Ramsey Cheung

All Publications

• Substantial gaps in evaluation and treatment of patients with hepatitis B in the US. Journal of hepatology Ye, Q., Kam, L. Y., Yeo, Y. H., Dang, N., Huang, D. Q., Cheung, R., Nguyen, M. H. 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

• Water-assisted colonoscopy: an international modified Delphi review on definitions and practice recommendations. Gastrointestinal endoscopy Cadoni, S. n., Ishaq, S. n., Hassan, C. n., Falt, P. n., Fuccio, L. n., Siau, K. n., Leung, J. W., Anderson, J. n., Binmoeller, K. F., Radaelli, F. n., Rutter, M. D., Sugimoto, S. n., Muhammad, H. n., Bhandari, P. n., Draganov, P. V., de Groen, P. n., Wang, A. Y., Yen, A. W., Hamerski, C. n., Thorlacius, H. n., Neumann, H. n., Ramirez, F. n., Mulder, C. J., Albéniz, E. n., Amato, A. n., Arai, M. n., Bak, A. n., Barret, M. n., Bayupurnama, P. n., Cheung, R. n., Ching, H. L., Cohen, H. n., Dolwani, S. n., Friedland, S. n., Harada, H. n., Hsieh, Y. H., Hayee, B. n., Kuwai, T. n., Lorenzo-Zúñiga, V. n., Liggi, M. n., Mizukami, T. n., Mura, D. n., Nylander, D. n., Olafsson, S. n., Paggi, S. n., Pan, Y. n., Parra-Blanco, A. n., Ransford, R. n., Rodriguez-Sanchez, J. n., Senturk, H. n., Suzuki, N. n., Tseng, C. W., Uchima, H. n., Uedo, N. n., Leung, F. W. 2020

  Abstract

  Since 2008, a plethora of research studies has compared the efficacy of water-assisted (aided) colonoscopy (WAC) and underwater resection (UWR) of colorectal lesions with standard colonoscopy. We reviewed and graded the research evidence with potential clinical application. We conducted a modified Delphi consensus among experienced colonoscopists on definitions and practice of water immersion (WI), water exchange (WE), and UWR.Major databases were searched to obtain research reports that could potentially shape clinical practice related to WAC and UWR. Pertinent references were graded (Grading of Recommendations, Assessment, Development and Evaluation). Extracted data supporting evidence-based statements were tabulated and provided to respondents. We received responses from 55 (85% surveyed) experienced colonoscopists (37 experts and 18 nonexperts in WAC) from 16 countries in 3 rounds. Voting was conducted anonymously in the second and third round, with ≥80% agreement defined as consensus. We aimed to obtain consensus in all statements.In the first and the second modified Delphi rounds, 20 proposed statements were decreased to 14 and then 11 statements. After the third round, the combined responses from all respondents depicted the consensus in 11 statements (S): definitions of WI (S1) and WE (S2), procedural features (S3-S5), impact on bowel cleanliness (S6), adenoma detection (S7), pain score (S8), and UWR (S9-S11).The most important consensus statements are that WI and WE are not the same in implementation and outcomes. Because studies that could potentially shape clinical practice of WAC and UWR were chosen for review, this modified Delphi consensus supports recommendations for the use of WAC in clinical practice.

  View details for DOI 10.1016/j.gie.2020.10.011

  View details for PubMedID 33069706

• Alanine Aminotransferase Results Differ by Analyzer Manufacturer in a National Integrated Health Setting, 2012-2017. Archives of pathology & laboratory medicine Beste, L. A., Icardi, M., Hunt, C. M., Gylys-Colwell, I., Lowy, E., Taylor, L., Morgan, T. R., Chang, M. F., Maier, M. M., Cheung, R. 2019

  Abstract

  CONTEXT.: Disease guidelines specify universal alanine aminotransferase (ALT) thresholds for clinical decision-making, yet the effect of variability among ALT analyzers remains unclear.OBJECTIVE.: To compare ALT results from different analyzers from 2012-2017.DESIGN.: Veterans Health Administration (VHA) laboratories perform external ALT proficiency testing using standardized College of American Pathologists (CAP) samples in analyzers by 5 manufacturers. In this operational analysis, we evaluated 22950 ALT values from 80 independent CAP samples tested at 223 laboratories. Using mixed effects modeling, we estimated the association between analyzer manufacturer and CAP outcome, adjusting for manufacturer, facility, and calendar year. We performed subgroup analyses on CAP samples with overall means near clinical guideline-specified thresholds, including less than 50 U/L (n = 10) and less than 35 U/L (n = 5).RESULTS.: The VHA used Abbott Laboratories (n = 3175; 14%), Beckman Coulter Diagnostics (n = 8723; 38%), Roche Diagnostics (n = 2595; 11%), Siemens Healthineers USA (n = 5713; 25%), and Vitros/Ortho Clinical Diagnostics (n = 2744; 12%) analyzers. The CAP samples (n = 80 samples, n = 22950 tests) covered a wide range of mean ALT values (21-268 U/L). The average difference in mean ALT value per sample between the highest-reading and lowest-reading manufacturers was 15.4 U/L (SD = 1.8) for the 10 samples with mean ALT less than 50 U/L, and it was 10.4 U/L (SD = 3.6) overall (n = 80). In linear mixed effects modeling, we found statistically significant differences in ALT values between the different manufacturers in each year.CONCLUSIONS.: We found statistically and clinically meaningful differences between analyzers across the ALT spectrum in each year, including at ALT levels lower than 50 U/L and lower than 35 U/L. Universal ALT thresholds should be avoided as a trigger for clinical action until differences between analyzers can be resolved.

  View details for DOI 10.5858/arpa.2018-0622-OA

  View details for PubMedID 31697169

• Preoperative Endoscopic Findings in Veterans Undergoing Bariatric Surgery: Prevalence and Predictors of Barrett's Esophagus. Obesity surgery Ozeki, K. A., Tran, S. A., Cheung, R. n., Eisenberg, D. n. 2019

  Abstract

  There is no consensus regarding the need for routine esophagogastroduodenoscopy (EGD) in patients before bariatric surgery. The aim of our study is to determine the frequency and predictors of EGD findings in a Veteran population presenting for bariatric surgery.This is a single-center retrospective analysis of Veterans who underwent RYGB or LSG, at a Veterans Affairs hospital between January 2008 and December 2017. All patients received a preoperative EGD. Data abstracted included demographics, comorbidities, preoperative laboratory values, and EGD findings. Univariate and multivariate analyses were performed for common EGD pathologies.Of the 260 Veterans included in our cohort, majority were male (75.0%), Caucasian (73.5%), and aged 54.0 ± 9.0 years old with a BMI of 44.9 ± 7.0 kg/m2. Most had hypertension (78.9%), previously smoked (63.9%), and recently used a proton pump inhibitor (PPI) (53.1%). One third of Veterans had a completely normal preoperative EGD. Common preoperative EGD findings included gastritis (35.8%), hiatal hernia (25.8%), esophagitis (20.8%), duodenitis (10.4%), Barrett's esophagus (7.4%), and Helicobacter pylori infection (4.6%). Preoperative predictors for a normal EGD were female gender, absence of hypertension, and no recent PPI use. Preoperative predictors of Barrett's esophagus included older age, recent PPI use, and recent histamine H2 receptor blocker (H2B) use. Increased age, male gender, and PPI use were associated with a change in surgical and/or medical management.Preoperative factors can be used to identify patients at risk for gastroesophageal pathology. Our data support preoperative EGD especially in older males with a history of PPI or H2B use.

  View details for DOI 10.1007/s11695-019-04234-3

  View details for PubMedID 31713148

• Hepatitis C Performance Measure on Hepatitis A and B Vaccination: Missed Opportunities? AMERICAN JOURNAL OF GASTROENTEROLOGY Hernandez, B., Hasson, N. K., Cheung, R. 2009; 104 (8): 1961-1967

  Abstract

  Prevention of hepatitis A virus (HAV) and hepatitis B virus (HBV) infection in patients with chronic hepatitis C (CHC) through vaccination is endorsed by all major professional societies. This study was conducted to determine adherence to the recently adopted physician performance measure on HAV and HBV vaccination.This was a retrospective study. Hepatitis A and B serology data and immunization records between 2000 and 2007 from CHC patients with detectable hepatitis C virus (HCV) RNA were analyzed.A total of 2,968 CHC patients were included in the study. Of these, 2,143 patients (72%) were tested for susceptibility to HAV, of which 53% had immunity. Of the non-immune patients, 746 (74%) were vaccinated as well as an additional 218 without prior testing. For HBV, 2,303 patients (78%) were tested for immunity and 782 (34%) were immune. Of the susceptible patients, 1,086 (71%) were vaccinated as well as an additional 197 patients without prior testing. The overall vaccination performance measure adherence rate was 71% for HAV, 70% for HBV, and 62% for both HAV and HBV. Random review of 176 charts found the major reasons for non-adherence were missed opportunity (41%), change of health care system (31%), and documented vaccination outside our health care system (22%).Our study found a high and improved adherence to the recommendations, but missed opportunity was still the main reason of non-adherence. This study also supported the strategy of selective vaccination in the veteran population.

  View details for DOI 10.1038/ajg.2009.252

  View details for Web of Science ID 000268965300011

  View details for PubMedID 19491840

• The impact of chronic hepatitis C and co-morbid illnesses on health-related quality of life QUALITY OF LIFE RESEARCH Kwan, J. W., Cronkite, R. C., Yiu, A., Goldstein, M. K., Kazis, L., Cheung, R. C. 2008; 17 (5): 715-724

  Abstract

  Determine the relative impact of chronic hepatitis C (CHC) and co-morbid illnesses on health-related quality of life (HRQoL) in 3023 randomly selected veterans with known hepatitis C virus antibody (anti-HCV) status who previously completed a veteran-specific HRQoL questionnaire (SF-36V).Multiple regression analyses were performed to measure the relative contribution of anti-HCV status, four demographic variables, and ten common medical and six psychiatric co-morbidities to HRQoL between 303 anti-HCV(+) and 2720 anti-HCV(-) patients.Anti-HCV(+) veterans were younger, reported a lower HRQoL on seven of eight 36-Item Short Form Health Survey for Veterans (SF-36V) subscales (P < or = 0.001) and the mental component summary (MCS) scale (P < 0.001). The ten medical and six psychiatric co-morbidities had variable impact on predicting lower HRQoL in both groups. After adjusting for demographic variables and co-morbid illnesses, we found that anti-HCV(+) patients reported a significantly lower MCS score (P < 0.001) and a trend toward a lower physical component summary (PCS) score (P < 0.07) compared to anti-HCV(-) veterans. Among the anti-HCV(+) veterans, co-morbid medical illnesses contributed to impaired PCS but not to MCS.Veterans with CHC were younger than HCV(-) veterans and hence less likely to have other co-morbid medical illnesses. Medical co-morbidities seen in those veterans with CHC contribute to impaired PCS but not MCS. Anti-HCV(+) status negatively affects HRQoL, particularly MCS, independently of medical and psychiatric co-morbidities.

  View details for DOI 10.1007/s11136-008-9344-3

  View details for Web of Science ID 000256522600007

  View details for PubMedID 18427949

• A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C HEPATOLOGY Huang, H., Shiffman, M. L., Friedman, S., Venkatesh, R., Bzowej, N., Abar, O. T., Rowland, C. M., Catanese, J. J., Leong, D. U., Sninsky, J. J., Layden, T. J., Wright, T. L., White, T., Cheung, R. C. 2007; 46 (2): 297-306

  Abstract

  Clinical factors such as age, gender, alcohol use, and age-at-infection influence the progression to cirrhosis but cannot accurately predict the risk of developing cirrhosis in patients with chronic hepatitis C (CHC). The aim of this study was to develop a predictive signature for cirrhosis in Caucasian patients. All patients had well-characterized liver histology and clinical factors; DNA was extracted from whole blood for genotyping. We validated all significant markers from a genome scan in the training cohort, and selected 361 markers for the signature building. Using a "machine learning" approach, a signature consisting of markers most predictive for cirrhosis risk in Caucasian patients was developed in the training set (N = 420). The Cirrhosis Risk Score (CRS) was calculated to estimate the risk of developing cirrhosis for each patient. The CRS performance was then tested in an independently enrolled validation cohort of 154 Caucasian patients. A CRS signature consisting of 7 markers was developed for Caucasian patients. The area-under-the-ROC curves (AUC) of the CRS was 0.75 in the training cohort. In the validation cohort, AUC was only 0.53 for clinical factors, increased to 0.73 for CRS, and 0.76 when CRS and clinical factors were combined. A low CRS cutoff of <0.50 to identify low-risk patients would misclassify only 10.3% of high-risk patients, while a high cutoff of >0.70 to identify high-risk patients would misclassify 22.3% of low-risk patients. Conclusion: CRS is a better predictor than clinical factors in differentiating high-risk versus low-risk for cirrhosis in Caucasian CHC patients. Prospective studies should be conducted to further validate these findings.

  View details for DOI 10.1002/hep.21695

  View details for Web of Science ID 000248501600005

  View details for PubMedID 17461418

• Incidence of statin hepatotoxicity in patients with hepatitis C CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Khorashadi, S., Hasson, N. K., Cheung, R. C. 2006; 4 (7): 902-907

  Abstract

  Statins are considered contraindicated in patients with chronic liver disease. Our objective was to determine the risk of developing hepatotoxicity from statin therapy in hyperlipidemic patients with hepatitis C.Changes in liver biochemistry values within 12 months compared with baseline were determined in 3 cohorts matched for age, sex, and body mass index: (I) 166 anti-hepatitis C virus (HCV)-positive hyperlipidemic veterans who were initiated on statin therapy; (II) 332 anti-HCV-positive veterans who had not received statin therapy; and (III) 332 anti-HCV-negative hyperlipidemic veterans who were initiated on statin therapy. An increase in liver biochemistry values was defined as mild-moderate or severe as proposed in a previous study on statin hepatotoxicity in a non-hepatitis C population.In patients with hepatitis C, statin therapy (cohort I) was associated with a higher incidence of mild-moderate liver biochemistry value increases compared with those not on statin therapy (cohort II) (22.9% vs 13.3%, respectively, P = .009), but a lower incidence of severe increases (1.2% vs 6.6%, respectively, P = .015). Among patients started on statin therapy (cohorts I and III), the incidence of mild-moderate liver biochemistry value increases (22.9% vs 16.3%, respectively, P = .094), severe increases (1.2% vs 1%, respectively, P = .874), or discontinuation of statin therapy as a result of hepatotoxicity (21.6% vs 9.2%, respectively, P = .147) were similar in hepatitis C-positive and hepatitis C-negative patients.Statin therapy was not associated with a higher risk of severe hepatotoxicity in patients with chronic hepatitis C and appeared safe.

  View details for DOI 10.1016/j.cgh.2006.03.014

  View details for Web of Science ID 000239202600018

  View details for PubMedID 16697272

• Epidemiology of hepatitis C virus infection in American Veterans AMERICAN JOURNAL OF GASTROENTEROLOGY Cheung, R. C. 2000; 95 (3): 740-747

  Abstract

  This study reports the findings of hepatitis C virus (HCV) infection in a large Department of Veterans Affairs Health Care System in suburban Northern California.All veterans who had anti-HCV (EIA II) tested during a 6-yr period (7/92 to 6/98) were included in this study. To estimate the seroprevalence of anti-HCV among our population, 126 consecutive bloodborne pathogen exposure accidents were studied.Of 8558 veterans tested for anti-HCV (EIA II), 2985 (35%) veterans were positive with a mean age of 48.4 yr (range, 28-89 yr). Sixty percent were between the age of 41 and 50 yr. Risk factors for HCV infection identified in 409 consecutive veterans were intravenous drug abuse (81%), unknown (11%), blood transfusion (3%), sexual/household contact (2%), transfusion and intravenous drug use (2%), and tattoo (1%). Of 215 consecutive anti-HCV-positive veterans whose sera were tested by polymerase chain reaction, 96% were viremic. The most common HCV genotypes were 1a (50.5%), 1b (22.8%), 3a (12.1%), 2b (9.7%), 2a (1.9%), undetermined (1.9%), and mixed infection (1%). Veterans infected with genotype 1b were significantly older. Among 126 consecutive bloodborne pathogen exposure accidents, hepatitis C serology was available for 72 index veterans involved in the accidents and 18% were positive.We found the epidemiology of hepatitis C infection was different in the veteran population when compared to other published data on nonveterans. Hepatitis C infection was much more common among veteran, within a very narrow age distribution and intravenous drug use was the major risk factor.

  View details for Web of Science ID 000085605200030

  View details for PubMedID 10710068

• Telehepatology Use and Satisfaction Among Vulnerable Cirrhosis Patients Across Three Healthcare Systems in the Coronavirus Disease Pandemic Era. Gastro hep advances Athavale, P., Wong, R. J., Satre, D. D., Monto, A., Cheung, R., Chen, J. Y., Batki, S. L., Ostacher, M. J., Snyder, H. R., Widiarto, B. D., Oh, S. Y., Liao, M., Viviani, A. M., Khalili, M. 2024; 3 (2): 201-209

  Abstract

  Telehealth has emerged as an important mode of cirrhosis care delivery, but its use and satisfaction among vulnerable populations (eg, racial/ethnic minorities, socioeconomically disadvantaged, substance use disorders) are unknown. We evaluated digital capacity, telehealth use, satisfaction and associated factors among patients receiving hepatology care via telehealth (telehepatology) across 2 Veterans Affairs and 1 safety-net Healthcare systems.English- and Spanish-speaking adults with cirrhosis (N = 256) completed surveys on telehealth use and satisfaction, quality of life, pandemic stress, alcohol use and depression. Logistic regression analyses assessed telehealth use and general linear models evaluated telehealth satisfaction.The mean age was 64.5 years, 80.9% were male and 35.9% Latino; 44.5% had alcohol-associated cirrhosis; 20.8% had decompensated cirrhosis; 100% had digital (phone/computer) capacity; and 75.0% used telehepatology in the prior 6 months. On multivariable analysis, participants with alcohol-associated (vs not) cirrhosis were less likely and those with greater pandemic stress were more likely to use telehepatology (odds ratio = 0.46 and 1.41, respectively; P < .05). Better quality of life was associated with higher telehepatology satisfaction and older age was associated with lower satisfaction (β = 0.01 and -0.01, respectively; P < .05). Latinos had higher satisfaction, but alcohol use disorder was associated with less satisfaction with telehepatology visits (β = 0.22 and -0.02, respectively; P < .05).Participants had high telehepatology capacity, yet demographics and alcohol-related problems influenced telehepatology use and satisfaction. Findings underscore the need for interventions to enhance patient experience with telehepatology for certain vulnerable groups including those with alcohol-associated cirrhosis in order to optimize care delivery.

  View details for DOI 10.1016/j.gastha.2023.11.006

  View details for PubMedID 39129958

  View details for PubMedCentralID PMC11307565

• Bariatric Surgery Reduced Long-Term Mortality in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease and Cirrhosis. Clinical and molecular hepatology Rouillard, N. A., Barnett, S. D., Zhang, X., Kam, L., Manikat, R., Cheung, R., Nguyen, M. H. 2024

  Abstract

  Objective: With the obesity pandemic, metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and a leading cause of end-stage liver disease and liver-related deaths in the U.S.A. Therefore, we aimed to compare the long-term outcomes of patients with MASLD and cirrhosis with and without bariatric surgery.Design: Patients were retrospectively identified from the California Department of Healthcare Access and Information database, 2005 to 2019, for a population-based cohort study. Propensity score matching (PSM) was used to balance background risks between patients with cirrhosis who underwent bariatric surgery and those who did not. Overall, liver-related, and non-liver-related mortality were analyzed.Results: Of 91,708 eligible patients with MASLD and cirrhosis, PSM yielded 2,107 patients who underwent bariatric surgery and 8,428 non-bariatric controls. Compared to matched controls, patients who underwent bariatric surgery had lower 5-year overall (24.9% vs. 37.1%; P < 0.0001), liver-related (3.3% vs. 14%; P < 0.0001), and non-liver-related mortality (22.3% vs. 26.9%; P = 0.046). In multivariable analysis, bariatric surgery was associated with decreased overall mortality (adjusted hazard ratio [aHR] = 0.63; P < 0.0001), liver-related (aHR = 0.24; P < 0.0001), and non-liver-related (aHR = 0.81; P = 0.0026) mortality. However, only laparoscopic surgeries were associated with lower overall mortality (aHR = 0.39; P < 0.0001) whereas open surgeries were associated with higher overall mortality (aHR = 1.24; P = 0.022).Conclusion: Patients with MASLD and cirrhosis who underwent bariatric surgery, specifically laparoscopic approaches, had significantly lower mortality risk than non-surgical counterparts.

  View details for DOI 10.3350/cmh.2024.0564

  View details for PubMedID 39541951

• Factors Associated With Motivation to Reduce Alcohol Use Among Patients With Chronic Liver Disease. Alimentary pharmacology & therapeutics Satre, D. D., Dasarathy, D., Batki, S. L., Ostacher, M. J., Snyder, H. R., Hua, W., Parekh, P., Shui, A. M., Cheung, R., Monto, A., Wong, R. J., Chen, J. Y., Liao, M., Tana, M., Chen, P. H., Haight, C. G., Fakadej, T., Khalili, M. 2024

  Abstract

  Alcohol use is prevalent among hepatology clinic patients with chronic liver disease (CLD). We explored factors associated with the importance and confidence dimensions of motivation to reduce drinking.Participants (N = 121) with unhealthy alcohol use (i.e., over NIH guidelines) receiving care in hepatology clinics from a safety-net hospital (SN, N = 54) and two Veterans Affairs Healthcare Systems (VA, N = 67) were enrolled in an alcohol intervention trial from March 2022 through October 2023. Baseline assessments included Generalised Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-8), Alcohol Use Disorders Identification Test (AUDIT), COVID-19 stress; and measures of importance and confidence to decrease alcohol use (readiness rulers, scales of 1-10). Liver disease aetiology and severity were extracted from electronic health records. We performed multivariable linear regression models with forward selection to assess pre-specified variables' associations with importance and confidence.The sample was 84% male, 40% Latino, 31% White, 18% Black and 11% other races; median age was 61 years. Median (Q1-Q3) AUDIT score was 16 (12-24), importance was 9 (6-10) and confidence was 8 (5-9). On multivariable analysis, VA site (vs. SN) participants had a 0.97-point lower importance score (p = 0.02); higher symptoms of depression (PHQ-8 score ≥ 10 vs. < 10) and AUDIT scores (for each point increase) were associated with higher importance score (estimates 1.2 and 0.08, p < 0.05, respectively). Liver disease aetiology and severity were not significantly associated with outcomes.Depression, alcohol problem severity and treatment site may influence motivation to reduce alcohol use and could inform future hepatology-based interventions.

  View details for DOI 10.1111/apt.18387

  View details for PubMedID 39523996

• Trends in Hepatocellular Carcinoma Mortality Rates in the US and Projections Through 2040. JAMA network open Qiu, S., Cai, J., Yang, Z., He, X., Xing, Z., Zu, J., Xie, E., Henry, L., Chong, C. R., John, E. M., Cheung, R., Ji, F., Nguyen, M. H. 2024; 7 (11): e2445525

  Abstract

  Importance: The burden of liver cancer varies worldwide. An upward trend in both hepatocellular carcinoma (HCC) incidence and mortality in the past 2 decades has been observed.Objective: To assess observed HCC-related age-standardized mortality rates (ASMRs) in the US for 2006 to 2022 and provide ASMR projections through 2040.Design, Setting, and Participants: This cross-sectional study used data from the National Vital Statistics System, which is accessible through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research website. Data on deaths attributed to HCC (from January 1, 2006, to December 31, 2022) were obtained for adults 25 years or older and were stratified by liver disease etiology, age, sex, and race and ethnicity. Etiologies included alcohol-associated liver disease (ALD), hepatitis B virus (HBV), hepatitis C virus (HCV), and metabolic dysfunction-associated steatotic liver disease (MASLD).Main Outcomes and Measures: The main outcomes were (1) observed ASMRs of HCC per 100 000 persons using Joinpoint regression (National Cancer Institute) to assess trends during 2006 to 2022 and (2) ASMRs projected for 2023 to 2040 using Prophet and AutoARIMA modeling.Results: This study included 188 280 HCC-related deaths from 2006 to 2022. Most deaths occurred among males (77.4%). The annual percentage change was 4.1% (95% CI, 2.2% to 7.7%) for 2006 to 2009 and decreased to 1.8% (95% CI, 0.7% to 2.0%) for 2009 to 2022, with an overall observed ASMR of 5.03 per 100 000 persons in 2022 and a projected ASMR of 6.39 per 100 000 persons by 2040, with consistent trends for both sexes. By etiology, ASMRs decreased for HCV- and HBV-related mortality but increased for ALD- and MASLD-related mortality. In 2022, MASLD surpassed HBV as the third-leading cause of HCC-related death and was projected to overtake HCV in 2032 as the second-leading cause; ALD was projected to be the leading cause of HCC-related death in 2026. In 2022, the ASMR was higher among individuals aged 65 years or older compared with those aged 25 to 64 years (18.37 vs 1.79 per 100 000 persons). The American Indian or Alaska Native population had the largest increase in projected ASMR by 2040 (14.71 per 100 000 persons) compared with the Asian population (3.03 per 100 000 persons).Conclusions and Relevance: In this cross-sectional study, ASMRs for ALD- and MASLD-related HCC death increased rapidly from 2006 to 2022; ALD-related HCC was projected to be the leading cause by 2026, with MASLD as the second-leading cause by 2032. These findings may serve as a reference for public health decision-making and timely identification of groups at high risk of HCC death.

  View details for DOI 10.1001/jamanetworkopen.2024.45525

  View details for PubMedID 39556395

• Incidence rates of hepatocellular carcinoma based on risk stratification in steatotic liver disease for precision medicine: A real-world longitudinal nationwide study. PLoS medicine Lai, R., Barnett, S., Zhang, X., Kam, L. Y., Cheung, R., Xie, Q., Nguyen, M. H. 2024; 21 (10): e1004479

  Abstract

  Detailed subgroup incidence rates for steatotic liver disease (SLD)-related hepatocellular carcinoma (HCC) are critical to inform practice and public health interventions but remain sparse. We aimed to fill in this gap.In a retrospective cohort study of adults with SLD from the United States (US) Merative Marketscan Research Databases (1/2007 to 12/2021), we estimated HCC incidence stratified by sex, age, cirrhosis, diabetes mellitus (DM), and a combination of all these 4 factors. We excluded patients with significant alcohol use and chronic viral hepatitis. We analyzed data from 741,816 patients with SLD (mean age 51.5 ± 12.8 years, 46% male, 14.7% cirrhosis). During a 2,410,166 person-years (PY) follow-up, 1,740 patients developed HCC. The overall HCC incidence yielded 0.72 per 1,000 PY (95% confidence interval [CI, 0.68, 0.75]). The incidence was higher in males (0.95, 95% CI [0.89, 1.01]) compared to females (0.52, 95% CI [0.48, 0.56]) (p < 0.001). For those with cirrhosis, the incidence was significantly higher at 4.29 (95% CI [4.06, 4.51]) compared to those without cirrhosis (0.14, 95% CI [0.13, 0.16]) (p < 0.001). Additionally, the incidence was higher in patients with DM (1.19, 95% CI [1.12, 1.26]) compared to those without DM (0.41, 95% CI [0.38, 0.44]) (p < 0.001). Chronic kidney disease (CKD) was also associated with a higher HCC incidence of 2.20 (95% CI [2.00, 2.41]) compared to those without CKD (0.58, 95% CI [0.55, 0.62]) (p < 0.001). Similarly, individuals with cardiovascular disease (CVD) had a higher HCC incidence of 1.89 (95% CI [1.75, 2.03]) compared to those without CVD (0.51, 95% CI [0.48, 0.54]) (p < 0.001). Finally, the incidence of HCC was significantly higher in patients with non-liver cancer (3.90, 95% CI [3.67, 4.12]) compared to those without other cancers (0.29, 95% CI [0.26, 0.31]) (p < 0.001). On further stratification, HCC incidence incrementally rose by 10-year age intervals, male sex, cirrhosis, and DM, reaching 19.06 (95% CI [16.10, 22.01]) and 8.44 (95% CI [6.78, 10.10]) in males and females, respectively, but only 0.04 for non-diabetic, noncirrhotic aged <40 years patients in both sexes. The main limitation of this methodology is the potential misclassification of the International Classification of Diseases (ICD) codes inherent in claims database studies.This nationwide study provided robust granular estimates for SLD-related HCC incidence stratified by several key risk factors. In addition to cirrhosis, future surveillance strategies, prevention, public health initiatives, and future research models should also take into account the impact of sex, age, and DM.

  View details for DOI 10.1371/journal.pmed.1004479

  View details for PubMedID 39453960

• Disease Progression for Histologic Diagnosis of Metabolic Dysfunction-Associated Steatotic Liver Disease in the Real-World: A Nationwide US Study. Digestive diseases (Basel, Switzerland) Zhang, X., Kam, L. Y., Barnett, S. D., Henry, L., Cheung, R., Nguyen, M. H. 2024: 1-10

  Abstract

  We compared clinical characteristics and outcomes in real-world metabolic dysfunction-associated steatotic liver disease (MASLD) patients with or without liver biopsy using a nationwide cohort in United States (USA) to fill in gaps in selection of biopsy patients.We conducted a retrospective cohort study of adult MASLD patients using Marketscan® Databases (1/2007-12/2021). Patients were categorized into those with or without liver biopsy during follow-up.We analyzed 540,326 MASLD patients: 23,732 with and 516,594 without biopsy. Only 4% of MASLD patients received liver biopsy and biopsy rate decreased in the last 5 years (9.4%-3.6%). After 1:5 propensity score matching on baseline characteristics including age, sex, and comorbidities, a total of 23,731 patients with biopsy and 118,396 matched patients without biopsy were analyzed. The incidence per 1,000 person-years for hepatocellular carcinoma (HCC) was 0.22 versus 2.18, cirrhosis 29.75 versus 90.44, and hepatic decompensation 15.84 versus 28.25 compared patients with and without biopsy. In multivariable analysis, patients with biopsy had more than 9 times higher risk of developing HCC, 3 times higher risk of cirrhosis, and 78% higher risk of hepatic decompensation. In subgroup analysis, the association remained consistent when stratified by age (<50 and ≥50), sex, and diabetes mellitus. Predictors of having biopsy included age, metabolic diseases, and living in North central or Northeast of USA.These data can inform clinical patient management that biopsy patients likely represent a selected group at higher risk for disease progression, especially in clinical trials for MASLD therapies.

  View details for DOI 10.1159/000541945

  View details for PubMedID 39401491

• Trends of chronic liver diseases by income level and socioeconomic factors in the United States: A population-based study. Alimentary pharmacology & therapeutics Lee, E. Y., Nguyen, V. H., Cheung, R., Nguyen, M. H. 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

• 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 Mao, X., Zhang, X., Kam, L., Chien, N., Lai, R., Cheung, K. S., Yuen, M. F., Cheung, R., Seto, W. K., Nguyen, M. H. 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

• Outcomes of a 1-Year Pilot Study Implementing Universal Hepatitis Delta Virus Testing Among Veterans With Chronic Hepatitis B. Journal of viral hepatitis Wong, R. J., Liao, M., Chen, Y., Kwan, M., Lee, J. H., Jou, J. H., Lim, J. K., Cheung, R. 2024

  Abstract

  Current US guidelines recommend risk-based testing for hepatitis delta virus (HDV) in persons with chronic hepatitis B (CHB). While there is debate as to whether a risk-based or universal testing approach is most effective, limited data exist on universal HDV testing programs in the United States. We performed a 1-year pilot study evaluating the outcomes of a universal HDV testing approach among US veterans with CHB. All consecutive adults with CHB receiving care at hepatology clinics at a single-centre Veterans Affairs Health System from 1 October 2022 to 30 September 2023 were prospectively tested for anti-HDV antibody (anti-HDV). Patients who were anti-HDV Ab-positive were subsequently tested for HDV RNA. Comparison of HDV testing between groups utilised chi-square testing. A total of 91 consecutive CHB patients (90.0% male, mean age 60.9 ± 14.1 years, 73.9% Asian, 26.1% non-Asia, 16.5% cirrhosis and 17.1% with active or past history of drug use) had anti-HDV ordered. Overall, 76.9% (n = 70) completed anti-HDV testing; 4.3% (n = 3) were positive. HDV RNA testing was ordered in all three patients; two patients completed HDV RNA testing and one had detectable HDV RNA. No significant differences in completion of anti-HDV testing was observed by age, sex, race/ethnicity, cirrhosis status or drug use history. Among a single-centre prospective cohort study piloting a universal HDV testing approach, one patient with viremic HDV was identified. Implementing true reflex testing of all CHB patients with anti-HDV, followed by automated HDV RNA testing for anti-HDV-positive patients would improve the HDV testing cascade and timely diagnosis of HDV.

  View details for DOI 10.1111/jvh.13992

  View details for PubMedID 39101377

• 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 Ji, F., Tran, S., Ogawa, E., Huang, C. F., Suzuki, T., Wong, Y. J., Toyoda, H., Jun, D. W., Li, L., Uojima, H., Nozaki, A., Chuma, M., Tseng, C. H., Hsu, Y. C., Ishigami, M., Honda, T., Atsukawa, M., Haga, H., Enomoto, M., Trinh, H., Preda, C. M., Vutien, P., Landis, C., Lee, D. H., Watanabe, T., Takahashi, H., Abe, H., Asai, A., Eguchi, Y., Li, J., Wang, X., Li, J., Liu, J., Liang, J., Lam, C. P., Huang, R., Ye, Q., Pan, H., Zhang, J., Cai, D., Wang, Q., Huang, D. Q., Wong, G., Wong, V. W., Li, J., Do, S., Furusyo, N., Nakamuta, M., Nomura, H., Kajiwara, E., Yoon, E. L., Ahn, S. B., Azuma, K., Dohmen, K., An, J., Song, D. S., Cho, H. C., Kawano, A., Koyanagi, T., Ooho, A., Satoh, T., Takahashi, K., Yeh, M. L., Tsai, P. C., Yasuda, S., Zhao, Y., Liu, Y., Okubo, T., Itokawa, N., Jun, M. J., Ishikawa, T., Takaguchi, K., Senoh, T., Zhang, M., Zhao, C., Alecu, R. I., Xuan Tay, W., Devan, P., Liu, J. K., Kozuka, R., Vargas-Accarino, E., Do, A. T., Maeda, M., Chuang, W. L., Huang, J. F., Dai, C. Y., Cheung, R., Buti, M., Niu, J., Xie, W., Ren, H., Lim, S. G., Wu, C., Yuen, M. F., Shang, J., Zhu, Q., Ueno, Y., Tanaka, Y., Hayashi, J., Yu, M. L., Nguyen, M. H. 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

• A prospective randomized controlled trial of water exchange plus cap versus water exchange colonoscopy in unsedated Veterans. Gastrointestinal endoscopy Leung, F. W., Cheung, R., Friedland, S., Jacob, N., Leung, J. W., Pan, J. Y., Quan, S. Y., Sul, J., Yen, A. W., Jamgotchian, N., Chen, Y., Dixit, V., Shaikh, A., Elashoff, D., Angshuman, S., Wilhalme, H. 2024

  Abstract

  BACKGROUND AND AIMS: Water exchange (WE) and cap-assisted colonoscopy (CAC) separately reduced pain during insertion in unsedated patients. We hypothesized that compared with WE, WECAC could significantly lower real-time maximum insertion pain (RTMIP).METHODS: Veterans without escort were recruited, randomized, blinded, and examined at three United States Veterans Affairs sites. The primary outcome was RTMIP, highest segmental pain (0 = no pain, 10 = most severe pain) during insertion.RESULTS: Randomization [WECAC (n = 143) and WE (n = 137)] produced even distribution of a racially diverse group of males and females of low socioeconomic status. Intention-to-treat analysis reported results of WECAC (listed first) and WE (listed second): cecal intubation [93%, 94.2%]; mean (SD) of RTMIP [2.9 (2.5), 2.6 (2.4)]; the proportion with no pain (28.7%, 27.7%); the insertion time [18.6 (15.6), 18.8 (15.9) min]; overall ADR (55.2%, 62.8%), all P values were > 0.05. When RTMIP was binarized as "no pain" (0) vs. "some pain" (1-10), or "low pain" (0-7) vs. "high pain" (8-10), different significant predictors (see text) of RTMIP were identified.CONCLUSIONS: Unsedated colonoscopy was appropriate for unescorted Veterans. WE alone was sufficient. Adding a cap did not reduce RTMIP. Patient specific factors and application of WE with insertion suction of infused water contributed to high and low RTMIP, respectively. For unesorted patients, selecting those with low anxiety, avoiding low body mass index, history of depression or self-reported poor health and adhering to the steps of WE can minimize RTMIP to ensure success of unsedated colonoscopy.

