METHODS: A retrospective analysis was conducted using the National Inpatient Sample database. We adjusted the costs to 2015 US dollars using a 3% inflation rate. National estimates of admissions were determined using discharge weights.RESULTS: We identified 1,627,348 admissions in cirrhotic patients between 2005 and 2015. From 2005 to 2015, the number of weighted admissions in cirrhotic patients almost doubled (from 505,032 to 961,650) and the total annual hospitalization cost in this population increased three times (from 5.8 to 16.3 billion US dollars). Notably, admission rates varied by liver disease etiology, decreasing from 2005 to 2015 among patients with hepatitis C virus (HCV)-related cirrhosis while increasing (almost tripled) among patients with nonalcoholic fatty liver disease (NAFLD)-related cirrhosis. The annual inpatient mortality rate per 1000 admissions overall decreased from 63.8 to 58.2 between 2005 and 2015 except for NAFLD (27.2 to 35.8) (P<0.001).CONCLUSIONS: Rates and costs of admissions in cirrhotic patients have increased substantially between 2005 and 2015 in the USA, but varied by liver disease etiology, with decreasing rate for HCV-associated cirrhosis and for HBV-associated cirrhosis but increasing for NAFLD-associated cirrhosis. Inpatient mortality also increased by one-third for NAFLD, while it decreased for other diseases. Cost also varied by etiology and lower for HCV-associated cirrhosis.
View details for DOI 10.1007/s10620-019-05869-z
View details for PubMedID 31598919
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SUBSTANTIAL GAP IN ASSESSMENT AND TREATMENT OF CHRONIC HEPATITIS B (CHB) PATIENTS IN THE UNITED STATES: A NATIONWIDE STUDY OF 7,124 PATIENTS
WILEY. 2019: 566A
View details for Web of Science ID 000488653502073
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What to Do When Fecal Immunochemical Test (FIT) Is Positive Following Normal Colonoscopy? Comparison of Adenoma Detection Rate (ADR) of Standard FIT-Colonoscopy and Relook Colonoscopy
LIPPINCOTT WILLIAMS & WILKINS. 2019: S192
View details for DOI 10.14309/01.ajg.0000590840.61215.b2
View details for Web of Science ID 000509756000328
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Sustained Decline of Noninvasive Fibrosis Index Values in Patients With Chronic Hepatitis C (CHC) With Sustained Virologic Response (SVR) After Receiving Direct-Acting Antiviral Agents (DAAs)
LIPPINCOTT WILLIAMS & WILKINS. 2019: S553–S554
View details for DOI 10.14309/01.ajg.0000593348.53707.0b
View details for Web of Science ID 000509756002173
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INCREASING AGE AND NON-LIVER COMORBIDITIES IN PATIENTS WITH CHRONIC HEPATITIS B IN TAIWAN: A NATIONWIDE POPULATION-BASED ANALYSIS
WILEY. 2019: 596A–597A
View details for Web of Science ID 000488653502126
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COMORBIDITY PREVALENCE AND HEALTH CARE UTILIZATION IN A POPULATION-BASED STUDY OF CHRONIC HEPATITIS B PATIENTS FROM 2007 TO 2016 IN SOUTH KOREA
WILEY. 2019: 582A
View details for Web of Science ID 000488653502101
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IMPROVEMENT IN VIROLOGIC, BIOCHEMICAL AND RENAL OUTCOMES IN CHRONIC HEPATITIS B (CHB) PATIENTS SWITCHED TO TENOFOVIR ALAFENAMIDE (TAF) IN ROUTINE CLINICAL PRACTICE
WILEY. 2019: 295A–296A
View details for Web of Science ID 000488653501033
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TENOFOVIR VERSUS ENTECAVIR FOR HEPATOCELLULAR CARCINOMA PREVENTION IN AN INTERNATIONAL CONSORTIUM OF CHRONIC HEPATITIS B
WILEY. 2019: 290A–291A
View details for Web of Science ID 000488653501025
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RACE DOES NOT AFFECT THE PERFORMANCE OF ROUTINELY AVAILABLE NONINVASIVE TESTS FOR THE DISCRIMINATION OF ADVANCED FIBROSIS DUE TO NONALCOHOLIC STEATOHEPATITIS (NASH) IN THE PHASE 3 STELLAR TRIALS OF SELONSERTIB
WILEY. 2019: 1029A–1030A
View details for Web of Science ID 000488653503400
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HCV CURE BY ALL ORAL DAA IMPROVES 5-YEAR OVERALL AND LIVER-RELATED SURVIVAL IN HCV-RELATED HCC PATIENTS: A REAL-WORLD, PROPENSITY SCORE-MATCHED STUDY FROM BOTH EAST AND WEST
WILEY. 2019: 28A
View details for Web of Science ID 000488653500041
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ASSOCIATIONS BETWEEN WEIGHT PERCEPTION AND THE INTENTION TO LOSE WEIGHT AND BETWEEN THE INTENTION TO DIET/EXERCISE AND REPORTED MET/CALORIE COUNT IN PERSONS WITH NAFLD: A US POPULATION-BASED STUDY OF 11,713 PARTICIPANTS, 2001-2014
WILEY. 2019: 753A–754A
View details for Web of Science ID 000488653502395
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PREVALENCE AND FACTORS ASSOCIATED WITH HEPATIC STEATOSIS (HS) AND HEPATIC FIBROSIS IN CHRONIC HEPATITIS B (CHB) ASSOCIATED WITH HS: A SYSTEMATIC REVIEW AND META-ANALYTIC ASSESSMENT OF 57 STUDIES AND 268,151 PARTICIPANTS
WILEY. 2019: 570A–571A
View details for Web of Science ID 000488653502081
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INCREASING PREVALENCE AND FACTORS ASSOCIATED WITH NAFLD IN MAINLAND CHINA: A META-ANALYSIS OF 124 STUDIES AND 1,232,281 PARTICIPANTS
WILEY. 2019: 742A–743A
View details for Web of Science ID 000488653502378
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DISTRIBUTION OF BMI, SERUM ALT, HEPATIC STEATOSIS AND LIVER FIBROSIS IN ASIANS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD): A SYSTEMATIC REVIEW AND META-ANALYSIS OF 108 STUDIES WITH 2,260,207 INDIVIDUALS
WILEY. 2019: 741A–742A
View details for Web of Science ID 000488653502377
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SYSTEMATIC REVIEW AND META-ANALYSIS: A NATURAL HISTORY STUDY TO INCLUDE NAFLD INCIDENCE, DISEASE TRANSITION AND OUTCOMES
WILEY. 2019: 743A
View details for Web of Science ID 000488653502379
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THE IMPACT OF COEXISTING HEPATIC STEATOSIS (HS) ON DEVELOPMENT OF CIRRHOSIS,HEPATOCELLULAR CARCINOMA (HCC) DEVELOPMENT AND HBsAg SEROCLEARANCE IN PATIENTS WITH CHRONIC HEPATITIS B (CHB)
WILEY. 2019: 1347A–1348A
View details for Web of Science ID 000488653505046
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IMPACT OF SVR ON LONG-TERM LIVER-RELATED OUTCOMES: RESULTS OF THE REAL-C REGISTRY AT 23 CENTERS FROM HONG KONG, KOREA, JAPAN AND TAIWAN
WILEY. 2019: 908A–909A
View details for Web of Science ID 000488653503199
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REDEFINING THE UPPER LIMIT OR NORMAL (ULN) OF ALANINE TRANSAMINASE (ALT) LEVELS FOR ASIANS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 60 STUDIES AND 335,163 INDIVIDUALS
WILEY. 2019: 1055A–1056A
View details for Web of Science ID 000488653504021
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INCREASING PREVALENCE AND ASSOCIATION BETWEEN SEVERITY OF RENAL INSUFFICIENCY WITH MORTALITY IN PERSONS WITH NAFLD, A UNITED STATES POPULATION-BASED STUDY
WILEY. 2019: 155A–156A
View details for Web of Science ID 000488653500238
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Changing incidence of reported viral hepatitis in China from 2004 to 2016: an observational study.
BMJ open
2019; 9 (8): e028248
Abstract
OBJECTIVE: China's national hepatitis burden is high. This study aims to provide a detailed national-level description of the reported incidence of viral hepatitis in China during 2004-2016.DESIGN: Observational study.SETTING: Data were obtained from China's National Notifiable Disease Reporting System, and changing trends were estimated by joinpoint regression analysis.PARTICIPANTS: In this system, 16 927 233 reported viral hepatitis cases occurring during 2004-2016 were identified.PRIMARY OUTCOME MEASURE: Incidence rates per 100000 person-years and changing trends were calculated.RESULTS: There were 16 927 233 new cases of viral hepatitis reported in China from 2004 to 2016. Hepatitis B (HBV) (n=13 543 137, 80.00%) and hepatitis C (HCV) (n=1 844 882, 10.90%) accounted for >90% of the cases. The overall annual percent change (APC) in reported cases of viral hepatitis and HBV were 0.3%(95% CI -2.0 to 0.8, p=0.6) and -0.2% (95% CI -1.6 to 1.2, p=0.8), respectively, showing a stable trend. HBV rates were highest in the 20-29year old age group and lowest in younger individuals, likely resulting from the universal HBV vaccination. The reported incidence of HCV and hepatitis E (HEV) showed increasing trends; the APCs were 14.5% (95% CI 13.1 to 15.9, p<0.05) and 4.7% (95% CI 2.8 to 6.7, p<0.05), respectively. The hepatitis A (HAV) reporting incidence decreased, and the APC was -13.1% (95% CI -15.1 to -11.0, p<0.05). There were marked differences in the reporting of hepatitis among provinces.CONCLUSIONS: HBV continues to constitute the majority of viral hepatitis cases in China. Over the entire study period, the HBV reporting incidence was stable, the HCV and HEV incidence increased and the HAV incidence decreased. There were significant interprovincial disparities in the burden of viral hepatitis, with higher rates in economically less-developed areas. Vaccination is important for viral hepatitis prevention and control.
View details for DOI 10.1136/bmjopen-2018-028248
View details for PubMedID 31427323
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Prevalence of NAFLD in China: What Did We Learn From the Recent Meta-Analysis?
Hepatology (Baltimore, Md.)
2019
Abstract
We would like to congratulate Zhou etal for performing the largest meta-analysis to date on nonalcoholic fatty liver disease (NAFLD) in China. However, we have several concerns with their findings due to the methods they used to determine and report the prevalence. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/hep.30892
View details for PubMedID 31390074
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Associations Between Body Fat, Muscle Mass, and Nonalcoholic Fatty Liver Disease: A Population-Based Study.
Hepatology communications
2019; 3 (8): 1061–72
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of liver disease worldwide and has emerged as a significant public health concern in China. A better understanding of the etiology of NAFLD can inform effective management strategies for this disease. We examined factors associated with NAFLD in two districts of Hangzhou, China, focusing on the relationship of regional body fat distribution, muscle mass, and NAFLD. We used baseline data to carry out a cross-sectional analysis among 3,589 participants from the Wellness Living Laboratory (WELL) China study, a longitudinal population-based study that aims to investigate and promote well-being among the Chinese population. NAFLD was defined using the widely validated fatty liver index (FLI). Multivariate logistic regressions were performed to assess independent associations between NAFLD and metabolic risk factors (e.g., insulin resistance) and dual x-ray absorptiometry (DXA)-derived measures (e.g., android fat ratio [AFR] and skeletal muscle index [SMI]). Of the 3,589 participants, 476 (13.3%) were classified as having FLI-defined NAFLD (FLI ≥60). Among those, 58.0% were men. According to our analysis, AFR (odds ratio [OR], 10.0; 95% confidence interval [CI], 5.8-18.5), insulin resistance (OR, 4.0; 95% CI, 3.0-5.3), high alanine aminotransferase levels (OR, 7.6; 95% CI, 5.8-10.0), smoking (OR, 2.0; 95% CI, 1.4-3.0), and male sex (OR, 2.9; 95% CI, 2.0-4.2) were positively associated with NAFLD risk, while SMI (OR, 0.1; 95% CI, 0.07-0.13) was inversely associated with NAFLD risk. Conclusion: In addition to known metabolic risk factors, DXA-derived AFR and SMI may provide additional insights to the understanding of NAFLD. Interventions that aim to decrease AFR and increase SMI may be important to reduce the burden of NAFLD in this population.
View details for DOI 10.1002/hep4.1392
View details for PubMedID 31388627
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Nonalcoholic fatty liver disease increases risk of incident advanced chronic kidney disease: A propensity-matched cohort study.
Journal of internal medicine
2019
Abstract
BACKGROUND: As the prevalence of non-alcoholic fatty liver disease (NAFLD) escalates, understanding its potential impact on the development of chronic kidney disease (CKD) is needed.OBJECTIVE: To determine the longitudinal association of NAFLD with the development of advanced CKD in the United States.METHODS: A retrospective cohort analysis of the Truven Health MarketScan Database (2006-2015) was conducted. We used Cox proportional hazards models to compare the risk of developing CKD stages 3-5 in NAFLD versus non-NAFLD patients, identified by ICD-9 codes, after 1:3 propensity score (PS) matching.RESULTS: In a cohort of 262,619 newly diagnosed NAFLD patients and 769,878 PS (1:3) - matched non-NAFLD patients, we identified 5766 and 8655 new advanced (stage 3-5) CKD cases, respectively. The crude CKD incidence rate was 8.2 and 5.5 per 1,000 person-years in NAFLD and non-NAFLD groups, respectively. In multivariable Cox model, NAFLD patients had a 41% increased risk of developing advanced CKD compared to non-NAFLD patients [adjusted hazard ratio (aHR), 1.41; 95% confidence interval (CI), 1.36-1.46]. In the sensitivity analysis adjusting for time-varying covariates after NAFLD diagnosis, NAFLD persisted as a significant CKD risk factor (aHR, 1.58; 95% CI, 1.52-1.66) and the association remained significant when stratified by age, gender, and pre-existing comorbidities. The risk of CKD increased in NAFLD with compensated cirrhosis (aHR, 1.47; 95% CI, 1.36-1.59) and decompensated cirrhosis (aHR, 2.28; 95% CI, 2.12-2.46).CONCLUSION: NAFLD was independently associated with an increased risk of advanced CKD development suggesting renal function screening and regular monitoring are needed in this population. This article is protected by copyright. All rights reserved.
View details for DOI 10.1111/joim.12964
View details for PubMedID 31359543
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Antiviral therapy and the development of osteopenia/osteoporosis among Asians with chronic hepatitis Bn
JOURNAL OF MEDICAL VIROLOGY
2019; 91 (7): 1288–94
View details for DOI 10.1002/jmv.25433
View details for Web of Science ID 000471755300014
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Deferred treatment with a fixed-dose combination of sofosbuvir-velpatasvir for chronic hepatitis C virus genotype 1, 2, 4, and 6 infection.
Journal of viral hepatitis
2019
Abstract
Sofosbuvir-velpatasvir is approved for the treatment of chronic hepatitis C virus (HCV) infection. In this single-arm, open-label, phase 3, deferred treatment study we investigated the efficacy and safety of sofosbuvir-velpatasvir among patients randomized to the placebo group in the ASTRAL-1 study. Patients received sofosbuvir-velpatasvir (400/100 mg) once daily for 12 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response 12 weeks after the end of therapy (SVR12). The primary safety endpoint was any adverse events (AEs) leading to the permanent discontinuation of study drug. Overall, 108/111 (97%, 95% confidence interval [CI], 92-99%) achieved SVR12, and only one patient had virological failure. SVR12 was achieved by 61/63 (97%, 95%CI, 89-100%) genotype 1 patients, 20/20 (100%; 95%CI, 83-100%) with genotype 2, 19/19 (100%; 95%CI, 82-100%) with genotype 4, and 8/9 (89%; 95% CI, 52-100%) with genotype 6. All (19/19; 95%CI, 82-100) patients with cirrhosis, and all (31/31, 95%CI, 89-100) with prior treatment experience achieved SVR12.The safety profile during treatment was similar to that observed in patients receiving placebo treatment. The most common AEs were headache, fatigue, and nausea. One patient (1%) discontinued treatment due to an AE of gallbladder carcinoma, which was not considered related to treatment. Of five reported serious AEs, none were considered related to study drug. Sofosbuvir-velpatasvir for 12 weeks was effective and well-tolerated among untreated and previously treated patients with HCV genotype 1, 2, 4, or 6 infection, including those with compensated cirrhosis. This article is protected by copyright. All rights reserved.
View details for DOI 10.1111/jvh.13159
View details for PubMedID 31216086
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Changing Landscape of Liver Cancer in California: A Glimpse Into the Future of Liver Cancer in the United States
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
2019; 111 (6): 550–56
View details for DOI 10.1093/jnci/djy180
View details for Web of Science ID 000474267400005
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Reduced Hepatocellular Carcinoma Risk vs Bleeding Risk Associated With Aspirin
JAMA ONCOLOGY
2019; 5 (6): 911
View details for DOI 10.1001/jamaoncol.2019.0614
View details for Web of Science ID 000474872000029
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Reply.
Gastroenterology
2019
View details for DOI 10.1053/j.gastro.2019.05.046
View details for PubMedID 31150598
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Hospital Cirrhosis Volume and Readmission in Patients with Cirrhosis in California (vol 63, pg 2267, 2018)
DIGESTIVE DISEASES AND SCIENCES
2019; 64 (5): 1392–94
View details for DOI 10.1007/s10620-019-05558-x
View details for Web of Science ID 000466886100045
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Red blood cell distribution width to albumin ratio as a novel prognostic indicator for patients with chronic hepatitis B-related liver cirrhosis
ELSEVIER SCIENCE BV. 2019: E694–E695
View details for Web of Science ID 000463481703140
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Mac-2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients With Chronic Hepatitis B or C Infection
HEPATOLOGY COMMUNICATIONS
2019; 3 (4): 493–503
View details for DOI 10.1002/hep4.1321
View details for Web of Science ID 000462816200005
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Mac-2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients With Chronic Hepatitis B or C Infection.
Hepatology communications
2019; 3 (4): 493-503
Abstract
Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel glycoprotein biomarker that correlates with liver fibrosis. It has been investigated in East Asian populations as a hepatocellular carcinoma (HCC) biomarker. We assessed M2BPGi as an HCC biomarker in an ethnically diverse cohort of patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We enrolled 947 treatment-naive patients mono-infected with HBV or HCV without HCC at baseline. Biomarker levels were measured from baseline sera and correlated with longitudinal clinical data. The primary outcome was HCC occurrence during long-term follow-up. Median M2BPGi was significantly higher among patients with cirrhosis (2.67 versus 0.80; P < 0.001) and patients who developed HCC (3.22 versus 1.16; P < 0.001). The area under the receiver operating characteristic (AUROC) for M2BPGi and alpha-fetoprotein (AFP) was similar overall (0.77 versus 0.72; P = 0.15), but M2BPGi outperformed AFP among patients with HBV (0.84 versus 0.75; P = 0.02). M2BPGi performed poorly among patients with HCV (AUROC, 0.51). M2BPGi was an independent predictor of HCC among patients with HBV but not among patients with HCV. M2BPGi performed better in patient subgroups with a lower prevalence of cirrhosis. Conclusion: In our HBV cohort, M2BPGi was more effective than AFP in predicting HCC and was an independent predictor of HCC. However, M2BPGi had limited predictive value in our HCV cohort, likely due to a high cirrhosis burden in this cohort. Further studies are needed to evaluate M2BPGi as an HCC biomarker in broader patient populations with more diverse disease etiology, non-Asian ethnicity, and more advanced fibrosis.
View details for DOI 10.1002/hep4.1321
View details for PubMedID 30976740
View details for PubMedCentralID PMC6442699
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Prognostic value of various liver scoring systems in cirrhotic chronic hepatitis B patients with and without tenofovir disoproxil fumarate treatment
ELSEVIER SCIENCE BV. 2019: E461
View details for Web of Science ID 000463481701491
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Hepatitis B and renal function: A matched study comparing non-hepatitis B, untreated, treated and cirrhotic hepatitis patients
LIVER INTERNATIONAL
2019; 39 (4): 655–66
View details for DOI 10.1111/liv.14009
View details for Web of Science ID 000462572800010
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Long-term renal and bone safety of tenofovir disoproxil fumarate in chronic hepatitis B patients with cirrhosis
ELSEVIER SCIENCE BV. 2019: E475–E476
View details for Web of Science ID 000463481702026
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Tenofovir disoproxil fumarate treatment in chronic hepatitis B patients with cirrhosis reduces hepatic decompensation, hepatocellular carcinoma and death
ELSEVIER SCIENCE BV. 2019: E475
View details for Web of Science ID 000463481702025
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Correction to: Hospital Cirrhosis Volume and Readmission in Patients with Cirrhosis in California.
Digestive diseases and sciences
2019
Abstract
The original version of the article unfortunately contained errors in 'Severity of illness' and 'Hospital characteristics' entries of Table1. Corrected version of Table1 is given below.
View details for PubMedID 30868408
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Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis
KOREAN JOURNAL OF INTERNAL MEDICINE
2019; 34 (2): 296-+
View details for DOI 10.3904/kjim.2017.194
View details for Web of Science ID 000459694200008
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GALAD Score for Hepatocellular Carcinoma Detection in Comparison with Liver Ultrasound and Proposal of GALADUS Score
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
2019; 28 (3): 531–38
View details for DOI 10.1158/1055-9965.EPI-18-0281
View details for Web of Science ID 000465326400014
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Rising Inpatient Encounters and Economic Burden for Patients with Nonalcoholic Fatty Liver Disease in the USA
DIGESTIVE DISEASES AND SCIENCES
2019; 64 (3): 698–707
View details for DOI 10.1007/s10620-018-5326-7
View details for Web of Science ID 000459414300016
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A Comparison Between Community and Academic Practices in the USA in the Management of Chronic Hepatitis B Patients Receiving Entecavir: Results of the ENUMERATE Study
DIGESTIVE DISEASES AND SCIENCES
2019; 64 (2): 358–66
View details for DOI 10.1007/s10620-018-5281-3
View details for Web of Science ID 000457497500013
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Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma: Analysis From the US Multicenter HCC Transplant Consortium.
Annals of surgery
2019
Abstract
MINI: In a large, multicenter study of patients undergoing liver transplantation for hepatocellular carcinoma, complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) portended significantly superior overall and recurrence-free survival. Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments.The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT).LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study.Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression.Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil-lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67).For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.
View details for PubMedID 30870180
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Antiviral therapy and hepatocellular carcinoma risk in hepatitis B patients with cirrhosis.
European journal of gastroenterology & hepatology
2019
Abstract
Our goal was to evaluate the effect of antiviral therapy on hepatocellular carcinoma incidence for cirrhotic patients with lower hepatitis B virus DNA levels.Consecutive cirrhosis patients from a US cohort (n = 381) and 408 patients from a Taiwan cohort were enrolled. Patients were classified into a low (<20 IU/ml) and high hepatitis B virus DNA group (≥20 IU/ml), and each was further stratified into treated and untreated subgroups.Except for hepatitis B e antigen, baseline characteristics were similar for both hepatitis B virus DNA groups. Antiviral therapy significantly reduced hepatocellular carcinoma incidence in cirrhotic patients with hepatitis B virus DNA ≥20 IU/ml at 5-years (12.2% vs. 22.8%) and 10-years (23.3% vs. 37.2%) (P = 0.0018). For cirrhotic patients with hepatitis B virus DNA <20 IU/ml, there was no statistically significant difference in cumulative hepatocellular carcinoma incidence between the treated and untreated groups. After adjusting for age, sex, and hepatitis B e antigen status, antiviral therapy was an independent predictor (hazard ratio 0.43, P < 0.0001) for reduced hepatocellular carcinoma risk in patients with hepatitis B virus DNA ≥20 IU/ml.Antiviral therapy was associated with a 57% reduction in hepatocellular carcinoma incidence in chronic hepatitis B patients with cirrhosis and hepatitis B virus DNA as low as 20 IU/ml (but no lower). However, hepatocellular carcinoma incidence remained substantial, regardless of hepatitis B virus DNA levels and treatment status, highlighting the need for ongoing hepatocellular carcinoma surveillance for all cirrhotic hepatitis B virus patients.
View details for DOI 10.1097/MEG.0000000000001639
View details for PubMedID 32129773
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Low Alanine Aminotransferase Cut-Off for Predicting Liver Outcomes; A Nationwide Population-Based Longitudinal Cohort Study.
Journal of clinical medicine
2019; 8 (9)
Abstract
Recent practice guidelines suggest healthy normal alanine aminotransferase (ALT) levels should be less than 30 U/L for males and 19 U/L for females. We tried to validate the prediction power of the "low cut off" for liver related outcomes in the general population.A total of 426,013 subjects were followed up for 10 years using the National Health Screening Cohort database. Prediction ability of long term mortality and liver related outcomes between conventional (<40 U/L in men and women) and low (<30 U/L in men and <19 U/L in women) ALT cut-off values were compared.Both conventional and low ALT cut-offs predicted liver related unfavorable outcomes in Kaplan-Meier analysis. Following adjustment for age, body mass index, smoking, exercise, alcohol consumption, fasting blood glucose, and cholesterol via multivariate Cox regression, abnormal ALT using new 'low ALT cut off' was a significant independent predictor for liver-related mortality, HCC, and decompensated liver events. When the low cut-off criteria were added to the prediction model, the ability to predetect liver-related hard outcomes significantly increased in both men and women (p-values < 0.0001). The C-index values for predicting liver-related adverse events were the same in both ALT cut-offs, after adjusting confounding factors (C index value: 0.73~0.88).New low ALT cut-off showed good prediction power for liver related unfavorable outcomes.
View details for DOI 10.3390/jcm8091445
View details for PubMedID 31514449
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An Automated, Quantitative, and Multiplexed Assay Suitable for Point-of-Care Hepatitis B Virus Diagnostics.
Scientific reports
2019; 9 (1): 15615
Abstract
Hepatitis B virus (HBV) infection has a global reach with high prevalence in resource-limited areas like China and Africa. HBV patients in these areas have limited access to the currently used, costly HBV assays, which are performed in centralized clinical laboratories using single-plexed assays with bulky and expensive instruments. We aim to overcome these limitations by developing a simple and affordable HBV diagnostic platform to allow for timelier diagnosis and intervention of HBV infection. Using giant magnetoresistive (GMR) biosensor chips, we developed an automated and multiplexed quantitative platform for the measurement of a panel of HBV serology markers, including HBV "e" antigen (HBeAg), HBV surface antigen (HBsAg), and the antibody against HBsAg (anti-HBs). Our assay platform was able to detect each HBV marker with high specificity and sensitivity (with three orders of magnitude in dynamic range for each marker). Blinded analysis of HBV patient sera showed excellent correlation between our multiplexed quantitative HBsAg results and the qualitative results obtained using FDA-approved immunoassays, as well as those obtained using quantitative, single-plexed, enzyme-linked immunosorbent assays (ELISAs). The portable, automated, multiplexed, quantitative HBV serology assay platform we designed shows great promise as a more accessible alternative for HBV screening, diagnosis, and treatment monitoring.
View details for DOI 10.1038/s41598-019-52147-z
View details for PubMedID 31666635
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Nonliver Comorbidities in Patients With Chronic Hepatitis B.
Clinical liver disease
2019; 14 (3): 126–30
View details for DOI 10.1002/cld.829
View details for PubMedID 31632664
View details for PubMedCentralID PMC6784802
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Only one-third of hepatocellular carcinoma cases are diagnosed via screening or surveillance: a systematic review and meta-analysis.
European journal of gastroenterology & hepatology
2019
Abstract
Early hepatocellular carcinoma diagnosis is associated with better long-term survival. Studies of at-risk patients who are monitored in routine practice have reported an overall adherence rate to hepatocellular carcinoma screening/surveillance of approximately 60% and suboptimal diagnostic efficacy of the current screening/surveillance tools. However, it is unclear how many hepatocellular carcinoma patients were actually diagnosed via screening/surveillance given these obstacles. Therefore, via a systematic review of PubMed and Scopus databases from 2000 to 2019, we aimed to identify the proportion of patients with hepatocellular carcinoma diagnosed via screening/surveillance in routine practice.We included original research articles of studies of patients already diagnosed with hepatocellular carcinoma that reported the proportion of hepatocellular carcinoma diagnosed via screening/surveillance.The study included 60 studies and 50 554 hepatocellular carcinoma cases. The pooled proportion of hepatocellular carcinoma diagnosed by screening/surveillance was 37% (95% confidence interval: 31%-44%) and differed by geographic region (North America/Asia/Europe/Oceania/Africa/South America, 31%/42%/41%/30%/29%/47%, P = 0.017, respectively) and by surveillance interval (<12 months 39% vs. 12 months 19%, P < 0.01) but not by disease etiology, cirrhosis status, clinical setting, practice setting, hepatocellular carcinoma diagnosis period, or surveillance method.Globally, hepatocellular carcinoma was diagnosed via screening/surveillance in less than half of the patients (37%) regardless of healthcare setting or liver disease etiology and without improvement over time despite several recent guideline updates. Research is needed to understand the barriers to screening/surveillance to include medical as well as social and cultural influences.
View details for DOI 10.1097/MEG.0000000000001523
View details for PubMedID 31490419
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Hip fracture risk in patients with cirrhosis: does diabetes mellitus matter?
Hepatology (Baltimore, Md.)
2019
Abstract
In this article, Dr. Lai discusses the risk of hip fractures in persons with cirrhosis and when diabetes is present, the risk for hip fracture is 2.5 times greater (9.72 vs. 22.3 per 1000 person-years). [1] We agree with the author that the presence of cirrhosis carries risk for many other comorbidities to include bone fractures. [2] In addition, the presence of diabetes in the presence of liver disease is known to hasten liver disease progression so when both are present the risk of having more severe comorbidities would also likely increase. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/hep.30560
View details for PubMedID 30762889
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Reduced Hepatocellular Carcinoma Risk vs Bleeding Risk Associated With Aspirin.
JAMA oncology
2019
View details for PubMedID 31046061
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Rationale and design of the Hepatocellular carcinoma Early Detection Strategy study: A multi-center longitudinal initiative of the National Cancer Institute's Early Detection Research Network
CONTEMPORARY CLINICAL TRIALS
2019; 76: 49–54
View details for DOI 10.1016/j.cct.2018.11.008
View details for Web of Science ID 000456756800007
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Nonalcoholic Fatty Liver Disease and Renal Function Impairment: A Cross-Sectional Population-Based Study on Its Relationship From 1999 to 2016.
Hepatology communications
2019; 3 (10): 1334–46
Abstract
There is growing evidence that links nonalcoholic fatty liver disease (NAFLD) with impairment of renal function. As such, we aimed to demonstrate the trend of NAFLD, NAFLD with renal insufficiency (RI), disease awareness, and mortality over time. Patient data were extracted from the National Health and Nutrition Examination Survey (NHANES) 1999-2016. A total of 14,255 adult study participants without competing liver disease or heavy drinking and with complete laboratory data were included. NAFLD was defined using the U.S. Fatty Liver Index (USFLI) and RI was defined using the Chronic Kidney Disease Epidemiology Collaboration equation and urine albumin:creatinine ratio. Death data were obtained from the National Death Index (up to December 31, 2015). Prevalence of NAFLD in participants was 31.2% (95% confidence interval [CI], 30.01-32.46); of these participants, 22.05% (95% CI, 20.34-23.85) had RI. From 1999 to 2016, prevalence of both NAFLD without RI (P = 0.048) and NAFLD-RI (P = 0.006) increased significantly. Among those with NAFLD-RI, awareness of kidney disease was 8.56% (95% CI, 6.69-10.89), while awareness of liver disease among all NAFLD was 4.49% (95% CI, 3.17-6.33). Among those with NAFLD, mortality incidence per 1,000 person years was highest among those with severe RI in all-cause mortality (104.4; 95% CI, 83.65-130.39) and other residual causes of mortality (mean, 50.88; 95% CI, 37.02-69.93). Conclusion: Prevalence of NAFLD and NAFLD-RI has increased over the past 2 decades in the United States. Low kidney disease and liver disease awareness are major public health issues as those with NAFLD-RI have significantly higher mortality than those with only NAFLD.
View details for DOI 10.1002/hep4.1408
View details for PubMedID 31592492
View details for PubMedCentralID PMC6771162
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Healthcare resource utilization and costs by disease severity in an insured national sample of US patients with chronic hepatitis B
JOURNAL OF HEPATOLOGY
2019; 70 (1): 24–32
View details for DOI 10.1016/j.jhep.2018.09.021
View details for Web of Science ID 000453228900007
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Patient-Reported Outcomes in Patients Chronic Viral Hepatitis without Cirrhosis: The Impact of Hepatitis B and C Viral Replication.
Liver international : official journal of the International Association for the Study of the Liver
2019
Abstract
Chronic infections with hepatitis B or C (HBV and HCV) are associated with adverse clinical outcomes and patient-reported outcomes (PROs). The aim is to compare PRO scores in patients with chronic HBV and HCV without advanced liver disease before and after suppression/clearance of their infection.Patients with HCV and HBV infection prior to initiation of antiviral treatment and after viral suppression/eradication completed PRO questionnaires.We included 132 patients with HBV and 132 matched patients with HCV. Baseline PRO scores were significantly higher in patients with HBV in the domains of Physical Functioning, Role Physical, Bodily Pain, Social Functioning, and Role Emotional of SF-36, SF-6D utility, Emotional and Fatigue domains of CLDQ, Presenteeism and total Work Productivity Impairment of WPAI:SHP in comparison to patients with HCV by 5.8% to 13.2% of a PRO score range (all p<0.05). After viral suppression (HBV DNA<20IU/mL after 48 weeks of treatment for HBV) or eradication (SVR-12 for HCV), only Physical Functioning and Role Physical scores remained higher in HBV by 6.7%-9.9%, while other PRO scores became similar between HBV and HCV groups (p>0.05). The most prominent improvement of PROs in HCV was noted in Vitality, Emotional, Fatigue, and Worry domains. In addition, General Health, Worry, and Work Productivity scores were the most improved in HBV.Prior to treatment, PRO scores were lower in patients with HCV in comparison to HBV. After successful treatment, both groups of patients experienced improvement in some PRO domains confirming the positive impact of treatment. This article is protected by copyright. All rights reserved.
View details for DOI 10.1111/liv.14171
View details for PubMedID 31173468
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Combining hepatitis B core-related and surface antigens at end of nucleos(t)ide analogue treatment to predict off-therapy relapse risk
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
2019; 49 (1): 107–15
View details for DOI 10.1111/apt.15058
View details for Web of Science ID 000452872100013
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Sustained virologic response rates in patients with chronic hepatitis C genotype 6 treated with ledipasvir plus sofosbuvir or sofosbuvir plus velpatasvir
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
2019; 49 (1): 99–106
View details for DOI 10.1111/apt.15043
View details for Web of Science ID 000452872100012
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Tenofovir disoproxil fumarate reduces hepatocellular carcinoma, decompensation and death in chronic hepatitis B patients with cirrhosis.
Alimentary pharmacology & therapeutics
2019
Abstract
Lamivudine and entecavir reduce hepatic events and death in chronic hepatitis B (CHB) patients with cirrhosis, but the impact of tenofovir disoproxil fumarate (TDF) is less well studied.To investigate the effectiveness of TDF therapy in CHB patients with cirrhosis.We studied TDF-treated and untreated CHB patients with cirrhosis from three tertiary centres. TDF cohort included consecutive patients who received TDF for ≥12 months while the untreated cohort were historical controls receiving routine clinical care prior to the availability of anti-viral therapy. The primary outcome was 5-year cumulative probability of hepatocellular carcinoma (HCC) with secondary outcomes being hepatic decompensation and death or liver transplantation (LT).A total of 1088 (291 untreated and 797 TDF-treated) patients were included in the study. Five-year cumulative probabilities in untreated vs TDF-treated cohorts were 14.9% vs 9.8% for HCC (P = .07), 22.3% vs 5.9% for decompensation (P < .01) and 13.1% vs 1.1% for death or LT (P < .01) respectively. On multivariable Cox regression, TDF treatment was independently associated with reduced risks of HCC (adjusted hazard ratio [aHR] 0.46, P < .01), decompensating events (aHR 0.28, P = .01) and death or LT (aHR 0.06, P < .01). On sensitivity analyses, these risk reductions with TDF treatment were consistently demonstrated regardless of severity of liver disease and prior anti-viral treatment. TDF treatment led to sustained improvements in most validated prognostic scores for predicting HCC, decompensation and death.Compared to untreated patients, TDF treatment reduces the risks of HCC, hepatic decompensation and death in CHB patients with cirrhosis at 5 years.