  View details for DOI 10.1016/j.gie.2024.07.010

  View details for PubMedID 39053653

• Sex and ethnic disparities in hepatitis B evaluation and treatment across the world. Journal of hepatology Kudaravalli, S., Huang, D. Q., Yeh, M., Trinh, L., Tsai, P. C., Hsu, Y., Kam, L. Y., Nguyen, V. H., Ogawa, E., Lee, D. H., Ito, T., Watanabe, T., Enomoto, M., Preda, C. M., Ko, M. K., Wan-Hin Hui, R., Atsukawa, M., Suzuki, T., Marciano, S., Barreira, A., Do, S., Uojima, H., Takahashi, H., Quek, S. X., Toe Wai Khine, H. H., Ishigami, M., Itokawa, N., Go, M. S., Kozuka, R., Marin, R. I., Sandra, I., Li, J., Zhang, J. Q., Wong, C., Yoshimaru, Y., Vo, D. K., Tseng, C., Lee, C., Inoue, K., Maeda, M., Hoang, J. K., Chau, A., Chuang, W., Dai, C., Huang, J., Huang, C., Buti, M., Tanaka, Y., Gadano, A. C., Yuen, M., Cheung, R., Lim, S. G., Trinh, H. N., Toyoda, H., Yu, M., Nguyen, M. H. 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

• Alcohol Use and Substance Use Treatment Engagement Among Patients With Alcohol-Associated Cirrhosis in Three Hospital-Based Hepatology Practices Snyder, H., Satre, D., Shumway, M., Batki, S., Ostacher, M., Tompkins, D., Monto, A., Wong, R., Cheung, R., Parekh, P., Hua, W., Widiarto, D., Oh, S., Liao, M., Khalili, M. ELSEVIER IRELAND LTD. 2024

  View details for DOI 10.1016/j.drugalcdep.2023.110450

  View details for Web of Science ID 001280690400468

• Letter of the Editor: Survey of attitudes and knowledge of early paracentesis guidelines and performance in providers in the veterans health administration. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Barnard Giustini, A., Patel, A., Cheung, R., Nobbe, A., Perumalswami, P. V., Johnson, R., Jakab, S., Patton, H., Morgan, T., Oleary, J., Bajaj, J. S., Rogal, S. 2024

  View details for DOI 10.1097/LVT.0000000000000426

  View details for PubMedID 38920367

• 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) Nguyen, B. T., Nguyen, V. H., Le, M., Henry, L., Cheung, R., Nguyen, M. H. 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

• A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease. Hepatology international Zhang, H., Targher, G., Byrne, C. D., Kim, S. U., Wong, V. W., Valenti, L., Glickman, M., Ponce, J., Mantzoros, C. S., Crespo, J., Gronbaek, H., Yang, W., Eslam, M., Wong, R. J., Machado, M. V., Yu, M. L., Ghanem, O. M., Okanoue, T., Liu, J. F., Lee, Y. H., Xu, X. Y., Pan, Q., Sui, M., Lonardo, A., Yilmaz, Y., Zhu, L. Y., Moreno, C., Miele, L., Lupsor-Platon, M., Zhao, L., LaMasters, T. L., Gish, R. G., Zhang, H., Nedelcu, M., Chan, W. K., Xia, M. F., Bril, F., Shi, J. P., Datz, C., Romeo, S., Sun, J., Liu, D., Sookoian, S., Mao, Y. M., Méndez-Sánchez, N., Wang, X. Y., Pyrsopoulos, N. T., Fan, J. G., Fouad, Y., Sun, D. Q., Giannini, C., Chai, J., Xia, Z. F., Jun, D. W., Li, G. J., Treeprasertsuk, S., Li, Y. X., Cheung, T. T., Zhang, F., Goh, G. B., Furuhashi, M., Seto, W. K., Huang, H., Di Sessa, A., Li, Q. H., Cholongitas, E., Zhang, L., Silveira, T. R., Sebastiani, G., Adams, L. A., Chen, W., Qi, X., Rankovic, I., De Ledinghen, V., Lv, W. J., Hamaguchi, M., Kassir, R., Müller-Wieland, D., Romero-Gomez, M., Xu, Y., Xu, Y. C., Chen, S. Y., Kermansaravi, M., Kuchay, M. S., Lefere, S., Parmar, C., Lip, G. Y., Liu, C. J., Åberg, F., Lau, G., George, J., Sarin, S. K., Zhou, J. Y., Zheng, M. H. 2024

  Abstract

  With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

  View details for DOI 10.1007/s12072-024-10702-5

  View details for PubMedID 38878111

  View details for PubMedCentralID 7309235

• Association of Baseline Hepatitis B Virus DNA and On-Treatment Risk of Cirrhosis and Hepatocellular Carcinoma. Gastroenterology research Yang, Z., Cheung, R. C., Jou, J. H., Lim, J. K., Lim, Y. S., Wong, R. J. 2024; 17 (3): 109-115

  Abstract

  Recent studies suggest an inverse relationship between baseline levels of hepatitis B virus (HBV) DNA and on-treatment risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). However, data are limited to Asian cohorts, and it is unclear if similar associations hold true for non-Asians with CHB. We aimed to evaluate association of baseline HBV DNA with long-term risks of cirrhosis and HCC among a predominantly non-Asian cohort of CHB patients in the USA.Using longitudinal data from the national Veterans Affairs database, we evaluated the risk of cirrhosis or HCC among adults with non-cirrhotic CHB who are on continuous antiviral therapy, stratified by moderate levels of baseline HBV DNA (4.00 - 6.99 log10 IU/mL) vs. high levels of baseline HBV DNA (7.00 log10 IU/mL or higher). Propensity score weighting was applied, and competing risks cumulative incidence functions and Cox proportional hazards models were utilized.Among 1,129 non-cirrhotic CHB patients (41% non-Hispanic White, 36% African American, mean age 57.0 years, 62.2% hepatitis B e antigen (HBeAg) positive), 585 had moderate levels of baseline HBV DNA and 544 had high HBV DNA. After propensity score weighting, no significant difference in risk of cirrhosis was observed between moderate vs. high baseline HBV DNA (4.55 vs. 5.22 per 100 person-years, hazard ratio (HR): 0.87, 95% confidence interval (CI): 0.69 - 1.09, P = 0.22), but risk of HCC was significantly higher in patients with moderate vs. high baseline HBV DNA (0.84 vs. 0.69 per 100 person-years, HR: 1.33, 95% CI: 1.09 - 1.62, P < 0.01).Among a national cohort of predominantly non-Asian US veterans with non-cirrhotic CHB on antiviral therapy, moderate levels of baseline HBV DNA was associated with higher risk of HCC than high HBV DNA.

  View details for DOI 10.14740/gr1735

  View details for PubMedID 38993547

  View details for PubMedCentralID PMC11236339

• Updates in characteristics and survival rates of cirrhosis in a nationwide cohort of real-world U.S. patients, 2003-2021. Alimentary pharmacology & therapeutics Tran, S., Zou, B., Lee, K., Kam, L., Yeo, Y., Henry, L., Cheung, R., Nguyen, M. H. 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

• Antiviral therapy response in patients with chronic hepatitis B and fatty liver: A systematic review and meta-analysis. Journal of viral hepatitis Rui, F., Garcia, E., Hu, X., Ni, W., Xue, Q., Xu, Y., Xu, X., Shi, J., Nguyen, M. H., Cheung, R. C., Li, J. 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

• Impact of Human Immunodeficiency Virus Infection on Liver and Cardiovascular Outcomes in Veterans with Metabolic Dysfunction Associated Steatotic Liver Disease. The American journal of gastroenterology Wong, R. J., Yang, Z., Yeoh, A., Do, A., Ahmed, A., Cheung, R. 2024

  Abstract

  Hepatic steatosis in highly prevalent in people living with human immunodeficiency virus (HIV). It remains unclear whether HIV in patients with metabolic dysfunction associated steatotic liver disease (MASLD) is associated with greater risks of liver disease progression and cardiovascular disease (CVD). We aim to evaluate the impact of HIV infection on risks of liver and CVD outcomes among U.S. Veterans with MASLD.Using national Veterans Administration data from 2010-2022, we created a propensity score matched cohort of MASLD patients with vs. without HIV. Primary outcomes were incidence of cirrhosis and hepatocellular carcinoma (HCC) among patients with vs. without HIV as well as MASLD-HIV patients on anti-retroviral therapy (ART) vs. not on ART. Secondary outcomes included incidence of major adverse cardiovascular events (MACE) and overall survival.The propensity matched cohort included 920 MASLD patients with HIV and 920 MASLD patients without HIV and were similar in demographics and co-morbidities. Compared to MASLD patients without HIV, incidences of cirrhosis and HCC were similar among MASLD with HIV. Compared to MASLD patients without HIV, incidence of MACE was higher among MASLD patients with HIV (5.18 vs. 4.48 per 100 person-years, p=0.03). Overall 5-year survival was significantly lower among MASLD patients with HIV and even lower among those not on ART.Among U.S. Veterans with MASLD, concurrent HIV infection, and particularly not being on ART, is associated with greater risks CVD and decreased overall survival. No differences in risks of cirrhosis or HCC were observed.

  View details for DOI 10.14309/ajg.0000000000002760

  View details for PubMedID 38477465

• Impact of Longitudinal Alcohol Use Patterns on Long-Term Risk of Cirrhosis Among U.S. Veterans with Steatotic Liver Disease. Gastroenterology Wong, R. J., Yang, Z., Cheung, R., Singal, A. K., Do, A., Ahmed, A., Yeoh, A. 2024

  Abstract

  BACKGROUND & AIMS: Conflicting data exists on impact of alcohol use on risk of liver disease progression in patients with steatotic liver disease. We aim to evaluate the effect of longitudinal alcohol use on risk of cirrhosis among Veterans with steatotic liver disease.METHODS: U.S. Veterans with steatotic liver disease were identified from January 2010 to December 2022. Alcohol use was assessed using documented AUDIT-C scores and categorized as no alcohol (AUDIT-C = 0), low-risk alcohol use (AUDIT-C 1-2 for women and 1-3 for men), high-risk alcohol (AUDIT-C > 3 for women and > 4 for men). Incidence of cirrhosis was evaluated with competing risks Nelson-Aalen methods. Adjusted multivariable regression models evaluated risks of cirrhosis associated with baseline alcohol use and changes in alcohol use during follow up.RESULTS: 1,156,189 Veterans with steatotic liver disease were identified (54.2% no alcohol, 34.6% low-risk alcohol, 11.2% high-risk alcohol). Veterans with steatotic liver disease and high-risk alcohol have 43% higher incidence of cirrhosis compared to patients reporting no alcohol use. Compared to patients with baseline high-risk alcohol who reported no change in alcohol use, those who decreased their alcohol use during follow up experienced a 39% reduction in long-term risk of cirrhosis (HR 0.61, 95% CI 0.45-0.83, p< 0.01).CONCLUSIONS: One in nine Veterans with steatotic liver disease report concurrent high-risk alcohol use, which is associated with 43% greater risk of cirrhosis compared to no alcohol use. However, reducing alcohol use lowers risk of cirrhosis, emphasizing the importance of timely alcohol use assessment and early interventions to address high-risk alcohol use in steatotic liver disease.

  View details for DOI 10.1053/j.gastro.2024.02.032

  View details for PubMedID 38428619

• Upper limit of normal ALT levels in health and metabolic diseases: Pooled analysis of 423,355 individuals with bootstrap modelling. Alimentary pharmacology & therapeutics Tan, E. X., Huang, D. Q., Yee, N. T., Wan, Z. H., Nerurkar, S. N., Kai, J. C., Goh, K. S., Ng, C. H., Muthiah, M., Zhou, Y., Woodward, A., Le, M. H., Yeo, Y. H., Barnett, S., Cheung, R., Nguyen, M. H. 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

• Problematic alcohol use and its impact on liver disease quality of life in a multicenter study of patients with cirrhosis. Hepatology communications Luk, J. W., Satre, D. D., Cheung, R., Wong, R. J., Monto, A., Chen, J. Y., Batki, S. L., Ostacher, M. J., Snyder, H. R., Shui, A. M., Liao, M., Haight, C. G., Khalili, M. 2024; 8 (2)

  Abstract

  Management of cirrhosis is challenging and has been complicated by the COVID-19 pandemic due to decreased access to care, increased psychological distress, and alcohol misuse. Recently, The National Institute on Alcohol Abuse and Alcoholism has broadened the definition of recovery from alcohol use disorder to include quality of life (QoL) as an indicator of recovery. This study examined the associations of alcohol-associated cirrhosis etiology and problematic drinking with liver disease QoL (LDQoL).Patients with cirrhosis (N=329) were recruited from 3 sites (63% from 2 Veterans Affairs Health Care Systems and 37% from 1 safety net hospital) serving populations that are economically or socially marginalized. Cirrhosis etiology was ascertained by chart review of medical records. Problematic drinking was defined by ≥8 on the Alcohol Use Disorders Identification Test. Multivariable general linear modeling adjusting for age, sex, race/ethnicity, site, pandemic-related stress, and history of anxiety/depressive disorder were conducted. Sensitivity analyses further adjusted for indicators of liver disease severity.Participants were on average 64.6 years old, 17% female, 58% non-White, 44% with alcohol-associated cirrhosis, and 17% with problematic drinking. Problematic drinking was significantly associated with worse LDQoL scores in the overall scale and in the memory/concentration and health distress subscales. These associations remained significant after adjusting for indicators of liver disease severity, including Model for End-Stage Liver Disease-Sodium score and decompensated cirrhosis status.Among patients with cirrhosis, problematic drinking was associated with worse LDQoL, especially in the domains of memory/concentration and health distress. Assessment and awareness of cognitive deficits and negative emotionality within the context of cirrhosis and problematic drinking may help clinicians provide better integrated care for this population.

  View details for DOI 10.1097/HC9.0000000000000379

  View details for PubMedID 38315141

• Cost-effectiveness study of FIB-4 followed by transient elastography screening strategy for advanced hepatic fibrosis in a NAFLD at-risk population. Liver international : official journal of the International Association for the Study of the Liver Park, H., Yoon, E. L., Kim, M., Kwon, S. H., Kim, D., Cheung, R., Kim, H. L., Jun, D. W. 2024

  Abstract

  The cost-effectiveness to screen hepatic fibrosis in at-risk population as recommended by several professional societies has been limited. This study aimed to investigate the cost-effectiveness of this screening strategy in the expanded at-risk population recently proposed by several societies.A combined model of the decision tree and Markov models was developed to compare expected costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) between screening and no screening groups. The model included liver disease-related health states and cardiovascular disease (CVD) states as a base-case analysis. Screening strategy consisted of fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE) and intensive lifestyle intervention (ILI) as a treatment for diagnosed patients.Cost-effectiveness analysis showed that screening the at-risk population entailed $298 incremental costs and an additional 0.0199 QALY per patient compared to no screening (ICER $14 949/QALY). Screening was cost-effective based on the implicit ICER threshold of $25 000/QALY in Korea. When the effects of ILI on CVD and extrahepatic malignancy were incorporated into the cost-effectiveness model, the ICER decreased by 0.85 times from the base-case analysis (ICER $12 749/QALY). In contrast, when only the effects of liver disease were considered in the model, excluding cardiovascular disease effects, ICER increased from the baseline case analysis to $16 305. Even when replacing with medical costs in Japan and U.S., it remained cost-effective with the estimate below the countries' ICER threshold.Our study provides compelling evidence supporting the cost-effectiveness of FIB-4-based screening the at-risk population for advanced hepatic fibrosis.

  View details for DOI 10.1111/liv.15838

  View details for PubMedID 38291809

• Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Clinical and molecular hepatology Le, M. H., Le, D. M., Baez, T. C., Dang, H., Nguyen, V. H., Lee, K., Stave, C. D., Ito, T., Wu, Y., Yeo, Y. H., Ji, F., Cheung, R., Nguyen, M. H. 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

• 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 Park, J. E., Nguyen, V. H., Tsai, P. C., Toyoda, H., Leong, J., Guy, J. E., Yeh, M. L., Huang, C. F., Yasuda, S., Abe, H., Hsu, Y. C., Tseng, C. H., Liu, J., Chen, Y. L., Lin, P. Y., Jun, D. W., Yoshimaru, Y., Ogawa, E., Ishigami, M., Enomoto, M., Tamori, A., Uojima, H., Wang, X. Z., Xu, Q., Takahashi, H., Eguchi, Y., Inoue, K., Huang, D. Q., Zhao, W. J., Chuang, W. L., Dai, C. Y., Huang, J. F., Barnett, S., Maeda, M., Cheung, R., Landis, C., Tanaka, Y., Roberts, L. R., Schwartz, M. E., Kumada, T., Yu, M. L., Nguyen, M. H. 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

• The Reply. The American journal of medicine Yeoh, A., Cheung, R., Ahmed, A., Chitnis, A. S., Do, A., Wong, R. J. 2024; 137 (1): e15

  View details for DOI 10.1016/j.amjmed.2023.08.024

  View details for PubMedID 38061829

• Differential Mortality Outcomes in Real-world Patients with Lean, Nonobese, and Obese Nonalcoholic Fatty Liver Disease. Journal of clinical and translational hepatology Nguyen, V. H., Ha, A., Rouillard, N. A., Le, R. H., Fong, A., Gudapati, S., Park, J. E., Maeda, M., Barnett, S., Cheung, R., Nguyen, M. H. 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

• Incidence and predictors of hepatocellular carcinoma in NAFLD without diagnosed cirrhosis: a nationwide real-world U.S. study. Hepatology international Huang, D. Q., Tran, S., Barnett, S., Zou, B., Yeo, Y. H., Cheung, R., Nguyen, M. H. 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

• Alcohol Use Patterns During and After the COVID-19 Pandemic Among Veterans in the United States. The American journal of medicine Wong, R. J., Yang, Z., Ostacher, M., Zhang, W., Satre, D., Monto, A., Khalili, M., Singal, A. K., Cheung, R. 2023

  Abstract

  BACKGROUND: Veterans may be especially susceptible to increased alcohol consumption following the COVID-19 pandemic. We aim to evaluate trends in alcohol use among U.S. Veterans before, during, and following the onset of the COVID-19 pandemic.METHODS: All U.S. Veterans utilizing Veterans Affairs healthcare facilities in the U.S. from March 1, 2018 to February 28, 2023 with ≥1 AUDIT-C score were categorized into 1) No alcohol use (AUDIT-C = 0), 2) Low-risk alcohol use (AUDIT-C 1-2 for women, 1-3 for men), and 3) High-risk alcohol use (AUDIT-C ≥ 3 for women, ≥ 4 for men). Trends in the proportion of Veterans reporting high-risk alcohol use, stratified by sex, age, race/ethnicity, and urbanicity were evaluated.RESULTS: Among a cohort of 2.15 to 2.60 million Veterans, 15.5% reported high-risk alcohol use during March 2018-February 2019, which declined to 14.6% during the first year of the pandemic, increased to 15.2% in the second year, and then decreased to 14.9% from March 2022-February 2023. Among non-Hispanic whites, African Americans, Asians, and Hispanics, the proportion of women reporting high-risk alcohol use surpassed that of men during the onset of the pandemic and beyond. The greatest proportion of high-risk alcohol use was observed among young Veterans aged 18-39 years (17-27%), which was consistent across all race/ethnic groups.CONCLUSIONS: High-risk alcohol use among U.S. Veterans has increased since the COVID-19 pandemic onset, and in the third year following pandemic onset, 15% of Veterans overall and over 20% of young Veterans aged 18-39 years reported high -risk alcohol use.

  View details for DOI 10.1016/j.amjmed.2023.11.013

  View details for PubMedID 38052382

• Updates in Characteristics and Survival Rates of Hepatocellular Carcinoma in a Nationwide Cohort of Real-World US Patients, 2003-2021. Journal of hepatocellular carcinoma Tran, S., Zou, B., Kam, L., Lee, K., Huang, D. Q., Henry, L., Cheung, R., Nguyen, M. H. 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

• Differential Mortality Outcomes in Real-world Patients with Lean, Nonobese, and Obese Nonalcoholic Fatty Liver Disease JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY Nguyen, V. H., Ha, A., Rouillard, N., Le, R., Fong, A., Gudapati, S., Park, J., Maeda, M., Barnett, S., Cheung, R., Nguyen, M. H. 2023

  View details for DOI 10.14218/JCTH.2023.00016

  View details for Web of Science ID 001119285500001

• 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 Kam, L. Y., Yeo, Y. H., Ji, F., Henry, L., Cheung, R., Nguyen, M. H. 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

• Increased spine bone density in patients with chronic hepatitis B switched to tenofovir alafenamide: A prospective, multinational study. Alimentary pharmacology & therapeutics Ogawa, E., Jun, D. W., Toyoda, H., Hsu, Y. C., Yoon, E. L., Ahn, S. B., Yeh, M. L., Do, S., Trinh, H. N., Takahashi, H., Enomoto, M., Kawada, N., Yasuda, S., Tseng, C. H., Kawashima, K., Lee, H. A., Inoue, K., Haga, H., Do, A. T., Maeda, M., Hoang, J. H., Cheung, R., Ueno, Y., Eguchi, Y., Furusyo, N., Yu, M. L., Tanaka, Y., Nguyen, M. H. 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

• Disparities in Antiviral Treatment among Adults with Hepatitis B Cirrhosis: An Analysis of the National Veterans Affairs Cohort. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Wong, R. J., Yang, Z., Cheung, R. 2023

  Abstract

  Timely antiviral therapy is critical in chronic hepatitis B (CHB) cirrhosis, to prevent further liver complications. Among a national cohort of US Veterans with CHB cirrhosis, only 52% were initiated on antiviral therapy; treatment was significantly lower among patients of non-Asian ethnicity, high-risk alcohol use, and in rural settings.

  View details for DOI 10.1093/cid/ciad617

  View details for PubMedID 37812689

• On-treatment risks of cirrhosis and hepatocellular carcinoma among a large cohort of predominantly non-Asian patients with non-cirrhotic chronic hepatitis B. JHEP reports : innovation in hepatology Yang, Z., Cheung, R. C., Chitnis, A. S., Zhang, W., Gish, R. G., Wong, R. J. 2023; 5 (10): 100852

  Abstract

  The vast majority of studies evaluating differences in on-treatment risks of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) have been conducted in Asia. Data on the course of CHB on antiviral therapy among predominantly non-Asian populations is less well described. We aimed to evaluate overall risks of cirrhosis and HCC and the influence of baseline factors on this risk among a predominantly non-Asian cohort of patients with CHB in the US.Using longitudinal data from the national Veterans Affairs database, we evaluated the incidence of cirrhosis or HCC among adults with non-cirrhotic CHB on continuous antiviral therapy. Cumulative incidence functions and adjusted Cox proportional hazards models employed competing risks methods and evaluated overall risk and predictors of developing cirrhosis or HCC while on treatment.Among 2,496 patients with non-cirrhotic CHB (39.1% African American, 38.4% non-Hispanic White, 18.8% Asian, mean age 58.0 ± 13.4 years), the overall incidences of cirrhosis and HCC were 3.99 per 100 person-years (95% CI 3.66-4.35) and 0.43 per 100 person-years (95% CI 0.33-0.54), respectively. The highest incidences of cirrhosis and HCC were observed in non-Hispanic White patients (5.74 and 0.52 per 100 person-years, respectively), which were significantly higher than in Asian patients (1.93 and 0.17 per 100 person-years, respectively, p <0.0001). On multivariate regression, only baseline FIB-4 score was consistently associated with long-term risk of cirrhosis or HCC.Using a longitudinal cohort of predominantly non-Asian Veterans with non-cirrhotic CHB on antiviral therapy (an understudied population), we provide important epidemiological data to describe long-term risks of cirrhosis and HCC.In one of the largest studies to date of a predominantly non-Asian cohort of patients with non-cirrhotic chronic hepatitis B, we provide important epidemiological data describing the long-term risks of cirrhosis and hepatocellular carcinoma among patients on antiviral therapies. Among this understudied population, the overall incidence of cirrhosis was 3.99 per 100-person-years (95% CI 3.66-4.35) and of HCC was 0.43 per 100-person-years (95% CI 0.33-0.54). These data also emphasize the importance of continued monitoring and HCC surveillance among CHB patients who are maintained on antiviral therapies.

  View details for DOI 10.1016/j.jhepr.2023.100852

  View details for PubMedID 37701335

  View details for PubMedCentralID PMC10494462

• High-Risk Alcohol Use Is Associated With Significantly Greater Risk of Incident Hepatocellular Carcinoma in a National Cohort of US Veterans With Metabolic Dysfunction Associated Fatty Liver Disease Wong, R. J., Yang, Z., Cheung, R., Singal, A. K., Do, A., Ahmed, A., Yeoh, A. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1043

  View details for Web of Science ID 001091849303063

• Evaluating the Association Between Concurrent Human Immunodeficiency Virus Infection and Risk of Cardiovascular Disease in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease Wong, R. J., Yang, Z., Yeoh, A., Do, A., Ahmed, A., Cheung, R. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1043-S1044

  View details for Web of Science ID 001091849303064

• Real Time Maximum Insertion Pain in Unsedated Colonoscopy - Water Exchange vs Water Exchange Plus Cap: A Multi-Site, Multi-Investigator Randomized Controlled Trial in Veterans Leung, F. W., Cheung, R., Friedland, S., Jacob, N., Leung, J., Pan, J., Quan, S. Y., Sul, J., Yen, A., Jamgotchian, N., Chen, Y., Vivek, D., Sheikh, A., Elashoff, D., Saha, A., Wilhalme, H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S541

  View details for Web of Science ID 001091849301286

• LOW ANTIVIRAL TREATMENT RATE FOR PATIENTS WITH HEPATITIS C (HCV)-RELATED HEPATOCELLULAR CARCINOMA (HCC)-A REAL-WORLD NATIONWIDE U. S. STUDY Kam, L., Yeo, Y., Ji, F., Henry, L., Cheung, R., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S62

  View details for Web of Science ID 001094865400059

• DIFFERENCES BETWEEN BIOPSY-PROVEN NASH PATIENTS WITH AND WITHOUT DIABETES MELLITUS Dang, H., Nguyen, V. H., Tsai, P., Ito, T., Kawanaka, M., Atsukawa, M., Arai, T., Hayama, K., Yeh, M., Maeda, M., Chuang, W., Huang, C., Dai, C., Huang, J., Cheung, R., Aishima, S., Toyoda, H., Yu, M., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S947-S948

  View details for Web of Science ID 001094865402133

• 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 Garcia, E., Chien, N., Yeo, Y., Nguyen, M. H., Cheung, R. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1829-S1830

  View details for Web of Science ID 001094865404305

• IMPACT OF SEX AND DIABETES ON LONG- TERM OUTCOMES OF PATIENTS WITH NAFLD Hand, C., Nguyen, V. H., Kam, L., Park, J., Le, R., Rouillard, N., Fong, A., Gudapati, S., Ha, A., Maeda, M., Barnett, S. D., Henry, L., Cheung, R., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S978-S979

  View details for Web of Science ID 001094865402162

• 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 Chau, A., Yeh, M., Tsai, P., Trinh, H. N., Tseng, C., Hsu, Y., Ito, T., Kawashima, K., Suzuki, T., Ishikawa, T., Nozaki, A., Inoue, K., Eguchi, Y., Uojima, H., Abe, H., Takahashi, H., Watanabe, T., Chuma, M., Ishigami, M., Hoang, J., Maeda, M., Huang, C., Dai, C., Huang, J., Chuang, W., Cheung, R., Yu, M., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S471-S472

  View details for Web of Science ID 001094865401092

• 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 Rouillard, N., Kam, L., Barnett, S. D., Manikat, R., Cheung, R. C., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1237-S1238

  View details for Web of Science ID 001094865403044

• DIFFERENCES IN INCIDENCE OF ADVERSE CLINICAL EVENTS AMONG NAFLD PARTICIPANTS WITH LIVER BIOPSY PROVEN NAFLD STRATIFIED BY NASH: A SYSTEMATIC REVIEW AND META-ANALYSIS Le, D. M., Baez, T., Le, M. H., Dang, H., Nguyen, V. H., Lee, K., Ito, T., Wu, Y., Yeo, Y., Ji, F., Cheung, R., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S949-S950

  View details for Web of Science ID 001094865402135

• INCIDENCE OF ADVERSE CLINICAL EVENTS IN PERSONS WITH NAFLD: A SYSTEMATIC REVIEW AND META- ANALYSIS Le, D. M., Baez, T., Le, M. H., Dang, H., Nguyen, V. H., Lee, K., Ito, T., Wu, Y., Yeo, Y., Ji, F., Cheung, R., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S983

  View details for Web of Science ID 001094865402166

• TRENDS OF CHRONIC LIVER DISEASES BY INCOME LEVEL AND SOCIOECONOMIC FACTORS IN THE US NATIONAL POPULATION Lee, E., Nguyen, V. H., Cheung, R., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1303-S1304

  View details for Web of Science ID 001094865403129

• CONCURRENT HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN PATIENTS WITH METABOLIC DYSFUNCTION ASSOCIATED FATTY LIVER DISEASE IS ASSOCIATED WITH SIGNIFICANTLY GREATER RISKS OF CIRRHOSIS AND HEPATOCELLULAR CARCINOMA Wong, R. J., Yang, Z., Yeoh, A., Do, A., Ahmed, A., Cheung, R. LIPPINCOTT WILLIAMS & WILKINS. 2023: S935-S936

  View details for Web of Science ID 001094865402123

• DEVELOPMENT AND VALIDATION OF A RISK SCORE FOR FIBROSIS STAGE 2 OR HIGHER: A REAL-NAFLD STUDY OF 1902 REAL-WORLD PATIENTS WITH BIOPSY Nguyen, V. H., Ito, T., Dang, H., Tsai, P., Kawanaka, M., Atsukawa, M., Arai, T., Hayama, K., Yeh, M., Maeda, M., Barnett, S. D., Chuang, W., Huang, C., Dai, C., Huang, J., Cheung, R., Yu, M., Aishima, S., Toyoda, H., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S943-S944

  View details for Web of Science ID 001094865402128

• REGIONAL AND SEX DIFFERENCES IN INCIDENCE OF ADVERSE CLINICAL EVENTS IN PERSONS WITH NAFLD: A SYSTEMATIC REVIEW AND META-ANALYSIS Baez, T., Le, D. M., Le, M. H., Dang, H., Nguyen, V. H., Lee, K., Ito, T., Wu, Y., Yeo, Y., Ji, F., Cheung, R., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1039

  View details for Web of Science ID 001094865402218

• IMPACT OF FAMILY INCOME-TO-POVERTY RATIO ON LONG-TERM MORTALITY OF PERSONS WITH CHRONIC LIVER DISEASE IN THE UNITED STATES, 1999-2018 Nguyen, B., Nguyen, V. H., Le, M. H., Henry, L., Cheung, R., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1286-S1287

  View details for Web of Science ID 001094865403112

• DIAGNOSIS IS DELAYED: PERICOMPLICATION DIAGNOSIS OF NONALCOHOLIC FATTY LIVER DISEASE Manikat, R., Tran, S., Kam, L., Dronamraju, D., Cheung, R. C., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S945-S946

  View details for Web of Science ID 001094865402130

• GLOBAL DIFFERENCES IN THE EVALUATION AND TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS B: A REAL- B STUDY Kudaravalli, S., Huang, D. Q., Kam, L., Nguyen, V. H., Trinh, H. N., Hsu, Y., Li, J., Zhang, J., Ogawa, E., Lee, D., Ito, T., Watanabe, T., Enomoto, M., Preda, C., Tanaka, Y., Yuen, M., Atsukawa, M., Marciano, S., Buti, M., Do, S. T., Wong, C., Uojima, H., Takahashi, H., Quek, S., Khine, H., Ishigami, M., Itokawa, N., Go, M., Marin, R., Sandra, I., Suzuki, T., Yoshimaru, Y., Ko, M., Hui, R., Wong, C., Vo, D., Barreira, A., Tseng, C., Lee, C., Inoue, K., Maeda, M., Hoang, J., Trinh, L., Chau, A., Chuang, W., Dai, C., Huang, J., Huang, C., Yeh, M., Gadano, A., Cheung, R., Lim, S., Toyoda, H., Yu, M., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S464-S466

  View details for Web of Science ID 001094865401086

• THE ASSOCIATION BETWEEN BASELINE ALCOHOL USE AND LONG-TERM RISK OF INCIDENT CIRRHOSIS AMONG A NATIONAL COHORT OF US VETERANS WITH METABOLIC DYSFUNCTION ASSOCIATED FATTY LIVER DISEASE Wong, R. J., Yang, Z., Cheung, R., Singal, A. K., Do, A., Ahmed, A., Yeoh, A. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1045-S1046

  View details for Web of Science ID 001094865402225

• COMPARISON OF CHARACTERISTICS AND OUTCOMES IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE WHO DID OR DIDN'T RECEIVE LIVER BIOPSY Zhang, X., Kam, L., Barnett, S. D., Henry, L., Cheung, R., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S931

  View details for Web of Science ID 001094865402121

• UPPER LIMIT OF NORMAL ALT LEVELS IN HEALTH AND METABOLIC DISEASES: POOLED ANALYSIS OF 484,177 INDIVIDUALS WITH BOOTSTRAP MODELLING Tan, E., Huang, D. Q., Yee, N., Hui, W., Nerurkar, S., Chua, J., Goh, K., Ng, C., Muthiah, M., Zhou, Y., Woodward, A., Le, M. H., Yeo, Y., Barnett, S. D., Cheung, R., Nguyen, M. H. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1676-S1677

  View details for Web of Science ID 001094865404119

• 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 Chau, A., Yeh, M. L., Tsai, P. C., Huang, D. Q., Kim, S. E., Trinh, H., Yoon, E. L., Oh, H., Jeong, J. Y., Ahn, S. B., An, J., Tseng, C. H., Hsu, Y. C., Jeong, S. W., Cho, Y. K., Shim, J. J., Kim, H. S., Ito, T., Marciano, S., Kawashima, K., Suzuki, T., Watanabe, T., Nozaki, A., Ishikawa, T., Inoue, K., Eguchi, Y., Uojima, H., Abe, H., Takahashi, H., Chuma, M., Ishigami, M., Hoang, J. K., Mayumi, M., Huang, C. F., Gadano, A., Dai, C. Y., Huang, J. F., Tanaka, Y., Chuang, W. L., Lim, S. G., Cheung, R., Yu, M. L., Jun, D. W., Nguyen, M. H. 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

• 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 Nguyen, V. H., Le, I., Ha, A., Le, R. H., Rouillard, N. A., Fong, A., Gudapati, S., Park, J. E., Maeda, M., Barnett, S., Cheung, R., Nguyen, M. H. 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

• Incidence of Cirrhosis and Hepatocellular Carcinoma Among Veterans With Noncirrhotic Metabolic Dysfunction-associated Fatty Liver Disease. Journal of clinical gastroenterology Yeoh, A., Yang, Z., Cheung, R., Do, A., Ahmed, A., Wong, R. J. 2023

  Abstract

  BACKGROUND AND AIMS: Despite the high prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD), the long-term incidence of cirrhosis or hepatocellular carcinoma (HCC) among adults with MAFLD is not well described. Using a national cohort of United States Veterans, we evaluated the overall incidence and predictors of cirrhosis and HCC among adults with noncirrhotic MAFLD.METHODS: Data from the 2010 to 2022 Veterans Affairs database were used to identify adults with noncirrhotic MAFLD using established definitions. Five and 10-year incidence of cirrhosis and HCC were assessed and stratified by demographics and relevant clinical variables. Multivariate Cox proportional hazard models were utilized to determine predictors of cirrhosis and HCC.RESULTS: Among 969,253 patients with noncirrhotic MAFLD (94.5% males, 70.2% non-Hispanic white, mean age of 62.7 ± 12.2 y), the 10-year incidence of cirrhosis and HCC was 3.70% (95% CI: 3.66-3.74) and 0.69% (95% CI: 0.67-0.70), respectively. When stratified by race/ethnicity, the 10-year incidence of cirrhosis was lowest among Asians (2.63%, 95% CI: 2.37-2.88) and highest among Hispanics (4.60%, 95% CI: 4.45-4.75), a pattern also observed with HCC. Significant disparities in risk of cirrhosis or HCC were observed when stratified by sex, substance use, and comorbidities. Risks of cirrhosis and HCC were highest in patients with baseline fibrosis-4 >2.67.CONCLUSION: This large study provides important epidemiological data describing the natural history of adults with MAFLD. Disparities in risk of cirrhosis and HCC were observed by demographic and clinical characteristics, emphasizing the importance of early identification of MAFLD with modifiable high-risk features to implement earlier interventions to improve long-term outcomes.

  View details for DOI 10.1097/MCG.0000000000001921

  View details for PubMedID 37678412

• Reply: Is lifestyle modification effective for individuals with high fibrosis-4 index without an additional 2nd tier test? Hepatology (Baltimore, Md.) Sangha, K., Chang, S. T., Cheung, R., Deshpande, V. S. 2023

  View details for DOI 10.1097/HEP.0000000000000510

  View details for PubMedID 37300380

• Real-world treatment outcome with protease inhibitor direct-acting antiviral in advanced hepatitis C cirrhosis: a REAL-C study. Hepatology international Wong, Y. J., Tran, S., Huang, C. F., Hsu, Y. C., Preda, C., Toyoda, H., Liu, J., Jun, D. W., Landis, C., Huang, D. Q., Gila, A., Negoita, L., Yasuda, S., Tseng, C. H., Tsai, P. C., Uojima, H., Nozaki, A., Chuma, M., Atsukawa, M., Ishigami, M., Itokawa, N., Iio, E., Lam, C. P., Watanabe, T., Asai, A., Yokohama, K., Abe, H., Enomoto, M., Kawada, N., Tamori, A., Lee, D. H., Jun, M. J., Do, S., Vo, D. K., Liu, L., Li, J., Ji, F., Wang, W., Li, Y., Wang, X., Guo, F., Xu, Q., Jing, L., Ye, Q., Pan, H., Zhang, J., Wen, X., Wang, Q., Ren, H., Cai, D., Shang, J., Liu, J., Lu, C., Zang, W., Li, J., Niu, J., Zhang, M., Wu, C., Huang, R., Maeda, M., Nakanishi, A., Yeh, M. L., Chuang, W. L., Huang, J. F., Dai, C., Ishikawa, T., Takaguchi, K., Senoh, T., Trinh, H. N., Takahashi, H., Eguchi, Y., Quek, S. X., Haga, H., Ogawa, E., Wong, G., Buti, M., Fukunishi, S., Ueno, Y., Yuen, M. F., Tanaka, Y., Lim, S. G., Cheung, R., Yu, M. L., Nguyen, M. H. 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

• Significant heterogeneity in long-term risks of cirrhosis or hepatocellular carcinoma among a national cohort of US veterans with non-cirrhotic, treatment naive chronic hepatitis B in the immune tolerant phase Yang, Z., Cheung, R. C., Wong, R. ELSEVIER. 2023: S1107

  View details for Web of Science ID 001037135105044

• Significant disparities in risk of cirrhosis and hepatocellular carcinoma among non-cirrhotic, treatment naive, e-antigen negative hepatitis B patients with low levels of serum alanine aminotransferase Yang, Z., Cheung, R. C., Wong, R. ELSEVIER. 2023: S1084-S1085

  View details for Web of Science ID 001037135105012

• Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis Wong, Y., Nguyen, V. H., Yang, H., Li, J., Le, M., Wu, W., Han, N., Fong, K., Chen, E., Wong, C., Rui, F., Xu, X., Xue, Q., Hu, X., Leow, W., Goh, B., Cheung, R. C., Wong, G., Wong, V., Yu, M., Nguyen, M. ELSEVIER. 2023: S1096-S1097

  View details for Web of Science ID 001037135105029

• Antiviral therapy substantially reduces hepatocellular carcinoma risk in chronic Hepatitis B patients in the indeterminate phase. Hepatology (Baltimore, Md.) Huang, D. Q., Tran, A., Yeh, M., Yasuda, S., Tsai, P., Huang, C., Dai, C. Y., Ogawa, E., Ishigami, M., Ito, T., Kozuka, R., Enomoto, M., Suzuki, T., Yoshimaru, Y., Preda, C. M., Marin, R. I., Sandra, I., Tran, S., Quek, S. X., Khine, H. H., Itokawa, N., Atsukawa, M., Uojima, H., Watanabe, T., Takahashi, H., Inoue, K., Maeda, M., Hoang, J. K., Trinh, L., Barnett, S., Cheung, R., Lim, S. G., Trinh, H. N., Chuang, W., Tanaka, Y., Toyoda, H., Yu, M., Nguyen, M. H. 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

• Reply: modeling concerns. Hepatology (Baltimore, Md.) Sangha, K., Chang, S. T., Cheung, R., Deshpande, V. S. 2023

  View details for DOI 10.1097/HEP.0000000000000446

  View details for PubMedID 37166119

• 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 Wong, Y. J., Nguyen, V. H., Yang, H. I., Li, J., Le, M. H., Wu, W. J., Han, N. X., Fong, K. Y., Chen, E., Kumar, R., Wong, C., Rui, F., Xu, X., Xue, Q., Hu, X. Y., Leow, W. Q., Goh, G. B., Cheung, R., Wong, G., Wong, V. W., Yu, M. W., Nguyen, M. H. 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

• 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 Kudaravalli, S., Kam, L. Y., Huang, D. Q., Cheung, R., Nguyen, M. H. 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

• 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 Le, M. H., Le, D. M., Baez, T. C., Wu, Y., Ito, T., Lee, E. Y., Lee, K., Stave, C. D., Henry, L., Barnett, S. D., Cheung, R., Nguyen, M. H. 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

• Cardiovascular Disease Risk and Statin Use Among Adults with Metabolic Dysfunction Associated Fatty Liver Disease. The American journal of medicine Yeoh, A., Cheung, R., Ahmed, A., Chitnis, A. S., Do, A., Wong, R. J. 2023

  Abstract

  BACKGROUND: A leading cause of mortality in fatty liver disease is cardiovascular disease. Metabolic dysfunction-associated fatty liver disease (MAFLD) is new terminology that classifies fatty liver due to metabolic dysfunction attributable to obesity and associated complications. We evaluated atherosclerotic cardiovascular disease (ASCVD) risk and statin use in adults with MAFLD.METHODS: Retrospective study of 2011-2018 National Health and Nutrition Examination Survey. Adults with MAFLD were identified using established criteria: presence of hepatic steatosis (US Fatty Liver Index>30) plus ≥1 of the following: (1) body mass index >25 kg/m2 in non-Asians or >23 kg/m2 in Asians, (2) diabetes mellitus, or (3) ≥2 metabolic risk factors. cardiovascular disease risk was estimated using the validated 10-year ASCVD risk score. Statin use was assessed in intermediate and high 10-year ASCVD risk groups.RESULTS: Prevalence of MAFLD was 34.8% (95% CI 33.9%-35.8%), comprising 54.4% men, 27.9% age ≥65y, and 38.2% non-Hispanic white. Among adults with MAFLD, 23.3% and 23.0% had intermediate and high 10-year ASCVD risk, respectively. Compared to women, men were more likely to have high 10-year ASCVD risk (28.7% vs. 16.1%, adjusted OR (aOR) 5.24, 95% CI 3.87-7.10, p<0.01). In intermediate and high ASCVD risk groups, overall statin use was 48.3% (95% CI 46.1-51.3).CONCLUSIONS: Over 46% of adults with MAFLD had intermediate or high 10-year ASCVD risk. Statin use was underutilized at 48.3% in those meeting statin criteria. These findings are alarming given high cardiovascular disease risk and low statin use in this cohort.

  View details for DOI 10.1016/j.amjmed.2023.03.010

  View details for PubMedID 37001720

• Characteristics and Outcomes of Elderly Hepatocellular Carcinoma Patients following Surgical Resection: Systematic Review and Meta-analysis DIGESTIVE DISEASES Garcia, E. M., Nerurkar, S. N., Tan, E. X., Tan, S. S., Peck, E., Quek, S. Z., Teh, R., Teng, M., Tran, A., Yeo, E., Le, M., Wong, C., Cheung, R., Huang, D. Q. 2023

  Abstract

  Due to ageing of the global population, hepatocellular carcinoma (HCC) is increasingly common among elderly patients, but outcomes after curative hepatic resection are unclear. Using a metanalytic approach, we aimed to estimate overall survival (OS), recurrence free survival (RFS) and complication rates in elderly HCC patients undergoing resection.We searched PubMed, Embase, and Cochrane databases from inception to Nov 10, 2020 for studies reporting outcomes in elderly (age ≥ 65 years) patients with HCC undergoing curative surgical resection. Pooled estimates were generated using a random-effects model.We screened 8,598 articles and included 42 studies (7,778 elderly patients). The mean age was 74.45 years (95% CI 72.89-76.02), 75.54% were male (95% CI 72.53-78.32) and 66.73% had cirrhosis (95% CI 43.93-83.96). The mean tumor size was 5.50 cm (95% CI 4.71-6.29) and 16.01% had multiple tumors (95% CI 10.74-23.19). The 1-year (86.02% versus 86.66%, p=0.84) and 5-year OS (51.60% versus 53.78%) between non-elderly versus elderly patients were similar. Likewise, there were no differences in the 1-year (67.32% versus 73.26%, p=0.11) and 5-year RFS (31.57% versus 30.25%, p=0.67) in non-elderly versus elderly patients. There was a higher rate of minor complications (21.95% versus 13.71%, p=0.03) among elderly patients compared with non-elderly patients, but no difference in major complications (p=0.43) Conclusion: This data shows that overall survival, recurrence and major complications after liver resection for HCC are comparable between elderly and non-elderly patients, and may inform clinical management of HCC in this population.

  View details for DOI 10.1159/000530101

  View details for Web of Science ID 001023703800001

  View details for PubMedID 36913917

• 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 Nguyen, V. H., Huang, D. Q., Le, M. H., Jin, M., Lee, E. Y., Henry, L., Nerurkar, S. N., Ogawa, E., Thin, K. N., Teng, M. L., Goh, K. S., Kai, J. C., Wong, C., Tan, D. J., Thuy, L. T., Hai, H., Enomoto, M., Cheung, R., Nguyen, M. H. 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

• 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 Liu, J., Kam, L. Y., Huang, D. Q., Henry, L., Cheung, R., Nguyen, M. H. 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

• Cost effectiveness of MRE vs VCTE in staging fibrosis for non-alcoholic fatty liver disease (NAFLD) patients with advanced fibrosis. Hepatology (Baltimore, Md.) Sangha, K., Chang, S., Cheung, R., Deshpande, V. 2023

  Abstract

  Non-alcoholic fatty liver disease (NAFLD) is a common cause of liver disease. To determine the optimal testing strategy for NAFLD patients with advanced fibrosis, several factors such as diagnostic accuracy, failure rates, costs of examinations, and potential treatment options need to be considered. The purpose of this study was to determine the cost-effectiveness of combination testing involving VCTE versus MRE as frontline imaging strategy for NAFLD patients with advanced fibrosis.A Markov model was developed from the U.S. perspective. The base-case scenario in this model included patients aged 50 years with FIB-4 score≥ 2.67 and suspected advanced fibrosis. The model included a decision tree and a Markov state-transition model including five health states: fibrosis stage 1-2, advanced fibrosis, compensated cirrhosis, decompensated cirrhosis, death. Both deterministic and probabilistic sensitivity analyses were performed.Staging fibrosis with MRE cost $8388 more than VCTE but led to an additional 1.19 QALYs with the incremental cost-effectiveness ratio (ICER) of $7048/QALY. The cost-effectiveness analysis of the 5 strategies revealed that MRE+biopsy and VCTE+MRE+biopsy were the most cost-effective with the ICERs of $8054/QALY and $8241/QALY respectively. Further, sensitivity analyses indicated that MRE remained cost-effective with a sensitivity≥0.77, while VCTE became cost-effective with a sensitivity≥0.82.MRE was not only cost effective than VCTE as the frontline modality for staging NAFLD patients with FIB-4≥2.67 with ICER of $7048/QALY but also remained cost effective when used as a follow-up in instances of VCTE failure to diagnose.

  View details for DOI 10.1097/HEP.0000000000000262

  View details for PubMedID 37018145

• Association of Direct-Acting Antiviral Therapy With Liver and Nonliver Complications and Long-term Mortality in Patients With Chronic Hepatitis C. JAMA internal medicine Ogawa, E., Chien, N., Kam, L., Yeo, Y. H., Ji, F., Huang, D. Q., Cheung, R., Nguyen, M. H. 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

• 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 Nguyen, V. H., Kam, L., Yeo, Y. H., Huang, D. Q., Henry, L., Cheung, R., Nguyen, M. H. 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

• Prevalence, characteristics, and mortality outcomes of obese and nonobese MAFLD in the United States. Hepatology international Dao, A. D., Nguyen, V. H., Ito, T., Cheung, R., Nguyen, M. H. 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

• Impact of advanced practice providers on characteristics and quality of care of patients with chronic hepatitis B. Alimentary pharmacology & therapeutics Kam, L. Y., Huang, D. Q., Tobias, A. F., Poon, K., Henry, L., Kwo, P., Cheung, R., Nguyen, M. H. 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

• CHARACTERISTICS AND CARE OF CHRONIC HEPATITIS B PATIENTS WITH ADVANCED PRACTICE PROVIDERS Kam, L., Huang, D., Tobias, A. F., Poon, K., Henry, L., Kwo, P., Cheung, R., Nguyen, M. H. WILEY. 2022: S279-S280

  View details for Web of Science ID 000870796600331

• High Burden of Concurrent Mental Health and Substance Use Disorders Contribute to Gaps in the Hepatitis B Care Cascade Among Underserved US Veterans Wong, R., Liao, M., Cheung, R. LIPPINCOTT WILLIAMS & WILKINS. 2022: S986-S987

  View details for Web of Science ID 000897916003206

• Racial/Ethnic Disparities in Long-Term Risks of Cirrhosis Among US Veterans With Metabolic Dysfunction-Associated Fatty Liver Disease Yeoh, A. J., Yang, Z., Cheung, R., Wong, R. LIPPINCOTT WILLIAMS & WILKINS. 2022: S869-S870

  View details for Web of Science ID 000897916003034

• 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 Park, J., Nguyen, V. H., Tsai, P., Toyoda, H., Leong, J., Guy, J. E., Yeh, M., Huang, C., Yasuda, S., Abe, H., Hsu, Y., Tseng, C., Liu, J., Chen, Y., Lin, P., Jun, D., Yoshimaru, Y., Ogawa, E., Ishigami, M., Enomoto, M., Tamori, A., Uojima, H., Wang, X., Xu, Q., Takahashi, H., Eguchi, Y., Inoue, K., Huang, D., Zhao, W., Chuang, W., Dai, C., Huang, J., Cheung, R., Landis, C., Tanaka, Y., Roberts, L. R., Schwartz, M. E., Kumada, T., Yu, M., Nguyen, M. H. WILEY. 2022: S403-S405

  View details for Web of Science ID 000870796601142

• 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 Park, J., Tran, S., Ogawa, E., Huang, C., Toyoda, H., Chen, C., Yeh, M., Tseng, C., Hsu, Y., Kawashima, K., Preda, C., Istratescu, D., Yasuda, S., Nozaki, A., Chuma, M., Oh, H., Shim, J., Jeong, S., An, J., Ahn, S., Kim, S., Yoon, E., Lee, H., Kim, H., Cho, Y., Uojima, H., Trinh, H., Atsukawa, M., Itokawa, N., Okubo, T., Abe, H., Lee, D., Jun, M., Landis, C., Liu, J., Enomoto, M., Watanabe, T., Ji, F., Wang, W., Yu, L., Xie, Q., Fukunishi, S., Asai, A., Yokohama, K., Ishikawa, T., Liu, L., Li, J., Takahashi, H., Inoue, K., Eguchi, Y., Ishigami, M., Ito, T., Huang, D., Wong, G. L., Wong, V., Lu, C., Zang, W., Li, J., Ueno, Y., Haga, H., Marciano, S., Jing, L., Ye, Q., Lam, C., Ho, D., Do, S. T., Huang, R., Takaguchi, K., Senoh, T., Chien, N., Maeda, M., Kudaravalli, S., Henry, L., Chuang, W., Dai, C., Huang, J., Gadano, A. C., Yuen, M., Lim, S., Cheung, R., Tanaka, Y., Jun, D., Yu, M., Nguyen, M. H. WILEY. 2022: S377-S379

  View details for Web of Science ID 000870796601110

• SEX DIFFERENCES IN CLINICAL PRESENTATION AND SURVIVAL IN PATIENTS WITH CIRRHOSIS Fong, A., Tran, A., Ha, A., Nguyen, V. H., Zhao, C., Jin, M., Gao, K., Cheung, R., Nguyen, M. H. WILEY. 2022: S1174-S1175

  View details for Web of Science ID 000870796603355

• DIFFERENTIAL CHARACTERISTICS AND SURVIVAL BY CHRONIC LIVER DISEASE (CLD) ETIOLOGY IN A NATIONWIDE REAL-WORLD COHORT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC), 2003-2021 Tran, S., Zou, B., Kam, L., Huang, D., Henry, L., Hsing, A., Cheung, R., Nguyen, M. H. WILEY. 2022: S1422-S1423

  View details for Web of Science ID 000870796604288

• PREDICTING HEPATOCELLULAR CARCINOMA DEVELOPMENT IN NAFLD PATIENTS WITHOUT CIRRHOSIS Huang, D., Lin, Y., Tran, S., Zou, B., Yeo, Y., Cheung, R., Nguyen, M. H. WILEY. 2022: S1430

  View details for Web of Science ID 000870796604298

• 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 Wong, Y., Tran, S., Huang, C., Hsu, Y., Preda, C., Toyoda, H., Liu, J., Jun, D., Landis, C., Huang, D., Gila, A., Negoita, L., Yasuda, S., Tseng, C., Tsai, P., Uojima, H., Nozaki, A., Chuma, M., Atsukawa, M., Ishigami, M., Itokawa, N., Iio, E., Lam, C., Watanabe, T., Yokohama, K., Abe, H., Enomoto, M., Tamori, A., Lee, D., Jun, M., Do, S. T., Ho, D., Liu, L., Li, J., Ji, F., Dang, S., Li, Z., Wang, W., Wang, X., Guo, F., Xu, Q., Jing, L., Ye, Q., Pan, H., Zhang, J., Xie, W., Wang, Q., Ren, H., Cai, D., Shang, J., Liu, J., Lu, C., Zang, W., Li, J., Niu, J., Zhang, M., Wu, C., Huang, R., Maeda, M., Nakanishi, A., Yeh, M., Chuang, W., Huang, J., Dai, C., Ishikawa, T., Takaguchi, K., Senoh, T., Trinh, H., Takahashi, H., Eguchi, Y., Kawada, N., Quek, S., Haga, H., Ogawa, E., Wong, G. L., Fukunishi, S., Ueno, Y., Yuen, M., Tanaka, Y., Lim, S., Cheung, R., Yu, M., Nguyen, M. H. WILEY. 2022: S45-S47

  View details for Web of Science ID 000870796600049

• 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 Kudaravalli, S., Kam, L., Huang, D., Cheung, R., Nguyen, M. H. WILEY. 2022: S282-S283

  View details for Web of Science ID 000870796600334

• 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 Tran, S., Zou, B., Kam, L., Huang, D., Henry, L., Cheung, R., Nguyen, M. H. WILEY. 2022: S1222-S1223

  View details for Web of Science ID 000870796604016

• 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) Ogawa, E., Chien, N., Kam, L., Tran, S., Huang, D., Yeo, Y., Ji, F., Henry, L., Cheung, R., Nguyen, M. H. WILEY. 2022: S373-S374

  View details for Web of Science ID 000870796601105

• ANTIVIRAL THERAPY REDUCES HEPATOCELLULAR CARCINOMA RISK AMONG HBV PATIENTS IN THE INDETERMINATE PHASE Huang, D., Tran, A., Yeh, M., Tsai, P., Chuang, W., Huang, C., Dai, C., Toyoda, H., Yasuda, S., Trinh, H., Ogawa, E., Ishigami, M., Ito, T., Kozuka, R., Enomoto, M., Tanaka, Y., Suzuki, T., Yoshimaru, Y., Preda, C., Marin, R., Sandra, I., Quek, S., Khine, H., Itokawa, N., Atsukawa, M., Uojima, H., Watanabe, T., Takahashi, H., Inoue, K., Maeda, M., Hoang, J., Trinh, L., Cheung, R., Lim, S., Yu, M., Nguyen, M. H. WILEY. 2022: S34-S35

  View details for Web of Science ID 000870796600037

• CHARACTERISTICS AND TREATMENT RATE OF PATIENTS WITH HEPATITIS C VIRUS INFECTION IN THE DAA AND COVID-19 ERAS IN THE UNITED STATES Nguyen, V. H., Kam, L., Yeo, Y., Huang, D., Henry, L., Cheung, R., Nguyen, M. H. WILEY. 2022: S370-S371

  View details for Web of Science ID 000870796601102

• 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 Ogawa, E., Jun, D., Toyoda, H., Hsu, Y., Yoon, E., Ahn, S., Do, S. T., Trinh, H. N., Takahashi, H., Enomoto, M., Kawada, N., Yasuda, S., Tseng, C., Yeh, M., Kawashima, K., Lee, H., Inoue, K., Haga, H., Do, A., Maeda, M., Hoang, J., Cheung, R., Ueno, Y., Eguchi, Y., Furusyo, N., Yu, M., Tanaka, Y., Nguyen, M. H. WILEY. 2022: S281-S282

  View details for Web of Science ID 000870796600333

• HIGH ENGAGEMENT AND SATISFACTION WITH TELEHEALTH SERVICES AMONG UNDERSERVED CIRRHOSIS PATIENTS ACROSS THREE HEALTHCARE SYSTEMS DURING THE COVID-19 PANDEMIC Wong, R. J., Satre, D. D., Shumway, M., Monto, A., Cheung, R., Chen, J. Y., Batki, S. L., Ostacher, M. J., Snyder, H., Parekh, P., Hua, W., Widiarto, B. D., Oh, S., Liao, M., Khalili, M. WILEY. 2022: S1072-S1073

  View details for Web of Science ID 000870796603229

• 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 Liu, J., Kam, L., Huang, D., Henry, L., Cheung, R., Nguyen, M. H. WILEY. 2022: S292

  View details for Web of Science ID 000870796600347

• CHARACTERISTICS AND OUTCOMES OF ELDERLY HEPATOCELLULAR CARCINOMA PATIENTS FOLLOWING SURGICAL RESECTION: A META-ANALYSIS OF 44 STUDIES AND 33,948 PATIENTS Garcia, E. M., Nerurkar, S., Tan, X., Tan, S., Peck, E., Quek, S., Teh, R., Teng, M., Tran, A., Yeo, E., Le, M., Wong, C., Cheung, R., Huang, D. WILEY. 2022: S474-S475

  View details for Web of Science ID 000870796601238

• Forecasted 2040 Global Prevalence of NAFLD using Hierarchical Bayesian Approach. Clinical and molecular hepatology Le, M. H., Yeo, Y. H., Zou, B., Barnet, S., Henry, L., Cheung, R., Nguyen, M. H. 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

• Effectiveness of entecavir vs tenofovir disoproxil fumarate for functional cure of chronic hepatitis B in an international cohort. Hepatology international Hsu, Y. C., Jun, D. W., Peng, C. Y., Yeh, M. L., Trinh, H., Wong, G. L., Kim, S. E., Chen, C. H., Oh, H., Lin, C. H., Trinh, L., Wong, V. W., Yoon, E., Ahn, S. B., Huang, D., Cho, Y. K., Jeong, J. Y., Jeong, S. W., Kim, H. S., Xie, Q., Liu, L., Riveiro-Barciela, M., Tsai, P. C., Accarino, E. V., Toyoda, H., Enomoto, M., Preda, C., Marciano, S., Hoang, J., Huang, C. F., Kozuka, R., Yasuda, S., Istratescu, D., Lee, D. H., Su, J. Y., Huang, Y. T., Huang, J. F., Dai, C. Y., Chuang, W. L., Yuen, M. F., Gadano, A., Cheung, R., Lim, S. G., Buti, M., Yu, M. L., Nguyen, M. H. 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

• Liver complications in untreated treatment-ineligible versus treated treatment-eligible patients with hepatitis B. Digestive diseases (Basel, Switzerland) Huang, D. Q., Lee, D. H., Le, M. H., Le, A., Yeo, Y. H., Trinh, H. N., Chung, M., Nguyen, V., Johnson, T., Zhang, J. Q., Wong, C., Wong, C., Li, J., Cheung, R., Nguyen, M. H. 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

• 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) Le, M. H., Henry, L., Cheung, R., Nguyen, M. H. 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

• Low Performance of Hepatitis Delta Virus Testing Among Two National Cohorts of Chronic Hepatitis B Patients in the United States. The American journal of gastroenterology Wong, R. J., Kaufman, H. W., Niles, J. K., Chen, C., Yang, Z., Kapoor, H., Cheung, R., Gish, R. G. 2022

  Abstract

  OBJECTIVE: To evaluate hepatitis delta virus (HDV) testing patterns among U.S. adults with CHB.METHODS: HDV testing was evaluated among CHB patients using Quest Diagnostics (2016-2020) and Veterans Affairs (VA) (2010-2020) data.RESULTS: Among 157,333 CHB patients (Quest), 6.7% received HDV testing, among which 2.2% were positive. HDV testing was higher in males, younger individuals, and in patients with advanced liver disease. Among 12,002 CHB patients (VA), 19.7% received HDV testing, among which 3.1% were positive. HDV testing was higher in younger individuals and Asians.CONCLUSIONS: Low HDV testing was observed among two large U.S. cohorts of adults with CHB.

  View details for DOI 10.14309/ajg.0000000000001947

  View details for PubMedID 35971233

• Increased mortality of patients with alcohol-related liver diseases during the COVID-19 pandemic in the United States. Journal of internal medicine Yeo, Y. H., Zou, B., Cheung, R., Nguyen, M. H. 2022

  View details for DOI 10.1111/joim.13545

  View details for PubMedID 35869603

• 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 Ogawa, E., Jun, D., Toyoda, H., Hsu, Y., Yoon, E., Ahn, S., Do, S., Huy Trinh, Takahashi, H., Enomoto, M., Yasuda, S., Tseng, C., Yeh, M., Kawashima, K., Lee, H., Inoue, K., Haga, H., Ai-Thien Do, Maeda, M., Hoang, J., Cheung, R. C., Ueno, Y., Eguchi, Y., Furusyo, N., Yu, M., Tanaka, Y., Nguyen, M. ELSEVIER. 2022: S875-S876

  View details for Web of Science ID 000826275104286

• Global Trends and The Impact of Chronic Hepatitis B and C on Disability-Adjusted Life Years. Liver international : official journal of the International Association for the Study of the Liver Veracruz, N., Gish, R. G., Cheung, R., Chitnis, A. S., Wong, R. J. 2022

  Abstract

  Advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) therapies have improved morbidity and mortality, but global disparities in viral hepatitis outcomes remain. We evaluate global trends in the impact of HBV and HCV on disability adjusted life years (DALYs).Using data from the 2010-2019 Global Burden of Diseases Study (GBD), overall all-cause DALYs for patients with acute HBV or HCV, HBV- or HCV-related cirrhosis, and HBV- or HCV-related hepatocellular carcinoma (HCC) were calculated as the sum of years of life lost due to premature death and years lived with disability. DALYs were presented as age-standardized rates per 100 000 population stratified by age and sex.From 2010 to 2019, overall global impact of HBV on DALYs per 100,000 decreased from 27.6 to 20.9 for acute HBV and 168.6 to 129.8 for HBV-related cirrhosis, but remained stable for HBV-related HCC. Impact of HCV on DALYs per 100,000 decreased from 5.23 to 3.3 for acute HCV, 159.2 to 146.2 for HCV-related cirrhosis, and 37.5 to 34.9 for HCV-related HCC. We observed significant differences in the impact of HBV and HCV on DALYs when stratified by world regions.Decreases in HBV and HCV DALYs during 2010 to 2019 were observed. Disparities in DALY improvements across world regions suggest unequal access to viral hepatitis care and treatment. Achieving goals of viral hepatitis elimination will require enhanced prevention efforts and funding for high burden regions and regions that have not had substantial reductions in DALYs due to HBV and HCV.

  View details for DOI 10.1111/liv.15347

  View details for PubMedID 35753064

• Meta-analysis: global prevalence, trend and forecasting of non-alcoholic fatty liver disease in children and adolescents, 2000-2021. Alimentary pharmacology & therapeutics Li, J., Ha, A., Rui, F., Zou, B., Yang, H., Xue, Q., Hu, X., Xu, Y., Henry, L., Barakhat, M., Stave, C. D., Shi, J., Wu, C., Cheung, R., Nguyen, M. H. 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

• 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 Ito, T., Nguyen, V. H., Tanaka, T., Park, H., Yeh, M. L., Kawanaka, M., Arai, T., Atsukawa, M., Yoon, E. L., Tsai, P. C., Toyoda, H., Huang, J. F., Henry, L., Jun, D. W., Yu, M. L., Ishigami, M., Nguyen, M. H., Cheung, R. C. 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

• Global incidence and mortality of hepatitis B and hepatitis C acute infections, cirrhosis and hepatocellular carcinoma from 2010 to 2019. Journal of viral hepatitis Veracruz, N., Gish, R. G., Cheung, R., Chitnis, A. S., Wong, R. J. 2022

  Abstract

  Hepatitis B virus (HBV) and hepatitis C virus (HCV) contribute to significant healthcare burden globally. We aim to provide an updated and comprehensive analysis of global trends in the incidence and mortality of HBV and HCV related acute infections, cirrhosis and hepatocellular carcinoma (HCC). Estimates of annual cause-specific disease incidence and mortality for HBV and HCV were analysed using the 2010-2019 Global Burden of Diseases, Injuries and Risk Factors Study database. Three distinct disease states were evaluated: acute infections, cirrhosis and HCC. Age-standardized disease incidence and mortality were presented per 100,000 population and stratified by age, sex, year and 21 world regions. From 2010 to 2019, overall incidence of acute HBV declined by 19.3% (95% CI 4.1-32.0, p<.05) and HBV cirrhosis declined by 15.0% (95% CI 9.8-20.7, p<.05). Incidence of HCV cirrhosis increased by 5.6% (95% CI 0.3-10.2, p<.05) and HCV HCC remained stable. Incidence of acute HCV declined until 2015, after which it began increasing. From 2010 to 2019, overall mortality for HBV cirrhosis and HCV cirrhosis declined, whereas mortality for acute infections and HCC remained stable. Major differences in HBV and HCV incidence and mortality trends were observed when stratified by world regions. In conclusion, while our analyses of global trends in HBV and HCV incidence and mortality demonstrate encouraging trends, disparities in disease epidemiology were observed across world regions. These observations will identify regions and populations where greater focus and resources are needed to continue progressing towards viral hepatitis elimination.

  View details for DOI 10.1111/jvh.13663

  View details for PubMedID 35274406

• Increased risk of liver-related outcomes in chronic hepatitis B patients with metabolic syndrome: A systematic review and meta-analysis. Digestive diseases (Basel, Switzerland) Thin, K. N., Tran, A., Li, J., Lee, E. Y., Yang, H., Rui, F., Liu, C., Stave, C. D., Cheung, R. C., Nguyen, M. H. 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

• Nonalcoholic Fatty Liver Disease in Children: where are we? Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Li, J., Cheung, R. 2022

  View details for DOI 10.1016/j.cgh.2022.02.008

  View details for PubMedID 35149222

• Efficacy and Safety of a Botanical Formula Fuzheng Huayu for Hepatic Fibrosis in Patients with CHC: Results of a Phase 2 Clinical Trial. Evidence-based complementary and alternative medicine : eCAM Hassanein, T., Tai, D., Liu, C., Box, T. D., Tong, M. J., Rossaro, L., Pozza, R., Glenn, J. S., Cheung, R., Hemaidan, A., He, Y., Behling, C., Hu, X., Makhlouf, H., Fan, H., Ren, Y., Khim Chng, E. L., Liu, P., Vierling, J. M. 2022; 2022: 4494099

  Abstract

  Background: Hepatitis C virus (HCV) is a common cause of progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma worldwide. Despite the availability of effective direct-acting antivirals, patients often have significant hepatic fibrosis at the time of diagnosis due to delay in diagnosis and comorbidities which promote fibrogenesis. Thus, antifibrotic agents represent an attractive adjunctive therapy. Fuzheng Huayu (FZHY), a traditional Chinese medicine botanical formulation, has been used as an antifibrotic agent in chronic HBV infection. Our aim was to assess FZHY in patients with HCV infection and active viremia.Method: We randomized 118 patients with active viremia from 8 liver centers in the U.S. to receive oral FZHY (n=59) or placebo (n=59) for 48 weeks. Efficacy was assessed by histopathologic changes at the end of therapy. A subset of biopsies was further analyzed using qFibrosis to detect subtle changes in fibrosis in different zones of the hepatic lobules.Results: FZHY was well tolerated and safe. Patients with baseline Ishak fibrosis stages F3 and F4 had better response rates to FZHY than patients with baseline F0-F2 (p=0.03). qFibrosis zonal analysis showed significant improvement in fibrosis in all zones in patients with regression of the fibrosis stage.Conclusions: FZHY produced antifibrotic effects in patients with baseline Ishak F3 and F4 fibrosis stages. Reduction in fibrosis severity was zonal and correlated with the severity of inflammation. Based on its tolerability, safety, and efficacy, FZHY should be further investigated as a therapy in chronic liver diseases because of its dual anti-inflammatory and antiibrotic properties. Lay Summary. This is the first US-based, multicenter and placebo-controlled clinical trial that shows statistically significant reduction in fibrosis in patients with active HCV using an antifibrotic botanical formula. This has important implications as there is an immediate need for effective antifibrotic agents in treating many chronic diseases including NASH that lead to scarring of the liver. With artificial intelligence-based methodology, qFibrosis, we may provide a more reliable way to assess the FZHY as a therapy in chronic liver diseases because of its dual anti-inflammatory and antifibrotic properties.