View details for DOI 10.1111/apt.15499
View details for PubMedID 31524304
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Antiviral therapy and the development of osteopenia/osteoporosis among Asians with chronic hepatitis B.
Journal of medical virology
2019
Abstract
Recent studies have suggested a potential increase in the incidence of osteoporosis for patients receiving tenofovir disoproxil fumarate (TDF), but this issue remains controversial.Retrospective cohort study of 1,224 Asian chronic hepatitis B (CHB) patients >18 years without baseline osteopenia/osteoporosis seen at four U.S. centers from 2008-2016. Patients were categorized into three groups-treatment naive patients who initiated therapy with TDF (1) or entecavir (ETV) (2), or untreated patients (3). Patients were followed until development of osteopenia/osteoporosis or end of study.Of the 1,224 study patients, 276 were treated with TDF, 335 with ETV, and 613 were untreated. The prevalence of cirrhosis was lower for untreated patients (2.6% vs. 16.3% for TDF and 17.6% for ETV, p<0.001). The 8-year cumulative incidence rate of osteopenia/osteoporosis was 13.17% for TDF, 15.09% for ETV and 10.17% for untreated patients, with no statistically significant difference among the three groups (p=0.218). On multivariate Cox regression controlling for demographics, osteoporosis risk factors, albumin, and hepatitis B virus (HBV) DNA levels, neither TDF (adjusted HR 0.74, 95% CI: 0.34, 1.59) nor ETV (adjusted HR 0.98, 95% CI: 0.51, 1.90) were associated with increased osteopenia/osteoporosis risk compared to untreated patients.Our retrospective study suggests there is no significant increase in incidence of osteopenia/osteoporosis for CHB patients treated with TDF or ETV during median follow-up of about 4-5 years. However, further study with longer follow-up is needed as anti-HBV therapy is often lifelong or long-term and the development of osteopenia/osteoporosis can be a slow process. This article is protected by copyright. All rights reserved.
View details for PubMedID 30776311
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Clinical Features Associated with Survival Outcome in African-American Patients with Hepatocellular Carcinoma
AMERICAN JOURNAL OF GASTROENTEROLOGY
2019; 114 (1): 80–88
View details for DOI 10.1038/s41395-018-0261-y
View details for Web of Science ID 000463156500014
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Chronic hepatitis B and NASH: Is "fat" all bad?
Hepatology (Baltimore, Md.)
2019
Abstract
We read with interest the recent paper by Choi et al(1) on the impact of biopsy-proven NASH on CHB outcomes. The study concluded that compared to patients with CHB alone, CHB patients with concomitant NASH were more likely to have advanced fibrosis (F3/4) and shorter time to liver complications, and that superimposed NASH predicted poorer outcomes in those with advanced fibrosis. However, prior studies have also suggested that CHB patients with co-existing hepatic steatosis may not be at higher risk for disease progression; and in fact, more favorable long-term outcomes were even reported by some.
View details for DOI 10.1002/hep.30983
View details for PubMedID 31595532
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Individual surveillance using model-based hepatocellular carcinoma risk estimates in chronic hepatitis C patients after antiviral treatment
JOURNAL OF HEPATOLOGY
2019; 70 (1): 209–11
View details for DOI 10.1016/j.jhep.2018.09.016
View details for Web of Science ID 000453228900026
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Comparison of renal safety of tenofovir and entecavir in patients with chronic hepatitis B: Systematic review with meta-analysis.
World journal of gastroenterology
2019; 25 (23): 2961–72
Abstract
Recently, the American Association for the Study of Liver Disease suggested no preference between tenofovir (TDF) and entecavir (ETV) regarding potential long-term risks of renal complications. Over the years, renal safety has become a critical concern in nucleos(t)ide analog-treated patients due to the long-term use of these drugs. However, existing studies do not show significant differences in renal dysfunction between these two drugs. Further, there is a paucity of studies comparing the long-term renal effects of TDF and ETV.To investigate the effects of TDF and ETV on renal function, we performed systematic review and meta-analysis.Two investigators independently searched the Cochrane Library, MEDLINE, and Embase databases for randomized controlled trials and nonrandomized studies (NRSs) using the keywords "CHB", "Tenofovir", and "Entecavir", and additional references were obtained from the bibliographies of relevant articles published through December 2017. The quality of each study was assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment, Development and Evaluation criteria. The primary outcome was the change in serum creatinine level in the TDF and ETV groups at baseline, 6 mo, 12 mo and 24 mo.Nine NRSs comprising 2263 participants met the inclusion criteria. Changes in creatinine levels were higher in the TDF group than in the ETV group at 6 mo [mean difference (MD) = 0.03 mg/dL; 95%CI: 0.02-0.04; I2 = 0%], 12 mo (MD = 0.05 mg/dL; 95%CI: 0.02-0.08; I2 = 78%), and 24 mo (MD = 0.07 mg/dL; 95%CI: 0.01-0.13; I2 = 93%). The change in estimated glomerular filtration rate (eGFR) was significantly higher in the TDF group than in the ETV group at 6 mo [standardized mean difference (SMD), -0.22; 95%Cl: -0.36--0.08; I2 = 0%], 12 mo (SMD = -0.24; 95%Cl: -0.43--0.05; I2 = 50%), and 24 mo (-0.35; 95%Cl: -0.61- -0.09; I2 = 67%).TDF statistically significantly increased serum creatinine levels and decreased the eGFR in 6-24 mo compared to ETV, with moderate to low quality of evidence. However, the differences are negligible.
View details for DOI 10.3748/wjg.v25.i23.2961
View details for PubMedID 31249453
View details for PubMedCentralID PMC6589741
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Reply to LTE 19-00352.
Gastroenterology
2019
View details for DOI 10.1053/j.gastro.2019.05.046
View details for PubMedID 31150608
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Genetic analysis reveals functions of atypical polyubiquitin chains
ELIFE
2018; 7
View details for DOI 10.7554/eLife.42955
View details for Web of Science ID 000454492400001
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Systematic review and meta-analysis: real-world effectiveness of direct-acting antiviral therapies in chronic hepatitis C genotype 3 in Asia
BMJ OPEN GASTROENTEROLOGY
2018; 5 (1)
View details for DOI 10.1136/bmjgast-2018-000209
View details for Web of Science ID 000457748000007
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Autoantibodies in chronic hepatitis C virus infection: impact on clinical outcomes and extrahepatic manifestations
BMJ OPEN GASTROENTEROLOGY
2018; 5 (1)
View details for DOI 10.1136/bmjgast-2018-000203
View details for Web of Science ID 000457748000002
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Real-world effectiveness of sofosbuvir plus ribavirin for chronic hepatitis C genotype 2 in Asia: a systematic review and meta-analysis
BMJ OPEN GASTROENTEROLOGY
2018; 5 (1)
View details for DOI 10.1136/bmjgast-2018-000207
View details for Web of Science ID 000457748000005
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Combining hepatitis B core-related and surface antigens at end of nucleos(t)ide analogue treatment to predict off-therapy relapse risk.
Alimentary pharmacology & therapeutics
2018
Abstract
BACKGROUND: There remains an unmet need for convenient biomarkers to assess the risks of discontinuing nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB).AIM: To investigate if hepatitis B core-related antigen (HBcrAg) is an independent of surface antigen (HBsAg) for risk prediction of NA cessation.METHODS: This prospective multicentre study enrolled 135 CHB patients who stopped entecavir or tenofovir after achieving viral remission for a median of 25.2months. All patients stopped NA with negative HBeAg and undetectable viral DNA, and were then observed for clinical relapse and HBsAg loss. Predictors including HBsAg and HBcrAg levels were explored using Cox proportional hazard model and weighted to develop a risk score.RESULTS: During a median follow-up of 25.9months, clinical relapse and HBsAg loss occurred in 66 and eight patients, respectively, with a 5-year cumulative incidence of 56.1% (95% CI 46.7-66.0%) and 8.8% (95% CI 4.3-17.4%), respectively. HBcrAg was an independent relapse predictor, as well as HBsAg, age, ALT and tenofovir use. A score (SCALE-B) was calculated by the equation of 35*HBsAg (logIU/mL)+20*HBcrAg (log U/mL)+2*age (year)+ALT (U/L)+40 for tenofovir use. The concordance rates for clinical relapse were 0.87, 0.88, 0.87, 0.85 and 0.90 at 1, 2, 3, 4 and 5years, respectively. Moreover, HBsAg loss occurred exclusively in low-risk patients predicted by the score.CONCLUSIONS: Serum HBcrAg and HBsAg levels were independent predictors of off-NA relapse and can be factored into a risk score to guide treatment cessation in patients with CHB.
View details for PubMedID 30450681
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Serum M2BPGi level and risk of hepatocellular carcinoma after oral anti-viral therapy in patients with chronic hepatitis B
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
2018; 48 (10): 1128–37
View details for DOI 10.1111/apt.15006
View details for Web of Science ID 000449555100009
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Increasing Age and Comorbidities in a Population-based Study of Chronic Hepatitis B (CHB) Patients from 2007 to 2016 in Korea
WILEY. 2018: 135
View details for Web of Science ID 000450260400204
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Prevalence of Hepatitis B Vaccination Coverage Versus Serologic Evidence of Hepatitis B Immunity in Children and Adolescents in the United States, 1999-2016
WILEY. 2018: 1192A–1193A
View details for Web of Science ID 000446020503320
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Increasing Age and Comorbidities in a Population-Based Study of Chronic Hepatitis B (CHB) Patients from 2007 to 2016 in Korea
WILEY. 2018: 1224A–1225A
View details for Web of Science ID 000446020503378
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Increased Prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) in Asia: A Systematic Review and Meta-Analysis of 164 Studies and 1,704,963 Subjects from 13 Countries
WILEY. 2018: 983A
View details for Web of Science ID 000446020502522
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High Proportion and Long-Term Outcomes of Patients with Chronic Hepatitis B Have Indeterminate Clinical Phenotype As per AASLD 2018 Guidelines
WILEY. 2018: 1213A
View details for Web of Science ID 000446020503355
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High Prevalence of CKD and Associations between Fibrosis and Mortality in Patients with NAFLD
WILEY. 2018: 956A
View details for Web of Science ID 000446020502476
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Differential Presentation and Survival of Asian and Non-Asian Patients with HBV-Related Hepatocellular Carcinoma: A Multicenter United States (US) Study.
WILEY. 2018: 1233A
View details for Web of Science ID 000446020503395
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Hepatitis B Core-Related Antigen and the Novel Scale-B Score to Predict Relapse Risk after Cessation of Nucleos(t)Ide Analogs in Patients with Chronic Hepatitis B
WILEY. 2018: 236A–237A
View details for Web of Science ID 000446020500400
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Real-World Experience of All-Oral Directly Acting Antivirals in Asian Chronic Hepatitis C Patients-Real-World Evidence from the Asia Liver Consortium for HCV (REAL-C)
WILEY. 2018: 421A–422A
View details for Web of Science ID 000446020500724
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The Majority of Previously Uninfected High-Risk Adults in the United States Do Not Have Immunity Against Hepatitis B Virus: A Population-Based Study
WILEY. 2018: 134A–135A
View details for Web of Science ID 000446020500216
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Development and Validation of a Risk Score System Inclusive of Antiviral Therapy for Liver Cirrhosis Risk in Chronic Hepatitis B Infection
WILEY. 2018: 1193A–1194A
View details for Web of Science ID 000446020503322
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Prevalence of NAFLD and Liver Fibrosis in Asian Americans: A Population Based US Study from Nhanes, 2011-2014
WILEY. 2018: 1293A
View details for Web of Science ID 000446020503514
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A Phenome- Wide Association Study of Patatin-like Phospholipase Domain Containing 3 (PNPLA3) I148M Variant in 337,536 Participants of the UK Biobank Study
WILEY. 2018: 65A–66A
View details for Web of Science ID 000446020500104
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Effectiveness and Safety of DAA Treatment for Chronic Hepatitis C Patients with Previous Hepatocellular Carcinoma: Results from a Real-World, Multicenter Study of Asian Countries
WILEY. 2018: 34A–35A
View details for Web of Science ID 000446020500052
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Serial Changes in Serum Levels of Mac-2 Binding Protein Glycosylation Isomer and Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Patients Treated with Nucleos(t)Ide Analogues
WILEY. 2018: 230A–231A
View details for Web of Science ID 000446020500388
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The Impact of Non-Alcoholic Fatty Liver Disease ( NAFLD) on the Rates of Biochemical and Virological Responses in Chronic Hepatitis B Patients Under Antiviral Therapy
WILEY. 2018: 259A–260A
View details for Web of Science ID 000446020500439
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Incidence and Predictors of HBsAg Seroclearance in 10,614 Untreated Patients on Long-Term Follow-up: A Collaborative Study from North America and Asia Pacific
WILEY. 2018: 132A–133A
View details for Web of Science ID 000446020500213
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Ethnic-Specific Prevalence of HBV Infection and Exposure in US-Born and Foreign-Born Persons in the United States from 2011-2016
WILEY. 2018: 1212A–1213A
View details for Web of Science ID 000446020503354
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The Impact of Nonalcoholic Fatty Liver Disease (NAFLD) on the Development of Hepatocellular Carcinoma (HCC) in Chronic Hepatitis B Infection Patients
WILEY. 2018: 1189A
View details for Web of Science ID 000446020503314
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Nonalcoholic Fatty Liver Disease Increases Risk of Incident Chronic Kidney Disease in a Large Cohort of U.S Population
WILEY. 2018: 967A–968A
View details for Web of Science ID 000446020502495
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Distribution of Etiologies in Cirrhosis Admissions and Its Year Trend Burden in California (CA): A Population-Based Study with the Office of Statewide Health Planning and Development (OSHPD)
WILEY. 2018: 461A
View details for Web of Science ID 000446020500796
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Initial Evaluation, Laboratory Monitoring, and Surveillance of Chronic Hepatitis B (CHB) Patients: Results of a Real-World Analysis of 85,922 Commercially-Insured Patients
WILEY. 2018: 82A
View details for Web of Science ID 000446020500132
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Medical Monitoring Among Cirrhotic Patients in Real World Practice: A Nationwide US Study with 43,915 Cirrhotics
WILEY. 2018: 283A
View details for Web of Science ID 000446020500482
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Sex, Time-Period and Birthplace Specific Prevalence of Hepatitis B and Hepatitis C Virus Infection in Children and Adolescents in the United States during 1999-2016
WILEY. 2018: 1193A
View details for Web of Science ID 000446020503321
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Prevalence of Hepatitis C Infection in Ethnically Diverse US Population Including Asian Americans and US-Born Vs Foreign-Born Persons: A Population-Base Study during 2011-2016
WILEY. 2018: 931A–932A
View details for Web of Science ID 000446020502431
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Estimations of the Total Number of Undiagnosed Patients and Antiviral Treatment Rate for Chronic Hepatitis B in the United States
WILEY. 2018: 1214A
View details for Web of Science ID 000446020503357
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The Prevalence, Diagnosis Rate, and Treatment Rate of Hepatitis C Infection in the United States: A Nationwide Study
WILEY. 2018: 281A
View details for Web of Science ID 000446020500479
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National Estimates of Overall and Liver-Related Inpatient Care Cost in Cirrhotic Patients with Diverse Etiologies and Ethnicities in the United States (US)
WILEY. 2018: 110A
View details for Web of Science ID 000446020500176
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Hospital Cirrhosis Volume and Readmission in Patients with Cirrhosis in California
DIGESTIVE DISEASES AND SCIENCES
2018; 63 (9): 2267–74
View details for DOI 10.1007/s10620-018-4964-0
View details for Web of Science ID 000441941000017
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Disparities in hepatocellular carcinoma incidence by race/ethnicity and geographic area in California: Implications for prevention
CANCER
2018; 124 (17): 3551–59
View details for DOI 10.1002/cncr.31598
View details for Web of Science ID 000447376600011
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Higher mortality and hospital charges in patients with cirrhosis and acute respiratory illness: a population-based study
SCIENTIFIC REPORTS
2018; 8
View details for DOI 10.1038/s41598-018-28317-w
View details for Web of Science ID 000436955000024
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Temporal Trends in Disease Presentation and Survival of Patients With Hepatocellular Carcinoma: A Real-World Experience From 1998 to 2015
CANCER
2018; 124 (12): 2588–98
View details for DOI 10.1002/cncr.31373
View details for Web of Science ID 000434350700019
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Racial/ethnic- and county-specific prevalence of chronic hepatitis B and its burden in California.
Hepatology, medicine and policy
2018; 3: 6
Abstract
In the United States, the highest burden of chronic hepatitis B (CHB) and CHB-related liver cancer is in the state of California, primarily in the San Francisco (SF) Bay and Los Angeles (LA) areas. The aim of this study was to estimate county-specific hepatitis B surface antigen (HBsAg) prevalence and quantify CHB cases by age, race/ethnicity, nativity, and disease activity status.Twelve counties in SF Bay Area and three large counties in LA area were included for this analysis. Race/ethnicity-specific prevalence of HBsAg for each county and the state of California as a whole, was estimated by including prevalence data from the National Health and Nutrition Examination Survey and various studies that estimated HBsAg prevalence in US and foreign-born Asian Pacific Islanders, Hispanic, and Black populations. In addition, clinical data of 2000 consecutive CHB patients (collected between 2009 and 2014) from a large clinical consortium in the SF Bay area were used to calculate the age-specific disease burden.Of the 15 counties analyzed, SF had the highest HBsAg prevalence (1.78%), followed by Santa Clara (1.63%) and Alameda (1.45%). The majority of CHB cases were estimated to be in LA County (83,770), followed by Santa Clara (31,273), and Alameda (23,764). Among the CHB cases, 12.7% is active HBeAg positive, 24.2% is active HBeAg negative, and 10.6% has cirrhosis.This study confirms and quantifies the current burden of CHB in high endemic counties in the state of California using population-level estimates combined with clinical data including those from the community.