  View details for DOI 10.1155/2022/4494099

  View details for PubMedID 35873630

• County-Level Variation in Cirrhosis-Related Mortality in the US, 1999-2019. JAMA network open Ha, A. Y., Le, M. H., Henry, L., Yeo, Y. H., Cheung, R. C., Nguyen, M. H. 2022; 5 (2): e2146427

  View details for DOI 10.1001/jamanetworkopen.2021.46427

  View details for PubMedID 35107576

• Clinical profiles of Asians with NAFLD: A systematic review and meta-analysis. Digestive diseases (Basel, Switzerland) Kam, L., Huang, D. Q., Teng, M. L., Takahashi, H., Tanaka, K., Yasuda, S., Fung, J., Lee, T. Y., Hyogo, H., Ono, M., Saruwatari, J., Oniki, K., Yeo, Y. H., Barnett, S., Henry, L., Li, J., Zou, B., Cheung, R. C., Kumada, T., Yuen, M. F., Eguchi, Y., Toyoda, H., Nguyen, M. H. 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

• 2019 global NAFLD prevalence - A systematic review and meta-analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Le, M. H., Yeo, Y. H., Li, X., Li, J., Zou, B., Wu, Y., Ye, Q., Huang, D. Q., Zhao, C., Zhang, J., Liu, C., Chang, N., Xing, F., Yan, S., Hui, W. Z., Sook Yee, N. T., Mayumi, M., Liu, X., Liu, C., Rui, F., Yang, H., Yang, Y., Jin, R., Le, R. H., Xu, Y., Le, D. M., Barnett, S., Stave, C. D., Cheung, R., Zhu, Q., Nguyen, M. H. 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

• Global Trends in the Incidence of Hepatitis B Virus and Hepatitis C Virus-Related Cirrhosis and Hepatocellular Carcinoma From 2010 to 2019 Veracruz, N., Cheung, R., Gish, R. G., Wong, R. LIPPINCOTT WILLIAMS & WILKINS. 2021: S534

  View details for Web of Science ID 000717526102137

• 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 Ji, F., Ogawa, E., Huang, C., Toyoda, H., Wong, Y., Iio, E., Jun, D., Liu, L., Uojima, H., Nozaki, A., Chuma, M., Tseng, C., Hsu, Y., Atsukawa, M., Haga, H., Enomoto, M., Tamori, A., Trinh, H. N., Landis, C., Lee, D., Watanabe, T., Takahashi, H., Abe, H., Yokohama, K., Asai, A., Eguchi, Y., Li, J., Wang, X., Li, J., Liu, J., Jing, L., Preda, C., Lam, C., Huang, R., Ye, Q., Pan, H., Zhang, J., Cai, D., Wang, Q., Huang, D., Wong, G. H., Li, J., Kato, M., Shimoda, S., Furusyo, N., Nakamuta, M., Nomura, H., Kajiwara, E., Yoon, E., Ahn, S., Azuma, K., Dohmen, K., Jung, J., Song, D., Kawano, A., Koyanagi, T., Ooho, A., Satoh, T., Takahashi, K., Yeh, M., Tsai, P., Yasuda, S., Dang, S., Li, Z., Okubo, T., Itokawa, N., Fukunishi, S., Jun, M., Ishikawa, T., Takaguchi, K., Senoh, T., Zhang, M., Zhao, C., Tran, S., Maeda, M., Chuang, W., Huang, J., Dai, C., Cheung, R. C., Buti, M., Niu, J., Xie, W., Ren, H., Lim, S., Wu, C., Yuen, M., Shang, J., Zhu, Q., Ueno, Y., Tanaka, Y., Hayashi, J., Yu, M., Nguyen, M. H. WILEY. 2021: 579A-581A

  View details for Web of Science ID 000707188003019

• GLOBAL NAFLD PREVALENCE NOW AND IN THE FUTURE- A META-ANALYSIS WITH TREND AND FORECASTING Le, M., Yeo, Y., Li, X., Li, J., Zou, B., Wu, Y., Ye, Q., Huang, D., Zhao, C., Zhang, J., Liu, C., Chang, N., Xing, F., Yan, S., Hui, W., Yee, N., Maeda, M., Liu, X., Liu, C., Rui, F., Yang, H., Yang, Y., Jin, R., Le, R. X., Xu, Y., Le, D. M., Barnett, S. D., Stave, C., Cheung, R. C., Zhu, Q., Nguyen, M. H. WILEY. 2021: 1011A-1012A

  View details for Web of Science ID 000707188005048

• GLOBAL TRENDS IN CAUSE-SPECIFIC MORTALITY AND DISABILITY ADJUSTED LIFE YEARS RELATED TO HEPATITIS B VIRUS AND HEPATITIS C VIRUS FROM 2010 TO 2019 Veracruz, N., Gish, R. G., Cheung, R. C., Wong, R. J. WILEY. 2021: 543A

  View details for Web of Science ID 000707188002299

• ENTECAVIR VERSUS TENOFOVIR DISOPROXIL FUMARATE FOR SEROCLEARANCE OF HEPATITIS B SURFACE ANTIGEN IN AN INTERNATIONAL REAL-WORLD COHORT Hsu, Y., Jun, D., Peng, C., Yeh, M., Trinh, H. N., Wong, G. H., Kim, S., Chen, C., Oh, H., Lin, C., Yoon, E., Ahn, S., Huang, D., Cho, Y., Jeong, J., Jeong, S., Kim, H., Xie, Q., Liu, L., Riveiro Barciela, M., Tsai, P., Vargas-Accarino, E., Toyoda, H., Enomoto, M., Preda, C., Marciano, S., Hoang, J., Huang, C., Kozuka, R., Yasuda, S., Istratescu, D., Lee, D., Su, J., Huang, Y., Huang, J., Dai, C., Chuang, W., Yuen, M., Gadano, A. C., Cheung, R. C., Lim, S., Buti, M., Wong, V., Yu, M., Nguyen, M. H. WILEY. 2021: 434A-436A

  View details for Web of Science ID 000707188002124

• DECLINING HBV IMMUNITY FOLLOWING HBV VACCINATION DURING CHILDHOOD/ADOLESCENCE AND AMNESTIC RESPONSE RATES TO BOOSTER: A SYSTEMATIC REVIEW AND META-ANALYSIS. Le, D. M., Le, M., Yeo, Y., Lee, E. Y., Cheung, R. C., Nguyen, M. H. WILEY. 2021: 451A

  View details for Web of Science ID 000707188002148

• 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 Ito, T., Nguyen, V. H., Tanaka, T., Park, H., Yeh, M., Kawanaka, M., Arai, T., Atsukawa, M., Yoon, E., Tsai, P., Toyoda, H., Fujishiro, M., Huang, J., Nguyen, M. H., Jun, D., Yu, M., Ishigami, M., Cheung, R. C. WILEY. 2021: 936A-937A

  View details for Web of Science ID 000707188004278

• ALT LEVELS IN HEPATITIS B PATIENTS WITH CONCURRENT FATTY LIVER DISEASE: A US NATIONWIDE STUDY Chang, C., Kam, L., Dang, N., Cheung, R. C., Nguyen, M. H. WILEY. 2021: 444A

  View details for Web of Science ID 000707188002137

• TREATMENT EVALUATION, TREATMENT ELIGIBILITY, AND ANTIVIRAL THERAPY AMONG ASIAN AND NON-ASIAN PATIENTS WITH CHRONIC HEPATITIS B (CHB) Huang, D., Nguyen, V. H., Trinh, H. N., Ogawa, E., Enomoto, M., Kozuka, R., Marciano, S., Suzuki, T., Yoshimaru, Y., Ko, K., Hui, R., Lee, D., Go, M., Lee, C., Preda, C., Quek, S., Khine, H., Takahashi, H., Inoue, K., Maeda, M., Hoang, J., Kudaravalli, S., Trinh, L., Chau, A., Li, J., Zhang, J., Wong, C., Wong, C., Cheung, R. C., Yuen, M., Tanaka, Y., Gadano, A., Lim, S., Nguyen, M. H. WILEY. 2021: 467A-468A

  View details for Web of Science ID 000707188002177

• 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 Le, M., Yeo, Y., Cheung, R. C., Nguyen, M. H. WILEY. 2021: 942A-943A

  View details for Web of Science ID 000707188004285

• DISPARITIES IN CIRRHOSIS-RELATED MORTALITY AMONG URBAN AND RURAL AREAS IN THE UNITED STATES: A POPULATION-BASED STUDY FROM 1999-2019 Ha, A., Le, M., Cheung, R. C., Nguyen, M. H. WILEY. 2021: 117A-118A

  View details for Web of Science ID 000707188000176

• 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 Huang, D., Tran, A., Tan, X., Quek, S., Nerurkar, S., Teh, R., Teng, M., Yeo, E., Zou, B., Wong, C., Cheung, R. C., Esquivel, C. O., Bonham, A., Nguyen, M. H. WILEY. 2021: 861A

  View details for Web of Science ID 000707188004154

• Prevalence of Hepatitis E Infection among Adults with Concurrent Chronic Liver Disease. Journal of viral hepatitis Wong, R. J., Cheung, R., Gish, R. G., Chitnis, A. S. 2021

  Abstract

  While hepatitis E virus (HEV) infection can increase risks of liver decompensation and death in patients with underlying chronic liver disease (CLD), prevalence of HEV in this cohort is not well reported. Using data from the 2011-2018 National Health and Nutrition Examination Survey, we aim to evaluate seroprevalence of HEV IgG among adults with nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), chronic hepatitis C virus (HCV), and chronic hepatitis B virus (HBV). HEV IgG seroprevalence between groups was evaluated with chi-square testing, and adjusted multivariate logistic regression models evaluated for predictors of seropositivity for HEV IgG. Seroprevalence of HEV IgG was 6.58% in ALD, 8.66% in HCV, 8.81% in NAFLD, and 19.86% in HBV. We observed increasing HEV IgG seroprevalence over time in our study period, and in 2015-2018, seroprevalence was highest among individuals with HCV (10.00%) and HBV (30.30%). Older age and being born outside of the U.S. were associated with seropositivity for HEV IgG in ALD, NAFLD, HBV, and for HCV, older age and being at or below poverty level were associated with seroprevalence for HEV IgG. In conclusion, we observed a relatively high prevalence of HEV among adults with CLD. These data highlight the need for greater awareness and education about the role of HEV in patients with underlying CLD, improving HEV test diagnostics, and revisiting the discussion about the potential role of HEV vaccines in CLD patients who are at higher risk of decompensation and death from acute HEV infection.

  View details for DOI 10.1111/jvh.13597

  View details for PubMedID 34415657

• Epidemiology and Prevention of Tuberculosis and Chronic Hepatitis B Virus Infection in the United States. Journal of immigrant and minority health Chitnis, A. S., Cheung, R., Gish, R. G., Wong, R. J. 2021

  Abstract

  Tuberculosis (TB) and chronic hepatitis B virus (CHB) infection can be prevented with treatment and vaccination, respectively. We reviewed epidemiology and guidelines for TB and CHB to inform strategies for reducing United States (U.S.) burden of both infections. Non-U.S.-born, compared to U.S.-born, persons have a 15-, 6-, and 8-fold higher TB incidence and latent TB infection (LTBI) and CHB prevalence, respectively; all infections disproportionately impact non-U.S.-born Asians. TB and CHB each are associated with~10% mortality that results in 7- and 14-years per life lost, respectively. LTBI and CHB have significant gaps in their care cascade as 40% of LTBI and 20% of CHB patients are diagnosed, and 20% of LTBI and CHB diagnosed patients receive treatment. Reducing TB and CHB burden will require healthcare provider-, system-, and policy-level interventions, and increased funding and collaboration between public health departments and healthcare systems.Institutional Review Board Statement: Since this review article did not include primary data on patients and only focused on reviewing published data, approval by an institutional review board was not needed.

  View details for DOI 10.1007/s10903-021-01231-6

  View details for PubMedID 34160726

• A population-based US study of hepatitis C diagnosis rate. European journal of gastroenterology & hepatology Yeo, Y. H., Kam, L. Y., Le, M. H., Jeong, D., Dang, N., Henry, L., Cheung, R., Nguyen, M. H. 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

• Treating the Hardest to Treat: Reframing the Hospital Admission as an Opportunity to Initiate Hepatitis C Treatment. Digestive diseases and sciences Le, E., Chee, G., Kwan, M., Cheung, R. 2021

  Abstract

  BACKGROUND: Chronic hepatitis C (CHC) is traditionally treated in the outpatient setting. Despite the excellent tolerability, shortened treatment duration, and high cure rates of newer direct-acting antivirals (DAAs), many vulnerable patients remain untreated due to issues with linkage to care.AIMS: This study sought to reframe and establish the hospital admission as a unique opportunity to initiate antiviral treatment for patients with CHC, particularly those with psychosocial or linkage to care issues.METHODS: Patients with untreated CHC were identified either on the Psychiatry or Med/Surg wards at the Veterans Affairs Palo Alto Health Care System (VAPAHCS). If found to be appropriate for treatment initiation, patients were started on antivirals during their hospitalization and followed closely while inpatient and after discharge to assess for sustained virologic response (SVR), treatment tolerability, and treatment completion.RESULTS: Overall, 36% (23) of potential treatment candidates were initiated on DAA treatment during their hospitalization. Of these patients, 91.3% had documented treatment completion with an intention-to-treat and modified intention-to-treat SVR rate of 91.3% and 100%, respectively.CONCLUSIONS: We establish the hospital admission as a valuable opportunity for HCV treatment initiation, yielding excellent treatment outcomes in those who would not otherwise be treated and achieved a modified intention-to-treat response rate of 100%.

  View details for DOI 10.1007/s10620-021-06941-3

  View details for PubMedID 33770327

• Low Prevalence of Vaccination or Documented Immunity to Hepatitis A and Hepatitis B Viruses Among Individuals with Chronic Liver Disease. The American journal of medicine Wong, R. J., Gish, R. G., Cheung, R., Chitnis, A. S. 2021

  Abstract

  BACKGROUND: Despite national guidelines emphasizing importance of vaccination or documenting immunity to hepatitis A virus and hepatitis B virus for patients with chronic liver disease, the success of adhering to these recommendations is sub-optimal. We aim to evaluate the prevalence of vaccination or documented reactivity to hepatitis A antibody and hepatitis B surface antibody among U.S. adults with chronic liver disease.METHODS: Using 2011-2018 National Health and Nutritional Examination Survey data, adults with nonalcoholic fatty liver disease, alcoholic liver disease, hepatitis B, and hepatitis C were evaluated to determine prevalence of vaccination (self-reported completion) and hepatitis A antibody reactivity or hepatitis B surface antibody reactivity.RESULTS: Overall prevalence of vaccination or hepatitis A antibody reactivity was lowest among individuals with nonalcoholic fatty liver disease (60.8%, 95% CI 57.9-63.6) and alcoholic liver disease (61.8%, 95% CI 59.0-64.6) and highest among individuals with hepatitis B (82.9%, 95% CI 76.8-89.0). Prevalence of vaccination or hepatitis B surface antibody reactivity was much lower: 38.6% (95% CI 35.7-41.4) in nonalcoholic fatty liver disease, 40.7% (95% CI 34.4-47.0) in chronic hepatitis C virus, and 47.1% (95% CI 44.3-49.9) in alcoholic liver disease.CONCLUSION: Among U.S. adults with chronic liver disease, prevalence of vaccination or documented reactivity to hepatitis A antibody virus and hepatitis B surface antibody was alarmingly low. These observations are particularly concerning given that underlying chronic liver disease increases risks of severe liver injury and decompensation from acute hepatitis A or hepatitis B infections.

  View details for DOI 10.1016/j.amjmed.2021.02.008

  View details for PubMedID 33775642

• Trends in the Prevalence of Metabolic Dysfunction Associated Fatty Liver Disease in the United States, 2011-2018. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Wong, R. J., Cheung, R. 2021

  View details for DOI 10.1016/j.cgh.2021.01.030

  View details for PubMedID 33493692

• 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 Huang, D. Q., Hoang, J. K., Leong, J. n., Riveiro-Barciela, M. n., Maeda, M. n., Yang, J. D., Accarino, E. V., Thin, K. n., Trinh, L. n., Cheung, R. C., Roberts, L. R., Buti, M. n., Schwartz, M. n., Nguyen, M. H. 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

• 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) Park, J. n., Lee, E. Y., Li, J. n., Jun, M. J., Yoon, E. n., Ahn, S. B., Liu, C. n., Yang, H. n., Rui, F. n., Zou, B. n., Henry, L. n., Lee, D. H., Jun, D. W., Cheung, R. C., Nguyen, M. H. 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

• ALT levels in Treatment-Naïve, Chronic Hepatitis B Patients with Concurrent Fatty Liver Disease: A U.S. Nationwide Study. Digestive diseases (Basel, Switzerland) Chang, C. Y., Kam, L., Dang, N., Cheung, R., Nguyen, M. H. 2021

  View details for DOI 10.1159/000518645

  View details for PubMedID 34348281

• Incidences and Determinants of Functional Cure during Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B. The Journal of infectious diseases Hsu, Y. C., Yeh, M. L., Wong, G. L., Chen, C. H., Peng, C. Y., Buti, M. n., Enomoto, M. n., Xie, Q. n., Trinh, H. n., Preda, C. n., Liu, L. n., Cheung, K. S., Yeo, Y. H., Hoang, J. n., Huang, C. F., Riveiro-Barciela, M. n., Kozuka, R. n., Istratescu, D. n., Tsai, P. C., Accarino, E. V., Lee, D. H., Wu, J. L., Huang, J. F., Dai, C. Y., Cheung, R. n., Chuang, W. L., Yuen, M. F., Wong, V. W., Yu, M. L., Nguyen, M. H. 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

• Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF: a REAL-B study. Hepatology international Mak, L. Y., Hoang, J., Jun, D. W., Chen, C. H., Peng, C. Y., Yeh, M. L., Kim, S. E., Huang, D. Q., Jeong, J. Y., Yoon, E., Oh, H., Tsai, P. C., Huang, C. F., Ahn, S. B., Trinh, H., Xie, Q., Wong, G. L., Enomoto, M., Shim, J. J., Lee, D. H., Liu, L., Kozuka, R., Cho, Y. K., Jeong, S. W., Kim, H. S., Trinh, L., Dao, A., Huang, R., Hui, R. W., Tsui, V., Quek, S., Khine, H. H., Ogawa, E., Dai, C. Y., Huang, J. F., Cheung, R., Wu, C., Chuang, W. L., Lim, S. G., Yu, M. L., Yuen, M. F., Nguyen, M. H. 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

• 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 Nguyen, V. H., Le, M. H., Cheung, R. C., Nguyen, M. H. 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

• Outcomes of Sequential Therapy With Tenofovir Alafenamide After Long-term Entecavir. The American journal of gastroenterology Nguyen, M. H., Atsukawa, M., Ishikawa, T., Yasuda, S., Yokohama, K., Trinh, H. N., Arai, T., Fukunishi, S., Ogawa, E., Hsu, Y. C., Maeda, M., Dang, H., Tseng, C. H., Takahashi, H., Jun, D. W., Watanabe, T., Chuma, M., Nozaki, A., Kawada, N., Cheung, R., Enomoto, M., Takaguchi, K., Toyoda, H. 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

• 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 Park, J., Le, A. K., Tseng, T. C., Yeh, M. L., Jun, D. W., Trinh, H., Wong, G. L., Chen, C. H., Peng, C. Y., Kim, S. E., Oh, H., Kwak, M. S., Cheung, K. S., Toyoda, H., Hsu, Y. C., Jeong, J. Y., Yoon, E. L., Ungtrakul, T., Zhang, J., Xie, Q., Ahn, S. B., Enomoto, M., Shim, J. J., Cunningham, C., Jeong, S. W., Cho, Y. K., Ogawa, E., Huang, R., Lee, D. H., Takahashi, H., Tsai, P. C., Huang, C. F., Dai, C. Y., Tseng, C. H., Yasuda, S., Kozuka, R., Li, J., Wong, C., Wong, C. C., Zhao, C., Hoang, J., Eguchi, Y., Wu, C., Tanaka, Y., Gane, E., Tanwandee, T., Cheung, R., Yuen, M. F., Lee, H. S., Yu, M. L., Kao, J. H., Yang, H. I., Nguyen, M. H. 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

• Prevalence of hepatic steatosis, fibrosis and associated factors in chronic hepatitis B. Alimentary pharmacology & therapeutics Zheng, Q., Zou, B., Wu, Y., Yeo, Y., Wu, H., Stave, C. D., Cheung, R. C., Nguyen, M. H. 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

• The Changing Epidemiology of Liver Disease Among US Children and Adolescents From 1999 to 2016. The American journal of gastroenterology Li, J., Le, M. H., Barakat, M. T., Cheung, R. C., Nguyen, M. H. 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

• Evaluation of ethnic influence in the application of a hepatocellular carcinoma predictive model for chronic hepatitis C. Journal of medical virology Wei, M. T., Le, M. H., Landis, C., Trinh, H., Wong, G., Le, A., Zhang, J., Cheung, R., Nguyen, M. H. 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

• Surveillance of patients with cirrhosis remains suboptimal in the United States. Journal of hepatology Yeo, Y. H., Hwang, J. n., Jeong, D. n., Dang, N. n., Kam, L. Y., Henry, L. n., Park, H. n., Cheung, R. n., Nguyen, M. H. 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

• Fatty Liver Index and Development of Cardiovascular Disease: Findings from the UK Biobank. Digestive diseases and sciences Zou, B. n., Yeo, Y. H., Cheung, R. n., Ingelsson, E. n., Nguyen, M. H. 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

• 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 Tran, S. n., Jeong, D. n., Henry, L. n., Cheung, R. C., Nguyen, M. H. 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

• In Reply. Archives of pathology & laboratory medicine Beste, L. A., Icardi, M. n., Hunt, C. M., Gylys-Colwell, I. n., Lowy, E. n., Taylor, L. n., Morgan, T. R., Chang, M. F., Maier, M. M., Cheung, R. n. 2021; 145 (2): 129b–130

  View details for DOI 10.5858/arpa.2020-0643-LE

  View details for PubMedID 33501499

• The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995-2040. Hepatology international Ito, T. n., Ishigami, M. n., Zou, B. n., Tanaka, T. n., Takahashi, H. n., Kurosaki, M. n., Maeda, M. n., Thin, K. N., Tanaka, K. n., Takahashi, Y. n., Itoh, Y. n., Oniki, K. n., Seko, Y. n., Saruwatari, J. n., Kawanaka, M. n., Atsukawa, M. n., Hyogo, H. n., Ono, M. n., Ogawa, E. n., Barnett, S. D., Stave, C. D., Cheung, R. C., Fujishiro, M. n., Eguchi, Y. n., Toyoda, H. n., Nguyen, M. H. 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

• Transition rates to cirrhosis and liver cancer by age, gender, disease and treatment status in Asian chronic hepatitis B patients. Hepatology international Liu, M. n., Tseng, T. C., Jun, D. W., Yeh, M. L., Trinh, H. n., Wong, G. L., Chen, C. H., Peng, C. Y., Kim, S. E., Oh, H. n., Kwak, M. S., Cheung, M. n., Toyoda, H. n., Hsu, Y. C., Jeong, J. Y., Yoon, E. L., Ungtrakul, T. n., Zhang, J. n., Xie, Q. n., Ahn, S. B., Enomoto, M. n., Shim, J. J., Cunningham, C. n., Jeong, S. W., Cho, Y. K., Ogawa, E. n., Huang, R. n., Lee, D. H., Takahashi, H. n., Tsai, P. C., Huang, C. F., Dai, C. Y., Tseng, C. H., Yasuda, S. n., Kozuka, R. n., Li, J. n., Wong, C. n., Wong, C. C., Zhao, C. n., Hoang, J. n., Eguchi, Y. n., Wu, C. n., Tanaka, Y. n., Gane, E. n., Tanwandee, T. n., Cheung, R. n., Yuen, M. F., Lee, H. S., Yu, M. L., Kao, J. H., Yang, H. I., Nguyen, M. H. 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

• Treatment and renal outcomes up to 96 weeks after tenofovir alafenamide switch from tenofovir disoproxil fumarate in routine practice. Hepatology (Baltimore, Md.) Toyoda, H. n., Leong, J. n., Landis, C. n., Atsukawa, M. n., Watanabe, T. n., Huang, D. Q., Liu, J. n., Quek, S. X., Ishikawa, T. n., Arai, T. n., Yokohama, K. n., Chuma, M. n., Takaguchi, K. n., Uojima, H. n., Senoo, T. n., Dang, H. n., Maeda, M. n., Hoang, J. n., Le, R. H., Yasuda, S. n., Thin, K. N., Tran, S. n., Chien, N. n., Henry, L. n., Asai, A. n., Fukunishi, S. n., Cheung, R. n., Lim, S. G., Trinh, H. N., Nguyen, M. H. 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

• 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 Huang, D. Q., Li, X. n., Le, M. H., Le, A. K., Yeo, Y. H., Trinh, H. N., Zhang, J. n., Li, J. n., Wong, C. n., Wong, C. n., Cheung, R. C., Yang, H. I., Nguyen, M. H. 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

• Prevalence of Hepatitis B Vaccination Coverage and Serologic Evidence of Immunity Among US-Born Children and Adolescents From 1999 to 2016. JAMA network open Le, M. H., Yeo, Y. H., So, S., Gane, E., Cheung, R. C., Nguyen, M. H. 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

• ALT Levels for Asians With Metabolic Diseases: A Meta-analysis of 86 Studies With Individual Patient Data Validation. Hepatology communications Huang, D. Q., Yeo, Y. H., Tan, E., Takahashi, H., Yasuda, S., Saruwatari, J., Tanaka, K., Oniki, K., Kam, L. Y., Muthiah, M. D., Hyogo, H., Ono, M., Barnett, S. D., Li, J., Zou, B., Fung, J., Lee, T. Y., Wong, V. W., Yuen, M. F., Dan, Y. Y., Lim, S. G., Cheung, R., Toyoda, H., Eguchi, Y., Nguyen, M. H. 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

• HCC RISK POST-SVR WITH DAAS IN EAST ASIANS: FINDINGS FROM THE REAL-C COHORT Tanaka, Y., Ogawa, E., Huang, C., Toyoda, H., Jun, D., Tseng, C., Hsu, Y., Enomoto, M., Takahashi, H., Furusyo, N., Yeh, M., Lio, E., Yasuda, S., Lam, C., Lee, D., Haga, H., Yoon, E., Ahn, S., Wong, G., Nakamuta, M., Nomura, H., Tsai, P., Jung, J., Song, D., Dang, H., Maeda, M., Henry, L., Cheung, R., Yuen, M., Ueno, Y., Eguchi, Y., Tamori, A., Yu, M., Hayashi, J., Nguyen, M. H., Azuma, K., Chuang, W., Dai, C., Dohmen, K., Huang, J., Jun, M., Kajiwara, E., Kato, M., Kawano, A., Koyanagi, T., Lee, M., Ooho, A., Satoh, T., Shimode, S., Takahashi, K., Yang, H. WILEY. 2020: 34A–36A

  View details for Web of Science ID 000574027000047

• VIROLOGIC, BIOCHEMICAL, AND RENAL OUTCOMES OF TREATMENT-NAIVE PATIENTS WITH SEQUENTIAL THERAPY FROM TENOFOVIR DISOPROXIL FUMARATE (TDF) TO TENOFOVIR ALAFENAMIDE (TAF) IN ROUTINE PRACTICE Toyoda, H., Trinh, H. N., Leong, J., Atsukawa, M., Watanabe, T., Chuma, M., Liu, J., Yokohama, K., Dang, H., Maeda, M., Le, R., Thin, K., Tran, S., Chien, N., Takaguchi, K., Fukunishi, S., Yasuda, S., Cheung, R., Nguyen, M. H. WILEY. 2020: 498A–499A

  View details for Web of Science ID 000574027001270

• DIFFERENTIAL CHARACTERISTICS AND OUTCOMES OF ASIAN AND NON-ASIAN PATIENTS WITH HBV-RELATED HEPATOCELLULAR CARCINOMA Huang, D., Hoang, J., Leong, J., Barciela, R., Maeda, M., Vargas-Accarino, E., Yang, J., Roberts, L. R., Cheung, R., Schwartz, M. E., Ferret, M., Nguyen, M. H. WILEY. 2020: 457A–458A

  View details for Web of Science ID 000574027001208

• THE EPIDEMIOLOGY OF NAFLD AND LEAN NAFLD IN JAPAN: A SYSTEMATIC REVIEW AND META-ANALYSIS WITH INDIVIDUAL PATIENT LEVEL DATA AND FORECASTING, 1995-2040 Ito, T., Ishigami, M., Zou, B., Tanaka, T., Takahashi, H., Kurosaki, M., Maeda, M., Thin, K., Tanaka, K., Takahashi, Y., Itoh, Y., Oniki, K., Seko, Y., Saruwatari, J., Kawanaka, M., Atsukawa, M., Hyogo, H., Ono, M., Ogawa, E., Barnette, S. D., Stave, C., Cheung, R., Fujishiro, M., Eguchi, Y., Toyoda, H., Nguyen, M. H. WILEY. 2020: 999

  View details for Web of Science ID 000574027004096

• HEPATOCELLULAR CARCINOMA INCIDENCE WITH TENOFOVIR VS ENTECAVIR IN CHRONIC HEPATITIS B: A SYSTEMATIC REVIEW AND META-ANALYSIS Tseng, C., Hsu, Y., Chen, T., Ji, F., Chen, I., Tsai, Y., Hai, H., Le, T., Hosaka, T., Sezaki, H., Borghi, J. A., Cheung, R., Enomoto, M., Nguyen, M. H. WILEY. 2020: 642A

  View details for Web of Science ID 000574027002191

• 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 Nguyen, M. H., Atsukawa, M., Ishikawa, T., Yasuda, S., Trinh, H. N., Yokohama, K., Fukunishi, S., Ogawa, E., Hsu, Y., Maeda, M., Dang, H., Tseng, C., Takahashi, H., Watanabe, T., Nozaki, A., Cheung, R., Kawada, N., Enomoto, M., Takaguchi, K., Toyoda, H. WILEY. 2020: 486A–487A

  View details for Web of Science ID 000574027001252

• 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 Park, J., Lee, E., Lee, D., Li, J., Zou, B., Jun, M., Liu, C., Yang, H., Rui, F., Cheung, R., Nguyen, M. H. WILEY. 2020: 964–65

  View details for Web of Science ID 000574027004040

• SEQUENTIAL THERAPY WITH TENOFOVIR ALAFENAMIDE (TAF) IN PATIENTS WITH CHRONIC HEPATITIS B (CHB): AN INTERIM ANALYSIS OF AN ONGOING MULTINATIONAL PROSPECTIVE STUDY Ogawa, E., Toyoda, H., Jun, D., Hsu, Y., Yoon, E., Ahn, S., Yeh, M., Yasuda, S., Kawashima, K., Do, S. T., Trinh, H. N., Takahashi, H., Enomoto, M., Tseng, C., Inoue, K., Haga, H., Maeda, M., Kam, L., Cheung, R., Ueno, Y., Eguchi, Y., Furusyo, N., Yu, M., Tanaka, Y., Nguyen, M. H. WILEY. 2020: 495A–496A

  View details for Web of Science ID 000574027001265

• 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 Hsu, Y., Yeh, M., Wong, G., Chen, C., Peng, C., Ferrets, M., Enomoto, M., Xie, Q., Trinh, H. N., Preda, C., Liu, L., Cheung, K., Hoang, J., Huang, C., Barciela, M., Kozuka, R., Istratescu, D., Tsai, P., Vargas-Accarino, E., Lee, D., Huang, J., Dai, C., Cheung, R., Chuang, W., Yuen, M., Wong, V., Yu, M., Nguyen, M. H. WILEY. 2020: 463A–464A

  View details for Web of Science ID 000574027001217

• 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 Mak, L., Hoang, J., Jun, D., Chen, C., Peng, C., Yet, M., Kim, S., Jeong, J., Yoon, E., Oh, H., Tsai, P., Huang, C., Ahn, S., Xie, Q., Wong, G., Enomoto, M., Trinh, H., Shim, J., Lee, D., Liu, L., Kozuka, R., Cho, Y., Jeong, S., Kim, H., Huang, R., Hui, R., Tsui, V., Ogawa, E., Dai, C., Huang, J., Cheung, R., Wu, C., Chuang, W., Yu, M., Yuen, M., Nguyen, M. H. WILEY. 2020: 17A–18A

  View details for Web of Science ID 000574027000022

• HIGH HCV CURE RATES WITH APPROVED INTERFERON-FREE DIRECT ACTING ANTIVIRALS AMONG DIVERSE MAINLAND CHINESE PATIENTS INCLUDING GENOTYPES 3a AND 3b Ji, F., Li, J., Liu, L., Jing, L., Wang, X., Liu, J., Cai, D., Huang, R., Zhang, J., Wang, Q., Nan, Y., Li, J., Ye, Q., Zhang, M., Xu, Q., Guo, F., Zhao, C., Liu, L., He, C., Yu, L., Wang, W., Kam, L., Tran, S., Maeda, M., Mizuta, A., Li, Z., Dang, S., Zhu, Q., Ren, W., Cheung, R., Niu, J., Xie, W., Pan, H., Ren, H., Wu, C., Shang, J., Wang, F., Nguyen, M. H. WILEY. 2020: 532A–533A

  View details for Web of Science ID 000574027002011

• Chronic Kidney Disease in Patients with Chronic Liver Disease: What Is the Price Tag? Hepatology communications Wong, R. J., Cheung, R. C. 2020; 4 (10): 1389–91

  View details for DOI 10.1002/hep4.1583

  View details for PubMedID 33024910

• ALT Levels for Asians With Metabolic Diseases: A Meta-analysis of 86 Studies With Individual Patient Data Validation HEPATOLOGY COMMUNICATIONS Huang, D. Q., Yeo, Y., Tan, E., Takahashi, H., Yasuda, S., Saruwatari, J., Tanaka, K., Oniki, K., Kam, L. Y., Muthiah, M. D., Hyogo, H., Ono, M., Barnett, S. D., Li, J., Zou, B., Fung, J., Lee, T., Wong, V., Yuen, M., Dan, Y., Lim, S., Cheung, R., Toyoda, H., Eguchi, Y., Nguyen, M. H. 2020

  View details for DOI 10.1002/hep4.1593

  View details for Web of Science ID 000570299500001

• Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients. Clinical and translational gastroenterology Yeo, Y. H., Tseng, T. C., Hosaka, T., Cunningham, C., Fung, J. Y., Ho, H. J., Kwak, M. S., Trinh, H. N., Ungtrakul, T., Yu, M. L., Kobayashi, M., Le, A. K., Henry, L., Li, J., Zhang, J., Sriprayoon, T., Jeong, D., Tanwandee, T., Gane, E., Cheung, R. C., Wu, C. Y., Lok, A. S., Lee, H. S., Suzuki, F., Yuen, M. F., Kao, J. H., Yang, H. I., Nguyen, M. H. 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

• Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY Yeo, Y., Tseng, T., Hosaka, T., Cunningham, C., Fung, J., Ho, H. J., Kwak, M., Trinh, H. N., Ungtrakul, T., Yu, M., Kobayashi, M., Le, A. K., Henry, L., Li, J., Zhang, J., Sriprayoon, T., Jeong, D., Tanwandee, T., Gane, E., Cheung, R. C., Wu, C., Lok, A. S., Lee, H., Suzuki, F., Yuen, M., Kao, J., Yang, H., Nguyen, M. H. 2020; 11 (9)

  View details for DOI 10.14309/ctg.0000000000000196

  View details for Web of Science ID 000575994700002

• Prevalence of Hepatitis C Virus Infection in the Veteran Population Undergoing Total Joint Arthroplasty: An Update. The Journal of arthroplasty Shapiro, C. B., Cheung, R. C., Giori, N. J. 2020

  Abstract

  BACKGROUND: In 2012, we reported on the prevalence of hepatitis C virus (HCV) infection in Veterans Affairs (VA) patients undergoing total joint arthroplasty (TJA) at our center. In this patient population, 8.4% were antibody positive and 4.5% were viremic with HCV. In 2014, the first all-oral direct-acting antiviral treatment for hepatitis C became available. The Department of Veterans Affairs then underwent an aggressive program to eradicate hepatitis C from the veteran population. The purpose of this report is to provide updated information on the prevalence of HCV viremia among patients undergoing primary TJA at the same center.METHODS: A retrospective review was performed of all patients undergoing primary TJA at a single VA medical center in 2019. Anti-HCV antibody and HCV viremia prevalence were calculated. Comparisons were made to data from a previously reported cohort of patients who had undergone TJA at the same center from 2007 to2009.RESULTS: Thirty-three (11.6%) of 285 patients screened preoperatively were positive for the hepatitis C antibody. Only one of the 33 anti-HCV-positive patients was viremic at the time of screening for an overall viremic prevalence of 0.4%. We found no statistically significant difference in the birth year, or anti-HCV antibody-positive rate from the prior cohort, but the prevalence of HCV viremia decreased significantly.CONCLUSION: Because direct-acting antiviral HCV treatment has become available, HCV viremia among VA patients undergoing TJA has been reduced from 4.5% to 0.4%. Surgeons are still advised to minimize the risk of sharps injury.