View details for DOI 10.1186/s41124-018-0034-7
View details for PubMedID 30288329
View details for PubMedCentralID PMC5987626
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Multiplexed precision genome editing with trackable genomic barcodes in yeast
NATURE BIOTECHNOLOGY
2018; 36 (6): 512-+
View details for DOI 10.1038/nbt.4137
View details for Web of Science ID 000434689200019
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Author response to "Cryptogenic hepatocellular carcinoma (HCC) had worse overall survival of disease than viral HCC patients"
LIVER INTERNATIONAL
2018; 38 (6): 1141
View details for DOI 10.1111/liv.13680
View details for Web of Science ID 000434228400023
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Editorial: the durability of seroconversion of hepatitis B e antigen in the treatment of chronic hepatitis B with PEG-interferon alfa-2a
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
2018; 47 (11): 1556–57
View details for DOI 10.1111/apt.14657
View details for Web of Science ID 000434038400028
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More advanced disease and worse survival in cryptogenic compared to viral hepatocellular carcinoma
LIVER INTERNATIONAL
2018; 38 (5): 895–902
View details for DOI 10.1111/liv.13613
View details for Web of Science ID 000435855300017
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Real-world rates of hepatitis B surface antigen seroclearance in patients with chronic hepatitis B: a systematic review, conventional aggregated data meta-analysis and individual patient data meta-analysis
ELSEVIER SCIENCE BV. 2018: S478–S479
View details for DOI 10.1016/S0168-8278(18)31207-8
View details for Web of Science ID 000461068602174
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Higher in-hospital and post-discharge mortality and hospital charges in cirrhotic patients with acute respiratory illness in the United States
ELSEVIER SCIENCE BV. 2018: S704–S705
View details for DOI 10.1016/S0168-8278(18)31672-6
View details for Web of Science ID 000461068603215
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Using Wisteria floribunda agglutinin-positive Mac2-binding protein in combination with the FIB-4 index to predict significant liver fibrosis
ELSEVIER SCIENCE BV. 2018: S650–S651
View details for DOI 10.1016/S0168-8278(18)31556-3
View details for Web of Science ID 000461068603099
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Validation of AASLD treatment guideline eligibility based on disease outcomes of large community and clinical cohorts of chronic hepatitis B patients
ELSEVIER SCIENCE BV. 2018: S503
View details for DOI 10.1016/S0168-8278(18)31253-4
View details for Web of Science ID 000461068602220
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Validation of a clinical scoring system to predict risk of hepatocellular carcinoma in an ethnically diverse cohort of patients with chronic hepatitis C virus infection
ELSEVIER SCIENCE BV. 2018: S305–S306
View details for DOI 10.1016/S0168-8278(18)30830-4
View details for Web of Science ID 000461068601222
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Soluble cytotoxic T-lymphocyte-associated antigen-4 and soluble programmed cell death protein-1 are predictive immune checkpoint seromarkers for spontaneous functional cure of chronic hepatitis B with opposite effects
ELSEVIER SCIENCE BV. 2018: S476
View details for DOI 10.1016/S0168-8278(18)31201-7
View details for Web of Science ID 000461068602168
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Renal outcomes in chronic hepatitis b patients treated with tenofovir disoproxil fumarate or entecavir: a propensity score matched study
ELSEVIER SCIENCE BV. 2018: S519–S520
View details for DOI 10.1016/S0168-8278(18)31287-X
View details for Web of Science ID 000461068602254
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Adherence to AASLD treatment guidelines on treatment initiation among treatment-eligible patients with chronic hepatitis B: Experiences from primary care and referral practices
ELSEVIER SCIENCE BV. 2018: S505–S506
View details for DOI 10.1016/S0168-8278(18)31258-3
View details for Web of Science ID 000461068602225
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Ethnic differences in HCV-related HCC outcomes: Report from the Real-world Evidence by the Asia Pacific Rim Liver Consortium for HCC (REAL-HCC)
ELSEVIER SCIENCE BV. 2018: S304–S305
View details for DOI 10.1016/S0168-8278(18)30828-6
View details for Web of Science ID 000461068601220
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Estimated the number of undiagnosed patients and antiviral treatment rate of chronic hepatitis B in the US based on the Truven Health MarketScan Database
ELSEVIER SCIENCE BV. 2018: S481–S482
View details for DOI 10.1016/S0168-8278(18)31212-1
View details for Web of Science ID 000461068602179
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Performance of Wisteria floribunda agglutinin-positive Mac2-binding protein as an HCC biomarker in an ethnically diverse cohort of patients with chronic HBV and HCV
ELSEVIER SCIENCE BV. 2018: S439
View details for DOI 10.1016/S0168-8278(18)31119-X
View details for Web of Science ID 000461068602086
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Clinical presentation and survival of Asian and non-Asian patients with HBV-related hepatocellular carcinoma (HBV-HCC): Results of 767 United States patients with long-term follow-up
ELSEVIER SCIENCE BV. 2018: S443
View details for DOI 10.1016/S0168-8278(18)31125-5
View details for Web of Science ID 000461068602092
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Treatment of chronic hepatitis B and renal impairment in patients with and without cirrhosis
ELSEVIER SCIENCE BV. 2018: S511–S512
View details for DOI 10.1016/S0168-8278(18)31271-6
View details for Web of Science ID 000461068602238
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The time trend of hospital admissions, inpatient mortality rate, and hospital cost of hospitalizations associated with cirrhosis in the United States: an analysis on the National Inpatient Sample
ELSEVIER SCIENCE BV. 2018: S733
View details for DOI 10.1016/S0168-8278(18)31726-4
View details for Web of Science ID 000461068603268
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Sustained virologic response rates (SVR-12) for chronic hepatitis C genotype 6 patients treated with Ledipasvir/Sofosbuvir or Sofosbuvir/Velpatasvir
ELSEVIER SCIENCE BV. 2018: S284–S285
View details for DOI 10.1016/S0168-8278(18)30786-4
View details for Web of Science ID 000461068601178
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Sustained virologic response (SVR) to direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC): a systematic review and meta-analysis
ELSEVIER SCIENCE BV. 2018: S259–S260
View details for DOI 10.1016/S0168-8278(18)30733-5
View details for Web of Science ID 000461068601125
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Is renal impairment associated with chronic hepatitis B - a propensity score matched study of healthy non-hepatitis B patients compared to patients with untreated chronic hepatitis B
ELSEVIER SCIENCE BV. 2018: S512–S513
View details for DOI 10.1016/S0168-8278(18)31272-8
View details for Web of Science ID 000461068602239
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The time trend of proportion and mortality rate of admissions associated with acute respiratory illness in cirrhotic patients with diverse ethnicityand socioeconomic status: an analysis on the US National Inpatient Sample
ELSEVIER SCIENCE BV. 2018: S146
View details for DOI 10.1016/S0168-8278(18)30507-5
View details for Web of Science ID 000461068600290
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Men have higher mortality in cirrhosis: outcomes by gender and etiology in a large, diverse cohort
ELSEVIER SCIENCE BV. 2018: S709–S710
View details for DOI 10.1016/S0168-8278(18)31680-5
View details for Web of Science ID 000461068603223
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Changes in serum levels of the novel mac-2 binding protein glycosylation isomer and risk of hepatocellular carcinoma among chronic hepatitis B patients treated with nucleos(t)ide analogues
ELSEVIER SCIENCE BV. 2018: S496–S498
View details for DOI 10.1016/S0168-8278(18)31242-X
View details for Web of Science ID 000461068602209
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A risk score combining quantitative hepatitis B surface antigen and core-related antigen levels to predict off-therapy relapse after cessation of nucleos(t)ide analogues in patients with chronic hepatitis B
ELSEVIER SCIENCE BV. 2018: S498
View details for DOI 10.1016/S0168-8278(18)31243-1
View details for Web of Science ID 000461068602210
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Suboptimal rates of effective hepatitis B vaccination in adults at high risk of infection in the United States from 1999-2014
ELSEVIER SCIENCE BV. 2018: S480–S481
View details for Web of Science ID 000461068602177
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Effective hepatitis B vaccination by serologic results in the United States: a population-based study from 1999-2016
ELSEVIER SCIENCE BV. 2018: S480
View details for Web of Science ID 000461068602176
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Economic and clinical burden of viral hepatitis in California: A population-based study with longitudinal analysis.
PloS one
2018; 13 (4): e0196452
Abstract
Economic burden of HBV and HCV infection are trending upwards.Compare hepatitis B virus (HBV) and hepatitis C virus (HCV) related hospital admission rates, charges, mortality rates, causes of death in a US population-based study.Retrospective cohort analysis of HBV and HCV patients from the California Office of Statewide Health Planning and Development (2006-2013) database.A total of 23,891 HBV and 148,229 HCV patients were identified. Across the 8-year period, the mean increase for all-cause ($1,863 vs $1,388) and liver-related hospitalization charges ($1,175 vs $675) were significantly higher for the HBV cohort compared to the HCV cohort. HBV patients had significantly higher liver-related hospital charges per person per year than HCV patients after controlling for covariates ($123,239 vs $111,837; p = 0.002). Compared to HCV patients, adjusted mortality hazard ratio was slightly lower in HBV patients (relative risk = 0.96; 95% CI 0.94-0.99). The major causes and places of death were different. The three major causes of death for HBV were: other malignant neoplasms (35%), cardiovascular disease/other circulatory disorders (17%), and liver-related disease (15%) whereas for HCV patients were: liver-related disease (22%), other malignant neoplasms (20%), and cardiovascular disease (16%). Regarding the place of death, 53% of HBV patients and 44% of HCV patients died in hospital inpatient, respectively.HBV patients incurred higher liver-related hospital charges and higher mean increase for all-cause and liver-related hospitalization charges over the 8-year period compared to HCV patients. HBV patients had slightly lower mortality rate and their major causes and places of death were noticeably different from HCV patients.
View details for PubMedID 29708985
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Changes in Renal Function in Patients With Chronic HBV infection Treated with Tenofovir Disoproxil Fumarate vs Entecavir.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2018
Abstract
It is unclear whether drugs used to treat chronic hepatitis B virus (HBV) infection cause significant renal impairment. We compare adjusted mean estimated glomerular filtration rates (eGFR; mL/min/1.73 m2) of patients with chronic HBV infection treated with tenofovir disoproxil fumarate (TDF) vs patients treated with entecavir.We performed a retrospective study of patients with chronic HBV infections treated with TDF (n=239) or entecavir (n=171), from 2000 through 2016, followed for a mean time of 43-46 months. Levels of serum creatinine were measured ≥12 months while patients received treatment. Patients did not have prior exposure to adefovir or HCV, HDV, or HIV co-infection. We performed propensity score matching (PSM) for age, sex, presence of hypertension, diabetes mellitus, baseline eGFR, cirrhosis, and follow-up duration. We performed multivariate generalized linear modeling, adjusting for cirrhosis, diabetes, and hypertension, to estimate adjusted mean eGFR for matched and unmatched cohorts. Cox regression was used to identify predictors of renal impairment RESULTS: eGFRs were ≥60, after PSM, in 116 patients given entecavir and in 116 patients given TDF; eGFRs were <60 in 32 patients given entecavir and 26 patients given TDF. Multivariate generalized linear modeling of the unmatched overall and <60 eGFR cohorts revealed significantly lower adjusted mean eGFRs in patients given TDF (all P<.001). However, in the eGFR ≥60 PSM cohort, the adjusted mean eGFR was similar between patients receiving either treatment. In Cox regression analysis, TDF was not associated with mild or moderate renal impairment compared with entecavir.In a retrospective study of patients with chronic HBV infections treated with TDF vs entecavir, we found that TDF was not associated with higher risk of worsening renal function during short- or intermediate-term follow-up periods, among patients without significant renal impairment. Additional studies, with longer follow-up periods, are needed because treatment for chronic HBV infection is generally long term or life-long. For patients with baseline renal impairment, significant renal decline was among patients given TDF compared to patients given entecavir.
View details for PubMedID 30130625
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Rising Inpatient Encounters and Economic Burden for Patients with Nonalcoholic Fatty Liver Disease in the USA.
Digestive diseases and sciences
2018
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the fastest-growing chronic liver disease. However, little is known about NAFLD inpatient resource utilization and clinical outcomes.The aim of this study was to quantify inpatient NAFLD encounters using patient-level data over time.This was a retrospective analysis of de-identified data for NAFLD patients from the California Patient Discharge Database from 2006 to 2013. NAFLD patients were identified by ICD9 codes 571.40, 571.41, 571.49, 571.8, and 571.9.NAFLD patients (n = 91,558) were predominantly female (60%), 45-65 years old (44%), and white (53%). Inpatient encounters increased from 8153 in 2006 to 16,457 in 2013 and were associated with a 207% increase in charges ($686 million in 2006 to $1.42 billion in 2013) and average increase in charges of 9.8% per year adjusting for inflation. Comorbidities (obesity, diabetes, hyperlipidemia, cardiovascular disease, other cancer, and renal disease) increased significantly over time (all P < 0.05). From 2006 to 2011, there were 11,463 deaths (1849 for liver-related hospitalizations) (mean follow-up 4.00 ± 2.13 years). The most significant predictors of death were age > 75 (aHR 3.9, P < 0.0001), male gender (aHR 1.10, P < 0.0001), white race (aHR 1.2, P < 0.0001), decompensated cirrhosis (aHR 2.1, P < 0.0001), and cancer other than HCC (aHR 3.2, P < 0.0001). Within the liver-related hospitalization cohort, mortality predictors were similar, except for Hispanic race (aHR 0.92, P < 0.0096) and renal disease (aHR 1.50, P < 0.0001).The number of NAFLD inpatient encounters increased significantly from 2006 to 2013, as did the inflation-adjusted inpatient charges. The most significant predictors of death were non-liver cancers (HR 3.11, P < 0.0001, CI 3.06-3.16) and age > 75 years (HR 3.94, P < 0.0001, HR 3.86-4.03).
View details for PubMedID 30327963
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Sustained virologic response rates in patients with chronic hepatitis C genotype 6 treated with ledipasvir+sofosbuvir or sofosbuvir+velpatasvir.
Alimentary pharmacology & therapeutics
2018
Abstract
Hepatitis C virus (HCV) genotype 6 (GT 6) is the predominant genotype among certain Asian populations. The availability of newer DAA options is limited in many parts of Asia.To compare sustained virologic response (SVR-12) rates between ledipasvir and sofosbuvir (LDV+SOF) and velpatasvir+SOF (SOF+VEL) for patients with HCVGT6 infection.Retrospective study of consecutive adult HCVGT6 patients identified via ICD 9 code: 070.5 from United States treatment centers. Treatment was LDV+SOF or SOF+VEL for 8-24 weeks. A 1:1 propensity score matching (PSM) on HCV RNA, cirrhosis, alanine aminotransferase, aspartate aminotransferase, platelets, and fibrosis score was conducted among the treatment-naïve HCVGT6 patients to balance groups and isolate treatment effects.After exclusion criteria, 149 patients remained (n = 135 treatment-naïve; n = 14 treatment-experienced). The mean age was 63.8 ± 10.2 years, 66.9% male, and 93.9% Vietnamese. In treatment-naïve arm, 52.2% LDV+SOF cohort were cirrhotic compared to 11.6% SOF+VEL cohort (P < 0.0001). SVR-12 for LDV+SOF was 96.4% and 100% for the SOF+VEL cohort (P = 0.22). SVR-12 for cirrhotic patients was 95.4% (n = 41/43) for LDV+SOF and 100.0% (n = 5/5) for SOF+VEL (P = 0.62). After PSM (n = 33 per group), LDV+SOF SVR-12 rate was 97.0% compared to SOF+VEL SVR-12 of 100% (P = 0.31). The treatment-experienced group (n = 14), were all treated with LDV+SOF-SVR-12 of 92.3%.Whether treatment-naïve, treatment-experienced, or cirrhotic patients with HCV GT 6 residing in the US had excellent outcomes when treated with SOF+VEL or LDV+SOF. Since LDV+SOF is more readily available globally, our results may provide clinicians with a treatment option when cost and availability limit the treatment choice.
View details for PubMedID 30467877
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GALAD Score for Hepatocellular Carcinoma Detection in Comparison to Liver Ultrasound and Proposal of GALADUS Score.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
2018
Abstract
The GALAD score is a serum biomarker-based model that predicts the probability of having hepatocellular carcinoma (HCC) in patients with chronic liver disease. We aimed to assess the performance of the GALAD score in comparison to liver ultrasound for detection of HCC.A single center cohort of 111 HCC and 180 controls with cirrhosis or chronic hepatitis B and a multicenter cohort of 233 early HCC and 412 cirrhosis patients from the Early Detection Research Network (EDRN) Phase 2 HCC Study were analyzed.The area under the ROC curve (AUC) of the GALAD score for HCC detection was 0.95 [95% confidence interval (CI): 0.93-97], which was higher than the AUC of ultrasound (0.82, P<0.01). At a cut off of -0.76, the GALAD score had a sensitivity of 91% and a specificity of 85% for HCC detection. The AUC of the GALAD score for early stage HCC detection remained high at 0.92 [95%CI: 0.88-0.96] (cut off -1.18, sensitivity 92%, specificity 79%). The AUC of the GALAD score for HCC detection was 0.88 (95% CI, 0.85-0.91) in the EDRN cohort. The combination of GALAD and ultrasound (GALADUS score) further improved the performance of the GALAD score in the single center cohort, achieving an AUC of 0.98 [95%CI: 0.96-0.99] (cut off -0.18, sensitivity 95%, specificity 91%).The performance of the GALAD score was superior to ultrasound for HCC detection. The GALADUS score further enhanced the performance of the GALAD score.The GALAD score was validated in the US.