  View details for DOI 10.1016/j.arth.2020.08.023

  View details for PubMedID 32900563

• 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 Ji, F., Li, J., Liu, L., Liang, J., Wang, X., Liu, J., Cai, D., Huang, R., Zhang, J., Wang, Q., Nan, Y., Li, J., Ye, Q., Zhang, M., Xu, Q., Guo, F., Zhao, C., Liu, L., He, C., Li, Y., Wang, W., Kam, L. Y., Tran, S., Maeda, M., Mizuta, A., Li, Z., Dang, S., Ren, W., Zhu, Q., Cheung, R., Niu, J., Xie, W., Pan, H., Ren, H., Wu, C., Shang, J., Wang, F., Nguyen, M. H. 2020

  View details for DOI 10.1111/jgh.15192

  View details for Web of Science ID 000555678900001

• Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing. BMC medicine Zhang, H., Dong, P., Guo, S., Tao, C., Chen, W., Zhao, W., Wang, J., Cheung, R., Villanueva, A., Fan, J., Ding, H., Schrodi, S. J., Zhang, D., Zeng, C. 2020; 18 (1): 200

  Abstract

  BACKGROUND: Circulating cell-free DNA (cfDNA) methylation has been demonstrated to be a promising approach for non-invasive cancer diagnosis. However, the high cost of whole genome bisulfite sequencing (WGBS) hinders the clinical implementation of a methylation-based cfDNA early detection biomarker. We proposed a novel strategy in low-pass WGBS (~5 million reads) to detect methylation changes in circulating cell-free DNA (cfDNA) from patients with liver diseases and hepatocellular carcinoma (HCC).METHODS: The effective small sequencing depth were determined by 5 pilot cfDNA samples with relative high-depth WGBS. CfDNA of 51 patients with hepatitis, cirrhosis, and HCC were conducted using low-pass WGBS. The strategy was validated in an independent WGBS cohort of 32 healthy individuals and 26 early-stage HCC patients. Fifteen paired tumor tissue and buffy coat samples were used to characterize the methylation of hepatitis B virus (HBV) integration regions and genome distribution of cfDNA.RESULTS: A significant enrichment of cfDNA in intergenic and repeat regions, especially in previously reported HBV integration sites were observed, as a feature of cfDNA and the bias of cfDNA release. Methylation profiles nearby HBV integration sites were a better indicator for hypomethylation of tumor genome comparing to Alu and LINE (long interspersed nuclear element) repeats, and were able to facilitate the cfDNA-based HCC prediction. Hypomethylation nearby HBV integration sites (5kb flanking) was detected in HCC patients, but not in patients with hepatitis and cirrhosis (MethylHBV5k, median:0.61 vs 0.72, P=0.0003). Methylation levels of integration sites certain candidate regions exhibited an area under the receiver operation curve (AUC) value >0.85 to discriminate HCC from non-HCC samples. The validation cohort achieved the prediction performance with an AUC of 0.954.CONCLUSIONS: Hypomethylation around viral integration sites aids low-pass cfDNA WGBS to serve as a non-invasive approach for early HCC detection, and inspire future efforts on tumor surveillance for oncovirus with integration activity.

  View details for DOI 10.1186/s12916-020-01667-x

  View details for PubMedID 32741373

• 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 Ji, F., Li, J., Liu, L., Liang, J., Wang, X., Liu, J., Cai, D., Huang, R., Zhang, J., Wang, Q., Nan, Y., Li, J., Ye, Q., Zhang, M., Xu, Q., Guo, F., Zhao, C., Liu, L., He, C., Li, Y., Wang, W., Kam, L. Y., Tran, S., Maeda, M., Mizuta, A., Li, Z., Dang, S., Ren, W., Zhu, Q., Cheung, R., Niu, J., Xie, W., Pan, H., Ren, H., Wu, C., Shang, J., Wang, F., Nguyen, M. H. 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

• 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 Li, J., Le, A. K., Chaung, K. T., Henry, L., Hoang, J. K., Cheung, R., Nguyen, M. H. 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

• Hepatocellular carcinoma incidence with tenofovir versus entecavir in chronic hepatitis B: a systematic review and meta-analysis. The lancet. Gastroenterology & hepatology Tseng, C. H., Hsu, Y. C., Chen, T. H., Ji, F. n., Chen, I. S., Tsai, Y. N., Hai, H. n., Thuy, L. T., Hosaka, T. n., Sezaki, H. n., Borghi, J. A., Cheung, R. n., Enomoto, M. n., Nguyen, M. H. 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

• Diagnosis Rates of Chronic Hepatitis B in Privately Insured Patients in the United States. JAMA network open Ogawa, E. n., Yeo, Y. H., Dang, N. n., Le, M. H., Jeong, D. n., Tran, S. n., Henry, L. n., Cheung, R. n., Nguyen, M. H. 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

• 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 Ye, Q. n., Zou, B. n., Yeo, Y. H., Li, J. n., Huang, D. Q., Wu, Y. n., Yang, H. n., Liu, C. n., Kam, L. Y., Tan, X. X., Chien, N. n., Trinh, S. n., Henry, L. n., Stave, C. D., Hosaka, T. n., Cheung, R. C., Nguyen, M. H. 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

• Development and validation of a risk score for liver cirrhosis prediction in untreated and treated chronic hepatitis B. The Journal of infectious diseases Le, A. K., Yang, H. I., Yeh, M. L., Jin, M. n., Trinh, H. N., Henry, L. n., Liu, A. n., Zhang, J. Q., Li, J. n., Wong, C. n., Wong, C. n., Cheung, R. n., Yu, M. L., Nguyen, M. H. 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

• Response to: Comparison of MAFLD and NAFLD diagnostic criteria in real world. Liver international : official journal of the International Association for the Study of the Liver Nguyen, V. H., Le, M. H., Henry, L. n., Cheung, R. n. 2020

  Abstract

  We have several concerns with the recent study by Lin et al..1 Recently, the terminology used to identify fatty liver disease with metabolic components has come under discussion. Proponents for a name change of non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD) state that MAFLD better captures the heterogeneity of this fatty liver disease based on risk factor and removes the exclusion of alcohol use (non-alcoholic).

  View details for DOI 10.1111/liv.14664

  View details for PubMedID 32941668

• Association between fatty liver and cirrhosis, hepatocellular carcinoma, and HBsAg seroclearance in chronic hepatitis B. The Journal of infectious diseases Li, J. n., Yang, H. I., Yeh, M. L., Le, M. H., Le, A. K., Yeo, Y. H., Dai, C. Y., Barnett, S. n., Zhang, J. Q., Huang, J. F., Trinh, H. N., Wong, C. n., Wong, C. n., Hoang, J. K., Cheung, R. n., Yu, M. L., Nguyen, M. H. 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

• Epidemiology of COVID-19: A Systematic Review and Meta-analysis of Clinical Characteristics, Risk factors and Outcomes. Journal of medical virology Li, J. n., Huang, D. Q., Zou, B. n., Yang, H. n., Hui, W. Z., Rui, F. n., Yee, N. T., Liu, C. n., Nerurkar, S. N., Kai, J. C., Teng, M. L., Li, X. n., Zeng, H. n., Borghi, J. A., Henry, L. n., Cheung, R. n., Nguyen, M. H. 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

• The epidemiology of NAFLD in Mainland China with analysis by adjusted gross regional domestic product: a meta-analysis. Hepatology international Wu, Y. n., Zheng, Q. n., Zou, B. n., Yeo, Y. H., Li, X. n., Li, J. n., Xie, X. n., Feng, Y. n., Stave, C. D., Zhu, Q. n., Cheung, R. n., Nguyen, M. H. 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

• HCC risk post-SVR with DAAs in East Asians: findings from the REAL-C cohort. Hepatology international Tanaka, Y. n., Ogawa, E. n., Huang, C. F., Toyoda, H. n., Jun, D. W., Tseng, C. H., Hsu, Y. C., Enomoto, M. n., Takahashi, H. n., Furusyo, N. n., Yeh, M. L., Iio, E. n., Yasuda, S. n., Lam, C. P., Lee, D. H., Haga, H. n., Yoon, E. L., Ahn, S. B., Wong, G. n., Nakamuta, M. n., Nomura, H. n., Tsai, P. C., Jung, J. H., Song, D. S., Dang, H. n., Maeda, M. n., Henry, L. n., Cheung, R. n., Yuen, M. F., Ueno, Y. n., Eguchi, Y. n., Tamori, A. n., Yu, M. L., Hayashi, J. n., Nguyen, M. H. 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

• Ethnicity-Specific Differences in Liver Transplant Outcomes Among Adults With Primary Sclerosing Cholangitis: 2005-2017 United Network for Organ Sharing/Organ Procurement and Transplantation Network. Journal of clinical and experimental hepatology Bayable, A. n., Ohabughiro, M. n., Cheung, R. n., Wong, R. J. 2020; 11 (1): 30–36

  Abstract

  Lack of effective medical therapies for primary sclerosing cholangitis (PSC) leads to continued disease progression to end-stage liver disease requiring liver transplantation (LT). Few studies have specifically evaluated whether ethnic disparities in LT outcomes exist among adults awaiting LT. We aimed to evaluate ethnicity-specific differences in LT outcomes among adults with PSC in the US.We retrospectively evaluated US adults (aged ≥ 18 years) with PSC without hepatocellular carcinoma listed for LT using the 2005-2017 United Network for Organ Sharing database. Ethnicity-specific differences in overall waitlist survival and probability of receiving LT were evaluated using competing risks regression analyses and adjusted multivariable Cox proportional hazards models. Overall survival after LT was evaluated with Kaplan-Meier methods and multivariable Cox proportional hazards models.Among 4046 patients with PSC listed for LT (69.2% men, 82.2% non-Hispanic white, 12.4% African American, 3.9% Hispanic, 1.6% Asian), significantly higher risk of waitlist death was men vs. women (Standardized hazard ratio (SHR) = 1.50, 95% CI: 1.05-2.12, P = 0.025), but no ethnicity-specific differences were observed. Compared with non-Hispanic whites, Hispanics had significantly lower probability of receiving LT (SHR = 0.73, 95% CI: 0.54-0.98, P = 0.035). Among patients with PSC and end-stage liver disease who underwent LT, African Americans had significantly higher risk of post-LT death compared with non-Hispanic whites (SHR = 1.68, 95% CI: 1.21-2.32, P = 0.002).Among a large cohort of US adults with PSC awaiting LT, significant ethnicity-specific disparities in LT outcomes were observed. Lower probability of LT in Hispanics and significantly higher risk of post-LT death in African Americans were observed.

  View details for DOI 10.1016/j.jceh.2020.06.004

  View details for PubMedID 33679046

  View details for PubMedCentralID PMC7897847

• A Nationwide Study of Inpatient Admissions, Mortality, and Costs for Patients with Cirrhosis from 2005 to 2015 in the USA. Digestive diseases and sciences Zou, B., Yeo, Y. H., Jeong, D., Park, H., Sheen, E., Lee, D. H., Henry, L., Garcia, G., Ingelsson, E., Cheung, R., Nguyen, M. H. 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

• SUBSTANTIAL GAP IN ASSESSMENT AND TREATMENT OF CHRONIC HEPATITIS B (CHB) PATIENTS IN THE UNITED STATES: A NATIONWIDE STUDY OF 7,124 PATIENTS Ye, Q., Yeo, Y., Dang, N., Kam, L., Cheung, R., Nguyen, M. H. WILEY. 2019: 566A

  View details for Web of Science ID 000488653502073

• Preoperative Endoscopic Findings in Veterans Undergoing Bariatric Surgery: Prevalence and Predictors of Barrett's Esophagus Ozeki, K., Tran, S., Cheung, R., Eisenberg, D. LIPPINCOTT WILLIAMS & WILKINS. 2019: S632

  View details for DOI 10.14309/01.ajg.0000594032.95148.63

  View details for Web of Science ID 000509756002337

• 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 Wei, M., Dao, A. T., Le, A., Nguyen, T., Tran, B., Trinh, L. L., Nguyen, H. A., Nguyen, K., Levitt, B. S., Shieh, E., Goyal, T., Cheung, R., Nguyen, M. H., Trinh, H. LIPPINCOTT WILLIAMS & WILKINS. 2019: S192

  View details for DOI 10.14309/01.ajg.0000590840.61215.b2

  View details for Web of Science ID 000509756000328

• More Severe Deficits in Performance Status at Time of Liver Transplant is Associated With Significantly Higher Risk of Death Following Liver Transplantation JOURNAL OF CLINICAL GASTROENTEROLOGY McCabe, P., Gish, R. G., Cheung, R., Wong, R. J. 2019; 53 (9): e392–e399

  View details for DOI 10.1097/MCG.0000000000001187

  View details for Web of Science ID 000485989900007

• 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 Dang, H., Yeo, Y., Yasuda, S., Huang, C., Iio, E., Landis, C. S., Jun, D., Enomoto, M., Ogawa, E., Tsai, P., Le, A., Liu, M., Maeda, M., Nguyen, B., Ramrakhiani, N., Henry, L., Cheung, R., Tamori, A., Kumada, T., Tanaka, Y., Yu, M., Toyoda, H., Nguyen, M. H. WILEY. 2019: 28A

  View details for Web of Science ID 000488653500041

• 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 Nguyen Hoang Vy, Yeo, Y., Zou, B., Le, M., Cheung, R., Nguyen, M. H. WILEY. 2019: 753A–754A

  View details for Web of Science ID 000488653502395

• 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 Zheng, Q., Wu, Y., Zou, B., Yeo, Y., Wu, H., Stave, C., Cheung, R., Nguyen, M. H. WILEY. 2019: 570A–571A

  View details for Web of Science ID 000488653502081

• INCREASING PREVALENCE AND FACTORS ASSOCIATED WITH NAFLD IN MAINLAND CHINA: A META-ANALYSIS OF 124 STUDIES AND 1,232,281 PARTICIPANTS Wu, Y., Zheng, Q., Zou, B., Yeo, Y., Li, X., Li, J., Feng, Y., Xie, X., Stave, C., Cheung, R., Zhu, Q., Nguyen, M. H. WILEY. 2019: 742A–743A

  View details for Web of Science ID 000488653502378

• 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 Kam, L., Yeo, Y., Huang, D., Fung, J., Lee, T., Yasuda, S., Wong, V., Saruwatari, J., Barnett, S., Oniki, K., Li, J., Zou, B., Cheung, R., Kumada, T., Yuen, M., Toyoda, H., Nguyen, M. H. WILEY. 2019: 741A–742A

  View details for Web of Science ID 000488653502377

• SYSTEMATIC REVIEW AND META-ANALYSIS: A NATURAL HISTORY STUDY TO INCLUDE NAFLD INCIDENCE, DISEASE TRANSITION AND OUTCOMES Wu, Y., Yeo, Y., Zou, B., Li, X., Zheng, Q., Li, J., Xie, X., Feng, Y., Stave, C., Cheung, R., Zhu, Q., Nguyen, M. H. WILEY. 2019: 743A

  View details for Web of Science ID 000488653502379

• 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) Li, J., Yang, H., Le, A., Henry, L., Hoang, J., Cheung, R., Yu, M., Nguyen, M. H. WILEY. 2019: 1347A–1348A

  View details for Web of Science ID 000488653505046

• 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 Tanaka, Y., Toyoda, H., Jun, D., Enomoto, M., Huang, C., Ogawa, E., Yasuda, S., Iio, E., Iwane, S., Haga, H., Dai, C., Jeong, J., Park, S., Wong, G. L., Lee, D., Takahashi, H., Huang, J., Tran, S., Maeda, M., Cheung, R., Ueno, Y., Eguchi, Y., Hayashi, J., Furusyo, N., Tamori, A., Kumada, T., Yu, M., Nguyen, M. H., Ahn, S., Henry, L., Hsu, Y., Huang, C., Jun, M., Jung, J., Kam, L., Lee, M., Liang, P., Mizuta, A., Song, D., Tsai, P., Tseng, C., Yang, H., Yeh, M., Yoon, E., Real-C Investigators WILEY. 2019: 908A–909A

  View details for Web of Science ID 000488653503199

• 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 Huang, D., Yeo, Y., Tan, X., Kam, L., Fung, J., Lee, T., Wong, V., Saruwatari, J., Muthiah, M., Barnett, S., Oniki, K., Li, J., Zou, B., Dan, Y., Lim, S., Cheung, R., Yuen, M., Nguyen, M. H. WILEY. 2019: 1055A–1056A

  View details for Web of Science ID 000488653504021

• INCREASING PREVALENCE AND ASSOCIATION BETWEEN SEVERITY OF RENAL INSUFFICIENCY WITH MORTALITY IN PERSONS WITH NAFLD, A UNITED STATES POPULATION-BASED STUDY Le, M., Yeo, Y., Henry, L., Cheung, R., Nguyen, M. H. WILEY. 2019: 155A–156A

  View details for Web of Science ID 000488653500238

• 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 Ji, F., Yeo, Y., Wei, M., Ogawa, E., Enomoto, M., Lee, D., Iio, E., Lubel, J., Wang, W., Wei, B., Ide, T., Preda, C., Conti, F., Minami, T., Bielen, R., Sezaki, H., Barone, M., Kolly, P., Chu, P., Virlogeux, V., Eurich, D., Henry, L., Bass, M. B., Kanai, T., Dang, S., Li, Z., Dufour, J., Zoulim, F., Andreone, P., Cheung, R. C., Tanaka, Y., Furusyo, N., Toyoda, H., Tamori, A., Nguyen, M. H. 2019; 71 (3): 473–85

  View details for DOI 10.1016/j.jhep.2019.04.017

  View details for Web of Science ID 000481571400005

• Prevalence of NAFLD in China: What Did We Learn From the Recent Meta-Analysis? Hepatology (Baltimore, Md.) Wu, Y., Yeo, Y. H., Nguyen, M. H., Cheung, R. C. 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

• Antiviral therapy and the development of osteopenia/osteoporosis among Asians with chronic hepatitis Bn JOURNAL OF MEDICAL VIROLOGY Wei, M. T., Le, A. K., Chang, M. S., Hsu, H., Nguyen, P., Zhang, J. Q., Wong, C., Wong, C., Cheung, R., Nguyen, M. H. 2019; 91 (7): 1288–94

  View details for DOI 10.1002/jmv.25433

  View details for Web of Science ID 000471755300014

• Chronic hepatitis B prevalence among foreign-born and US-born adults in the United States, 1999-2016. Hepatology (Baltimore, Md.) Le, M. H., Yeo, Y. H., Cheung, R., Henry, L., Lok, A. S., Nguyen, M. H. 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

• Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999-2019: a systematic review and meta-analysis LANCET GASTROENTEROLOGY & HEPATOLOGY Li, J., Zou, B., Yeo, Y., Feng, Y., Xie, X., Lee, D., Fujii, H., Wu, Y., Kam, L. Y., Ji, F., Li, X., Chien, N., Wei, M., Ogawa, E., Zhao, C., Wu, X., Stave, C. D., Henry, L., Barnett, S., Takahashi, H., Furusyo, N., Eguchi, Y., Hsu, Y., Lee, T., Ren, W., Qin, C., Jun, D., Toyoda, H., Wong, V., Cheung, R., Zhu, Q., Nguyen, M. H. 2019; 4 (5): 389–98

  View details for DOI 10.1016/S2468-1253(19)30039-1

  View details for Web of Science ID 000463786300024

• Hepatitis B and renal function: A matched study comparing non-hepatitis B, untreated, treated and cirrhotic hepatitis patients LIVER INTERNATIONAL Vinh Vu, Trinh, S., An Le, Johnson, T., Hoang, J., Jeong, D., Henry, L., Barnett, S., Cheung, R., Nguyen, M. H. 2019; 39 (4): 655–66

  View details for DOI 10.1111/liv.14009

  View details for Web of Science ID 000462572800010

• Changes in Renal Function in Patients With Chronic HBV Infection Treated With Tenofovir Disoproxil Fumarate vs Entecavir CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Trinh, S., Le, A. K., Chang, E. T., Hoang, J., Jeong, D., Chung, M., Lee, M., Wang, U., Henry, L., Cheung, R., Nguyen, M. H. 2019; 17 (5): 948-+

  View details for DOI 10.1016/j.cgh.2018.08.037

  View details for Web of Science ID 000461795700029

• Poor Adherence to Guidelines for Treatment of Chronic Hepatitis B Virus Infection at Primary Care and Referral Practices CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Nguyen, V. H., Le, A. K., Trinh, H. N., Chung, M., Johnson, T., Wong, C., Wong, C., Zhang, J., Li, J., Levitt, B. S., Nguyen, H. A., Nguyen, K. K., Henry, L., Cheung, R., Nguyen, M. H. 2019; 17 (5): 957-+

  View details for DOI 10.1016/j.cgh.2018.10.012

  View details for Web of Science ID 000461795700030

• Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999-2019: a systematic review and meta-analysis. The lancet. Gastroenterology & hepatology Li, J., Zou, B., Yeo, Y. H., Feng, Y., Xie, X., Lee, D. H., Fujii, H., Wu, Y., Kam, L. Y., Ji, F., Li, X., Chien, N., Wei, M., Ogawa, E., Zhao, C., Wu, X., Stave, C. D., Henry, L., Barnett, S., Takahashi, H., Furusyo, N., Eguchi, Y., Hsu, Y., Lee, T., Ren, W., Qin, C., Jun, D. W., Toyoda, H., Wong, V. W., Cheung, R., Zhu, Q., Nguyen, M. H. 2019

  Abstract

  BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Asia is a large, heterogeneous area with substantial variation in socioeconomic status and prevalence of obesity. We estimated the prevalence, incidence, and outcomes of NAFLD in the Asian population to assist stakeholders in understanding NAFLD disease burden.METHODS: We searched PubMed, EMBASE, and the Cochrane Library from database inception to Jan 17, 2019, for studies reporting NAFLD prevalence, incidence, or outcome in Asia. We included only cross-sectional and longitudinal observational studies of patients with NAFLD diagnosed by imaging, serum-based indices, or liver biopsy. Studies that included patients with overlapping liver disease or that did not screen for excess alcohol consumption were excluded. Two investigators independently screened and extracted data. The main outcomes were pooled NAFLD prevalence, incidence, and hepatocellular carcinoma incidence and overall mortality in patients with NAFLD. Summary estimates were calculated using a random-effects model. This study is registered with PROSPERO, number CRD42018088468.FINDINGS: Of 4995 records identified, 237 studies (13 044 518 participants) were included for analysis. The overall prevalence of NAFLD regardless of diagnostic method was 29·62% (95% CI 28·13-31·15). NAFLD prevalence increased significantly over time (25·28% [22·42-28·37] between 1999 and 2005, 28·46% [26·70-30·29] between 2006 and 2011, and 33·90% [31·74-36·12] between 2012 and 2017; p<0·0001). The pooled annual NAFLD incidence rate was 50·9 cases per 1000 person-years (95% CI 44·8-57·4). In patients with NAFLD, the annual incidence of hepatocellular carcinoma was 1·8 cases per 1000 person-years (0·8-3·1) and overall mortality rate was 5·3 deaths per 1000 person-years (1·5-11·4).INTERPRETATION: NAFLD prevalence in Asia is increasing and is associated with poor outcomes including hepatocellular carcinoma and death. Targeted public health strategies must be developed in Asia to target the drivers of this rising epidemic and its associated complications, especially in high-risk groups, such as older obese men.FUNDING: None.

  View details for PubMedID 30902670

• Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis KOREAN JOURNAL OF INTERNAL MEDICINE Lee, H., Jun, D., Kim, H., Oh, H., Saeed, W., Ahn, H., Cheung, R. C., Nguyen, M. H. 2019; 34 (2): 296-+

  View details for DOI 10.3904/kjim.2017.194

  View details for Web of Science ID 000459694200008

• More Severe Deficits in Performance Status at Time of Liver Transplant is Associated With Significantly Higher Risk of Death Following Liver Transplantation. Journal of clinical gastroenterology McCabe, P., Gish, R. G., Cheung, R., Wong, R. J. 2019

  Abstract

  GOAL: To evaluate the impact of Karnofsky Performance Status score (KPSS) at the time of liver transplantation (LT) on post-LT survival.BACKGROUND: While the Model for End-Stage Liver Disease (MELD) score is used to prioritize individuals for LT, it does not specifically incorporate functional status into patient assessment for LT.METHODS: Using 2005 to 2016 United Network for Organ Sharing data, all adults (age 18y and above) undergoing LT were identified. The association of KPSS at the time of LT (KPSS 1: functional status 80% to 100%, KPSS 2: 60% to 70%, KPSS 3: 40% to 50%, KPSS 4: 10% to 30%) with post-LT survival was evaluated using Kaplan-Meier methods and adjusted multivariate logistic regression models.RESULTS: Among 66,397 LT recipients (68% male, 72% non-Hispanic white, 22% hepatocellular carcinoma, median age: 55 to 57), women were more likely to be KPSS 4 at the time of LT compared with men (27.95% vs. 22.79%; P<0.001) and African Americans (25.43% vs. 23.03%; P<0.001) and Hispanics (31.69% vs. 23.03%; P<0.001) were more likely to be KPSS 4 than non-Hispanic whites. Worse KPSS at LT correlated with higher post-LT mortality [compared with KPSS 1: Hazard Ratio (HR) for KPSS 2: 1.16, 95% confidence interval (CI): 1.10-1.22; HR for KPSS 3: 1.40; 95% CI: 1.32-1.49; HR for KPSS 4: 1.67; 95% CI: 1.55-1.79]. This increased mortality seen with worse KPSS was observed among all liver disease etiologies and in patients with and without hepatocellular carcinoma.CONCLUSIONS: Worse functional status at the time of LT is strongly associated with higher risk of mortality following LT, emphasizing the importance of optimizing performance status in the preoperative period.

  View details for PubMedID 30762610

• Only one-third of hepatocellular carcinoma cases are diagnosed via screening or surveillance: a systematic review and meta-analysis. European journal of gastroenterology & hepatology Zhao, C. n., Xing, F. n., Yeo, Y. H., Jin, M. n., Le, R. n., Le, M. n., Jin, M. n., Henry, L. n., Cheung, R. n., Nguyen, M. H. 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

• Direct-acting antivirals in East Asian hepatitis C patients: real-world experience from the REAL-C Consortium. Hepatology international Huang, C. F., Iio, E. n., Jun, D. W., Ogawa, E. n., Toyoda, H. n., Hsu, Y. C., Haga, H. n., Iwane, S. n., Enomoto, M. n., Lee, D. H., Wong, G. n., Liu, C. H., Tada, T. n., Chuang, W. L., Cheung, R. n., Hayashi, J. n., Tseng, C. H., Yasuda, S. n., Tran, S. n., Kam, L. n., Henry, L. n., Jeong, J. Y., Nomura, H. n., Park, S. H., Nakamuta, M. n., Huang, J. F., Tai, C. M., Lo, G. H., Lee, M. H., Yang, H. I., Kao, J. H., Tamori, A. n., Eguchi, Y. n., Ueno, Y. n., Furusyo, N. n., Tanaka, Y. n., Yu, M. L., Nguyen, M. H. 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

• 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 Zou, B. n., Yeo, Y. H., Le, M. H., Henry, L. n., Chang, E. T., Lok, A. S., Cheung, R. n., Nguyen, M. H. 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

• Antiviral therapy and the development of osteopenia/osteoporosis among Asians with chronic hepatitis B. Journal of medical virology Wei, M. T., Le, A. K., Chang, M. S., Hsu, H. n., Nguyen, P. n., Zhang, J. Q., Wong, C. n., Wong, C. n., Cheung, R. n., Nguyen, M. H. 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

• Liver transplantation for non-alcoholic steatohepatitis in Europe: Where do we stand? Journal of hepatology Durand, F. n., Pavesi, M. n., Cheung, R. n. 2019

  View details for DOI 10.1016/j.jhep.2019.05.018

  View details for PubMedID 31229271

• Clinical Features Associated with Survival Outcome in African-American Patients with Hepatocellular Carcinoma AMERICAN JOURNAL OF GASTROENTEROLOGY Estevez, J., Yang, J., Leong, J., Nguyen, P., Giama, N. H., Zhang, N., Ali, H. A., Lee, M., Cheung, R., Roberts, L., Schwartz, M., Nguyen, M. H. 2019; 114 (1): 80–88

  View details for DOI 10.1038/s41395-018-0261-y

  View details for Web of Science ID 000463156500014

• Chronic hepatitis B and NASH: Is "fat" all bad? Hepatology (Baltimore, Md.) Li, J. n., Cheung, R. C., Nguyen, M. H. 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

• Low Rates of Retention Into Hepatocellular Carcinoma (HCC) Surveillance Program After Initial HCC Screening JOURNAL OF CLINICAL GASTROENTEROLOGY Robinson, A., Tavakoli, H., Cheung, R., Liu, B., Bhuket, T., Wong, R. J. 2019; 53 (1): 65–70

  View details for DOI 10.1097/MCG.0000000000001024

  View details for Web of Science ID 000453562800017

• 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 Ji, F. n., Yeo, Y. H., Wei, M. T., Ogawa, E. n., Enomoto, M. n., Lee, D. H., Iio, E. n., Lubel, J. n., Wang, W. n., Wei, B. n., Ide, T. n., Preda, C. M., Conti, F. n., Minami, T. n., Bielen, R. n., Sezaki, H. n., Barone, M. n., Kolly, P. n., Chu, P. S., Virlogeux, V. n., Eurich, D. n., Henry, L. n., Bass, M. B., Kanai, T. n., Dang, S. n., Li, Z. n., Dufour, J. F., Zoulim, F. n., Andreone, P. n., Cheung, R. C., Tanaka, Y. n., Furusyo, N. n., Toyoda, H. n., Tamori, A. n., Nguyen, M. H. 2019

  Abstract

  Questions remain about the effect of hepatocellular carcinoma (HCC) on response to interferon-free direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC) patients compared to those without HCC. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response among CHC patients with active, inactive and no HCC.PubMed, Embase, Web of Science, and the Cochrane Controlled Trials Register were searched from 1/1/2013 to 9/24/2018. The pooled sustained virologic response (SVR) rates were computed using DerSimonian-Laird random-effects models.We included 49 studies from 15 countries, comprised of 3,341 HCC and 35,701 non-HCC patients. Overall, the pooled SVR was lower in HCC than in non-HCC patients (89.6%, 95% CI 86.8-92.1%, I2=79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2=95.0%, P=0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. Also on meta-regression analyses, the largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, P=0.002). Meanwhile, HCC patients with prior liver transplant (LT) had higher SVR compared to non-LT HCC patients (P<0.001). Regarding specific DAA regimens, HCC patients treated with ledipasvir/sofosbuvir had lower SVR rates than non-HCC patients (92.6%, n=884 vs. 97.8%, n=13,141, P=0.026) but heterogeneity was high (I2=84.7%, P<0.001). For the few HCC patients treated with paritaprevir/ritonavir, ombitasvir ± dasabuvir (n=101), SVR was similar to non-HCC patient (97.2% vs. 94.8%, P=0.79). Daclatasvir/asunaprevir-treated HCC and non-HCC patients also had similar SVR rates though both were low (91.7% vs. 89.8%, P=0.66).Overall, SVR was lower in HCC compared to non-HCC patients, especially in those with active HCC though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose and treat HCC to ensure higher CHC cure rates.There are now medications ("DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, liver cancer patients are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.

  View details for PubMedID 31096005

• 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 Ogawa, E. n., Toyoda, H. n., Iio, E. n., Jun, D. W., Huang, C. F., Enomoto, M. n., Hsu, Y. C., Haga, H. n., Iwane, S. n., Wong, G. n., Lee, D. H., Tada, T. n., Liu, C. H., Chuang, W. L., Hayashi, J. n., Cheung, R. n., Yasuda, S. n., Tseng, C. H., Takahashi, H. n., Tran, S. n., Yeo, Y. H., Henry, L. n., Barnett, S. D., Nomura, H. n., Nakamuta, M. n., Dai, C. Y., Huang, J. F., Yang, H. I., Lee, M. H., Jung Jun, M. n., Kao, J. H., Eguchi, Y. n., Ueno, Y. n., Tamori, A. n., Furusyo, N. n., Yu, M. L., Tanaka, Y. n., Nguyen, M. H., Ahn, S. B., Azuma, K. n., Dohmen, K. n., Yoon Jeong, J. n., Jung, J. H., Kajiwara, E. n., Kato, M. n., Kawano, A. n., Koyanagi, T. n., Ooho, A. n., Park, S. H., Satoh, T. n., Shimoda, S. n., Song, D. S., Takahashi, K. n., Yeh, M. L., Yoon, E. L. 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

• Cure with Interferon Free DAA is Associated with Increased Survival in Patients with HCV related HCC from both East and West. Hepatology (Baltimore, Md.) Dang, H. n., Yeo, Y. H., Yasuda, S. n., Huang, C. F., Iio, E. n., Landis, C. n., Jun, D. W., Enomoto, M. n., Ogawa, E. n., Tsai, P. C., Le, A. n., Liu, M. n., Maeda, M. n., Nguyen, B. n., Ramrakhiani, N. n., Henry, L. n., Cheung, R. n., Tamori, A. n., Kumada, T. n., Tanaka, Y. n., Yu, M. L., Toyoda, H. n., Nguyen, M. H. 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

• Race/Ethnicity and Insurance-Specific Disparities in In-Hospital Mortality Among Adults with Primary Biliary Cholangitis: Analysis of 2007-2014 National Inpatient Sample. Digestive diseases and sciences Galoosian, A. n., Hanlon, C. n., Tana, M. n., Cheung, R. n., Wong, R. J. 2019

  Abstract

  Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease that can result in cirrhosis and end-stage liver disease.We aim to evaluate hospitalization burden and in-hospital mortality among PBC patients in the USA.Using data from the Nationwide Inpatient Sample from 2007 to 2014, hospitalizations among US adults with PBC were stratified by sex, age, and race/ethnicity. Overall in-hospital mortality was stratified by these variables and adjusted multivariate regression models evaluated for predictors of in-hospital mortality.From 2007 to 2014, there were 18,279 hospitalizations among adults with PBC (15.0% male, mean age 63.8 years, 41.3% cirrhosis). Among non-Hispanic whites, the proportion of total PBC hospitalizations increased from 57.8% in 2007 to 71.2% in 2014, compared to 4.1-6.3% for African-Americans, 8.6-10.9% for Hispanics, and 1.7-2.8% for Asians (p < 0.001 for all). While overall in-hospital mortality was low (4.2%), increasing age was associated with higher odds of in-hospital mortality (OR: 1.02, 95% CI 1.01-1.03, p < 0.001). Compared to non-Hispanic white PBC patients, higher in-hospital mortality was observed in African-American PBC patients (OR: 1.40, 95% CI 1.16-2.03, p < 0.05). Compared to patients with private/commercial insurance, significantly higher odds of in-hospital mortality were observed in patients with Medicaid insurance (OR 1.42, 95% CI 1.00-1.99, p < 0.05).In summary, among adults with PBC hospitalized in the USA from 2007 to 2014, the overall number of hospitalizations is increasing. Significant disparities in in-hospital mortality were observed; African-Americans with PBC and Medicaid patients with PBC have disproportionately higher odds of in-hospital mortality.