View details for PubMedID 30464023
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Rationale and design of the Hepatocellular carcinoma Early Detection Strategy study: A multi-center longitudinal initiative of the National Cancer Institute's early Detection Research Network.
Contemporary clinical trials
2018
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy with a steadily rising incidence and associated morbidity and mortality. Cirrhosis of the liver is presently the leading risk factor for developing HCC. Abdominal imaging, with or without alpha-fetoprotein (AFP) testing, every 6 months is the current surveillance strategy for patients at risk. The available biomarkers for detecting this cancer at an early stage have inadequate sensitivity and specificity.The Hepatocellular carcinoma Early Detection Strategy (HEDS) study, a multi-center initiative of the National Cancer Institutes' (NCI) Early Detection Research Network (EDRN), launched an effort to establish what has become the nation's largest comprehensive biorepository and database on patients at high risk of developing HCC. The cohort has been developed in six clinical centers across the country. Subjects are enrolled for a five-year period involving data and specimen collection every six months in accordance with standard surveillance for HCC. Extensive clinical data are collected and specimens are stored at a central repository.The database and biorepository contain longitudinally collected clinical data and serum and plasma samples from 1482 participants with cirrhosis and without evidence of HCC at baseline. Fifty-six percent are male, 85% Caucasian, 30% have a history of chronic HCV and 71% have compensated cirrhosis.The HEDS cohort provides opportunities for the continued study of the incidence and course of HCC in a comprehensively followed population of patients at high risk for this malignancy. Further, the EDRN biorepository provides a distinct opportunity for the development of novel biomarkers. Trial registry URL: https://edrn.nci.nih.gov/protocols/316-hepatocellular-carcinoma-early-detection-strategy.
View details for PubMedID 30439517
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Reduced Incidence of Hepatocellular Carcinoma with Tenofovir in Chronic Hepatitis B Patients with and without Cirrhosis - a Propensity Score Matched Study.
The Journal of infectious diseases
2018
Abstract
The effect of newer oral anti-HBV medication, tenofovir disoproxil (TDF), on liver related outcomes among Asians is limited. We examined the effect of TDF on incidence of hepatocellular carcinoma (HCC) within an Asian chronic hepatitis B (CHB) population.Retrospective cohort study: 6914 adult, non-transplant, CHB mono-infected patients recruited from 6 U.S. referral, community medical centers, and a community based Taiwan cohort: 774 patients received TDF; 6140 not treated. Propensity score matching [(PSM); age, sex, HBeAg, HBV DNA, ALT, baseline cirrhosis status, follow-up time] balanced the groups (n=591, treated vs. untreated). Kaplan-Meier estimated cumulative risk of HCC. Cox proportional hazards models estimated HCC risk between groups.The eight-year cumulative HCC incidence was significantly higher in PSM untreated group (20.13% vs 4.69%, p<0.0001). Cirrhosis was a significant predictor for HCC (aHR: 5.36; 95% CI: 2.73 - 10.51, p<0.001). On multivariate analysis adjusting for age, sex, HBV DNA, ALT and study site, TDF was associated with a 77% [0.23 (0.56 - 0.92)] HCC risk reduction in patients with cirrhosis and 73% [0.27 (0.07 - 0.98)] reduction in patients without cirrhosis.Among cirrhotic and non-cirrhotic Asian CHB patients, TDF therapy was significantly associated with an eight-year HCC cumulative incidence rate reduction.
View details for PubMedID 29982737
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A New Conception-Pre-HCC Disease.
Hepatology (Baltimore, Md.)
2018
Abstract
The American Association for the Study of Liver Diseases (AASLD) recently updated the clinical practice guidelines on management of hepatocellular carcinoma (HCC)(1). The guidelines provide detailed recommendations in surveillance, diagnosis, and treatments for patients with HCC, we notice there is still a void in the recommendations for pre-HCC disease, which is not yet overtly cancerous but appears to be on the way to developing a HCC. Considering the high incidence and mortality of HCC worldwide, the prevention of HCC should be a high priority consideration, and there should be more focus on the pre-HCC disease.
View details for PubMedID 30070377
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Racial/ethnic- and county-specific prevalence of chronic hepatitis B and its burden in California
Hepatology, Medicine and Policy
2018; 3 (6)
View details for DOI 10.1186/s41124-018-0034-7
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Editorial: the durability of seroconversion of hepatitis B e antigen in the treatment of chronic hepatitis B with PEG-interferon alfa-2a.
Alimentary pharmacology & therapeutics
2018; 47 (11): 1556–57
View details for PubMedID 29878418
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Autoantibodies in chronic hepatitis C virus infection: impact on clinical outcomes and extrahepatic manifestations.
BMJ open gastroenterology
2018; 5 (1): e000203
Abstract
To examine the role that autoantibodies (auto-abs) play in chronic hepatitis C virus (HCV) regarding demographics, presence of extrahepatic manifestations and long-term outcomes in a large US cohort.Auto-abs have been reported to be prevalent in patients with chronic HCV infection, but data on the natural history of these patients are limited.The study included 1556 consecutive patients with HCV without concurrent HIV and/or HBV who had testing for antinuclear antibody (ANA), antimitochondrial antibody (AMA), antismooth muscle antibody (ASMA) and/or antiliver kidney microsomal antibody (LKM). Primary outcomes included development of cirrhosis, hepatic decompensations, hepatocellular carcinoma (HCC), mortality and/or sustained virological response (SVR) to antiviral therapy.A total of 388 patients tested positive for any auto-ab (ANA 21.8%, ASMA 13.3%, AMA 2.2% and LKM 1.2%). Patients who tested positive versus negative were more likely to be women (29.3% vs 20.9%, p<0.001) and less likely to achieve SVR with most treated patients receiving interferon-based therapies (37.2% vs 47.1%, p=0.031). There was no difference between groups for baseline laboratory data, disease state or rate of extrahepatic manifestations (42.8% vs 45.0%, p=0.44). Kaplan-Meier analysis revealed no statistically significant difference between groups for the 10-year development of cirrhosis, hepatic decompensations, HCC nor survival. Furthermore, auto-ab positivity was only found to be a predictor for a lower rate of SVR on multivariate analysis (adjusted OR=1.61, 95 % CI 1.00 to 2.58, p=0.048).In our cohort, auto-ab positivity was common, especially in women, and predicted a lower rate of SVR but otherwise had no impact on the natural history of chronic HCV or presence of extrahepatic manifestations.
View details for PubMedID 29755758
View details for PubMedCentralID PMC5942460
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Safety and Efficacy of Vesatolimod (GS-9620) in Patients with Chronic Hepatitis B Who Are Not Currently on Antiviral Treatment.
Journal of viral hepatitis
2018
Abstract
Vesatolimod is an oral agonist of toll-like receptor 7 designed to minimize systemic exposure and side effects. We assessed the safety and efficacy of vesatolimod in viremic chronic hepatitis B (CHB) patients not currently on oral antiviral treatment (OAV) in a Phase 2, multicenter, double-blind, randomized, placebo-controlled study.192 patients stratified by HBeAg status and alanine aminotransferase level were randomized 2:2:2:1 to receive oral vesatolimod (1-, 2-, or 4-mg) or placebo once weekly for 12 weeks; tenofovir disoproxil fumarate (300-mg daily) was administered daily for 48 weeks. Efficacy was assessed by quantitative serum HBsAg decline at Week 24 from baseline. In addition to safety assessments, changes in whole blood interferon-stimulated gene (ISG) transcripts and serum cytokines were explored.Most patients were male (64.1%) and HBeAg-negative (60.9%) at baseline. Among vesatolimod-treated patients, most (60.4-69.1%) experienced ≥1 treatment emergent adverse event; the majority were mild or moderate in severity. No clinically meaningful differences in HBsAg changes from baseline were observed between treatment groups. No patients experienced HBsAg loss, while 3 patients experienced HBeAg loss and hepatitis B e-antibody seroconversion. HBV DNA suppression rates were similar across all treatment arms at Week 24. ISG15 induction was dose-dependent and did not correlate with HBsAg changes. A small proportion of patients exhibited dose-dependent interferon-α induction that correlated with grade of influenza-like adverse events. Overall, vesatolimod is safe and well-tolerated in CHB patients. Though consistent dose-dependent pharmacodynamic induction of ISGs was demonstrated, it did not result in clinically significant HBsAg decline. This article is protected by copyright. All rights reserved.
View details for PubMedID 29851204
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Higher risk of hepatocellular carcinoma in Hispanic patients with hepatitis C cirrhosis and metabolic risk factors.
Scientific reports
2018; 8 (1): 7164
Abstract
The effect of metabolic syndrome on chronic liver diseases other than non-alcoholic fatty liver disease has not been fully elucidated. Our goal was to evaluate if metabolic syndrome increased the risk of liver-related complications, specifically hepatocellular carcinoma (HCC) and decompensation, in cirrhotic chronic hepatitis C (CHC) patients. We conducted a retrospective cohort study of 3503 consecutive cirrhotic CHC patients seen at Stanford University from 1997-2015. HCC developed in 238 patients (8-year incidence 21%) and hepatic decompensation in 448 patients (8-year incidence 61%). The incidence of HCC and decompensation increased with Hispanic ethnicity, diabetes, and number of metabolic risk factors. Multivariate Cox regression analysis demonstrated that, independent of HCV therapy and cure and other background risks, Hispanic ethnicity with ≥2 metabolic risk factors significantly increased the risk of HCC and hepatic decompensation. There was no interaction between Hispanic ethnicity and metabolic risk factors. All in all, metabolic risk factors significantly increase the risk of liver-related complications in cirrhotic CHC patients, especially HCC among Hispanics. As the prevalence of metabolic syndrome increases globally, targeted health interventions are needed to help curb the effects of metabolic syndrome in CHC patients.
View details for PubMedID 29740031
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Effects of Treatment of Chronic HBV Infection on Patient-reported Outcomes.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2018
Abstract
Chronic infection with hepatitis B virus (HBV) causes liver disease and cirrhosis. It is not clear how treatment of chronic HBV infection affects patient-reported outcomes (PROs). We aimed to assess changes in PROs in patients treated for chronic HBV infection.We collected and analyzed PRO data from 242 patients with chronic HBV infection (without advanced fibrosis or cirrhosis) enrolled in 2 international phase 2 blinded controlled clinical trials from 2015 through 2017. In these trials, patients were treated with an approved oral antiviral regimen (tenofovir, entecavir, adefovir, lamivudine, or telbivudine) and then randomly assigned to groups given vesatolimod (an oral agonist of toll like receptor 7) or placebo. PROs were collected using the Short Form-36, the Chronic Liver Disease Questionnaire, and the Work Productivity and Activity Impairment: Specific Health Problem scoring system before treatment, on treatment weeks 12, 24, and 48.We did not observe significant differences in PROs between patients receiving vesatolimod vs placebo. At baseline, patients with viral suppression (level of HBV DNA <20 IU/mL) had higher PRO scores (by up to +10.6% of a PRO range size). During treatment, there were significant increases in scores for some domains of Chronic Liver Disease Questionnaire and in General Health scores of Short Form-36 (increases of up to 4.9%; P<.05). Patients with a decrease of at least 2.7 log10IU/mL in level of HBV DNA had substantially larger increases in PRO scores (mean increases of up to 7.2% by week 48; P<.05 for 10 of 22 studied PROs). In multivariate analysis, a reduction in viral load was independently associated with increases in PROs (betas values up to 1.6% per log10IU/mL decrease; P<.05).In an analysis of data from phase 2 trials, we associated active treatment of chronic HBV infection with increased PRO scores. These findings support inclusion of PRO endpoints in assessments of efficacy and safety in clinical trials of treatments for HBV infection.
View details for PubMedID 29505905
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Rate of hepatocellular carcinoma surveillance remains low for a large, real-life cohort of patients with hepatitis C cirrhosis.
BMJ open gastroenterology
2018; 5 (1): e000192
Abstract
In patients with chronic hepatitis C (CHC) cirrhosis, imaging for hepatocellular carcinoma (HCC) is recommended every 6 months to maximise eligibility for curative treatment. The aim was to determine the adherence rate and outcomes among patients with CHC cirrhosis and whether the adherence rate has improved over time.Retrospective cohort study of patients with CHC cirrhosis (n=2366) monitored for ≥1 year at Stanford University Medical Center between January 2001 and August 2015.Overall demographics: mean age 54; 62.3% men; 48.3% Caucasian. 24.4% adherent to imaging every 6 months per European Association for the Study of the Liver 2000 and American Association for the Study of Liver Diseases (AASLD) 2011 criteria and 44% at least every 12 months per AASLD 2005 criteria. No significant change in adherence before and after 2011. Predictors of multivariable analysis of adherence were age >54 (OR 1.74, p<0.0001), Asian ethnicity (OR 2.23, p<0.0001), liver decompensation (OR 2.40, p<0.0001) and having ≥2 clinical visits per year (OR 1.33, p=0.01). During follow-up, 9.6% were diagnosed with HCC. Adherent patients were more likely to have smaller tumours (2.3 vs 3.3 cm, p=0.0020), be within the Milan criteria for liver transplants (73.2% vs 54.8%, p=0.006) and receive curative HCC treatment (43.6% vs 24.0%, p=0.005). On multivariable analysis, curative treatment (HR 0.32, p=0.001) and every 6-month imaging (HR 0.34, p=0.005), but not every 6-12 month imaging, were associated with reduced risk of mortality.Adherence to HCC surveillance continues to be poor. Adherent patients with HCC were more likely to undergo curative treatment and have better survival. Research understanding barriers to surveillance is needed.
View details for PubMedID 29607053
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Hospital Cirrhosis Volume and Readmission in Patients with Cirrhosis in California.
Digestive diseases and sciences
2018
Abstract
Patients with cirrhosis are at high readmission risk. Using a large statewide database, we evaluated the effect of hospital cirrhosis-related patient volume on 30-day readmissions in patients with cirrhosis.We conducted a retrospective study of the Healthcare Cost and Utilization Project State Inpatient Database for adult patients with cirrhosis, as defined by International Classification of Diseases, Ninth Revision (ICD-9) codes, hospitalized in California between 2009 and 2011. Multivariable logistic regression analysis was performed to evaluate the effect of hospital volume on 30-day readmissions.A total of 69,612 patients with cirrhosis were identified in 405 hospitals; 24,062 patients were discharged from the top 10% of hospitals (N = 41) by cirrhosis volume, and 45,550 patients in the bottom 90% (N = 364). Compared with higher-volume centers, lower-volume hospitals cared for patients with similar average Quan-Charlson-Deyo (QCD) comorbidity scores (6.54 vs. 6.68), similar proportion of hepatitis B and fatty liver disease, lower proportion of hepatitis C (34.8 vs. 41.5%) but greater proportion of alcoholic liver disease (53.1 vs. 47.4%). Multivariable logistic regression analysis demonstrated admission to a lower-volume hospital did not predict 30-day readmission (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.92-1.01) after adjusting for sociodemographics, QCD score, cirrhosis severity, and hospital characteristics. Instead, liver transplant center status significantly decreased the risk of readmission (OR 0.87, 95% CI 0.80-0.94). Ascites, hepatic encephalopathy, hepatocellular carcinoma, higher QCD, and presence of alcoholic liver disease and hepatitis C were also independent predictors.Readmissions within 30 days were common among patients with cirrhosis hospitalized in California. While hospital cirrhosis volume did not predict 30-day readmissions, liver transplant center status was protective of readmissions. Medically complicated patients with cirrhosis at hospitals without liver transplant centers may benefit from additional support to prevent readmission.
View details for PubMedID 29457210
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Hepatitis B and Renal Function: A Matched Study Comparing Non-Hepatitis B, Untreated, Treated and Cirrhotic Hepatitis Patients.
Liver international : official journal of the International Association for the Study of the Liver
2018
Abstract
Renal impairment is associated with chronic hepatitis B (CHB). To overcome prior study design differences, we used propensity score matching to balance the non- CHB and CHB cohorts and generalized linear modeling (GLM, models using probit and logit linking functions for complex models) to evaluate the effect of CHB, treatment, and cirrhosis on renal function.A retrospective cohort (1996-2017) from one U.S. university medical center. Included patients had ≥12 months of serial creatinine labs and a baseline estimated glomerular filtration rate (eGFR, by the Modification of Diet in Renal Disease Study equation) ≥60 mL/min/1.73 m2 . Propensity score matching was performed using age, sex, ethnicity, diabetes, hypertension, and baseline eGFR. GLM was performed to generate adjusted mean eGFR over time.Adjusted mean eGFR was significantly higher for non-CHB vs. untreated CHB patients (eGFR 87.4 vs. 85.6, p=0.004, n=580, median follow-up=82 months). A significant difference in adjusted mean eGFR between untreated vs. entecavir (ETV)-treated CHB patients (eGFR 85.1 vs. 83.5, p=0.02, n=340, median follow-up=70 months) was found among non-cirrhotic CHB. Among treated CHB, there was no difference in adjusted mean eGFR between non-cirrhotic vs. cirrhotic patients (eGFR 77.0 vs. 76.5; p=0.66, n=112, median follow-up=58 months).After PSM and GLM, the significant predictors for worsening renal function were age, hypertension, and diabetes mellitus but not CHB, ETV, or cirrhosis. However, given small sample size, data regarding the use of ETV in patients with cirrhosis should be interpreted with caution and requires additional investigation. This article is protected by copyright. All rights reserved.