  View details for DOI 10.1007/s10620-019-05809-x

  View details for PubMedID 31489564

• Systematic review and meta-analysis: real-world effectiveness of direct-acting antiviral therapies in chronic hepatitis C genotype 3 in Asia BMJ OPEN GASTROENTEROLOGY Wei, B., Ji, F., Yeo, Y., Ogawa, E., Stave, C. D., Dang, S., Li, Z., Furusyo, N., Cheung, R. C., Nguyen, M. H. 2018; 5 (1)

  View details for DOI 10.1136/bmjgast-2018-000209

  View details for Web of Science ID 000457748000007

• Real-world effectiveness of sofosbuvir plus ribavirin for chronic hepatitis C genotype 2 in Asia: a systematic review and meta-analysis BMJ OPEN GASTROENTEROLOGY Wei, B., Ji, F., Yeo, Y., Ogawa, E., Zou, B., Stave, C. D., Dang, S., Li, Z., Furusyo, N., Cheung, R. C., Nguyen, M. H. 2018; 5 (1)

  View details for DOI 10.1136/bmjgast-2018-000207

  View details for Web of Science ID 000457748000005

• Prevalence of Hepatitis B Vaccination Coverage Versus Serologic Evidence of Hepatitis B Immunity in Children and Adolescents in the United States, 1999-2016 Le, M., Yeo, Y., So, S. K., Gane, E. J., Cheung, R., Nguyen, M. H. WILEY. 2018: 1192A–1193A

  View details for Web of Science ID 000446020503320

• 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) Wei, B., Wei, M., Jeong, D., Henry, L., Cheung, R., Nguyen, M. H. WILEY. 2018: 461A

  View details for Web of Science ID 000446020500796

• Initial Evaluation, Laboratory Monitoring, and Surveillance of Chronic Hepatitis B (CHB) Patients: Results of a Real-World Analysis of 85,922 Commercially-Insured Patients Tran, S., Jeong, D., Yeo, Y., Le, M., Henry, L., Cheung, R., Nguyen, M. H. WILEY. 2018: 82A

  View details for Web of Science ID 000446020500132

• Medical Monitoring Among Cirrhotic Patients in Real World Practice: A Nationwide US Study with 43,915 Cirrhotics Yeo, Y., Jeong, D., Tran, S., Cheung, R., Nguyen, M. H. WILEY. 2018: 283A

  View details for Web of Science ID 000446020500482

• 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 Zou, B., Yeo, Y., Le, M., Cheung, R., Nguyen, M. H. WILEY. 2018: 1193A

  View details for Web of Science ID 000446020503321

• Alanine Aminotransferase Results Differ between Analyzer Manufacturers in a US National Integrated Health Setting Beste, L. A., Icardi, M., Gylys-Colwell, I., Lowy, E., Taylor, L., Morgan, T. R., Hunt, C. M., Chang, M. F., Maier, M., Cheung, R. WILEY. 2018: 286A

  View details for Web of Science ID 000446020500487

• 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 Zou, B., Le, M., Yeo, Y., Cheung, R., Nguyen, M. H. WILEY. 2018: 931A–932A

  View details for Web of Science ID 000446020502431

• Estimations of the Total Number of Undiagnosed Patients and Antiviral Treatment Rate for Chronic Hepatitis B in the United States Ogawa, E., Jeong, D., Yeo, Y., Henry, L., Tran, S., Cheung, R., Nguyen, M. H., Furusyo, N. WILEY. 2018: 1214A

  View details for Web of Science ID 000446020503357

• The Prevalence, Diagnosis Rate, and Treatment Rate of Hepatitis C Infection in the United States: A Nationwide Study Yeo, Y., Jeong, D., Sally Tran, Ogawa, E., Cheung, R., Nguyen, M. H. WILEY. 2018: 281A

  View details for Web of Science ID 000446020500479

• National Estimates of Overall and Liver-Related Inpatient Care Cost in Cirrhotic Patients with Diverse Etiologies and Ethnicities in the United States (US) Zou, B., Yeo, Y., Jeong, D., Cheung, R., Sheen, E., Park, H., Lee, D., Garcia, G., Nguyen, M. H. WILEY. 2018: 110A

  View details for Web of Science ID 000446020500176

• African-Americans with Cirrhosis Are Less Likely to Receive Endoscopic Variceal Screening Within One Year of Cirrhosis Diagnosis JOURNAL OF RACIAL AND ETHNIC HEALTH DISPARITIES Robinson, A., Tavakoli, H., Liu, B., Bhuket, T., Cheung, R., Wong, R. J. 2018; 5 (4): 860–66

  Abstract

  Esophageal variceal hemorrhage is a complication of cirrhosis that carries high mortality, and can be reduced with timely endoscopic variceal screening and treatment.We aim to evaluate overall rates of and disparities in receipt of endoscopic variceal screening among an ethnically diverse urban safety-net hospital.All consecutive adults with cirrhosis (7/1/2014 to 12/31/2015) were retrospectively evaluated to determine the rates of receiving esophageal variceal screening within 6 months and within 1 year after cirrhosis diagnosis. Race-/ethnicity-specific differences in rates of variceal screening were compared using chi-square testing and multivariate regression methods.Among 157 patients (65% male, 33.8% Hispanic, 22.3% African-American, 44.6% alcoholic liver disease, 29.9% chronic HCV), 56.8% received variceal screening within 6 months and 65.8% received screening within 1 year. Compared to non-Hispanic whites with cirrhosis, African-Americans (52.2 vs. 76.2%, p < 0.05), Asians (57.1 vs. 76.2%, p < 0.05), and Hispanics (43.9 vs. 76.2%, p < 0.05) were all significantly less likely to receive endoscopic variceal screening within 6 months after cirrhosis diagnosis. On multivariate analysis, African-Americans with cirrhosis were 66% less likely to receive variceal screening compared to non-Hispanic whites (HR 0.34, 95% CI 0.15-0.77, p < 0.01).Among adults with cirrhosis at a community-based safety-net hospital system, overall first-time variceal screening remains suboptimal. African-Americans were the least likely to receive timely variceal screening. These findings are particularly concerning given the significant barriers that ethnic minorities and safety-net populations already face in timely access to medical care.

  View details for PubMedID 29052175

• Low Rates of Retention Into Hepatocellular Carcinoma (HCC) Surveillance Program After Initial HCC Screening. Journal of clinical gastroenterology Robinson, A., Tavakoli, H., Cheung, R., Liu, B., Bhuket, T., Wong, R. J. 2018

  Abstract

  GOALS: To evaluate rates and predictors of retention into hepatocellular carcinoma (HCC) surveillance beyond initial screening among underserved cirrhosis patients.BACKGROUND: Although initial HCC screening among cirrhosis patients remains low, few studies have evaluated retention to HCC surveillance beyond initial screening.METHODS: We retrospectively evaluated all consecutive adults with cirrhosis from 2014 to 2017 at a single underserved safety net hospital system to determine rates of HCC surveillance at 6 months and at 1 year beyond initial screening. Rates of HCC surveillance was stratified by sex, race/ethnicity, and etiology of liver disease. Multivariate Cox proportional hazards models evaluated predictors of retention into HCC surveillance.RESULTS: Among 235 cirrhosis patients [hepatitis C virus: 35.7%, hepatitis B virus (HBV): 15.7%, alcoholic cirrhosis: 36.2%, nonalcoholic steatohepatitis (NASH): 8.1%], mean age of cirrhosis diagnosis was 54.2±8.9 years. Overall, 74.8% received initial screening within 1 year of cirrhosis diagnosis. Among those who completed initial screening, 47.6% [95% confidence interval (CI), 41.4-54.2) received second surveillance within 1 year. On multivariate analyses, patients with NASH and HBV were significantly more likely to receive second HCC surveillance compared with hepatitis C virus, HBV (hazard ratio, 2.32; 95% CI, 1.18-4.56; P=0.014) and NASH (hazard ratio, 2.49; 95% CI, 1.22-5.11; P=0.012). No sex or race-specific/ethnicity-specific differences in HCC surveillance retention were observed.CONCLUSIONS: Although overall rates of initial HCC screening among cirrhosis patients is nearly 75%, retention into continued HCC surveillance is poor, with less than half of patients undergoing subsequent HCC surveillance. Cirrhosis patients with HBV and NASH were more likely to be retained into HCC surveillance.

  View details for PubMedID 29629906

• Real-world effectiveness of sofosbuvir plus ribavirin for chronic hepatitis C genotype 2 in Asia: a systematic review and meta-analysis. BMJ open gastroenterology Wei, B. n., Ji, F. n., Yeo, Y. H., Ogawa, E. n., Zou, B. n., Stave, C. D., Dang, S. n., Li, Z. n., Furusyo, N. n., Cheung, R. C., Nguyen, M. H. 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

• Clinical Features Associated with Survival Outcome in African-American Patients with Hepatocellular Carcinoma. The American journal of gastroenterology Estevez, J. n., Yang, J. D., Leong, J. n., Nguyen, P. n., Giama, N. H., Zhang, N. n., Ali, H. A., Lee, M. H., Cheung, R. n., Roberts, L. n., Schwartz, M. n., Nguyen, M. H. 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

• Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis. The Korean journal of internal medicine Lee, H. Y., Jun, D. W., Kim, H. J., Oh, H. n., Saeed, W. K., Ahn, H. n., Cheung, R. C., Nguyen, M. H. 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

• 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 Vu, V. n., Trinh, S. n., Le, A. n., Johnson, T. n., Hoang, J. n., Jeong, D. n., Henry, L. n., Barnett, S. n., Cheung, R. n., Nguyen, M. H. 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

• 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 Nguyen, V. H., Le, A. K., Trinh, H. N., Chung, M. n., Johnson, T. n., Wong, C. n., Wong, C. n., Zhang, J. n., Li, J. n., Levitt, B. S., Nguyen, H. A., Nguyen, K. K., Henry, L. n., Cheung, R. n., Nguyen, M. H. 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

• Systematic review and meta-analysis: real-world effectiveness of direct-acting antiviral therapies in chronic hepatitis C genotype 3 in Asia. BMJ open gastroenterology Wei, B. n., Ji, F. n., Yeo, Y. H., Ogawa, E. n., Stave, C. D., Dang, S. n., Li, Z. n., Furusyo, N. n., Cheung, R. C., Nguyen, M. H. 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

• 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 Trinh, S. n., Le, A. K., Chang, E. T., Hoang, J. n., Jeong, D. n., Chung, M. n., Lee, M. H., Wang, U. n., Henry, L. n., Cheung, R. n., Nguyen, M. H. 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

• 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 Wei, B., Ji, F., Yeo, Y., Ogawa, E., Henry, L., Li, Z., Dang, S., Furusyo, N., Cheung, R., Nguyen, M. H. WILEY. 2017: 857A–858A

  View details for Web of Science ID 000412089801741

• Low Rates of Retention into Hepatocellular Carcinoma (HCC) Surveillance Program After Initial HCC Screening Examination Robinson, A., Tavakoli, H., Cheung, R., Liu, B., Bhuket, T., Wong, R. J. WILEY. 2017: 319A

  View details for Web of Science ID 000412089800585

• 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 Ji, F., Wei, B., Yeo, Y., Zou, B., Ogawa, E., Henry, L., Li, Z., Cheung, R., Furusyo, N., Dang, S., Nguyen, M. H. WILEY. 2017: 596A–597A

  View details for Web of Science ID 000412089801253

• 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 Ji, F., Wei, B., Yeo, Y., Zou, B., Ogawa, E., Henry, L., Dang, S., Cheung, R., Furusyo, N., Li, Z., Nguyen, M. H. WILEY. 2017: 812A–813A

  View details for Web of Science ID 000412089801662

• 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 Wei, B., Ji, F., Yeo, Y., Zou, B., Ogawa, E., Henry, L., Cheung, R., Li, Z., Dang, S., Furusyo, N., Nguyen, M. H. WILEY. 2017: 811A

  View details for Web of Science ID 000412089801660

• Prevalence of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the United States PLOS ONE Le, M. H., Devaki, P., Ha, N. B., Jun, D. W., Te, H. S., Cheung, R. C., Nguyen, M. H. 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

• Adapting a computer-delivered brief alcohol intervention for veterans with Hepatitis C. Informatics for health & social care Cucciare, M. A., Jamison, A. L., Combs, A. S., Joshi, G., Cheung, R. C., Rongey, C., Huggins, J., Humphreys, K. 2017: 1-15

  Abstract

  This study adapted an existing computer-delivered brief alcohol intervention (cBAI) for use in Veterans with the hepatitis C virus (HCV) and examined its acceptability and feasibility in this patient population.A four-stage model consisting of initial pilot testing, qualitative interviews with key stakeholders, development of a beta version of the cBAI, and usability testing was used to achieve the study objectives.In-depth interviews gathered feedback for modifying the cBAI, including adding HCV-related content such as the health effects of alcohol on liver functioning, immune system functioning, and management of HCV, a preference for concepts to be displayed through "newer looking" graphics, and limiting the use of text to convey key concepts. Results from usability testing indicated that the modified cBAI was acceptable and feasible for use in this patient population.The development model used in this study is effective for gathering actionable feedback that can inform the development of a cBAI and can result in the development of an acceptable and feasible intervention for use in this population. Findings also have implications for developing computer-delivered interventions targeting behavior change more broadly.

  View details for DOI 10.1080/17538157.2016.1255628

  View details for PubMedID 28068154

• Sex-Specific and Race/Ethnicity-Specific Disparities in Hepatitis B Virus-Related Liver Transplantation Outcomes in the United States Young, K., Liu, B., Bhuket, T., Tana, M. M., Cheung, R., Wong, R. J. WILEY. 2016: 514A

  View details for Web of Science ID 000385493802282

• Comparison of Renal safety of Tenofovir (TDF) and Entecavir (ETV) in Patients with Chronic Hepatitis B (CHB): A Systematic Review with Meta-Analysis Lee, H., Jun, D., Cheung, R., Nguyen, M. H. WILEY. 2016: 935A

  View details for Web of Science ID 000385493804251

• Race/Ethnicity-Specific Disparities in the Receipt of Screening for Esophageal Varices Among Patients with Cirrhosis Tavakoli, H., Robinson, A., Liu, B., Bhuket, T., Cheung, R., Wong, R. NATURE PUBLISHING GROUP. 2016: S389

  View details for Web of Science ID 000395764601323

• Education Level and Household Income is Significantly Associated with Disparities in Hepatocellular Carcinoma Stage at Diagnosis and Treatment Received Ha, J., Yan, M., Wang, J., Tana, M. M., Cheung, R., Bhuket, T., Liu, B., Wong, R. J. WILEY. 2016: 675A–676A

  View details for Web of Science ID 000385493803156

• Colonoscopy with polypectomy is associated with a low rate of complications in patients with cirrhosis. Endoscopy international open Huang, R. J., Perumpail, R. B., Thosani, N., Cheung, R., Friedland, S. 2016; 4 (9): E947-52

  Abstract

  Cirrhotic patients are at a theoretically increased risk of bleeding. The safety of polypectomy in cirrhosis is poorly defined.We performed a retrospective review of patients with cirrhosis who underwent colonoscopic polypectomy at a tertiary-care hospital. Patient characteristics and polyp data were collected. Development of complications including immediate bleeding, delayed bleeding, hospitalization, blood transfusion, perforation, and death were recorded to 30-day follow-up. Clinical characteristics between bleeders and non-bleeders were compared, and predictors of bleeding were determined.A total of 307 colonoscopies with 638 polypectomies were identified. Immediate bleeding occurred in 7.5 % (95 % CI 4.6 % - 10.4 %) and delayed bleeding occurred in 0.3 % (95 % CI 0.0 % - 0.9 %) of colonoscopies. All cases of immediate bleeding were controlled endoscopically and none resulted in serious complication. The rate of hospitalization was 0.7 % (95 % CI 0.0 % - 1.6 %) and repeat colonoscopy 0.3 % (95 % CI 0.0 % - 0.9 %); no cases of perforation, blood transfusion, or death occurred. Lower platelet count, higher INR, presence of ascites, and presence of esophageal varices were associated with increased risk of bleeding. Use of electrocautery was associated with a lower risk of immediate bleeding. There was no significant difference between bleeding and non-bleeding polyps with regard to size, morphology, and histology.Colonoscopy with polypectomy appears safe in patients with cirrhosis. There is a low risk of major complications. The risk of immediate bleeding appears higher than an average risk population; however, most bleeding is self-limited or can be controlled endoscopically. Bleeding tends to occur with more advanced liver disease. Both the sequelae of portal hypertension and coagulation abnormalities are predictive of bleeding.

  View details for DOI 10.1055/s-0042-111317

  View details for PubMedID 27652299

  View details for PubMedCentralID PMC5025305

• Improved Survival Among all Interferon-alpha-Treated Patients in HCV-002, a Veterans Affairs Hepatitis C Cohort of 2211 Patients, Despite Increased Cirrhosis Among Nonresponders DIGESTIVE DISEASES AND SCIENCES Cozen, M. L., Ryan, J. C., Shen, H., Cheung, R., Kaplan, D. E., Pocha, C., Brau, N., Aytaman, A., Schmidt, W. N., Pedrosa, M., Anand, B. S., Chang, K., Morgan, T., Monto, A. 2016; 61 (6): 1744-1756

  Abstract

  As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated.To more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients.Patients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review.A total of 2211 patients were followed for an average of 8.5 years after enrollment. Thirty-one percent of patients received HCV antiviral therapy, 15 % with standard IFN/ribavirin only, 16 % with pegylated IFN/ribavirin, and 26.7 % of treated patients achieved sustained virologic response (SVR). Cirrhosis developed in 25.8 % of patients. Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma, compared to untreated patients, whereas SVR patients were only marginally protected from cirrhosis. Nearly 6 % developed hepatocellular carcinoma, and 27.1 % died during the follow-up period. Treated patients, regardless of response, had a significant survival benefit compared to untreated patients (HR 0.58, CI 0.46-0.72). Improved survival was also associated with college education, younger age, lower levels of alcohol consumption, and longer duration of medical service follow-up-factors typically associated with treatment eligibility.As more hepatitis C patients are now being assessed for all-oral combination therapy, these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported.

  View details for DOI 10.1007/s10620-016-4122-5

  View details for PubMedID 27059981

• Birth cohort-specific disparities in hepatocellular carcinoma stage at diagnosis, treatment, and long-term survival JOURNAL OF HEPATOLOGY Yan, M., Ha, J., Aguilar, M., Bhuket, T., Liu, B., Gish, R. G., Cheung, R., Wong, R. J. 2016; 64 (2): 326-332

  Abstract

  Individuals born between 1945 and 1965 account for nearly 75% of hepatitis C virus (HCV) infections in the United States. As this cohort ages, progressive HCV-related liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) will place a significant burden on the healthcare system. We aim to evaluate birth cohort-specific disparities in HCC stage at diagnosis, treatment rates, and overall survival with a focus on the 1945-1965 birth cohort.A population-based retrospective cohort study of adult patients with HCC identified in the Surveillance, Epidemiology, and End Results 2003-2011 registry evaluated birth cohort-specific disparities in the prevalence and outcomes of HCC, including multivariate logistic regression models to evaluate disparities in HCC stage at diagnosis and HCC treatment received. Birth cohort-specific survival was evaluated with Kaplan-Meier methods and multivariate Cox proportional hazard models.The proportion of HCC represented by the 1945-1965 cohort increased by 64% from 2003-2011, and accounted for 57.4% of all HCC in 2011. Compared to patients born after 1965, the 1945-1965 cohort were more likely to have HCC within Milan criteria (OR, 3.66; 95% CI, 3.13-4.28; p<0.001). However, among patients with HCC within Milan criteria, the 1945-1965 cohort had no difference in receipt of surgical treatment, but had higher overall long-term survival (HR, 0.82; 95% CI, 0.69-0.97; p<0.03).The 1945-1965 birth cohort accounts for the majority of HCC in the United States. Despite earlier HCC stage at diagnosis, no difference in receipt of surgical treatment was observed, but higher overall survival was achieved.

  View details for DOI 10.1016/j.jhep.2015.10.027

  View details for Web of Science ID 000368280200011

• Birth cohort-specific disparities in hepatocellular carcinoma stage at diagnosis, treatment, and long-term survival. Journal of hepatology Yan, M., Ha, J., Aguilar, M., Bhuket, T., Liu, B., Gish, R. G., Cheung, R., Wong, R. J. 2016; 64 (2): 326-332

  Abstract

  Individuals born between 1945 and 1965 account for nearly 75% of hepatitis C virus (HCV) infections in the United States. As this cohort ages, progressive HCV-related liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) will place a significant burden on the healthcare system. We aim to evaluate birth cohort-specific disparities in HCC stage at diagnosis, treatment rates, and overall survival with a focus on the 1945-1965 birth cohort.A population-based retrospective cohort study of adult patients with HCC identified in the Surveillance, Epidemiology, and End Results 2003-2011 registry evaluated birth cohort-specific disparities in the prevalence and outcomes of HCC, including multivariate logistic regression models to evaluate disparities in HCC stage at diagnosis and HCC treatment received. Birth cohort-specific survival was evaluated with Kaplan-Meier methods and multivariate Cox proportional hazard models.The proportion of HCC represented by the 1945-1965 cohort increased by 64% from 2003-2011, and accounted for 57.4% of all HCC in 2011. Compared to patients born after 1965, the 1945-1965 cohort were more likely to have HCC within Milan criteria (OR, 3.66; 95% CI, 3.13-4.28; p<0.001). However, among patients with HCC within Milan criteria, the 1945-1965 cohort had no difference in receipt of surgical treatment, but had higher overall long-term survival (HR, 0.82; 95% CI, 0.69-0.97; p<0.03).The 1945-1965 birth cohort accounts for the majority of HCC in the United States. Despite earlier HCC stage at diagnosis, no difference in receipt of surgical treatment was observed, but higher overall survival was achieved.

  View details for DOI 10.1016/j.jhep.2015.09.006

  View details for PubMedID 26386160

• Diabetes Mellitus Increases Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Virus Patients: A Systematic Review. Digestive diseases and sciences Dyal, H. K., Aguilar, M., Bartos, G., Holt, E. W., Bhuket, T., Liu, B., Cheung, R., Wong, R. J. 2016; 61 (2): 636-645

  Abstract

  Rising rates of obesity, diabetes mellitus (DM), and nonalcoholic fatty liver disease (NAFLD) among chronic hepatitis C (HCV) patients may contribute to higher hepatocellular carcinoma (HCC) risk.To perform a systematic review evaluating the impact of DM, body mass index (BMI), or steatosis on HCC risk among chronic HCV patients.A structured keyword search of PubMed from January 1, 2001, to July 1, 2014, was performed to identify original articles evaluating the association of DM, BMI, or steatosis with HCC among adults with chronic HCV. Studies involving HCV patients co-infected with human immunodeficiency virus, hepatitis B virus, or other chronic liver diseases with the exception of NAFLD were excluded. Quality assessment utilized the Newcastle-Ottawa scale.Nine studies (seven cohorts, two case-controls) met inclusion criteria for the final analysis. Five of seven studies analyzing DM demonstrated significantly increased HCC risk associated with concurrent DM with effect sizes ranging from HR 1.73 (95 % CI 1.30-2.30) to RR 3.52 (95 % CI 1.29-9.24). One of three studies analyzing BMI demonstrated a significant association with HCC risk (BMI ≥ 30.0 vs. BMI < 23: RR 4.13, 95 % CI 1.38-12.40). Two of the three studies analyzing steatosis demonstrated significantly higher risk of HCC associated with steatosis ranging from RR 2.81 (95 % CI 1.49-4.41) to OR 6.39 (95 % CI 1.04-39.35).Concurrent DM is associated with increased HCC risk among chronic HCV patients. BMI and steatosis may also increase HCC risk, but the limitations of the current studies do not allow us to draw strong conclusions.

  View details for DOI 10.1007/s10620-015-3983-3

  View details for PubMedID 26703125

• Integrated Care Increases Treatment and Improves Outcomes of Patients With Chronic Hepatitis C Virus Infection and Psychiatric Illness or Substance Abuse. Clinical gastroenterology and hepatology Ho, S. B., Bräu, N., Cheung, R., Liu, L., Sanchez, C., Sklar, M., Phelps, T. E., Marcus, S. G., Wasil, M. M., Tisi, A., Huynh, L., Robinson, S. K., Gifford, A. L., Asch, S. M., Groessl, E. J. 2015; 13 (11): 2005-2014 e3

  Abstract

  Patients with hepatitis C virus (HCV) infection with psychiatric disorders and/or substance abuse face significant barriers to antiviral treatment. New strategies are needed to improve treatment rates and outcomes. We investigated whether an integrated care (IC) protocol, which includes multidisciplinary care coordination and patient case management, could increase the proportion of patients with chronic HCV infection who receive antiviral treatment (a combination of interferon-based and direct-acting antiviral agents) and achieve a sustained virologic response (SVR).We performed a prospective randomized trial at 3 medical centers in the United States. Participants (n = 363 patients attending HCV clinics) had been screened and tested positive for depression, post-traumatic stress disorder, and/or substance use; they were assigned randomly to groups that received IC or usual care (controls) from March 2009 through February 2011. A midlevel mental health practitioner was placed at each HCV clinic to provide IC with brief mental health interventions and case management, according to formal protocol. The primary end point was SVR.Of the study participants, 63% were non-white, 51% were homeless in the past 5 years, 64% had psychiatric illness, 65% were substance abusers within 1 year before enrollment, 57% were at risk for post-traumatic stress disorder, 71% had active depression, 80% were infected with HCV genotype 1, and 23% had advanced fibrosis. Over a mean follow-up period of 28 months, a greater proportion of patients in the IC group began receiving antiviral therapy (31.9% vs 18.8% for controls; P = .005) and achieved a SVR (15.9% vs 7.7% of controls; odds ratio, 2.26; 95% confidence interval, 1.15-4.44; P = .018). There were no differences in serious adverse events between groups.Integrated care increases the proportion of patients with HCV infection and psychiatric illness and/or substance abuse who begin antiviral therapy and achieve SVRs, without serious adverse events. ClinicalTrials.gov # NCT00722423.

  View details for DOI 10.1016/j.cgh.2015.02.022

  View details for PubMedID 25724704

• Concurrent Obesity, Diabetes, and Steatosis Increase Risk of Advanced Fibrosis Among HCV Patients: A Systematic Review. Digestive diseases and sciences Dyal, H. K., Aguilar, M., Bhuket, T., Liu, B., Holt, E. W., Torres, S., Cheung, R., Wong, R. J. 2015; 60 (9): 2813-2824

  Abstract

  Rising rates of obesity, diabetes mellitus (DM), and nonalcoholic fatty liver disease among patients with chronic hepatitis C virus infection (HCV) may contribute to more rapid disease progression.To evaluate the impact of concurrent obesity, DM, and steatosis on disease progression among HCV patients.A systematic review using structured keyword search of MEDLINE and EMBASE from January 1, 2001, to July 1, 2014, was performed to identify original articles evaluating the association of obesity, DM, and steatosis with advanced fibrosis (AF) among adults with chronic HCV. Studies involving HCV patients coinfected with human immunodeficiency virus, hepatitis B virus, hepatocellular carcinoma, or other chronic liver diseases were excluded. Quality assessment utilized Newcastle-Ottawa Scale.Twenty cohort studies met inclusion criteria for analyses. Obesity was associated with increased risk of AF in seven studies with effect size ranging from OR 1.08 to 7.69. However, four studies did not demonstrate a significant association between obesity and AF. The presence of advanced steatosis among HCV patients was associated with increased risk of AF in 12 studies (OR 1.80-14.3). Concurrent DM was associated with increased risk of AF in six studies (OR 2.25-9.24). Thirteen studies were good quality, and seven studies were fair quality.Concurrent DM and steatosis are associated with increased risk of AF among chronic HCV patients. The majority of studies demonstrated significant associations of obesity with AF. Targeted interventions to optimize management of obesity-related diseases among HCV patients may help mitigate HCV disease progression.

  View details for DOI 10.1007/s10620-015-3760-3

  View details for PubMedID 26138651

• Concurrent Obesity, Diabetes, and Steatosis Increase Risk of Advanced Fibrosis Among HCV Patients: A Systematic Review DIGESTIVE DISEASES AND SCIENCES Dyal, H. K., Aguilar, M., Bhuket, T., Liu, B., Holt, E. W., Torres, S., Cheung, R., Wong, R. J. 2015; 60 (9): 2813-2824

  Abstract

  Rising rates of obesity, diabetes mellitus (DM), and nonalcoholic fatty liver disease among patients with chronic hepatitis C virus infection (HCV) may contribute to more rapid disease progression.To evaluate the impact of concurrent obesity, DM, and steatosis on disease progression among HCV patients.A systematic review using structured keyword search of MEDLINE and EMBASE from January 1, 2001, to July 1, 2014, was performed to identify original articles evaluating the association of obesity, DM, and steatosis with advanced fibrosis (AF) among adults with chronic HCV. Studies involving HCV patients coinfected with human immunodeficiency virus, hepatitis B virus, hepatocellular carcinoma, or other chronic liver diseases were excluded. Quality assessment utilized Newcastle-Ottawa Scale.Twenty cohort studies met inclusion criteria for analyses. Obesity was associated with increased risk of AF in seven studies with effect size ranging from OR 1.08 to 7.69. However, four studies did not demonstrate a significant association between obesity and AF. The presence of advanced steatosis among HCV patients was associated with increased risk of AF in 12 studies (OR 1.80-14.3). Concurrent DM was associated with increased risk of AF in six studies (OR 2.25-9.24). Thirteen studies were good quality, and seven studies were fair quality.Concurrent DM and steatosis are associated with increased risk of AF among chronic HCV patients. The majority of studies demonstrated significant associations of obesity with AF. Targeted interventions to optimize management of obesity-related diseases among HCV patients may help mitigate HCV disease progression.

  View details for DOI 10.1007/s10620-015-3760-3

  View details for Web of Science ID 000359997700092

• The impact of pretransplant hepatic encephalopathy on survival following liver transplantation LIVER TRANSPLANTATION Wong, R. J., Aguilar, M., Gish, R. G., Cheung, R., Ahmed, A. 2015; 21 (7): 873-880

  Abstract

  Hepatic encephalopathy (HE) is a surrogate marker of liver disease severity, and more severe HE is associated with higher mortality among patients with chronic liver disease. However, whether severity of HE at the time of liver transplantation (LT) directly impacts post-LT survival or whether this suspected mortality linkage is due to more severe liver disease and subsequently higher rates of post-LT infection is not well defined. Using population-based data from the 2003 to 2013 United Network for Organ Sharing registry, we evaluated the impact of HE at the time of LT on post-LT survival among adults in the United States. Survival was stratified by HE severity (none, grade 1-2, grade 3-4) and Model for End-Stage Liver Disease score and was evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards models. From 2003 to 2013, 59,937 patients underwent LT (36.1%, no HE; 53.8%, grade 1-2 HE; 10.2%, grade 3-4 HE). Compared to no HE, patients with grade 3-4 HE had significantly lower overall post-LT survival (1-year, 82.5% versus 90.3%; P < 0.001; 5-year, 69.1% versus 74.4%; P < 0.001). On multivariate regression, grade 3-4 HE was independently associated with lower overall post-LT survival (HR, 1.27; 95% CI, 1.17-1.39; P < 0.001). However, the increased mortality associated with HE is observed primarily within the first year following LT and was a reflection of higher rates of infection-related deaths among patients with more severe HE. In conclusion, grade 3-4 HE at the time of LT is associated with lower post-LT survival, with a proposed direct or indirect association of more severe HE before LT with increased rates of post-LT infections. Increased awareness and vigilance toward treating HE before LT and more aggressive monitoring and treatment for infections in the perioperative setting may improve LT outcomes. Liver Transpl 21:873-880, 2015. © 2015 AASLD.

  View details for DOI 10.1002/lt.24153

  View details for PubMedID 25902933

• Treating substance use disorders in patients with hepatitis C ADDICTION Cucciare, M. A., Cheung, R. C., Rongey, C. 2015; 110 (7): 1057–59

  View details for PubMedID 25816843

• Poor Sustained Virological Response in a Multicenter Real-Life Cohort of Chronic Hepatitis C Patients Treated with Pegylated Interferon and Ribavirin plus Telaprevir or Boceprevir DIGESTIVE DISEASES AND SCIENCES Vo, K. P., Vutien, P., Akiyama, M. J., Vu, V. D., Ha, N. B., Piotrowski, J. I., Wantuck, J., Roytman, M. M., Tsai, N., Cheung, R., Li, J., Nguyen, M. H. 2015; 60 (4): 1045-1051

  Abstract

  There are limited data analyzing the effectiveness of boceprevir (BOC) or telaprevir (TVR) in combination with pegylated interferon (PEG-IFN) plus ribavirin (RBV) in a real-life patient cohort.In clinical trials, patients with chronic hepatitis C (CHC) treated with BOC or TVR plus PEG-IFN and RBV achieved sustained virological response (SVR) rates of 70 %. However, it is not clear whether similar results can be realized in routine practice. Our goal is to examine SVR rates of these triple regimens for CHC in a multicenter real-life patient cohort.We retrospectively studied 200 consecutive CHC genotype 1 patients who were initiated on PEG-IFN, RBV, and either TVR (n = 113) or BOC (n = 87) from July 2011 to February 2014 at two US academic liver clinics, a Veterans Affairs liver clinic and a community gastroenterology clinic.Both BOC and TVR treatment groups were similar in regard to comorbidities, BMI, and HCV RNA levels. BOC patients were more likely to have cirrhosis than TVR patients (47 vs. 24 %, P = 0.001). SVR rates were low in both cohorts (40 % for BOC, 53 % for TVR, P = 0.05). On multivariate logistic regression, treatment adherence by the "80/80/80 rule," diagnosis of cirrhosis, and use of erythropoietin were statistically significant predictors for SVR. Of these, treatment adherence was the strongest predictor (OR 4.43, 95 % CI 2.8-6.06, P < 0.001).SVR was much lower in a real-life patient cohort than in clinical trials (53 % for TVR and 40 % for BOC, compared to 66-75 % in clinical trials).

  View details for DOI 10.1007/s10620-015-3621-0

  View details for Web of Science ID 000354464900038

  View details for PubMedID 25821099

• Diabetes Mellitus, and Not Obesity, Is Associated with Lower Survival Following Liver Transplantation DIGESTIVE DISEASES AND SCIENCES Wong, R. J., Cheung, R., Perumpail, R. B., Holt, E. W., Ahmed, A. 2015; 60 (4): 1036-1044

  Abstract

  The impact of obesity on survival following liver transplantation is unclear, and existing studies report conflicting results. Our current study aims to further delineate the impact of obesity using population-based registry data from the USA.All US adult liver transplant recipients from 2003 to 2012 were evaluated using the United Network for Organ Sharing registry. The impact of obesity on survival following liver transplantation was further stratified into class I obesity [body mass index (BMI) 30.0-34.9 kg/m(2)], class II obesity (BMI 35.0-39.9 kg/m(2)), and class III obesity (BMI ≥ 40 kg/m(2)) and evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards models.Overall, 57,255 patients with chronic liver disease underwent liver transplantation, among which 32.9 % had BMI ≥ 30 kg/m(2). While patients in all obesity classes had similar survival to patients with BMI 18.0-24.9 kg/m(2), the presence of concurrent diabetes mellitus resulted in significantly lower post-transplant survival. After multivariate regression, post-transplant survival in patients with class II obesity (HR 0.97; 95 % CI 0.89-1.05) or class III obesity (HR 0.99; 95 % CI 0.90-1.09) was not significantly lower than patients with BMI 18.0-24.9 kg/m(2), but diabetes mellitus was independently associated with lower post-transplant survival (HR 1.29; 95 % CI 1.21-1.36).In conclusion, obesity alone was not associated with lower post-transplant survival. However, DM, either alone or comorbid with obesity, is associated with significantly greater post-transplant mortality.

  View details for DOI 10.1007/s10620-014-3469-8

  View details for Web of Science ID 000354464900037

  View details for PubMedID 25596720

• Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology Wong, R. J., Aguilar, M., Cheung, R., Perumpail, R. B., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2015; 148 (3): 547-555

  Abstract

  Nonalcoholic steatohepatitis (NASH) has been predicted to become the leading indication for liver transplantation (LT) in the United States. However, few studies have evaluated changes in the etiology of liver diseases among patients awaiting LT, and none have focused on the effects of NASH on liver transplant waitlists in the United States.We collected data from the United Network for Organ Sharing and Organ Procurement and Transplantation Network registry from 2004 through 2013, on liver transplant waitlist registrants with hepatitis C virus (HCV) infection, NASH, alcoholic liver disease (ALD), or a combination of HCV infection and ALD. We compared differences in survival within 90 days of registration (90-day survival) and probability of LT among patients with different diseases using Kaplan-Meier and multivariate logistic regression models.Between 2004 and 2013, new waitlist registrants with NASH increased by 170% (from 804 to 2174), with ALD increased by 45% (from 1400 to 2024), and with HCV increased by 14% (from 2887 to 3291); registrants with HCV and ALD decreased by 9% (from 880 to 803). In 2013, NASH became the second-leading disease among liver transplant waitlist registrants, after HCV. Patients with ALD had a significantly higher mean Model for End-Stage Liver Disease score at time of waitlist registration than other registrants. However, after multivariate adjustment, patients with ALD were less likely to die within 90 days when compared with patients with NASH (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.67-0.89; P < .001); patients with HCV infection or HCV and ALD had similar odds for 90-day survival compared with NASH patients. Compared with patients with NASH, patients with HCV (OR = 1.45; 95% CI: 1.35-1.55; P < .001), ALD (OR = 1.15; 95% CI: 1.06-1.24; P < .001), or HCV and ALD (OR = 1.29; 95% CI: 1.18-1.42; P < .001) had higher odds for 90-day survival.Based on data from US adult LT databases, since 2004 the number of adults with NASH awaiting LTs has almost tripled. However, patients with NASH are less likely to undergo LT and less likely to survive for 90 days on the waitlist than patients with HCV, ALD, or HCV and ALD.

  View details for DOI 10.1053/j.gastro.2014.11.039

  View details for PubMedID 25461851

• Increased Long-term Survival Among Patients With Hepatocellular Carcinoma After Implementation of Model for End-stage Liver Disease Score CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Wong, R. J., Devaki, P., Long Nguyen, L., Cheung, R., Cho-Phan, C., Nguyen, M. H. 2014; 12 (9): 1534-U323

  Abstract

  Assignment of model for end-stage liver disease (MELD) exception points to patients with hepatocellular carcinoma (HCC) who fall within Milan criteria, which began in 2003, increases their priority on liver transplantation waitlists. However, little is known about how this change affected survival of all patients with HCC (transplant eligible and ineligible). We compared long-term survival of HCC patients before and after this change.We performed a large population-based cohort study using the Surveillance, Epidemiology, and End Results cancer registry to investigate survival times of patients with HCC before those who met the Milan criteria were given MELD exception points (1998-2003) and afterward (2004-2010), using Kaplan Meier methods. Multivariate Cox proportional hazards models evaluated independent predictors of survival.During 2004-2010, a significantly higher percentage of patients with HCC survived for 5 years compared to 1998-2003 (21.9% vs 13.0%, P<.001). This difference remained significant among all treatment groups (no therapy: 15.2% vs 10.2%, P<0.001; local tumor destruction: 37.6% vs 22.1%, P<0.001; resection: 55.5% vs 39.2%, P<0.001; transplantation: 77.2% vs 73.1%, P =0.12). Multivariate Cox proportional hazards models, inclusive of sex, age, ethnicity, Milan criteria, number and stage of tumor, and time period, showed increased survival of patients during 2004-2010 (hazard ratio [HR], 0.87; 95% confidence interval, 0.83-0.91; P<.001). Compared to non-Hispanic whites, Asians (HR, 0.81; 95% CI, 0.77-0.86; P<.001) and Hispanics (HR, 0.89, 95% CI, 0.84-0.95; P<.001) had longer survival times, whereas blacks had a trend toward shorter survival times (HR, 1.05; 95% CI 0.98-1.13; P=.16).Patients with HCC who met Milan criteria had significantly longer survival times after implementation of the MELD exception points, regardless of sex or ethnicity. Blacks continued to have the lowest rates of 5 year survival.

  View details for DOI 10.1016/j.cgh.2013.12.008

  View details for Web of Science ID 000341127900024

• Increased Long-term Survival Among Patients With Hepatocellular Carcinoma After Implementation of Model for End-stage Liver Disease Score. Clinical gastroenterology and hepatology Wong, R. J., Devaki, P., Nguyen, L., Cheung, R., Cho-Phan, C., Nguyen, M. H. 2014; 12 (9): 1534-1540 e1

  Abstract

  Assignment of model for end-stage liver disease (MELD) exception points to patients with hepatocellular carcinoma (HCC) who fall within Milan criteria, which began in 2003, increases their priority on liver transplantation waitlists. However, little is known about how this change affected survival of all patients with HCC (transplant eligible and ineligible). We compared long-term survival of HCC patients before and after this change.We performed a large population-based cohort study using the Surveillance, Epidemiology, and End Results cancer registry to investigate survival times of patients with HCC before those who met the Milan criteria were given MELD exception points (1998-2003) and afterward (2004-2010), using Kaplan Meier methods. Multivariate Cox proportional hazards models evaluated independent predictors of survival.During 2004-2010, a significantly higher percentage of patients with HCC survived for 5 years compared to 1998-2003 (21.9% vs 13.0%, P<.001). This difference remained significant among all treatment groups (no therapy: 15.2% vs 10.2%, P<0.001; local tumor destruction: 37.6% vs 22.1%, P<0.001; resection: 55.5% vs 39.2%, P<0.001; transplantation: 77.2% vs 73.1%, P =0.12). Multivariate Cox proportional hazards models, inclusive of sex, age, ethnicity, Milan criteria, number and stage of tumor, and time period, showed increased survival of patients during 2004-2010 (hazard ratio [HR], 0.87; 95% confidence interval, 0.83-0.91; P<.001). Compared to non-Hispanic whites, Asians (HR, 0.81; 95% CI, 0.77-0.86; P<.001) and Hispanics (HR, 0.89, 95% CI, 0.84-0.95; P<.001) had longer survival times, whereas blacks had a trend toward shorter survival times (HR, 1.05; 95% CI 0.98-1.13; P=.16).Patients with HCC who met Milan criteria had significantly longer survival times after implementation of the MELD exception points, regardless of sex or ethnicity. Blacks continued to have the lowest rates of 5 year survival.

  View details for DOI 10.1016/j.cgh.2013.12.008

  View details for PubMedID 24361414

• Nonalcoholic Steatohepatitis Is the Most Rapidly Growing Indication for Liver Transplantation in Patients With Hepatocellular Carcinoma in the U. S. HEPATOLOGY Wong, R. J., Cheung, R., Ahmed, A. 2014; 59 (6): 2188-2195

  Abstract

  Nonalcoholic steatohepatitis (NASH) is currently the third leading indication for liver transplantation (LT) in the U.S. and is predicted to become the leading indication for LT in the near future. The trends in NASH-related hepatocellular carcinoma (HCC) among LT recipients in the U.S. remain undefined. We performed a retrospective cohort study to evaluate trends in the etiology of HCC among adult LT recipients in the U.S. from 2002 to 2012, utilizing national data from the United Network for Organ Sharing registry. From 2002-2012, there were 61,868 adults who underwent LT in the U.S., including 10,061 patients HCC. The total number and proportion of HCC LT recipients demonstrated a significant increase following the implementation of the model for end stage liver disease (MELD) scoring system in 2002 (3.3%, n=143 in 2000 vs. 12.2%, n=714 in 2005 vs. 23.3%, n=1336 in 2012). The proportion of HCV-related HCC increased steadily from 2002 to 2012, and HCV remained the leading etiology of HCC throughout the MELD era (43.4% in 2002 vs. 46.3% in 2007 vs. 49.9% in 2012). NASH-related HCC also increased significantly, and NASH is the second leading etiology of HCC-related LT (8.3% in 2002 vs. 10.3% in 2007 vs. 13.5% in 2012). From 2002 to 2012, the number of patients undergoing LT for HCC secondary to NASH increased by nearly 4-fold, and the number of LT patients with HCC secondary to HCV increased by 2-fold. Conclusion: NASH is the second leading etiology of HCC leading to LT in the U.S. More importantly, NASH is currently the most rapidly growing indication for LT in patients with HCC in the U.S. (Hepatology 2013;).

  View details for DOI 10.1002/hep.26986

  View details for Web of Science ID 000337567100020

  View details for PubMedID 24375711

• Ethnic disparities and liver transplantation rates in hepatocellular carcinoma patients in the recent era: Results from the surveillance, epidemiology, and end results registry LIVER TRANSPLANTATION Wong, R. J., Devaki, P., Long Nguyen, L., Cheung, R., Nguyen, M. H. 2014; 20 (5): 528-535

  Abstract

  Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality. Following implementation of the model for end stage liver disease (MELD) system, rates of liver transplantation (LT) for HCC patients increased. However, it is not clear if this trend continued into the recent time period. Utilizing the Surveillance, Epidemiology, and End Results 1998-2010 registry, we retrospectively analyzed trends in LT among HCC patients using three time periods: 1998-2003, 2004-2008, and 2009-2010). A total of 60,772 HCC patients were identified. With more recent time periods, the proportion of localized stage HCC increased (45.0% in 1998-2003 vs. 50.4% in 2004-2008 vs. 51.7% in 2009-2010, p<0.001). While the proportion of HCC patients within Milan criteria also increased with time (22.8% vs. 31.8% vs. 37.1%, p<0.001), the proportion of these patients receiving LT increased from 1998-2003 to 2004-2008, but decreased in 2009-2010. However, the actual frequency of LT was similar in 2004-2008 (208.2/year) and 2009-2010 (201.5/year). Multivariate logistic regression, inclusive of sex, age, ethnicity, Milan criteria, tumor stage, tumor size and number, and time periods, demonstrated a lower likelihood of LT in 2009-2010 compared to 1998-2003 (OR 0.63, 95% CI 0.57-0.71). Blacks (OR 0.48, 95% CI 0.41-0.56), Asians (OR 0.65, 95% CI 0.57-0.73), and Hispanics (OR 0.76, 95% CI 0.68-0.85) were all less likely to receive LT compared to non-Hispanic whites. Despite increasing proportion of earlier staged HCC diagnosed, LT rates are declining in the recent era. In addition, ethnic minorities were significantly less likely to receive LT. The growing imbalance between the number of transplant-eligible HCC patients and the shortage of donor livers emphasizes the need to improve donor availability and curative alternatives to LT. Liver Transpl , 2014. © 2014 AASLD.

  View details for DOI 10.1002/lt.23820

  View details for Web of Science ID 000334953000004

  View details for PubMedID 24415542

• Comparative effectiveness of the hepatitis C virus protease inhibitors boceprevir and telaprevir in a large US cohort ALIMENTARY PHARMACOLOGY & THERAPEUTICS Backus, L. I., Belperio, P. S., Shahoumian, T. A., Cheung, R., Mole, L. A. 2014; 39 (1): 93-103

  Abstract

  Limited data exist on the effectiveness of boceprevir and telaprevir in routine practice.To assess the comparative effectiveness of boceprevir and telaprevir regimens.In this observational, intent-to-treat cohort analysis of hepatitis C genotype 1-infected veterans initiated on peginterferon/ribavirin and boceprevir (n = 661) or telaprevir (n = 198), we determined sustained virological response (SVR), treatment discontinuation rates and adverse haematological events. Inverse probability-of-treatment weighting (IPTW) was used to estimate the effect of one drug over the other, with matched pairs and unweighted logistic regression on the entire cohort for comparison.Of 835 veterans, SVR occurred in 50% and 52% receiving boceprevir- and telaprevir-based treatment, respectively (P = 0.72). No significant differences occurred among subgroups: cirrhotics (37% vs. 39%, P = 0.94), null responders (23% vs. 18%, P = 0.81), partial responders (39% vs. 58%, P = 0.15) and relapsers (60% vs. 77%, P = 0.11). Early discontinuation rates for boceprevir and telaprevir, respectively, were 31% and 28% by week 24 (P = 0.46) and 54% and 45% by 48 weeks (in those completing at least 28 weeks) (P = 0.14). Choice of telaprevir over boceprevir was significantly associated with SVR in multivariate models (IPTW OR: 1.57, 95% CI: 1.10-2.25, P = 0.01; matched-pairs OR: 1.91, 95% CI: 1.23-3.00, P = 0.004; unweighted OR: 1.50 95% CI: 1.05-2.14, P = 0.02). Rates of haematological adverse events in boceprevir- and telaprevir-treated patients were as follows: anaemia 59% vs. 51%, P = 0.30, thrombocytopenia 41% vs. 48%, P = 0.26, neutropenia 41% vs. 27%, P = 0.04.Sustained virological response was more likely with telaprevir-based regimens compared with boceprevir-based regimens in routine medical practice, after accounting for patient differences. Early discontinuation and haematological events, however, were similar.

  View details for DOI 10.1111/apt.12546

  View details for Web of Science ID 000327659000009

  View details for PubMedID 24206566

• The Impact of Pre-Transplant Obesity and Diabetes on Survival Following Liver Transplantation among Hepatitis C Virus Patients With and Without Hepatocellular Carcinoma Wong, R. J., Cheung, R., Holt, E. W., Ahmed, A. WILEY-BLACKWELL. 2014: 537A–538A

  View details for Web of Science ID 000344483802191

• Pre-Transplant Hepatic Encephalopathy is Associated with Significantly Lower Survival Following Liver Transplantation Wong, R. J., Gish, R. G., Cheung, R., Ahmed, A. WILEY-BLACKWELL. 2014: 392A

  View details for Web of Science ID 000344483801319

• Poor Sustained Virologic Response (SVR) in a Multicenter Real-Life Cohort of Chronic Hepatitis C (CHC) Patients Treated with Pegylated Interferon (PEG IFN) and Ribavirin (RBV) plus Telaprevir (TVR) or Boceprevir (BOC) Vo, K. P., Vutien, P., Akiyama, M. J., Vu, V. D., Piotrowski, J. I., Ha, N. B., Wantuck, J. M., Roytman, M., Cheung, R., Li, J., Tsai, N., Nguyen, M. H. WILEY-BLACKWELL. 2014: 673A–674A

  View details for Web of Science ID 000344483803026

• Treatment Tolerability and Persistency Rate in Chronic Hepatitis C (CHC) Patients Treated with Pegylated Interferon (PEG IFN) and Ribavirin (RBV) plus Telaprevir (TVR) versus Boceprevir (BOC) Vo, K., Akiyama, M., Ha, N., Vutien, P., Piotrowski, J., Wantuck, J., Roytman, M., Tsai, N., Cheung, R., Li, J., Nguyen, M. NATURE PUBLISHING GROUP. 2013: S155–S156

  View details for Web of Science ID 000330178100528

• Comparative Effectiveness of Boceprevir- and Telaprevir-Based Therapy in US Veterans Backus, L. I., Belperio, P. S., Shahoumian, T. A., Cheung, R., Mole, L. A. WILEY-BLACKWELL. 2013: 1094A–1095A

  View details for Web of Science ID 000330252205198

• Early Virologic Responses and Hematologic Safety of Direct-Acting Antiviral Therapies in Veterans With Chronic Hepatitis C CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Belperio, P. S., Hwang, E. W., Thomas, I. C., Mole, L. A., Cheung, R. C., Backus, L. I. 2013; 11 (8): 1021-1027

  Abstract

  There are limited data on the early effectiveness of direct-acting antiviral (DAA) therapies for patients with hepatitis C virus (HCV) infection in routine medical practice. We aimed to evaluate real-world experience with DAA-based regimens.By using the Veterans Affairs' Clinical Case Registry, we conducted a prospective observational intent-to-treat analysis of veterans infected with HCV genotype 1 who began treatment with pegylated interferon, ribavirin, and boceprevir (BOC, n = 661) or telaprevir (TVR, n = 198) before January 2012. We determined rates of virologic response at treatment weeks 4, 8, 12, and 24; futility; early discontinuation; and adverse hematologic events.About one third of patients discontinued treatment by week 24 (30% BOC, 34% TVR). A higher percentage of treatment-naive, noncirrhotic patients receiving BOC had undetectable levels of virus at week 24 than patients receiving TVR (74% vs 60%; P = .03). There were no significant differences in rates of early response within subgroups of cirrhotic patients, prior relapsers, prior partial responders, or prior null responders. By week 24, treatment was determined to be futile for 14% of patients receiving BOC and 17% of those receiving TVR. No differences were observed in overall rates of anemia (50% BOC, 49% TVR) or thrombocytopenia (16% BOC, 18% TVR); higher rates of neutropenia were observed in BOC-treated patients (34% BOC, 21% TVR; P = .008).HCV-infected veterans treated in routine medical practice with DAA-based regimens (BOC or TVR) had rates of early response comparable with those reported in clinical trials. However, they had higher rates of futility and early discontinuation than clinical trial participants. Further studies are needed to determine rates of sustained viral response.

  View details for DOI 10.1016/j.cgh.2013.03.006

  View details for Web of Science ID 000322707100027

  View details for PubMedID 23524130

• Increasing antiviral treatment through integrated hepatitis C care: a randomized multicenter trial. Contemporary clinical trials Groessl, E. J., Sklar, M., Cheung, R. C., Bräu, N., Ho, S. B. 2013; 35 (2): 97-107

  Abstract

  Most individuals infected with the hepatitis C have not received antiviral treatment, with mental health and substance abuse problems being the primary barrier. Interventions have been developed to address these barriers among HCV patients considered "high-risk" for antiviral treatment. We present the design and methods of a prospective, randomized controlled multisite trial being conducted in the Veterans Affairs Healthcare System. The study employed a parallel design and the three study sites randomized a total of 364 VA patients with HCV to either Integrated Care (IC) or Usual Care (UC). The IC intervention consisted of a mental health provider (MHP) performing a) brief interventions to address risk factors; b) collaborative consultation with the HCV treatment clinicians; and c) case management prior to and during antiviral treatment. Clinical outcomes were abstracted from patient medical records and self-report questionnaires were completed at baseline, 4-months, 16-months, and 22-months after enrollment. The primary outcome of the study was sustained viral response (SVR). Secondary clinical outcomes were HCV treatment initiation and completion rates. Other secondary outcomes included substance use, depression, PTSD symptoms, quality of life, healthcare satisfaction, and healthcare utilization. The Integrated Care intervention has the potential to transform HCV antiviral treatment by increasing the number of HCV-infected individuals that can be successfully treated.

  View details for DOI 10.1016/j.cct.2013.05.002

  View details for PubMedID 23669414

• Increasing antiviral treatment through integrated hepatitis C care: A randomized multicenter trial CONTEMPORARY CLINICAL TRIALS Groessl, E. J., Sklar, M., Cheung, R. C., Braeu, N., Ho, S. B. 2013; 35 (2): 97-107

  Abstract

  Most individuals infected with the hepatitis C have not received antiviral treatment, with mental health and substance abuse problems being the primary barrier. Interventions have been developed to address these barriers among HCV patients considered "high-risk" for antiviral treatment. We present the design and methods of a prospective, randomized controlled multisite trial being conducted in the Veterans Affairs Healthcare System. The study employed a parallel design and the three study sites randomized a total of 364 VA patients with HCV to either Integrated Care (IC) or Usual Care (UC). The IC intervention consisted of a mental health provider (MHP) performing a) brief interventions to address risk factors; b) collaborative consultation with the HCV treatment clinicians; and c) case management prior to and during antiviral treatment. Clinical outcomes were abstracted from patient medical records and self-report questionnaires were completed at baseline, 4-months, 16-months, and 22-months after enrollment. The primary outcome of the study was sustained viral response (SVR). Secondary clinical outcomes were HCV treatment initiation and completion rates. Other secondary outcomes included substance use, depression, PTSD symptoms, quality of life, healthcare satisfaction, and healthcare utilization. The Integrated Care intervention has the potential to transform HCV antiviral treatment by increasing the number of HCV-infected individuals that can be successfully treated.

  View details for DOI 10.1016/j.cct.2013.05.002

  View details for Web of Science ID 000322560900011

• Assessment and Utilization of Rapid Virologic Response in US Veterans With Chronic Hepatitis C Evaluating Provider Adherence to Practice Guidelines JOURNAL OF CLINICAL GASTROENTEROLOGY Hwang, E. W., Thomas, I., Cheung, R., Backus, L. I. 2013; 47 (3): 264-270

  Abstract

  There are limited data on the extent to which medical providers adhere to practice guidelines for the antiviral treatment of patients with chronic hepatitis C virus (HCV) infection. As representative of overall provider adherence to practice guidelines, provider adherence to specific recommendations regarding rapid virologic response (RVR) was assessed.From the Department of Veterans Affairs' Clinical Case Registry, all patients with HCV genotype 1 who initiated peginterferon and ribavirin between January 1, 2007 and December 31, 2008 were identified. The rate of testing for RVR was determined. Patient, provider, and facility characteristics were assessed to determine the factors that predicted improved provider adherence. For patients who achieved RVR, the overall treatment duration was calculated as a secondary measure of provider adherence.About one half of the cohort (54%) had HCV RNA testing for RVR. Among several significant predictors, testing for RVR was more likely in gastroenterology/hepatology specialty clinics, by midlevel providers such as nurse practitioners and physician assistants, and in facilities with a higher volume of HCV patients. Most patients who achieved RVR completed a treatment course within the recommended range. However, 27% of the cohort received more or less than the recommended duration of treatment, thereby unnecessarily increasing their risk for adverse events or decreasing their potential for cure.More aggressive education is needed to improve provider adherence to HCV antiviral treatment guidelines and optimize the outcomes of HCV patients, especially with the recent approval of complicated direct-acting antiviral regimens.

  View details for DOI 10.1097/MCG.0b013e31827035cf

  View details for Web of Science ID 000314863800016

  View details for PubMedID 23269309

• Acute exacerbation among chronic hepatitis C patients: Tip of the iceberg that deserves more attention. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Wong, R. J., Cheung, R. C. 2013

  View details for DOI 10.1016/j.cgh.2013.05.023

  View details for PubMedID 23735449

• Prevalence of Hepatitis C Virus Infection in the Veteran Population Undergoing Total Joint Arthroplasty JOURNAL OF ARTHROPLASTY Calore, B. L., Cheung, R. C., Giori, N. J. 2012; 27 (10): 1772-1776

  Abstract

  Many orthopedic surgeons train or are employed at the Department of Veterans Affairs (VA) hospitals. We sought to determine the prevalence of hepatitis C antibody-positive and hepatitis C-viremic patients in the VA population undergoing total joint arthroplasty. In this prospective cohort study, 381 of 408 patients undergoing primary total joint arthroplasty for 22 consecutive months were tested for hepatitis C virus (HCV) infection preoperatively. Thirty-two (8.4%) of 381 patients were positive for hepatitis C virus antibody. Seventeen were actually viremic at the time of total joint arthroplasty (4.5%). The prevalence of detectable hepatitis C antibody in VA patients undergoing total joint arthroplasty is about 6 times the general population (1.3%). Surgeons practicing on populations with a high prevalence of hepatitis C such as this should do all they can to minimize the risk of sharps injury.

  View details for DOI 10.1016/j.arth.2012.05.016

  View details for Web of Science ID 000311583500006

  View details for PubMedID 22770853

• Week 24 and End of Treatment Response for Direct Acting Antiviral (DAA)-Based Therapy in Veterans with Chronic Hepatitis C Backus, L. I., Belperio, P. S., Thomas, I., Cheung, R., Mole, L. A. WILEY-BLACKWELL. 2012: 1534–35

  View details for Web of Science ID 000314288900031

• Tenofovir Monotherapy and Tenofovir Plus Entecavir Combination as Rescue Therapy for Entecavir Partial Responders DIGESTIVE DISEASES AND SCIENCES Yip, B., Chaung, K., Wong, C. R., Trinh, H. N., Nguyen, H. A., Ahmed, A., Cheung, R., Nguyen, M. H. 2012; 57 (11): 3011-3016

  Abstract

  Despite high potency, a significant proportion of patients treated with entecavir achieve only partial viral suppression. Our goal was to examine the complete viral suppression rate (undetectable HBV DNA PCR levels) with alternative therapies in such patients.We retrospectively studied 42 consecutive patients with partial response to entecavir (detectable HBV DNA at ≥12 months of therapy) who were treated at three clinics with rescue therapies: entecavir + adefovir (n = 5), tenofovir (n = 6), and entecavir + tenofovir (n = 31). Antiviral resistance was excluded by negative mutation analysis and/or absence of virologic breakthrough (increase >1 log(10)IU/mL from nadir).All patients were Asian and 57 % were male with a median age of 36 (22-64) years. Only a few patients had prior exposure to lamivudine (7 %) or adefovir (7 %). Almost all patients (95 %) had positive HBeAg. Overall, the complete viral suppression rate was 79 %, and the alanine aminotransferase normalization rate was 83 % in entecavir partial responders after 6 months on rescue therapies. Cumulative complete viral suppression rates were significantly different (P = 0.0164) among the entecavir + adefovir, tenofovir, and entecavir + tenofovir treatment groups at 6 months (20 vs. 83 vs. 83 %, respectively) and 12 months (20 vs. 100 vs. 97 %). All three patients without complete viral suppression on entecavir + adefovir became aviremic 6 months after switching to entecavir + tenofovir.Virologic response to entecavir + tenofovir combination therapy and tenofovir monotherapy appeared to be similar in most patients, but not with the entecavir + adefovir combination.

  View details for DOI 10.1007/s10620-012-2402-2

  View details for PubMedID 23010744

• Early Virologic Response and Futility of Direct Acting Antiviral (DAA)-Based Therapy in Veterans with Chronic Hepatitis C 63rd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Backus, L. I., Belperio, P. S., Thomas, I., Hwang, E. W., Cheung, R., Mole, L. A. WILEY-BLACKWELL. 2012: 1036A–1037A

  View details for Web of Science ID 000310955603405

• Multisite randomized trial of an Integrated Care (IC) model for HCV patients with psychiatric and substance use co-morbidities: final results of impact on treatment initiation Ho, S. B., Groessl, E. J., Brau, N., Cheung, R., Weingart, K. R., Ward, M., Sklar, M., Phelps, T. E., Marcus, S., Wasil, M. M., Tisi, A. S., Huynh, L. K., Robinson, S. WILEY-BLACKWELL. 2012: 1000A–1001A

  View details for Web of Science ID 000310955603332

• Early virologic outcomes and hematologic safety of direct-acting antiviral (DAA)-based therapy in US veterans with cirrhosis from hepatitis C virus (HCV) genotype 1 63rd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Hwang, E. W., Thomas, I., Belperio, P. S., Cheung, R., Mole, L. A., Backus, L. I. WILEY-BLACKWELL. 2012: 1001A–1002A

  View details for Web of Science ID 000310955603334

• The water exchange method for colonoscopy-effect of coaching. Journal of interventional gastroenterology Leung, F., Cheung, R., Fan, R., Fischer, L., Friedland, S., Ho, S., Hsieh, Y., Hung, I., Li, M., Matsui, S., McQuaid, K., Ohning, G., OJURI, A., Sato, T., Shergill, A., Shoham, M., Simons, T., Walter, M., Yen, A. 2012; 2 (3): 122-125

  Abstract

  The growing popularity of water immersion is supported by its long history as an adjunct to air insufflation; after facilitating colonoscope passage, the infused water is conveniently removed during withdrawal. Water exchange, a modification of water immersion to minimize discomfort in scheduled unsedated patients in the U.S. is new. Even though it may be superior in reducing pain and increasing adenoma detection, the paradigm shift to complete exclusion of air during insertion necessitates removal of infused water containing residual feces, a step often perceived as laborious and time-consuming. The nuances are the efficient steps to remove infused water predominantly during insertion to maintain minimal distension and deliver salvage cleansing. Mastery of the novel maneuvers with practice returns insertion time towards baseline. In this observational study the impact of direct verbal coaching on the primary outcome of intention-to-treat cecal intubation was assessed. The results showed that 14 of 19 (74%) experienced colonoscopists achieved 100% intention-to-treat cecal intubation. Initiation of the examination with water exchange did not preclude completion when conversion to the more familiar air insufflation method was deemed necessary to achieve cecal intubation (total 98%). The overall intention-to-treat cecal intubation rate was 88%, 90% in male and 87% in female. Only 2.7% of bowel preparation was rated as poor during withdrawal. The mean volume of water infused and cecal intubation time was 1558 ml and 18 min, respectively. Direct coaching appears to facilitate understanding of the nuances of the water exchange method. Studies of individual learning curves are necessary.

  View details for PubMedID 23805391

  View details for PubMedCentralID PMC3655365

• Implications of rapid virological response in hepatitis C therapy in the US veteran population ALIMENTARY PHARMACOLOGY & THERAPEUTICS Hwang, E. W., Thomas, I., Cheung, R., Backus, L. I. 2012; 35 (1): 105-115

  Abstract

  Early predictors of response to hepatitis C virus (HCV) therapy, such as rapid virological response, are valuable for the identification of patients with a higher likelihood of treatment success.To identify predictors of rapid virological response in a real world setting.Using the VA Clinical Case Registry, we identified patients with HCV mono-infection, without liver transplantation, who initiated peginterferon (PEG-IFN) and ribavirin (RBV) in 2007 or 2008 and had HCV RNA testing for RVR. Significant baseline characteristics from genotype specific univariate analyses were used in backwards stepwise models to identify significant independent predictors of RVR.The final cohort consisted of 2424 patients with genotype 1 (G1), 666 patients with genotype 2 (G2), and 419 patients with genotype 3 (G3). Rapid virological response rates were 15% for G1, 71% for G2 and 57% for G3. Sustained virological response rates were significantly higher in patients with rapid virological response than without, increasing from 18% to 52% in G1, 39% to 71% in G2, and 40% to 60% in G3 (P < 0.0001). A baseline HCV RNA < 500,000 IU/mL positively predicted RVR across all genotypes studied. In addition, for G1, Black race, Hispanic ethnicity, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≥ 0.6, ferritin ≥ 350 ng/mL, LDL< 100 mg/dL and diabetes; for G2, BMI ≥ 30 kg/m(2), platelets < 150 K/μL, LDL< 100 mg/dL and the use of PEG-IFN alfa-2b; and for G3, AST/ALT ≥ 1.0, all negatively predicted rapid virological response.We found several novel independent predictors of rapid virological response, including BMI, AST/ALT ratio, ferritin, platelets, LDL, diabetes and type of PEG-IFN prescribed, which may be useful in guiding treatment decisions in routine medical practice.

  View details for DOI 10.1111/j.1365-2036.2011.04903.x

  View details for Web of Science ID 000297922600011

  View details for PubMedID 22060887

• Changes in Depressive Symptoms and Impact on Treatment Course Among Hepatitis C Patients Undergoing Interferon-alpha and Ribavirin Therapy: A Prospective Evaluation AMERICAN JOURNAL OF GASTROENTEROLOGY Chapman, J., Oser, M., Hockemeyer, J., Weitlauf, J., Jones, S., Cheung, R. 2011; 106 (12): 2123–32

  Abstract

  Accounting for severity of depressive symptoms at baseline (pretreatment), this study describes (i) depressive symptom change over the course of antiviral treatment among patients with hepatitis C virus (HCV), and (ii) the relationship of such symptom change to treatment duration and response.Depressive symptoms, measured with the Beck Depression Inventory (BDI), were examined prospectively among 129 HCV patients (95% male) who endorsed minimal (n=91), mild (n=28), or moderate depressive symptoms (n=10) prior to commencement of antiviral therapy. Assessments were obtained at baseline, 2 weeks, 4 weeks, and thereafter at 4-week intervals until treatment was discontinued or completed.The average depression score of the participants prior to commencing treatment was 7.4 (minimal depression). Depressive symptoms increased over the course of treatment, with average scores of 12.6 (mild depression) at the final assessment at the end of treatment. Patients with mild depressive symptoms at baseline demonstrated the greatest increase (M(increase)=12.7) and the greatest change (M(Δ)=5.8) in depressive symptoms from baseline to treatment completion. Patients who were minimally depressed at baseline completed the least amount of treatment (74%). Likewise, minimally depressed patients were less likely than mildly and moderately depressed patients to attain an antiviral treatment response.Depressive symptoms may worsen during antiviral therapy among patients with HCV. Notable changes in patients with subclinical depressive symptoms at baseline may be of significant concern, as the present work suggests that their depressive symptom changes are the most unstable. Thus, findings suggest that the degree of within treatment symptom change may be a more useful predictor (compared with baseline depression status) of ability to tolerate treatment. As the findings of the present study are preliminary, we urge further research and replication before drawing firm conclusions.

  View details for DOI 10.1038/ajg.2011.252

  View details for Web of Science ID 000298251400008

  View details for PubMedID 21826113

• CLASSIFICATION OF VIROLOGIC RESPONSE IN US VETERANS WITH CHRONIC HEPATITIS C VIRUS WHO FAILED PEGINTERFERON/RIBAVIRIN TREATMENT: ASSESSING THE POTENTIAL SUCCESS OF RETREATMENT WITH PROTEASE INHIBITOR-BASED REGIMENS IN ROUTINE MEDICAL PRACTICE 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Hwang, E. W., Thomas, I., Cheung, R., Backus, L. WILEY-BLACKWELL. 2011: 438A–439A

  View details for Web of Science ID 000295578002160

• Utilization and Antiviral Therapy in Patients with Chronic Hepatitis C: Analysis of Ambulatory Care Visits in the US DIGESTIVE DISEASES AND SCIENCES Cheung, R., Mannalithara, A., Singh, G. 2010; 55 (6): 1744-1751

  Abstract

  Studies on mostly veterans found the majority of chronic hepatitis C (CHC) patients were not treated. Little information exists on a broad-based population.To determine the national trend of ambulatory visits with a diagnosis of hepatitis C and the prescription of antiviral therapy associated with such visits.Retrospective analysis of national cross-sectional databases, the National Ambulatory Medical Care Survey (NAMCS), and the National Hospital Ambulatory Medical Care Survey (NHAMCS) encompassing all ambulatory visits from 2000 to 2006.During the study period, 16.5 million visits (0.21% of all visits) carried a diagnosis of hepatitis C and the number initially increased. Characteristics of the hepatitis C patients were: 65% male; 71% white, 22% black; 69% >or=45 years old. Overall, 47% had private insurance, 24% had Medicaid, and 12% had Medicare. Only 9.1% of these patients were prescribed antiviral treatment for CHC. There was no significant difference between those who received treatment and those who did not in terms of age, gender, race, and insurance status. HIV infection, mood, substance-use disorders, and anemia were more common in the CHC group.Less than 10% of the ambulatory visits for hepatitis C were associated with a prescription for antiviral therapy, independent of demographic and insurance status. Purposes of the clinic visits were different in the CHC group compared to the general population. The reason for the low treatment rate is not clear but deserves further investigation.

  View details for DOI 10.1007/s10620-010-1147-z

  View details for Web of Science ID 000278578800036

  View details for PubMedID 20186486

• Multiple variants in toll-like receptor 4 gene modulate risk of liver fibrosis in Caucasians with chronic hepatitis C infection JOURNAL OF HEPATOLOGY Li, Y., Chang, M., Abar, O., Garcia, V., Rowland, C., Catanese, J., Ross, D., Broder, S., Shiffman, M., Cheung, R., Wright, T., Friedman, S. L., Sninsky, J. 2009; 51 (4): 750-757

  Abstract

  Seven genomic loci, implicated by single nucleotide polymorphisms (SNPs), have recently been associated with progression to advanced fibrosis (fibrosis risk) in patients with chronic hepatitis C virus. Other variants in these loci have not been examined but may be associated with fibrosis risk independently of or due to linkage disequilibrium with the original polymorphisms.We carried out dense genotyping and association testing of additional SNPs in each of the 7 regions in Caucasian case control samples.We identified several SNPs in the toll-like receptor 4 (TLR4) and syntaxin binding protein 5-like (STXBP5L) loci that were associated with fibrosis risk independently of the original significant SNPs. Haplotypes consisting of these SNPs in TLR4 and STXBP5L were strongly associated with fibrosis risk (global P=3.04 x 10(-5) and 4.49 x 10(-6), respectively).Multiple variants in TLR4 and STXBP5L genes modulate risk of liver fibrosis. These findings are of relevance for understanding the pathogenesis of HCV-induced liver disease in Caucasians and may be extended to other ethnicities as well.

  View details for DOI 10.1016/j.jhep.2009.04.027

  View details for Web of Science ID 000270749000022

  View details for PubMedID 19586676

  View details for PubMedCentralID PMC2883297

• A COMMON, FUNCTIONAL POLYMORPHISM IN DDX5 IS ASSOCIATED WITH CIRRHOSIS IN CHRONIC HEPATITIS C AND NAFLD PATIENTS Li, Y., Bambha, K., Christopherson, C. D., Kwok, S. Y., Chang, M., Catanese, J., Schrodi, S. J., Ross, D. A., Campos, G. M., Monto, A., Wright, T. L., Layden, T. J., Cooper, C., Shiffman, M. L., Cheung, R., Friedman, S. L., Sninsky, J., Still, C. D., Bass, N. M., Gerhard, G. S. JOHN WILEY & SONS INC. 2009: 389A

  View details for Web of Science ID 000270456000183

• Adenovirus-Induced Acute Liver Failure DIGESTIVE DISEASES AND SCIENCES Rothenberg, M., Cheung, R., Ahmed, A. 2009; 54 (2): 218-221

  View details for DOI 10.1007/s10620-008-0628-9

  View details for Web of Science ID 000262968200006

  View details for PubMedID 19034647

• Can we predict the degree of fibrosis in chronic hepatitis C patients using routine blood tests in our daily practice? JOURNAL OF CLINICAL GASTROENTEROLOGY Cheung, R. C., Currie, S., Shen, H., Bini, E. J., Ho, S. B., Anand, B. S., Hu, K., Wright, T. L., Morgan, T. R. 2008; 42 (7): 827-834

  Abstract

  To determine the validity of fibrosis indexes based on simple laboratory tests in daily practice.Fibrosis indexes were developed in referral centers using high-quality data.We compared the performance characteristics of several such indexes with liver biopsies in a cohort of 490 diverse veterans with chronic hepatitis C from 24 centers. All laboratory tests including interpretation of the liver biopsy were done locally. The following indexes were calculated and correlated with a 5-point fibrosis stage (F0-F4) on liver biopsies: platelet counts (<100 or <150x10(9)/L), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), Pohl score, AST-to-platelet ratio index (APRI) and "Lok's model."Our cohort was predominantly male with 24% blacks, and fibrosis stages of 0, 1, 2, 3, and 4 in 11%, 24%, 28%, 24%, and 13%, respectively. All indexes performed better in predicting advanced (F3-4) than significant (F2-4) fibrosis. When patients with F3-4 were compared to those with F0-2, the area under the receiver operating characteristics curve were 0.534 and 0.641 for platelet count <100 and <150x10(9)/L, respectively, 0.524 for AAR, 0.534 for Pohl score, 0.693 for Lok's model, and 0.765 for APRI. The sensitivity, specificity, and predictive values of APRI and Lok's model were only slightly lower than those reported by the authors using the recommended cutoffs in clinical trial settings. Alcohol use within 12 months, normalization of AST, ALT, and race (blacks/non-blacks) had minimal impact on the performance.AAR, Pohl, and platelet counts <100x10(9)/L have limited ability to predict significant/advanced fibrosis with area under the receiver operating characteristics curve similar to 0.5. However, platelet counts <150x10(9)/L, Lok's model and APRI performed well for advanced fibrosis in our daily practice setting.