View details for PubMedID 30460749
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Poor Adherence to Guidelines for Treatment of Chronic HBV Infection at Primary Care and Referral Practices.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2018
Abstract
The American Association for the Study of Liver Diseases (AASLD) guidelines for treatment of chronic hepatitis B virus (HBV) infection have changed with time. We assessed rates of treatment evaluation and initiation in patients with chronic HBV infection from different practice settings in the past 14 years.Treatment-naïve patients with chronic HBV infection were recruited from different practice settings in California from January 2002 through December 2016. The study population comprised 4130 consecutive, treatment-naïve patients with chronic HBV infection seen by community primary care physicians (n=616), community gastroenterologists (n=2251), or university hepatologists (n=1263). Treatment eligibility was assessed using data from the first 6 months after initial presentation based on AASLD criteria adjusted for changes over time.Within the first 6 months of care, the proportions of patients evaluated by all 3 relevant tests (measurements of alanine aminotransferase, hepatitis B virus e-antigen, and HBV DNA) were: 36.69% of in community primary care, 59.80% in gastroenterologist care, and 79.97% in the hepatology care (P<.0001 among the three groups). Higher proportions of patients were eligible for treatment in specialty practices: 12.76% in community primary care, 24.96% in gastroenterologist care, and 29.43% in hepatology care (P<.0001). Among treatment-eligible patients, there was no significant difference in the proportions of patients who began antiviral therapy between those receiving treatment from a gastroenterologist (55.65%) vs a hepatologist (57.90%; P=.56). Of 243 evaluable patients receiving community primary care, only 31 were eligible for treatment and only 12 of these (38.71%) received treatment.In an analysis of patients receiving care for chronic HBV infection, we found the proportions evaluated and receiving treatment to be suboptimal, according to AASLD criteria, in all practice settings. However, rates of evaluation and treatment were lowest for patients receiving community primary care.
View details for PubMedID 30326298
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A Comparison Between Community and Academic Practices in the USA in the Management of Chronic Hepatitis B Patients Receiving Entecavir: Results of the ENUMERATE Study.
Digestive diseases and sciences
2018
Abstract
The management of chronic hepatitis B patients is not well characterized in real-world practice. We compared baseline characteristics of CHB patients on entecavir, the frequency of on-treatment monitoring, and the effectiveness of ETV treatment between academic and community practices.Treatment-naïve CHB patients ≥18 years old, treated with ETV for ≥12 months from 2005 to 2013, in 26 community and academic practices throughout the USA were retrospectively evaluated.Of 841 patients enrolled, 658 (65% male, 83% Asian, median age 47, 9% with cirrhosis) met inclusion criteria. Half of the patients (52%) were from community practices. A lower percentage of patients in community practices had cirrhosis or liver cancer (5 vs. 14%). Community practices more often treated patients with baseline ALT < 2 × ULN. Over a median follow-up of 4 years, community practices were more likely to discontinue ETV with less frequent laboratory monitoring compared to academic practices. The 5-year cumulative probability of ALT normalization was greater among patients treated in community practices (70 vs. 50%, p < 0.001), but the 5-year cumulative probability of undetectable HBV DNA was lower (45 vs. 70%, p < 0.001) than those treated in academic practices.Academic practices saw CHB patients with more advanced liver disease, more often followed AASLD guidelines, and monitored patients on ETV treatment more frequently than community practices. While patients in community practices were less likely to achieve undetectable HBV DNA and more likely to achieve ALT normalization, the rates of HBeAg loss and seroconversion as well as HBsAg loss were similar.
View details for PubMedID 30238203
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Serum M2BPGi level and risk of hepatocellular carcinoma after oral anti-viral therapy in patients with chronic hepatitis B.
Alimentary pharmacology & therapeutics
2018
Abstract
Mac-2 binding protein glycosylation isomer (M2BPGi) is an emerging biomarker for risk prediction of liver disease, but data remain sparse for patients with chronic hepatitis B (CHB) who are treated with nucleos(t)ide analogues (NA).To clarify serial changes in M2BPGi and its association with subsequent hepatocellular carcinoma (HCC) development in NA-treated CHB patients.We enrolled 384 previously untreated CHB patients who received NAs. Among them, 195 had baseline cirrhosis (n = 142:48:5 for Child A:B:C). Sera were collected at NA initiation, and after 1 and 2 years. Serum M2BPGi levels were measured and expressed as cut-off index (COI) at different time points. The association between M2BPGi and HCC was evaluated by the Cox proportional hazard model.The median M2BPGi levels significantly decreased from 1.68 COI at baseline, to 1.0 at year 1, and 0.88 at year 2. During median follow-up of 72.7 months, HCC occurred in 37 patients, 36 of whom had cirrhosis. In patients with cirrhosis, baseline M2BPGi level was associated with HCC risk (adjusted hazard ratio, 1.07 per COI; 95% CI, 1.01-1.14) on the multivariable Cox analysis, whereas levels at year 1 or 2 were not independently predictive. A risk score for HCC was developed using baseline M2BPGi, age and body mass index with c statistics of 0.77, 0.79 and 0.87 at 3, 5 and 10 years, respectively.Serum M2BPGi level significantly decreases after NA treatment in CHB patients. Baseline level can be factored into the risk prediction of HCC in NA-treated patients with cirrhosis.
View details for PubMedID 30306612
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Racial/ethnic- and county-specific prevalence of chronic hepatitis B and its burden in California
Hepatology, Medicine and Policy
2018; 3 (6)
View details for DOI 10.1186/s41124-018-0034-7
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Individual surveillance using model-based hepatocellular carcinoma risk estimates in chronic hepatitis C patients after antiviral treatment.
Journal of hepatology
2018
View details for PubMedID 30337127
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Disparities in Hepatocellular Carcinoma Incidence by Race/Ethnicity and Geographic Area in California: Implications for Prevention.
Cancer
2018
Abstract
The incidence of hepatocellular carcinoma (HCC) has been rising rapidly in the United States. California is an ethnically diverse state with the largest number of incident HCC cases in the country. Characterizing HCC disparities in California may inform priorities for HCC prevention.By using data from the Surveillance, Epidemiology, and End Results 18-Registry Database and the California Cancer Registry, age-adjusted HCC incidence in California from 2009 through 2013 was calculated by race/ethnicity and neighborhood ethnic enclave status. A geographic analysis was conducted using Medical Service Study Areas (MSSAs) as the geographic unit, and race/ethnicity-specific standardized incidence ratios (SIRs) were calculated to identify MSSAs with higher-than-expected HCC incidence compared with the statewide average.During 2009 through 2013, the age-adjusted incidence of HCC in California was the highest in Asians/Pacific Islanders (APIs) and Hispanics (>100% higher than whites), especially those living in more ethnic neighborhoods (20%-30% higher than less ethnic neighborhoods). Of the 542 MSSAs statewide, 42 had elevated HCC incidence (SIR ≥ 1.5; lower bound of 95% confidence interval > 1) for whites, 14 for blacks, 24 for APIs, and 36 for Hispanics. These MSSAs have 24% to 52% higher proportions of individuals below the 100% federal poverty line than other MSSAs.APIs and Hispanics residing in more ethnic neighborhoods and individuals residing in lower income neighborhoods require more extensive preventive efforts tailored toward their unique risk factor profiles. The current race/ethnicity-specific geographic analysis can be extended to other states to inform priorities for HCC targeted prevention at the subcounty level, eventually reducing HCC burden in the country. Cancer 2018;000:000-000. © 2018 American Cancer Society.
View details for PubMedID 30113700
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Systematic review and meta-analysis: real-world effectiveness of direct-acting antiviral therapies in chronic hepatitis C genotype 3 in Asia.
BMJ open gastroenterology
2018; 5 (1): e000209
Abstract
Genotype 3 (GT3) is a common chronic hepatitis C (CHC) genotype in Asia. Direct-acting antiviral (DAA) regimens have high cure rates, but real-world results are limited for Asia.To determine the real-world effectiveness of DAAs for patients with CHC GT3 in Asia.A systematic search was performed in PubMed (including MEDLINE), Embase, and selected international meeting abstract repositories. Eligible studies were postmarketing observational studies from Asia with the primary outcome of sustained virological response 12 weeks after completion of treatment (SVR12).A total of 15 studies with 4230 patients yielded a pooled SVR12 of 92.7%. High heterogeneity (I2=93.2%, P<0.0001) was noted. In subgroup analyses, patients with cirrhosis had 10.9% lower SVR12 than non-cirrhotic patients (88.6% vs 98.9%; P<0.0001) and contributed 69.5% of the heterogeneity. Prior treatment failure did not reduce the pooled SVR12 (treatment-naïve: 94.6%, 95% CI 91.3% to 96.7% vs treatment-experienced: 94.0%, 95% CI 77.5% to 98.6%; P=0.89). Twenty-four weeks of sofosbuvir+ribavirin dual therapy was the most commonly used regimen which led to similar SVR12 (OR=1.1, P=0.73) but lower adverse event rate than 12 weeks of sofosbuvir+ribavirin+pegylated interferon triple therapy.Sofosbuvir+ribavirin for 24 weeks is the most widely used and generally well-tolerated DAA therapy in Asia. However, its effectiveness is not optimal in GT3 patients with cirrhosis.
View details for PubMedID 30147941
View details for PubMedCentralID PMC6104766
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Higher mortality and hospital charges in patients with cirrhosis and acute respiratory illness: a population-based study.
Scientific reports
2018; 8 (1): 9969
Abstract
Both cirrhosis and acute respiratory illness (ARI) carry substantial disease and financial burden. To compare hospitalized patients with cirrhosis with ARI to cirrhotic patients without ARI, a retrospective cohort study was conducted using the California Office of Statewide Health Planning and Development database. To balance the groups, propensity score matching (PSM) was used. We identified a total of 46,192 cirrhotic patients during the three study periods (14,049, 15,699, and 16,444 patients, respectively). Among patients hospitalized with cirrhosis, the ARI prevalence was higher in older age groups (p < 0.001), the Asian population (p = 0.002), non-Hispanic population (p = 0.001), and among Medicare patients (p < 0.001). Compared to controls, patients with ARI had 53.8% higher adjusted hospital charge ($122,555 vs. $79,685 per patient per admission, p < 0.001) and 35.0% higher adjusted in-hospital mortality (p < 0.001). Older patients, patients with alcoholic liver disease or liver cancer were at particularly higher risk (adjusted hazard ratio = 2.94 (95% CI: 2.26-3.83), 1.22 (95% CI: 1.02-1.45), and 2.17 (95% CI: 1.76-2.68) respectively, p = 0.028 to <0.001). Mortality rates and hospital charges in hospitalized cirrhotic patients with ARI were higher than in cirrhotic controls without ARI. Preventive efforts such as influenza and pneumococcal vaccination, especially in older patients and those with liver cancer, or alcoholic liver disease, would be of value.
View details for PubMedID 29967363
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Real-world effectiveness of sofosbuvir plus ribavirin for chronic hepatitis C genotype 2 in Asia: a systematic review and meta-analysis.
BMJ open gastroenterology
2018; 5 (1): e000207
Abstract
Sofosbuvir plus ribavirin (SOF+RBV) for 12 weeks is the standard treatment for chronic hepatitis C (CHC) genotype 2 (GT2) in most of Asia despite availability of new CHC medications. SOF-RBV real-world effectiveness has only been reported in small and/or single-centre studies. Our goal was to determine the real-world effectiveness of 12-week SOF+RBV therapy for CHC GT2 in Asia.A systematic search on PubMed and Embase was conducted through 30 June 2017. We identified full articles and conference proceedings of at least 10 adult patients with CHC GT2 treated with SOF+RBV for 12 weeks under real-world setting in Asia.A total of 2208 patients from 13 studies were included. The pooled sustained virological response 12 weeks after the end of treatment (SVR12) was 95.8% (95% CI 94.6% to 96.9%) with non-significant heterogeneity (I2=34.4%). Anaemia (27.9%) was the most common adverse event (AE), with serious AEs in 2.0% and only 0.7% discontinued therapy prematurely. In subgroup analyses, patients with cirrhosis had 8.7% lower SVR12 than non-cirrhotic patients (P<0.0001), and treatment-experienced patients had 7.2% lower SVR12 than treatment-naïve patients (P=0.0002). Cirrhotic treatment-experienced patients had the lowest SVR12 at 84.5%. There were no significant differences in pooled SVR12 among patient subgroups: RBV dose reduction versus no dose reduction (P=0.30); hepatocellular carcinoma (HCC) versus no HCC (P=0.10); GT 2a versus 2b (P=0.86); and <65 vs ≥65 years of age (P=0.20).SOF+RBV for 12 weeks was safe and effective for patients with CHC GT2 in Asia, although those with cirrhosis and prior treatment failure had a lower pooled SVR12 rate.CRD42017067928.
View details for PubMedID 30002863
View details for PubMedCentralID PMC6038840
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Author response to "Cryptogenic hepatocellular carcinoma (HCC) had worse overall survival of disease than viral HCC patients".
Liver international : official journal of the International Association for the Study of the Liver
2018; 38 (6): 1141
View details for PubMedID 29863312
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Temporal trends in disease presentation and survival of patients with hepatocellular carcinoma: A real-world experience from 1998 to 2015.
Cancer
2018
Abstract
Hepatocellular carcinoma (HCC) is one of the few cancers whose incidence continues to increase. The goal of the current study was to investigate the presentation and survival trends of patients with HCC presenting to a university hospital between 1998 and 2015.Study data were ascertained by individual chart review with survival data also supplemented by National Death Index query up to December 31, 2015. Patients were divided into three 6-year groups by diagnosis date (1998-2003, 2004-2009, and 2010-2015).A total of 2106 consecutive patients with HCC were included. The majority of patients had either hepatitis C (56.7%) or hepatitis B (22.1%), but cases of nonalcoholic steatohepatitis HCC increased by 68% over the most recent time period. Screening/surveillance identified 61% of HCC cases, but only 31% of these patients underwent curative treatment, which did not increase significantly over time. The overall median survival was 29.8 months (2.48 years) and without improvement over time. On multivariable analysis, Asian or Hispanic ethnicity, meeting Milan criteria, and receiving any of the standard HCC treatments were found to be significantly associated with improved survival, but diagnosis time period and liver disease etiology were not.Over the last 18 years, the percentage of cases of nonalcoholic steatohepatitis HCC has increased but not overall survival. It is interesting to note that only 31% of patients with HCC identified via screening/surveillance received any curative treatment. Further research is needed to better understand the barriers to curative care for patients with HCC and the causes of the lack of improvement in survival in the more recent patient cohort. Cancer 2018. © 2018 American Cancer Society.
View details for PubMedID 29624631
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Anti-viral therapy is associated with improved survival but underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience.
Alimentary pharmacology & therapeutics
2018
Abstract
Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis.This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death.Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001).Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed.
View details for PubMedID 29797518
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Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis.
The Korean journal of internal medicine
2018
Abstract
A number of clinical trials reported varying effects of cholesterol lowering agents in nonalcoholic fatty liver disease (NAFLD) patients. We, therefore, assessed the changes in hepatic steatosis and NAFLD activity score (NAS) after treatment with cholesterol lowering agents in NAFLD patients by metaanalysis.The Cochrane Library, the MEDLINE, and the Embase databases were searched until May 2015, without any language restrictions, for randomized controlled trials (RCTs) and nonrandomized studies (NRSs). Additional references were obtained from review of bibliography of relevant articles. The quality of evidence was assessed using the grading of recommendations assessment, development and evaluation guidelines.Three RCTs (n = 98) and two NRSs (n = 101) met our study inclusion criteria (adult, NAFLD, liver biopsy). Liver biopsy was performed in all five studies, but only the three studies reported NAS. Ezetimibe significantly decreased NAS (standardized mean difference [SMD], -0.30; 95% confidence interval [CI], -0.57 to -0.03) but not hepatic steatosis in RCT (SMD, -0.1; 95% CI, -0.53 to 0.32), while the effect was significant for both NAS and intrahepatic content in NRSs (SMD, -3.0; 95% CI, -6.9 to 0.91).Ezetimibe decreased NAS without improving hepatic steatosis.
View details for PubMedID 29551054
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Editorial: rifaximin-a kick in the gut for spontaneous bacterial peritonitis? Authors' reply.
Alimentary pharmacology & therapeutics
2018; 47 (2): 303
View details for PubMedID 29265465
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Systematic review with meta-analysis: effectiveness and tolerability of interferon-free direct-acting antiviral regimens for chronic hepatitis C genotype 1 in routine clinical practice in Asia.
Alimentary pharmacology & therapeutics
2018
Abstract
Direct-acting antiviral (DAA) regimens have shown high efficacy and tolerability for patients with HCV genotype 1/1b (GT1/1b) in clinical trials. However, robust real-world evidence of interferon (IFN)-free DAA treatment for HCV GT1-infected patients in Asia is still lacking.To systematically review and meta-analyse the effectiveness and tolerability of IFN-free DAA therapy for HCV GT1 infection in Asia.We included studies that enrolled adult patients with HCV GT1 infection in routine clinical practice in Asia, using IFN-free DAA regimens, and reported sustained virological response (SVR) after 12/24 weeks end-of-treatment by 31 May 2017. The pooled SVR rates were computed with a random-effects model. Subgroup analysis and meta-regression as previously registered in PROSPERO were performed to determine how pre-planned variables might have affected the pooled estimates.We included 41 studies from eight countries and regions, comprising of 8574 individuals. The pooled SVR rates for GT1 were 89.9% (95% CI 88.6-91.1, I2 = 55.1%) with daclatasvir/asunaprevir (DCV/ASV) and 98.1% (95% CI 97.0-99.0, I2 = 41.0%) with ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV). Baseline cirrhosis but not prior treatment history and age, attenuated the effectiveness of both regimens. Baseline resistance associated substitutions (RASs) severely attenuated SVR of DCV/ASV (65.4% vs 94.3%, P < 0.001) and only minimally with LDV/SOF ± RBV (94.5% vs 99.2%, P = 0.003). Patients with renal dysfunction treated with DCV/ASV showed a higher SVR rate (93.9% vs 89.8%, P = 0.046). Patients with hepatocellular carcinoma (HCC) LDV/SOF ± RBV achieved a lower SVR than those without HCC (94.1% vs 98.7%, P = 0.001).All oral DAA treatment of HCV GT1 resulted in high cure rates in Asian patients in routine clinical practice setting including elderly patients and those with end-stage renal disease.
View details for PubMedID 29327780
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Increasing co-morbidities in chronic hepatitis B patients: experience in primary care and referral practices during 2000-2015.
Clinical and translational gastroenterology
2018; 9 (3): 141
Abstract
Data on liver and non-liver co-morbidities in chronic hepatitis B (CHB) patients are limited. This study analyzes the prevalence of co-morbidities in a multicenter CHB cohort evaluated over 15 years.This study included 2734 consecutive adult American CHB patients from a university medical center and several community primary care clinics. Data were analyzed by time periods (patients in each time period were unique without overlapping): 2000-2005 (n = 885), 2006-2010 (n = 888), and 2011-2015 (n = 961). Patients were identified via electronic query using diagnosis code with data confirmed and extracted via individual chart review. Most patients were male (57.9%) and Asian (89.6%).Mean age increased significantly from 43.3 ± 13.4 years during 2000-2005 to 49.1 ± 14.4 during 2011-2015 (p < 0.001). Between 2000-2005 and 2011-2015, fatty liver disease among new CHB patients increased from 1.6 to 6.8% (p < 0.001). Advanced liver diseases also increased (p < 0.001): cirrhosis (12.6-24.6%), hepatic decompensation (1.1-7.9%), and hepatocellular carcinoma (HCC) (4.9-9.1%). Similar trends were observed for non-liver co-morbidities (p < 0.001). Specifically, diabetes increased almost fivefold (4.9-22.9%), hypertension increased threefold (12.3-36.1%) and chronic kidney disease increased 4.5-fold (4.4-19.7%). Prevalence of osteopenia and osteoporosis also increased in CHB patients: 5.4-13.4% (p < 0.001) and 2.9-8.7% (p < 0.001), respectively. These trends were observed in both liver clinics and primary care clinics (except for advanced liver disease), treated and untreated patients, and for both sexes.The CHB patient population is aging and now presents with significantly more co-morbidities. Early diagnosis and linkage to care is needed to prevent and mitigate liver as well as non-liver co-morbidities.
View details for PubMedID 29540676
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Hepatitis B DNA level for guidance of antiviral initiation timing in pregnant women for MTCT reduction
MOSBY-ELSEVIER. 2017: 720
View details for Web of Science ID 000416950700053
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Real-world Effectiveness (RWE) and Adverse Events with Sofosbuvir plus Ribavirin (SOF plus RBV) Based Therapies in Chronic Hepatitis C Genotype 3 (CHC GT 3) Patients in Asia-A Systematic Review of 8 Studies and 3510 Patient
WILEY. 2017: 857A–858A
View details for Web of Science ID 000412089801741
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Is antiviral treatment for chronic hepatitis B (CHB) in Asian patients associated with osteopenia/osteoporosis? A comparison study of tenofovir (TDF), entecavir (ETV) and untreated (UTx) patients
WILEY. 2017: 516A–517A
View details for Web of Science ID 000412089801108
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REAL-B (Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for HBV) - A Risk Score for the Prediction of Hepatocellular Carcinoma (HCC) in Chronic Hepatitis (CHB) Patients Treated with Oral Anti-HBV Therapy
WILEY. 2017: 98A–99A
View details for Web of Science ID 000412089800172
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Age and gender-specific disease progression rates to cirrhosis and hepatocellular carcinoma (HCC) in treated and untreated patients with chronic hepatitis B
WILEY. 2017: 994A
View details for Web of Science ID 000412089802230
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Effect of Tenofovir Disoproxyl (TDF) on Hepatocellular Carcinoma (HCC) Incidence in Patients with Chronic Hepatitis B (CHB) compared to Untreated Patients: a Multicenter Study with Propensity Score Matching (PSM)
WILEY. 2017: 482A–483A
View details for Web of Science ID 000412089801048
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Progression to advanced liver disease in nonalcoholic fatty liver disease (NAFLD) differs among Asians compared to Caucasians and Hispanics
WILEY. 2017: 1172A–1173A
View details for Web of Science ID 000412089802570
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Cirrhotic patients with acute respiratory illness in the United States encounter substantial hospital charge burden
WILEY. 2017: 408A
View details for Web of Science ID 000412089800761
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Association of different types of chronic liver diseases with hepatocellular carcinoma in the United States
WILEY. 2017: 541A–542A
View details for Web of Science ID 000412089801154
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The impact of treatment of chronic hepatitis B (CHB) on patient-reported outcomes (PROs)
WILEY. 2017: 1020A
View details for Web of Science ID 000412089802280
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Recurrence-Free Survival in Liver Transplant Recipients with Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Results from the US Multicenter HCC Transplant Consortium
WILEY. 2017: 900A–901A
View details for Web of Science ID 000412089802045
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Suboptimal rates, trends and predictors of hepatitis B vaccination in a population-based sample of children and adolescents in the United States (US) between 1999 and 2014
WILEY. 2017: 1003A
View details for Web of Science ID 000412089802247
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Prevalence and predictors of hepatitis B immunization in adults without immunity for hepatitis B from 1999-2014: a population-based study of 27,713 adults in the US
WILEY. 2017: 1004A
View details for Web of Science ID 000412089802249
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Safety and Efficacy of Vesatolimod (GS-9620) in Patients with Chronic Hepatitis B (CHB) Who Are Not Currently on Antiviral Treatment
WILEY. 2017: 497A–498A
View details for Web of Science ID 000412089801073
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Serum Biomarkers Improve Prognostic Ability of BCLC Staging System
WILEY. 2017: 754A–755A
View details for Web of Science ID 000412089801550
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A multicenter study revealing chronic hepatitis B comorbidity trends over the last 15 years in the United States
WILEY. 2017: 990A
View details for Web of Science ID 000412089802222
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Long-Term Follow-Up of Patient-Reported Outcomes (PROs) in Chronic Hepatitis C (HCV) Patients with Compensated and Decompensated Cirrhosis with Sustained Virologic Response (SVR)
WILEY. 2017: 599A
View details for Web of Science ID 000412089801257
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Real Life Effectiveness of Direct-Acting Antivirals (DAAs) in Asian Patients with Chronic Hepatitis C Genotype 1: Systematic Review and Meta-analysis of 33 Published Articles and 7942 patients
WILEY. 2017: 596A–597A
View details for Web of Science ID 000412089801253
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Sustained Virological Response 12 Weeks after Therapy (SVR12) with Direct-Acting Antivirals (DAA) in Select Asian Populations with Chronic Hepatitis C Genotype 1 (HCV GT 1): A Meta-Analysis of Real-World Effectiveness from Asia
WILEY. 2017: 812A–813A
View details for Web of Science ID 000412089801662
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Real-world Effectiveness (RWE) of Sofosbuvir plus Ribavirin (SOF plus RBV) Chronic Hepatitis C Genotype 2 (CHC GT 2) in Asia: A Systemic Review and Meta-analysis of Pooled SVR12
WILEY. 2017: 811A
View details for Web of Science ID 000412089801660
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Barriers to care for chronic hepatitis C in the direct-acting antiviral era: a single-centre experience
BMJ OPEN GASTROENTEROLOGY
2017; 4 (1)
View details for DOI 10.1136/bmjgast-2017-000181
View details for Web of Science ID 000440227600019
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COST-EFFECTIVENESS ANALYSIS OF FIRST-LINE ADMINISTRATION OF TENOFOVIR ALAFENAMIDE (TAF), A NOVEL NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITOR (NRTI), FOR THE MANAGEMENT OF CHRONIC HEPATITIS B (CHB) IN THE UNITED STATES (US)
ELSEVIER SCIENCE INC. 2017: A78
View details for Web of Science ID 000405448001076
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Increased Prevalence of Metabolic Risk Factors in Asian Americans With Hepatocellular Carcinoma.
Journal of clinical gastroenterology
2017; 51 (4): 384-390
Abstract
We used metabolic risk factors to estimate the prevalence and clinical significance of nonalcoholic fatty liver disease in Asian Americans with hepatocellular carcinoma (HCC).This is a retrospective cohort study of 824 consecutive Asian HCC patients at Stanford University Medical Center from 1998 to 2015. Patients were subdivided as: Chinese, other East Asian (Japanese and Korean), South East Asian (Vietnamese, Thai, and Laotian), Maritime South East Asian (MSEA: Malaysian, Indonesian, Filipino, and Singaporean), and South West Asian (Indian, Pakistani, and Middle Eastern). Metabolic risk factors studied were body mass index, hypertension, type II diabetes, and hyperlipidemia.Most patients were male (76%) with mean age 63 years. Metabolic risk factors were highly prevalent on presentation and increased over time (P<0.001), as did the prevalence of cryptogenic HCC (P<0.004). Compared with other Asian subgroups, MSEAs had the highest body mass index (26.3) and higher rates of type II diabetes (44% vs. 23% to 35%, P=0.004), hypertension (59% vs. 38% to 55%, P=0.04), and cryptogenic HCC (15% vs. 4% to 10%, P=0.01). They were more likely to be symptomatic on presentation (44% vs. 32% to 58%, P=0.07), less likely to present within Milan criteria (34% vs. 35% to 63%, P<0.0001), and trended toward decreased 10-year survival rates compared with other ethnic subgroups (9% vs. 25% to 32%, P=0.07).Metabolic risk factors were increasingly prevalent among Asian Americans with HCC. MSEAs, who had the highest incidence of these risk factors, had more advanced tumor stage and trended toward worse survival.
View details for DOI 10.1097/MCG.0000000000000689
View details for PubMedID 27636408
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Prevalence of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the United States
PLOS ONE
2017; 12 (3)
Abstract
In the United States, non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and associated with higher mortality according to data from earlier National Health and Nutrition Examination Survey (NHANES) 1988-1994. Our goal was to determine the NAFLD prevalence in the recent 1999-2012 NHANES, risk factors for advanced fibrosis (stage 3-4) and mortality. NAFLD was defined as having a United States Fatty Liver Index (USFLI) > 30 in the absence of heavy alcohol use and other known liver diseases. The probability of low/high risk of having advanced fibrosis was determined by the NAFLD Fibrosis Score (NFS). In total, 6000 persons were included; of which, 30.0% had NAFLD and 10.3% of these had advanced fibrosis. Five and eight-year overall mortality in NAFLD subjects with advanced fibrosis was significantly higher than subjects without NAFLD ((18% and 35% vs. 2.6% and 5.5%, respectively) but not NAFLD subjects without advanced fibrosis (1.1% and 2.8%, respectively). NAFLD with advanced fibrosis (but not those without) is an independent predictor for mortality on multivariate analysis (HR = 3.13, 95% CI 1.93-5.08, p<0.001). In conclusion, in this most recent NHANES, NAFLD prevalence remains at 30% with 10.3% of these having advanced fibrosis. NAFLD per se was not a risk factor for increased mortality, but NAFLD with advanced fibrosis was. Mexican American ethnicity was a significant risk factor for NAFLD but not for advanced fibrosis or increased mortality.
View details for DOI 10.1371/journal.pone.0173499
View details for Web of Science ID 000399174300007
View details for PubMedID 28346543
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Ledipasvir and sofosbuvir combination for hepatitis C virus infection in three patients aged 85 years and older.
European journal of gastroenterology & hepatology
2017
View details for DOI 10.1097/MEG.0000000000000873
View details for PubMedID 28328620
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Serum Aminotransferase Flares in Pregnant and Postpartum Women With Current or Prior Treatment for Chronic Hepatitis B.
Journal of clinical gastroenterology
2017
Abstract
Antiviral therapy is recommended for pregnant women with chronic hepatitis B (CHB) and hepatitis B virus (HBV) DNA>200,000 IU/mL, but there is less consensus on management of women who discontinue therapy in anticipation of pregnancy or who become pregnant while on therapy. The goal of this study was to describe flares in alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women with current and/or prior treatment.This was a multicenter, retrospective study of 67 pregnancies in 56 CHB women treated before and/or during pregnancy. Main outcomes were frequency, severity, and resolution of ALT flare (≥5× upper limit of normal or ≥3× baseline, whichever was higher).During pregnancy, ALT flares (95 to 1064 U/L) were observed in 16% (7/43) of women who stopped treatment before pregnancy and 31% (4/13) of women who discontinued treatment during first trimester, many of whom had high HBV DNA levels (4.9 to 8.0 log IU/mL). No flares (0/11) were observed in women who continued treatment. Postpartum ALT flares (104 to 1584 U/L) were observed in 0% (0/15) of women who were completely untreated during pregnancy, 29% (2/7) of women who discontinued treatment in first trimester, 33% (3/9) of women who stopped treatment at delivery, and 22% (4/18) of women who continued treatment postpartum.In previously treated women with CHB, ALT flares were common during pregnancy and postpartum, especially if antiviral therapy was discontinued shortly before pregnancy, during first trimester, or at delivery. Thus, these pregnant women should be monitored closely throughout pregnancy and the early postpartum period; larger studies are needed to further characterize the natural history of HBV infection during pregnancy and postpartum.
View details for DOI 10.1097/MCG.0000000000000822
View details for PubMedID 28323748
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Real-world experience with interferon-free, direct acting antiviral therapies in Asian Americans with chronic hepatitis C and advanced liver disease.
Medicine
2017; 96 (6)
Abstract
Real-life data on interferon (IFN)-free direct acting antiviral (DAA) therapies for chronic hepatitis C (CHC) is limited for Asian Americans.To evaluate sustained virologic response (SVR) and adverse events (AE) in Asian Americans treated with sofosbuvir (SOF)-based, IFN-free DAA therapies.This is a retrospective study of 110 consecutive Asian Americans with HCV genotypes 1 to 3 or 6 treated with IFN-free SOF-based regimens for 8 to 24 weeks between February 2014 and March 2016 at a university center in Northern California.Mean age was 63 ± 12 years, mean BMI was 25 ± 6 (kg/m), and about half (52%) were male. Most patients were infected with HCV genotype 1 (HCV-1, 64%), followed by HCV-2 (14%), HCV-6 (13%), and HCV-3 (8%). Half had cirrhosis, and the majority of these (67%) had decompensation. Overall SVR12 was 93% (102/110), and highest among patients without cirrhosis, liver transplant, or HCC (100%, 37/37). SVR12 was lower among patients with HCC (82%, 14/17), decompensated cirrhosis (84%, 31/37), or liver transplant (89%, 17/19), regardless of treatment and genotype. Most common AEs were anemia (25%), fatigue (20%), and headache (12%). Anemia was highest in patients receiving SOF/RBV (67%). There was 1 treatment-unrelated serious adverse effect (SAE). There were 7 dose reductions due to anemia or fatigue from RBV and 2 treatment discontinuations due to fatigue or loss of insurance authorization.This real-life cohort of Asian American CHC patients treated with IFN-free SOF-based therapies showed high overall treatment response and good tolerability, despite very high rates of advanced disease and prior treatment failure.
View details for DOI 10.1097/MD.0000000000006128
View details for PubMedID 28178174
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HCV Prevalence in Asian Americans in California
JOURNAL OF IMMIGRANT AND MINORITY HEALTH
2017; 19 (1): 91-97
Abstract
The World Health Organization estimates that 170 million persons are infected with HCV worldwide, but only 22 million are from the Americas and Europe, compared to 94 million from Asia. HCV prevalence in the general US population is 1.6 %, but data for Asian Americans are limited. Our goal was to examine HCV prevalence in Asian Americans in a large ethnically diverse patient cohort seeking primary care at a free clinic in Northern California. A total of 1347 consecutive patients were seen from September 2009 to October 2012 and were studied via individual chart review using case report forms. HCV infection was defined as positive HCV antibody (anti-HCV) or HCV RNA by PCR. 699 out of 1347 patients were screened for HCV. Asian Americans comprised 57.2 % of these patients and 29 (4.1 %) patients tested positive for HCV. Of these 29 HCV-positive patients, 22 (75.9 %) were Asian, yielding a prevalence of 5.5 % for Asians and 2.3 % for non-Asians (P = 0.038). The highest HCV prevalence was seen in Vietnamese patients at 7.9 %, and 6.0 % in Chinese patients. Of the HCV-positive Asians, none had a history of intravenous drug use (IVDU), tattoos, or sexual exposure. On multivariate analysis, significant independent predictors for positive HCV infection were male gender (OR 2.53, P = 0.02) and presence of known risk factors (OR 21.1, P < 0.001). However, older age and Asian ethnicity were found to be significant predictors of HCV infection (OR 1.03, P = 0.05 and 2.31, P = 0.066, respectively). In our study, HCV prevalence in patients seeking routine primary care was 5.5 % in Asian Americans, which was over double the prevalence for non-Asians at 2.3 %. Known risk factors were also notably absent in Asian patients with HCV infection. The high prevalence of HCV in Asian-Americans is likely reflective of the higher prevalence of HCV in their countries of origin in Asia. Asian-Americans immigrants from endemic countries are at higher risk of HCV infection and should be screened for HCV, regardless of their exposure risk profile.
View details for DOI 10.1007/s10903-016-0342-1
View details for Web of Science ID 000394213200012
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Letter: reduction in chronic hepatitis B-related hepatocellular carcinoma with anti-viral therapy, including low-risk patients - more questions than answers. Authors' reply.
Alimentary pharmacology & therapeutics
2017; 45 (1): 186–87
View details for PubMedID 27910142
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Black hepatocellular carcinoma patients diagnosed after 2010 have worse long-term survival than white patients
ELSEVIER SCIENCE BV. 2017: S447–S448
View details for DOI 10.1016/S0168-8278(17)31271-0
View details for Web of Science ID 000401056601114
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Advancing age and comorbidities in chronic hepatitis B patients: results of 10-year longitudinal analysis of a diverse population-based cohort of 44,026 chronic hepatitis B patients in the United States
ELSEVIER SCIENCE BV. 2017: S60
View details for DOI 10.1016/S0168-8278(17)30383-5
View details for Web of Science ID 000401056600121
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Prevalence of osteoporosis and bone fracturewas 2-fold higher in chronic hepatitis B compared to non-chronic hepatitis B patients and continued to increase in the last decade: results of a United States population-based cohort study
ELSEVIER SCIENCE BV. 2017: S61
View details for DOI 10.1016/S0168-8278(17)30385-9
View details for Web of Science ID 000401056600123
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Metabolic risk factors increase the risk of hepatocellular carcinoma in patients with hepatitis C cirrhosis
ELSEVIER SCIENCE BV. 2017: S125–S126
View details for DOI 10.1016/S0168-8278(17)30517-2
View details for Web of Science ID 000401056600255
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Rising healthcare utilization and cost of chronic hepatitis B: real-world analysis of 44,026 chronic hepatitis B patients and 121,568 matched non-chronic hepatitis B controls in the United States
ELSEVIER SCIENCE BV. 2017: S266–S267
View details for DOI 10.1016/S0168-8278(17)30845-0
View details for Web of Science ID 000401056600582
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SVR reduces ethnic disparities in progression to advanced liver disease in patients with chronic hepatitis C
ELSEVIER SCIENCE BV. 2017: S283–S284
View details for DOI 10.1016/S0168-8278(17)30884-X
View details for Web of Science ID 000401056600621
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3 times higher healthcare cost in chronic hepatitis B patients compared to non-chronic hepatitis B controls especially those with decompensated liver disease: United States real world healthcare utilization and cost analysis
ELSEVIER SCIENCE BV. 2017: S369–S370
View details for DOI 10.1016/S0168-8278(17)31083-8
View details for Web of Science ID 000401056600820
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High rate of progression to cirrhosis in patients with chronic hepatitis B (CHB) and non-alcoholic fatty liver (FL)
ELSEVIER SCIENCE BV. 2017: S488
View details for DOI 10.1016/S0168-8278(17)31369-7
View details for Web of Science ID 000401056601212
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Higher and rising prevalence and incidence of renal impairment and chronic kidney disease in chronic hepatitis B patients compared to matched non-chronic hepatitis B controls in the United States: results of a real-world analysis
ELSEVIER SCIENCE BV. 2017: S677–S678
View details for DOI 10.1016/S0168-8278(17)31826-3
View details for Web of Science ID 000401056601668
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Integrated analysis of controlled clinical trials evaluating efficacy and safety of sofosbuvir-based regimens in chronic hepatitis C genotype 6 (HCV GT 6)
ELSEVIER SCIENCE BV. 2017: S723
View details for DOI 10.1016/S0168-8278(17)31931-1
View details for Web of Science ID 000401056601770
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Viral kinetics in women of child bearing potential with chronic hepatitis B virus following treatment with tenofovir alafenamide or tenofovir disoproxil fumarate
ELSEVIER SCIENCE BV. 2017: S258–S259
View details for DOI 10.1016/S0168-8278(17)30826-7
View details for Web of Science ID 000401056600563
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Significantly lower rates of cirrhosis and worse long-term survival in cryptogenic hepatocellular carcinoma compared to viral etiologies: results of a multi-center international cohort
ELSEVIER SCIENCE BV. 2017: S623
View details for DOI 10.1016/S0168-8278(17)31691-4
View details for Web of Science ID 000401056601534
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Thyroid cancer mortality higher in Filipinos in United States: an analysis using national mortality records from 2003-2012.
Cancer
2017
View details for DOI 10.1002/cncr.30958
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Hepatitis B DNA level for guidance of antiviral initiation timing in pregnant women for MTCT reduction
MOSBY-ELSEVIER. 2017: S242–S243
View details for Web of Science ID 000414256402030
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More advanced disease and worse survival in cryptogenic compared to viral hepatocellular carcinoma.
Liver international : official journal of the International Association for the Study of the Liver
2017
Abstract
Although hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major risk factors for hepatocellular carcinoma (HCC), non-viral causes of HCC, particularly non-alcoholic fatty liver disease, are becoming increasingly prevalent. The aim of this study was to compare the clinical characteristics and survival of cryptogenic and viral HCC.We conducted a retrospective cohort study involving 3,878 consecutive HCC patients seen at two tertiary centers in the United States and one in Taiwan from 2004-2014. We compared the clinical characteristics, treatment and survival of patients by underlying etiology: cryptogenic (n=696), HBV (n=1,304), or HCV (n=1,878).Cirrhosis was present in 66.8% of the cryptogenic HCC patients, compared with 74.7% of HBV-HCC (p=0.001) and 85.9% of HCV-HCC (p<0.001). Compared to viral HCC, cryptogenic HCC patients presented with larger tumors and at later stages of disease. Five-year overall survival was 16.3% among cryptogenic HCC patients compared with 31.9% among HBV-HCC patients and 27.7% among HCV-HCC patients (p<0.001 for both by the log-rank test). HCC etiology was not an independent predictor of survival, though ethnicity, cirrhosis status, meeting Milan criteria and treatment allocation were.Compared with viral HCC patients, those with cryptogenic HCC had lower prevalence of cirrhosis, were diagnosed with larger tumors at more advanced stages of disease, and had poorer overall survival. Additional efforts are needed to identify patients at risk of cryptogenic HCC and to identify cryptogenic HCC at earlier stages of disease. This article is protected by copyright. All rights reserved.
View details for PubMedID 29045023
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Effects of antiviral therapy in patients with chronic hepatitis B and cirrhosis.
Expert review of gastroenterology & hepatology
2017
Abstract
Hepatitis B virus (HBV) infection is the major cause of cirrhosis worldwide. The ultimate goal of current antiviral treatments for chronic hepatitis B (nucleos(t)ide analogs and interferon-α) is to prevent the development of end-stage liver diseases. Areas covered: We present a review of the current literature on antiviral therapy in patients with chronic hepatitis B and cirrhosis. Medline search was performed to identify relevant literature from 1993 through January of 2017. Expert commentary: One randomized controlled trial and a number of observational studies have shown that nucleos(t)ide analogs can decrease the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B patients with advanced fibrosis. Data from clinical trials of entecavir and tenofovir have shown that histological improvement and regression of fibrosis can be achieved in the majority of patients with chronic hepatitis B by successful viral suppression. Entecavir and tenofovir are the preferred antiviral agents for treatment of chronic hepatitis B in patients with cirrhosis due to their high antiviral potency and high genetic barrier to resistance. Pegylated interferon-α is another therapeutic option for chronic hepatitis B patients with well-compensated cirrhosis. However, interferon therapy is contraindicated in patients with decompensated cirrhosis, and evidence for reduced HCC is currently insufficient.
View details for PubMedID 28752768
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Regional differences in the presentation and management of patients with hepatocellular carcinoma by liver disease etiology
ELSEVIER SCIENCE BV. 2017: S458
View details for Web of Science ID 000401056601139
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Systematic review with meta-analysis: rifaximin for the prophylaxis of spontaneous bacterial peritonitis.
Alimentary pharmacology & therapeutics
2017
Abstract
The primary and secondary prevention of spontaneous bacterial peritonitis (SBP) is recommended in high-risk patients with cirrhosis. Several studies evaluating the efficacy of rifaximin for SBP prophylaxis have yielded conflicting results. Rifaximin has the potential advantage of preventing bacterial overgrowth and translocation without the systemic side effects of broad-spectrum antibiotics.To evaluate the efficacy of rifaximin in the primary and secondary prevention of SBP.A literature search using five databases was performed to identify studies on the association between rifaximin and SBP. We performed two meta-analyses: (1) rifaximin compared to systemic antibiotics and (2) rifaximin compared to no antibiotics. Random-effect modelling was conducted to determine overall pooled estimates and 95% confidence intervals (CIs).Five studies with 555 patients (295 rifaximin, 260 systemic antibiotics) compared rifaximin with systemic antibiotics. The pooled odds ratio (OR) for SBP was 0.45 (95% CI 0.16-1.27; P = .13) in patients receiving rifaximin and strengthened on sensitivity analysis (OR 0.38, 95% CI 0.19-0.76, P = .01). In the analysis comparing rifaximin with no antibiotics, there were five studies with 784 patients (186 rifaximin, 598 no antibiotics). The OR for SBP was 0.34 (95% CI 0.11-0.99; P < .05) in patients receiving rifaximin. In subgroup analysis, rifaximin reduced the risk of SBP by 47% compared to no antibiotics for primary prophylaxis and by 74% compared to systemic antibiotics for secondary prophylaxis.Rifaximin may be effective in preventing SBP in patients with cirrhosis and ascites compared to systemically absorbed antibiotics and compared to placebo.
View details for PubMedID 28994123
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Soluble intercellular adhesion molecule-1 is associated with hepatocellular carcinoma risk: multiplex analysis of serum markers.
Scientific reports
2017; 7 (1): 11169
Abstract
Individualized assessment of hepatocellular carcinoma (HCC) risk in chronic liver disease remains challenging. Serum biomarkers including cytokines may offer helpful adjuncts to standard parameters for risk prediction. Our aim was to identify markers associated with increased HCC incidence. This was a prospective cohort study of 282 patients with both viral or non-viral chronic liver disease. Baseline serum cytokines and other markers were measured in multiplex with a commercially-available Luminex-based system. Patients were followed until death or HCC diagnosis. We performed Lasso-based survival analysis to determine parameters associated with HCC development. Cytokine mean florescence intensity (MFI) was the primary predictor and HCC development the primary outcome. 25 patients developed HCC with total follow-up of 1,363 person-years. Parameters associated with increased HCC incidence were cirrhosis, hepatic decompensation, and soluble serum intercellular adhesion molecule 1 (sICAM-1) MFI. No other molecules increased predictive power for HCC incidence. On univariate analysis, the parameters associated with HCC incidence in patients with cirrhosis were age, antiviral treatment, and high sICAM-1 MFI; on multivariate analysis, sICAM-1 remained associated with HCC development (adjusted HR = 2.75). On unbiased screening of serum cytokines and other markers in a diverse cohort, baseline sICAM-1 MFI is associated with HCC incidence.
View details for PubMedID 28894136
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Poor adherence to hepatocellular carcinoma surveillance: a systematic review and meta-analysis of a complex issue.
Liver international : official journal of the International Association for the Study of the Liver
2017
Abstract
Hepatocellular carcinoma (HCC) surveillance is associated with improved outcomes and long-term survival. Our goal is to evaluate adherence rates to HCC surveillance.We performed a systematic search of the PubMed and Scopus databases and abstract search of relevant studies from recent major liver meetings. All searches and data extraction were performed independently by 2 authors. Analysis was via random-effects models and multivariate meta-regression.A total of 22 studies (n=19,511) met inclusion criteria (original non-interventional studies with defined cirrhosis or chronic hepatitis B or chronic hepatitis C with advanced fibrosis populations, and surveillance tests and intervals). Overall adherence rate was 52% (95% CI 38-66%). Adherence was significantly higher in cirrhotic patients compared to chronic hepatitis B and other high risk patients, in European compared to North American studies, in less than 12-month compared to yearly surveillance intervals, and in prospective compared to retrospective studies (71%, 95% CI 64-78% vs. 39%, 95% CI 26-51%, P<0.001). The between-study heterogeneity of all above analyses was significant (P<0.001). Only the study design (retrospective vs. prospective cohort) had statistical significance in a multivariate meta-regression model (P<0.05) and could account for some of the differences above.Overall adherence rate to HCC surveillance was suboptimal at 52% with no significant differences by liver disease etiology or study location in multivariate meta-regression analysis. Further research and educational efforts are needed to improve the current rate of HCC surveillance. This article is protected by copyright. All rights reserved.
View details for PubMedID 28834146
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Tenofovir alafenamide as compared to tenofovir disoproxil fumarate in the management of chronic hepatitis B with recent trends in patient demographics.
Expert review of gastroenterology & hepatology
2017
Abstract
Tenofovir alafenamide (TAF) has recently been approved for chronic hepatitis B (CHB). It is more stable than tenofovir disoproxil fumarate (TDF) in the plasma and can provide similar efficacy with lower circulating concentration in patients with hepatitis B virus (HBV) infection. Areas covered: This synopsis will review the current anti-HBV standard practice and the changing epidemiology of CHB, specifically the controversies surrounding the renal and bone safety associated with TDF use in the context of an aging CHB population. We will review data from phase 3 registration trials, which demonstrated TAF was not inferior to TDF in antiviral efficacy for both HBeAg-positive and HBeAg-negative patients, while associated with less reduction in the estimated glomerular filtration rate and bone mineral density. Expert commentary: Current data supports the use of TAF as one of the first-line antiviral agents for general CHB patients without hepatic decompensation. However, more real-world data with long-term observation are needed to better define the role of TAF among other oral regimens. Additional studies are also needed to evaluate the efficacy and safety of TAF in special populations such as those with impaired hepatic function, existing impaired renal and/or bone function, and in pregnant women.
View details for PubMedID 28965428
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Survival after treatment with curative intent for hepatocellular carcinoma among patients with vs without non-alcoholic fatty liver disease.
Alimentary pharmacology & therapeutics
2017
Abstract
Non-alcoholic fatty liver disease (NAFLD) is expected to become a leading aetiology of hepatocellular carcinoma (HCC)-related mortality in the United States. HCC treatments with curative intent (OLT, orthotopic liver transplantation; resection; RFA, radiofrequency ablation) can improve survival in carefully selected patients.To compare survival after receipt of curative treatment for NAFLD and non-NAFLD-HCC aetiologies (HCV, chronic hepatitis C; HBV, chronic hepatitis B; ALD, alcoholic liver disease) and by treatment was performed.A cohort of 17 664 patients was assembled using linked Surveillance, Epidemiology, and End Results and Medicare data from 1991 to 2011 with confirmed diagnosis of HCC.The cohort was mostly male, aged 70 (21-106) years, without cardiovascular disease, and had liver cirrhosis without decompensation, metastatic HCC or large tumour size (>5 cm). The NAFLD-HCC group was mostly female and older with more cardiovascular disease, metastatic HCC, and large tumour size and less cirrhosis and decompensated liver disease than the non-NAFLD-HCC groups. The NAFLD group was 47% less likely to receive any curative treatment as compared with non-NAFLD aetiologies (OR 0.53, P < .001). NAFLD-HCC had worse median survival after OLT (3.2, 0-12.9 years, P = .01) but had improved survival after resection (2.4, 0-12.0 years, P < .001) as compared with non-NAFLD-HCC. No significant survival differences existed for RFA by HCC aetiology. NAFLD was not an independent predictor of mortality after OLT, resection or RFA.Patients with NAFLD-HCC had worse survival after OLT but favourable survival after resection, particularly in the absence of cirrhosis, as compared with non-NAFLD-HCC aetiologies.
View details for PubMedID 28960360
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Epidemiology of hepatitis B and the role of vaccination.
Best practice & research. Clinical gastroenterology
2017; 31 (3): 239–47
Abstract
Hepatitis B virus (HBV) is a major cause of morbidity and mortality with a disproportionate impact on Asia and Africa. Current guidelines recommend screening at-risk populations for chronic HBV infection so that diagnosed individuals can be linked to appropriate hepatitis care. The vast majority of infected individuals are undiagnosed and untreated, and are at risk of developing cirrhosis, liver failure, and hepatocellular carcinoma. In individuals who are not yet infected, the HBV vaccine is safe and highly effective at preventing disease transmission. Countries with successful vaccination programs have been able to dramatically reduce their HBV prevalence. A concerted effort to screen, treat, and vaccinate at-risk individuals has the potential to eliminate HBV as a public health threat by 2030.
View details for PubMedID 28774405
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Physician perspectives on the management of viral hepatitis and hepatocellular carcinoma in Myanmar.
PloS one
2017; 12 (8): e0181603
Abstract
In Myanmar, over five million people are infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). Hepatitis has been a recent focus with the development of a National Strategic Plan on Hepatitis and plans to subsidize HCV treatment.During a two-day national liver disease symposium covering HCV, HBV, hepatocellular (HCC), and end-stage liver disease (ESLD), physician surveys were administered using the automated response system (ARS) to assess physician knowledge, perceptions of barriers to screening and treatment, and proposed solutions. Multivariate logistic regression was used to estimate odds ratio (OR) relating demography and practice factors with higher provider knowledge and improvement.One hundred two physicians attending from various specialty areas (31.0% specializing in gastroenterology/hepatology and/or infectious disease) were of mixed gender (46.8% male), were younger than or equal to 40 years old (51.1% 20 to 40 years), had less experience (61.6% with ≤10 years of medical practice), were from the metropolitan area of Yangon (72.1%), and saw <10 liver disease patients per week (74.3%). The majority of physicians were not comfortable with treating or managing patients with liver disease. The post-test scores demonstrated an improvement in liver disease knowledge (9.0% ± 27.0) compared to the baseline pre-test scores; no variables were associated with significant improvement in hepatitis knowledge. Physicians identified the cost of diagnostic blood tests and treatment as the most significant barrier to treatment. Top solutions proposed were universal screening policies (46%), removal of financial barriers for treatment (29%), patient education (14%) and provider education (11%).Physician knowledge improved after this symposium, and many other needs were revealed by the physician input on barriers to care and their solutions. These survey results are important in guiding the next steps to improve liver disease management and future medical education efforts in Myanmar.
View details for PubMedID 28797080
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Barriers to care for chronic hepatitis C in the direct-acting antiviral era: a single-centre experience.
BMJ open gastroenterology
2017; 4 (1): e000181
Abstract
Cure rates for chronic hepatitis C have improved dramatically with direct-acting antivirals (DAAs), but treatment barriers remain. We aimed to compare treatment initiation rates and barriers across both interferon-based and DAA-based eras.We conducted a retrospective cohort study of all patients with chronic hepatitis C seen at an academic hepatology clinic from 1999 to 2016. Patients were identified to have chronic hepatitis C by the International Classification of Diseases, Ninth Revision codes, and the diagnosis was validated by chart review. Patients were excluded if they did not have at least one visit in hepatology clinic, were under 18 years old or had prior treatment with DAA therapy. Patients were placed in the DAA group if they were seen after 1 January 2014 and had not yet achieved virological cure with prior treatment. All others were considered in the interferon group.3202 patients were included (interferon era: n=2688; DAA era: n=514). Despite higher rates of decompensated cirrhosis and medical comorbidities in the DAA era, treatment and sustained virological response rates increased significantly when compared with the interferon era (76.7% vs 22.3%, P<0.001; 88.8% vs 55%, P<0.001, respectively). Lack of follow-up remained a significant reason for non-treatment in both groups (DAA era=24% and interferon era=45%). An additional 8% of patients in the DAA era were not treated due to insurance or issues with cost. In the DAA era, African-Americans, compared with Caucasians, had significantly lower odds of being treated (OR=0.37, P=0.02).Despite higher rates of medical comorbidities in the DAA era, considerable treatment challenges remain including cost, loss to follow-up and ethnic disparities.
View details for PubMedID 29333275
- Ethnic disparities in progression to advanced liver disease and overall survival in patients with chronic hepatitis C: impact of a sustained virological response. Alimentary pharmacology & therapeutics