  View details for Web of Science ID 000258389800012

  View details for PubMedID 18285716

• Monitoring of epithelial cell caspase activation via detection of durable keratin fragment formation JOURNAL OF PATHOLOGY Tao, G., Li, D. H., Zhou, Q., Toivola, D. M., Strnad, P., Sandesara, N., Cheung, R. C., Hong, A., Omary, M. B. 2008; 215 (2): 164-174

  Abstract

  Keratins 18 and 19 (K18/K19) are epithelial-specific intermediate filament proteins. Apoptosis induces caspase cleavage at the highly conserved K18 or K19 Asp237, which in K18 is preceded by cleavage at Asp396. We characterized the keratin N-terminal fragments that are generated upon caspase digestion of K18/K19 at Asp237 in order to study keratin dynamics during apoptosis. This was carried out by generating and characterizing antibodies selective to K18/K19 Asp237. K18 or K19 peptides that expose Asp237 in 234VEVD were used for rabbit immunization. The generated antibodies recognized cleaved but not intact K18/K19, exclusively, as determined by blotting or immunofluorescence staining of apoptotic human HT29 cells or livers isolated from Fas-Ab-injected mice. Antibodies to K18/K19 Asp237 recognized the common VEVD-motif as determined by immunoblotting of cells transfected with K18, K19 or K20. The K18/K19 VEVD-directed antibodies demonstrated sequential Asp396 then Asp237 K18 cleavage during apoptosis. Specific-keratin selectivity of the anti-Asp237 antibodies was confirmed by their inability to recognize K14 after UV-induced apoptosis in transfected cells. The Asp237-containing apoptotic keratin fragments are secreted into the medium of cultured HT29 cells and are stable up to 96 h after inducing apoptosis. Furthermore, the generated antibodies recognize keratin apoptotic fragments in sera of mice undergoing hepatocyte apoptosis and sera of patients with cirrhosis, and also recognize apoptotic cells in various epithelial human tumours. Therefore, the N-terminal caspase-generated K18 fragment is stable in tissues and biological fluids. The Asp237-directed antibodies provide a powerful tool to study apoptosis in human and mouse tissues, cells and serum, using a broad range of detection modalities.

  View details for DOI 10.1002/path.2344

  View details for Web of Science ID 000256456900009

  View details for PubMedID 18393369

• Persistence with hepatitis C therapy in the Department of Veterans Affairs JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS Iqbal, S. U., Cunningham, F., Lee, A., Miller, D. R., Li, N., Cheung, R., Kazis, L. 2008; 33 (3): 251-261

  Abstract

  Persistence with Hepatitis C therapy has been identified as a key variable for predicting treatment success. The primary purpose of this study was to assess the persistence with therapy for patients undergoing hepatitis C treatment in the VA healthcare system with two forms of combination therapies: peginterferon alfa-2a with Ribavirin (peg-IFN alpha-2a/Rib) and peginterferon alpha-2b with Ribavirin (peg-IFN alpha-2b/Rib).A retrospective cohort study design was used to analyse persistence in VA patients undergoing hepatitis C therapy during FY 2003-2004 using a large national VA data set. Stringent inclusion and exclusion criteria along with various defining variables were used to identify the inception cohort. Persistence rates were calculated for each of the two treatment groups at 3, 6, 9 and 11 months using the Kaplan-Meier method. Likelihood ratio test of equality between the two treatment groups was performed to detect any differences in persistence rates.A total of 5816 hepatitis C patients formed the inception cohort. Persistence rates for the overall duration showed significantly higher rates for patients on peg-IFN alpha-2a/Rib than peg-IFN alpha-2b/Rib. Cox regression analysis also showed favourable hazard ratio of persistence (0.88) for peg-IFN alpha-2a/Rib over peg-IFN alpha-2b/Rib.Peg alfa-2A/Rib showed slightly higher persistence rates for the overall duration of treatment as compared to Peg alfa-2B/Rib. However the differences, even though statistically significant, are small and not likely to translate into any substantial clinical advantage. Further research involving other approaches is required to confirm these findings.

  View details for Web of Science ID 000255485400006

  View details for PubMedID 18452412

• Diagnostic markers for hepatitis virus infection. Expert opinion on medical diagnostics Charuworn, P., Cheung, R. 2008; 2 (3): 303-314

  Abstract

  Background: Accurate diagnosis and characterization of hepatitis viruses are essential from a public health perspective and for clinical management. Objective: To review recent advances in the diagnosis of viral hepatitis A - D and their clinical utilities. Methods: Review of the literature published up to 2007. Result/conclusion: Recent advances in the sensitivity and ease of serologic and molecular diagnostics have improved our understanding of the natural history of viral hepatitis, are helpful in the pretreatment evaluation and provide guidance to antiviral therapy. As the technology improves, this will be reflected in an increased reliance and expanded role of these tests in clinical management and improved safety of the blood supply.

  View details for DOI 10.1517/17530059.2.3.303

  View details for PubMedID 23495660

• Treatment eligibility and outcomes in elderly patients with chronic hepatitis C: Results from the VA HCV-001 study DIGESTIVE DISEASES AND SCIENCES Tsui, J. I., Currie, S., Shen, H., Bini, E. J., Brau, N., Wright, T. L. 2008; 53 (3): 809-814

  Abstract

  We undertook this study to determine if treatment candidacy and outcomes were similar between elderly and non-elderly patients.This was a prospective cohort study that screened 4,025 patients with chronic hepatitis C for HCV antiviral treatment at 24 Veterans Affairs Medical Centers throughout the country. We used multivariable logistic regression to determine whether there was an independent association between being elderly (age > 60 vs.

  View details for DOI 10.1007/s10620-007-9926-x

  View details for Web of Science ID 000253570700033

  View details for PubMedID 17823868

• Diagnostic markers for hepatitis virus infection Expert Opinion Med Diagnostics Charuworn P, Cheung RC 2008; 2: 303-314
• Positive CAGE screen correlates with cirrhosis in veterans with chronic hepatitis C DIGESTIVE DISEASES AND SCIENCES Kamal, A., Cheung, R. 2007; 52 (10): 2564-2569

  Abstract

  The current study examines the relationship between problem alcohol use and severity of liver disease by self-administered questionnaires using both the CAGE questionnaire and beverage-specific quantity-frequency questions. The cohort consisted of 38 patients with cirrhosis (10 with decompensated liver disease) and 62 with mild fibrosis (stage 0-1), of comparable mean age and estimated duration of infection. Although mean alcohol consumption was similar in both groups, a positive CAGE screen (defined as two or more affirmative answers) was significantly more common among cirrhotics (OR = 5.24; 95% CI, 1.78-15.39) and tended to be associated with decompensated liver disease (OR = 13.3; 95% CI, 0.67-256) among cirrhotics. In multivariate analysis, only inflammatory grade on liver biopsy (OR = 67.7; 95% CI, 10.6-431) and positive CAGE score (OR = 8.09; 95% CI, 1.15-57.1) were independent predictors of cirrhosis. These findings suggest that the CAGE questionnaire predicts advanced liver disease better than daily or lifetime drinking measures.

  View details for DOI 10.1007/s10620-006-9668-1

  View details for Web of Science ID 000249300100016

  View details for PubMedID 17415636

• Multiple genetic markers in TLR4 region are associated with cirrhosis risk in CHC patients Huang, H., Abar, O., Rowland, C., Venkatesh, R., Catanese, J., Shiffman, M. L., Cheung, R., Wright, T. L., Layden, T. J., Bzowej, N. H., White, T., Friedman, S. L. JOHN WILEY & SONS INC. 2007: 715A

  View details for Web of Science ID 000249910401338

• Hepatitis C treatment candidacy and outcomes among 4318 US veterans with chronic hepatitis C virus infection - Does a history of injection drug use matter? JOURNAL OF CLINICAL GASTROENTEROLOGY Seal, K. H., Currie, S. L., Shen, H., Anand, B. S., Bini, E. J., Brau, N., Jeffers, L., Wright, T. L. 2007; 41 (2): 199-205

  Abstract

  Many patients with a history of injection drug use (IDU) are excluded from hepatitis C virus (HCV) treatment. This prospective multicenter study aimed to determine the impact of IDU history on HCV treatment candidacy and outcomes.Between 1999 and 2001, 4318 HCV-infected patients seen at 24 VA Medical Centers were evaluated for HCV treatment candidacy and followed prospectively. Univariate and multivariate logistic regression analyses were used to determine whether an IDU history was associated with HCV treatment candidacy, HCV treatment acceptance, early treatment discontinuation, and virologic response.Of 4318 participants, 2611 (61%) reported an IDU history. IDU history was not significantly associated with HCV treatment candidacy, acceptance, early discontinuation of therapy, or virologic response (all P values nonsignificant). Instead, reduced HCV treatment candidacy was independently associated with low-income [odds ratio (OR)=1.46, 95% confidence interval (CI)=1.22-1.74), education < or = 12 years (OR=1.23, 95% CI=1.03-1.46), and alcohol consumption > or = 3 drinks/d (OR=2.08, 95% CI=1.68-2.57), whereas early discontinuation of HCV therapy was independently associated with low-income and consuming > or = 3 alcoholic drinks/d.A history of IDU was not associated with HCV treatment candidacy or outcomes, supporting national guidelines to evaluate former IDUs on a case-by-case basis for HCV treatment.

  View details for Web of Science ID 000244133400014

  View details for PubMedID 17245220

• Clinical implications of hepatic steatosis in patients with chronic hepatitis C: A multicenter study of US Veterans 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases Hu, K., Currie, S. L., Shen, H., Cheung, R. C., Ho, S. B., Bini, E. J., McCracken, J. D., Morgan, T., Brau, N., Schmidt, W. N., Jeffers, L., Wright, T. L. SPRINGER. 2007: 570–78

  Abstract

  Studies have indicated a high prevalence of hepatic steatosis in patients with chronic hepatitis C (CHC). To address the impact of steatosis on the clinical course of CHC and treatment response requires large multicenter studies. The present study analyzed hepatitis C virus (HCV)-infected veterans enrolled in a U.S. Veteran Administration multicenter study of the epidemiology and response to interferon alpha-2b and ribavirin treatment. Of the 357 patients, 97.1% were males, with a mean age of 48.7+/-6.4 years, and 184 (51.5%) had hepatic steatosis. The mean body mass index (BMI) was 29.3+/-5.2 kg/m(2), including 37.1% who were obese (BMI, > or =30 kg/m(2)). Stage III-IV fibrosis was present in 111 of 334 (33.3%) of the patients. After adjusting for age, race, and history of alcohol use in the past 12 months, only stage III-IV fibrosis was independently and significantly associated with hepatic steatosis (P=0.03). There was a trend of association between obesity and steatosis independent of the other factors. Only HCV genotype was independently associated with a sustained virological response (SVR) to interferon alpha-2b and ribavirin treatment after adjusting for age, alcohol use, steatosis, BMI, stage III-IV fibrosis, serum AFP, and HCV load. In conclusion, analyses of our multicenter trial data demonstrated that the prevalence of hepatic steatosis is 51.5% in HCV-infected U.S. veterans. We found that steatosis is independently associated with stage III-IV fibrosis. However, only HCV genotype, and not steatosis, obesity, or stage III-IV fibrosis, was associated with SVR to interferon alpha-2b and ribavirin treatment.

  View details for DOI 10.1007/s10620-006-9418-4

  View details for Web of Science ID 000243904600046

  View details for PubMedID 17226072

• Screening for esophageal varices in cirrhotic patients: endoscope, platelet count, or both? GASTROINTESTINAL ENDOSCOPY Charuworn, P., Cheung, R. 2006; 64 (6): 865-867

  View details for DOI 10.1016/j.gie.2006.08.033

  View details for Web of Science ID 000242774900003

  View details for PubMedID 17140887

• Phenotypic and functional status of intrahepatic T cells in chronic hepatitis C 10th International Meeting on Hepatitis C Virus and Related Viruses Wang, J., Holmes, T. H., de Guevara, L. L., Cheung, R., Wright, T. L., He, X., Greenberg, H. B. OXFORD UNIV PRESS INC. 2006: 1068–77

  Abstract

  Polychromatic flow-cytometric assays were used to analyze paired intrahepatic and peripheral lymphocyte samples from 37 patients with chronic hepatitis C. Compared with peripheral cells, intrahepatic T cells were selectively enriched with CD45RO+ memory T cells but had a lower percentage of CD4+ T cells expressing the differentiation markers CD27 and CD28. The percentage of intrahepatic CD45RO+ and CD28+ T cells correlated with the degree of liver inflammation, which suggests that memory T cells at relatively early stages of differentiation are directly involved in liver inflammation. Despite their memory phenotype, intrahepatic T cells were defective in proliferation capability, produced less interferon- gamma in response to stimulation by T cell receptor, and contained less perforin but expressed higher levels of Fas and Fas ligand, compared with their counterparts in peripheral blood. The distinct characteristics of intrahepatic T cells suggest that they play an important role in the immunopathogenesis of chronic hepatitis C.

  View details for Web of Science ID 000240548500007

  View details for PubMedID 16991081

• A single tube multiplex research assay to assess the risk of cirrhosis in subjects with chronic hepatitis C 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases Shiffman, M. L., Cheung, R. C., Friedman, S., Chang, S., Catanese, J. J., Lew, D., Abar, O. T., Sigua, C. L., Santini, C. D., Vess, T. M., Leong, D. U., Venkatesh, R., Wright, T. L., Layden, T. J., Bzowej, N., White, T. J., Sninsky, J. J., Huang, H. WILEY-BLACKWELL. 2006: 272A–272A

  View details for Web of Science ID 000241362300222

• National multicenter study of HIV testing and HIV seropositivity in patients with chronic hepatitis C virus infection JOURNAL OF CLINICAL GASTROENTEROLOGY Bini, E. J., Currie, S. L., Shen, H., Brau, N., Schmidt, W., Anand, B. S., Cheung, R., Wright, T. L. 2006; 40 (8): 732-739

  Abstract

  Although HIV testing is recommended for persons with hepatitis C virus (HCV) infection who are at risk for HIV, little is known about HIV testing in this population.Data were prospectively collected in 4364 HCV-infected patients at 24 Veterans Affairs medical centers across the United States, including demographics, risk factors for HIV infection, and self-reported information on HIV testing.Overall, 76.8% had been tested for HIV at least once, 14.8% were never tested, 6.6% did not know if they were tested, and 1.8% declined to answer. Multivariable analysis identified injection drug use, needlestick injury, sex with a same-sex partner, a greater number of lifetime sexual partners, and sex with an injection drug user as factors that were independently associated with HIV testing. At least one risk factor for HIV infection was present in 84.5% of the 646 patients who were never HIV tested. Among the 3350 subjects who were tested for HIV, 8.4% were positive, 88.3% were negative, 2.4% did not know the results of their test, and 0.9% declined to answer. Multivariable analysis identified African American and Hispanic race/ethnicity, income < or = 10,000 dollars, sex with a same-sex partner, and sex with an injection drug user as the only variables that were independently associated with HIV seropositivity.Although a substantial proportion of HCV-infected patients have been tested for HIV, missed opportunities for early diagnosis of HIV infection exist. Public health strategies to improve HIV testing among patients with chronic HCV infection are needed.

  View details for Web of Science ID 000240159900014

  View details for PubMedID 16940888

• Global transcriptional response to interferon is a determinant of HCV treatment outcome and is modified by race HEPATOLOGY He, X., Ji, X., Hale, M. B., Cheung, R., Ahmed, A., Guo, Y., Nolan, G. P., Pfeffer, L. M., Wright, T. L., Risch, N., Tibshirani, R., Greenberg, H. B. 2006; 44 (2): 352-359

  Abstract

  Interferon (IFN)-alpha-based therapy for chronic hepatitis C is effective in fewer than 50% of all treated patients, with a substantially lower response rate in black patients. The goal of this study was to investigate the underlying host transcriptional response associated with interferon treatment outcomes. We collected peripheral blood mononuclear cells from chronic hepatitis C patients before initiation of IFN-alpha therapy and incubated the cells with or without IFN-alpha for 6 hours, followed by microarray assay to identify IFN-induced gene transcription. The microarray datasets were analyzed statistically according to the patients' race and virological responses to subsequent IFN-alpha treatment. The global induction of IFN-stimulated genes (ISGs) was significantly greater in sustained virological responders compared with nonresponders and in white patients compared with black patients. In addition, a significantly greater global induction of ISGs was observed in sustained virological responders compared with nonresponders within the group of white patients. The level of IFN-induced signal transducer and activator of transcription (STAT) 1 activation, a key component of the Janus kinase (JAK)-STAT signaling pathway, correlated with the global induction of ISGs and was significantly higher in white patients than in black patients. In conclusion, both treatment outcome and race are associated with different transcriptional responses to IFN-alpha. Because this difference is evident in the global induction of ISGs rather than a selective effect on a subset of such genes, key factors affecting the outcome of IFN-alpha therapy are likely to act at the JAK-STAT pathway that controls transcription of downstream ISGs.

  View details for DOI 10.1002/hep.21267

  View details for PubMedID 16871572

• The impact of chronic hepatitis C and comorbid psychiatric illnesses on health-related quality of life JOURNAL OF CLINICAL GASTROENTEROLOGY Lim, J. K., Cronkite, R., Goldstein, M. K., Cheung, R. C. 2006; 40 (6): 528-534

  Abstract

  To determine the relative impact of chronic hepatitis C (CHC) and comorbid psychiatric illness on the health-related quality of life (HRQoL).Psychiatric conditions are more common among patients with CHC but their relative influence on HRQoL is not well understood.We identified 864 veterans who had previously completed a veteran-specific HRQoL questionnaire (SF-36V) as part of the 1999 VA Large Health Survey with known HCV antibody (anti-HCV) status before the survey. For 201 anti-HCV(+) and 663 anti-HCV(-) patients, we compared the HRQoL status and the prevalence of 6 major psychiatric diagnoses. We conducted multiple regression analyses to measure the effect of anti-HCV status and psychiatric comorbidity.Compared with the anti-HCV(-) group, anti-HCV(+) veterans were more likely to have alcohol dependence (P<0.001), depression (P=0.01), or posttraumatic stress disorder (PTSD) (P<0.004). The anti-HCV(+) group also reported lower HRQoL on 4 of the 8 SF-36V subscales (P<0.01) and the mental component summary scale (P<0.001). Even after adjusting for demographic variables and comorbid psychiatric illness, anti-HCV(+) patients reported a significantly lower mental component summary score (P<0.01) than did anti-HCV(-) patients. Multiple regression analysis found that depression and PTSD predicted lower HRQoL scores for all 8 HRQoL subscales (P<0.01) and both the physical (P<0.001) and mental component (P<0.03) summary scales independent of anti-HCV status.The HRQoL is significantly impaired in veterans with CHC, particularly the mental health components of HRQoL. In contrast, comorbid depression and PTSD are associated with both lower physical and mental components of HRQol, independent of CHC.

  View details for Web of Science ID 000239136700012

  View details for PubMedID 16825936

• Effectiveness of a screening program for hepatitis C DIGESTIVE DISEASES AND SCIENCES Cheung, R. C., Cunningham, B. A., Cooper, A. D. 2006; 51 (5): 976-981

  Abstract

  We sought to determine the outcomes of a screening program for hepatitis C virus (HCV) infection. Of 536 veterans initially screened between July 2000 and June 2001 for risk factors and then tested positive for antibody for HCV, only 260 (48.5%) kept their initial appointments for further evaluation; 51 were not viremic and only 19 (9.1%) were treatment eligible. Of the 276 who did not keep their initial appointments, 92 were subsequently evaluated over the next 2 years and 23 (25%) were treatment eligible, along with another 15 from the first group. Thus, with appropriate intervention and long-term follow-up, there were 57 treatment candidates. In conclusion, most veterans who tested positive either failed to keep their appointment or were ineligible for treatment when first evaluated. Over the following 2 years, some were lost to follow-up, many continued to have contraindication(s) to antiviral therapy, and relatively few were treatment candidates.

  View details for DOI 10.1007/s10620-006-9100-x

  View details for Web of Science ID 000238847600027

  View details for PubMedID 16642419

• Alcohol use and treatment of hepatitis C virus: Results of a national multicenter study GASTROENTEROLOGY Anand, B. S., Currie, S., Dieperink, E., Bin, E. J., Shen, H., Ho, S. B., Wright, T. 2006; 130 (6): 1607-1616

  Abstract

  Patients with hepatitis C virus (HCV) infection who use alcohol have been excluded from clinical trials; therefore, outcomes with antiviral therapy are unknown. The aim of the study was to determine the impact of alcohol use on HCV treatment outcomes.Subjects using alcohol were categorized as follows: no alcohol versus regular alcohol use, quantity consumed (none, <6 drinks/day, >/=6 drinks/day), CAGE score <2 or >/=2, and recent alcohol use (past 12 months). Patients were treated with interferon plus ribavirin.A total of 4061 subjects were enrolled, and 726 (18%) received treatment. Alcohol use (past and within 12 months) reduced treatment candidacy. Past alcohol use did not affect the end-of-treatment response, sustained virologic response (SVR), and treatment discontinuation rates. However, recent alcohol use resulted in higher treatment discontinuation (40% vs 26%; P = .0002) and tended to reduce the SVR (14% vs 20%; P = .06), but when patients who discontinued treatment were excluded from analysis, the trend in favor of nondrinkers for SVR disappeared (25% vs 23%). These findings were also consistent in subgroup analyses on race and genotype.Eligibility for anti-HCV treatment was reduced in past and recent drinkers. Recent alcohol use was associated with increased treatment discontinuation and lower SVR. However, patients who use alcohol and completed the treatment had a response comparable to that of nondrinkers. Patients with a history of alcohol use should not be excluded from HCV therapy. Instead, additional support should be provided to these patients to ensure their ability to complete treatment.

  View details for DOI 10.1053/j.gastro.2006.02.023

  View details for Web of Science ID 000237686700011

  View details for PubMedID 16697724

• Identification of two gene variants associated with risk of advanced fibrosis in patients with chronic hepatitis C GASTROENTEROLOGY Huang, H., Shiffman, M. L., Cheung, R. C., Layden, T. J., Friedman, S., Abar, O. T., Yee, L., Chokkalingam, A. P., Schrodi, S. J., Chan, J., Catanese, J. J., Leong, D. U., Ross, D., Hu, X., Monto, A., McAllister, L. B., Broder, S., White, T., Sninsky, J. J., Wright, T. L. 2006; 130 (6): 1679-1687

  Abstract

  Previously identified clinical risk factors such as sex, alcohol consumption, and age at infection do not accurately predict which patients with chronic hepatitis C (CHC) will develop advanced fibrosis (bridging fibrosis and cirrhosis). The aim of this study was to identify genetic polymorphisms that can predict the risk of advanced fibrosis in patients with CHC.A total of 916 subjects with CHC was enrolled from 2 centers. A gene-centric disease association study of 24,832 putative functional, single nucleotide polymorphisms (SNPs) was performed. Of the 1609 SNPs that were significantly associated (P

  View details for DOI 10.1053/j.gastro.2006.02.032

  View details for Web of Science ID 000237686700019

  View details for PubMedID 16697732

• Black patients with chronic hepatitis C have a lower sustained viral response rate than non-Blacks with genotype 1, but the same with genotypes 2/3, and this is not explained by more frequent dose reductions of interferon and ribavirin JOURNAL OF VIRAL HEPATITIS Brau, N., Bini, E. J., Currie, S., Shen, H., Schmidt, W. N., King, P. D., Ho, S. B., Cheung, R. C., Hu, K. Q., Anand, B. S., SIMON, F. R., Aytaman, A., Johnson, D. P., Awad, J. A., Ahmad, J., Mendenhall, C. L., Pedrosa, M. C., Moseley, R. H., Hagedorn, C. H., Waters, B., Chang, K. M., Morgan, T. R., Rossi, S. J., Jeffers, L. J., Wright, T. L. 2006; 13 (4): 242-249

  Abstract

  In previous hepatitis C virus (HCV) treatment studies, Black patients not only had a lower sustained viral response (SVR) rate to interferon and ribavirin (RBV) than non-Black patients but also a higher frequency of HCV genotype 1 (GT-1) infection. The aim of this community-based study was to determine whether Black patients have a lower SVR rate independent of genotype. We prospectively enrolled 785 patients (24.8% Black, 71.5% White, 3.7% others) who received interferon alpha-2b 3 MU three times weekly + RBV 1000-1200 mg/day for 24 weeks (GT-2/3) or 48 weeks (GT-1). Black patients were more commonly infected with GT-1 (86.8%vs 64.8%, P < 0.001) and less frequently had an SVR compared with non-Black patients (8.4%vs 21.6%, P < 0.001). Within GT-1, Black patients had a lower SVR rate than non-Black patients (6.1%vs 14.1%, P = 0.004) but not within GT-2/3 (50.0%vs 36.5%, P = 0.47). Black patients had lower baseline haemoglobin levels (14.8 vs 15.3 g/dL, P < 0.001) and neutrophil counts (2900 vs 4100/mm(3), P < 0.001) and required more frequent dose reductions of RBV (29.8%vs 18.5%, P < 0.001) and interferon (4.7%vs 1.6%, P = 0.012). However, dose reductions were not associated with lower SVR rates while early treatment discontinuations were (2.9%vs 25.7%, P < 0.001). Independent predictors of SVR were GT-1 [odds ratio (OR) 0.33; 95% confidence interval (CI) 0.20-0.55; P < 0.001], Black race (OR 0.45; 95% CI 0.22-0.93; P = 0.030), and advanced fibrosis, stages 3 + 4 (OR 0.53; 95% CI 0.31-0.92; P = 0.023). In conclusion, Black patients infected with HCV GT-1 (but not GT-2/3) have a lower SVR rate than non-Black patients. This is not explained by their lower baseline haemoglobin levels and neutrophil counts that lead to higher rates of ribavirin and interferon dose reductions.

  View details for DOI 10.1111/j.1365-2893.2005.00682.x

  View details for Web of Science ID 000236065100005

  View details for PubMedID 16611190

• Hepatitis B vaccines INFECTIOUS DISEASE CLINICS OF NORTH AMERICA Yu, A. S., Cheung, R. C., Keeffe, E. B. 2006; 20 (1): 27-?

  Abstract

  Immunization is the most effective way to prevent transmission of HBV and, hence, the development of acute or chronic hepatitis B. The national strategy to eliminate transmission of the virus in the United States includes vaccination of all newborn infants, children, adolescents, and high-risk adults. Postexposure prophylaxis is also advocated, depending on the vaccination and anti-HBs status of the exposed person. Seroprotection after vaccination, defined as anti-HBs > or = 10 mIU/mL, is achieved in over 95% of all vaccinees. The hepatitis B vaccines are very well tolerated with usually minimal adverse effects. Predictors of non-response include increasing age, male gender, obesity, tobacco smoking, and immunocompromising chronic dis-ease. For those who remain nonresponders after the second series of vaccination, adjuvants such as GM-CSF may be considered, but their results are variable.

  View details for DOI 10.1016/j.idc.2006.01.004

  View details for Web of Science ID 000236520400003

  View details for PubMedID 16527647

• A multi-gene signature accurately predicts the risk of bridging fibrosis/cirrhosis in patients with chronic hepatitis C 41st Annual Meeting of the European-Association-for-the-Study-of-the-Liver Huang, H., Wright, T. L., Cheung, R. C., Layden, T. J., Friedman, S., Bzowej, N., Cooper, C., Jacobson, A., Venkatesh, R., Abar, O. T., Chan, J., Catanese, J. J., Leong, D. U., Yee, L., White, T. J., Sninsky, J. J., Shiffman, M. ELSEVIER SCIENCE BV. 2006: S21–S21

  View details for Web of Science ID 000237328100045

• Chronic hepatitis C in Latinos: Natural history, treatment eligibility, acceptance, and outcomes AMERICAN JOURNAL OF GASTROENTEROLOGY Cheung, R. C., Currie, S., Shen, H., Ho, S. B., Bini, E. J., Anand, B. S., Brau, N., Wright, T. L. 2005; 100 (10): 2186-2193

  Abstract

  The natural history of chronic hepatitis C and treatment response are different between blacks and Caucasians, but little comparable data is available about Latinos.A cross-sectional secondary analysis to investigate differences between 421 anti-HCV-positive, treatment-naïve, HCV-viremic Latinos and 2,510 Caucasians in 24 VA medical centers enrolled in a prospective study.Latinos were infected at a younger age and were less likely to have blood contact during combat, surgery, and needle stick injury, but were more frequently HIV coinfected (20.4%vs 3.9%, p < 0.0001) and prior HAV infection (39.9%vs 26.4%, p= 0.0001). Latinos were more likely to be treatment candidates, but less likely to actually initiate treatment. Liver histology (123 Latinos, 743 Caucasians) showed no difference in fibrosis or fibrosis rate, but steatosis (54.7%vs 43.2%, p= 0.038) was more common in Latinos. Eighty-eight Latinos and 481 Caucasians were subsequently treated with interferon-ribavirin: body mass index (BMI), duration of infection, baseline tests, liver histology and genotype distribution were similar. Compared with Caucasians, Latinos discontinued treatment prematurely more often (39.8%vs 28.9%, p= 0.043) and tended to have lower sustained virological response (SVR) rates (14.8%vs 22.5%, p= 0.10). Multivariate analysis found Latino race and history of recent alcohol use to be associated with early treatment discontinuation, whereas genotype and viral load but not ethnicity to be associated with SVR.Latinos were infected younger, more frequently HIV coinfected, more likely to meet criteria for antiviral therapy yet less likely to initiate treatment and had a trend toward lower SVR rates than Caucasians, but not in severity of liver disease. Latino ethnicity was associated with early discontinuation but not as an independent predictor of SVR.

  View details for DOI 10.1111/j.1572-0241.2005.00240.x

  View details for Web of Science ID 000231950500009

  View details for PubMedID 16181367

• Amantadine in treatment of chronic hepatitis C virus infection? JOURNAL OF VIRAL HEPATITIS Lim, J. K., Wooten, D., Siegel, R., Cheung, R. C. 2005; 12 (5): 445-455

  Abstract

  Treatment of chronic hepatitis C (CHC) continues to be an important and growing challenge. As the response rate to FDA-approved treatment improved over the past decade, we are facing increasing number of difficult-to-treat patients such as those who have failed prior anti-viral therapy. The role of amantadine in the treatment of CHC remains unclear. Studies thus far have produced conflicting results, and type II error could not be excluded. This review summarized results published in the literature from 1997 to 2003, and reviewed the existing questions and controversies regarding the use of amantadine. Current literature suggests that amantadine is ineffective as monotherapy. Amantadine increased the sustained virologic response of certain treatment naïve patients when used in combination with interferon, and may be effective as an adjunct to interferon-based combination therapy in some patients who have failed or relapsed on prior therapy. Factors such as small sample size, patient characteristics, and differences in treatment protocols including amantadine preparation and duration of therapy might explain the conflicting observations of various studies. Further investigations are needed to define optimal dosing and formulation of amantadine, and its appropriate role in management of CHC infection.

  View details for DOI 10.1111/j.1365-2893.2005.00622.x

  View details for Web of Science ID 000231223400001

  View details for PubMedID 16108758

• Practice patterns and treatment outcomes in the management of chronic hepatitis C (CHC) infection in a large managed care cohort 70th Annual Meeting of the American-College-of-Gastroenterology Bobbola, M., Momi, J., Lim, J. K., Ready, J., Cheung, R. C. NATURE PUBLISHING GROUP. 2005: S283–S283

  View details for Web of Science ID 000231853502019

• Prospective multicenter study of eligibility for antiviral therapy among 4,084 US veterans with chronic hepatitis C virus infection AMERICAN JOURNAL OF GASTROENTEROLOGY Bini, E. J., Brau, N., Currie, S., Shen, H., Anand, B. S., Hu, K. Q., Jeffers, L., Ho, S. B., Johnson, D., Schmidt, W. N., King, P., Cheung, R., Morgan, T. R., Awad, J., Pedrosa, M., Chang, K. M., Aytaman, A., Simon, F., Hagedorn, C., Moseley, R., Ahmad, J., Mendenhall, C., Waters, B., Strader, D., Sasaki, A. W., Rossi, S., Wright, T. L. 2005; 100 (8): 1772-1779

  Abstract

  Many veterans may not be candidates for hepatitis C virus (HCV) treatment due to contraindications to therapy. The aims of this study were to determine the proportion of HCV-infected veterans who were eligible for interferon alfa and ribavirin therapy and to evaluate barriers to HCV treatment.We prospectively enrolled 4,084 veterans who were referred for HCV treatment over a 1-yr period at 24 Veterans Affairs (VA) Medical Centers. Treatment candidacy was assessed using standardized criteria and the opinion of the treating clinician.Overall, 32.2% (95% CI, 30.8-33.7%) were candidates for HCV treatment according to standardized criteria, whereas 40.7% (95% CI, 39.2-42.3%) were candidates in the opinion of the treating clinician. Multivariable analysis identified ongoing substance abuse (OR = 17.68; 95% CI, 12.24-25.53), comorbid medical disease (OR = 9.62; 95% CI, 6.85-13.50), psychiatric disease (OR = 9.45; 95% CI, 6.70-13.32), and advanced liver disease (OR = 8.43; 95% CI, 4.42-16.06) as the strongest predictors of not being a treatment candidate. Among patients who were considered treatment candidates, 76.2% (95% CI, 74.0-78.3%) agreed to be treated and multivariable analysis showed that persons >/=50 yr of age (OR = 1.37; 95% CI, 1.07-1.76) and those with >50 lifetime sexual partners (OR = 1.44; 95% CI, 1.08-1.93) were more likely to decline treatment.The majority of veteran patients are not suitable candidates for HCV treatment because of substance abuse, psychiatric disease, and comorbid medical disease, and many who are candidates decline therapy. Multidisciplinary collaboration is needed to overcome barriers to HCV therapy in this population.

  View details for DOI 10.1111/j.1572-0241.2005.41860.x

  View details for Web of Science ID 000230992100021

  View details for PubMedID 16086714

• High mortality rate in patients with advanced liver disease independent of exposure to general anesthesia JOURNAL OF CLINICAL ANESTHESIA Cheung, R. C., McAuley, R. J., Pollard, J. B. 2005; 17 (3): 172-176

  Abstract

  To evaluate the survival of patients with advanced liver disease to determine if known exposure to general anesthesia within a 5-year period has a measurable effect on mortality.Retrospective survival analysis of male veterans with advanced liver disease.Tertiary referral VA Medical Center and university-affiliated teaching hospital.One hundred twenty-seven patients with a history of alcoholic cirrhosis and documented hepatitis C infection and stable platelet counts were identified and then divided into 3 groups. The 5-year survival rates in all 3 groups were compared using Kaplan-Meier survival curves.Ninety patients had marked thrombocytopenia (<100000/mm3). Their survival rates with and without known exposure to general anesthesia were compared with those of control subjects with alcoholic cirrhosis and hepatitis C infection but with platelet counts greater than 100000/mm3. The 5-year survival rate of 57% in the group that received general anesthesia was comparable to the 58% rate observed in the group without this exposure. Both groups' rates were statistically lower than the 5-year survival rate of 77% in the group with advanced liver disease but without thrombocytopenia.Comparably high mortality rates were observed in patients with advanced liver disease with or without exposure to general anesthesia. Higher survival rates were noted in patients with advanced liver disease who were not thrombocytopenic.

  View details for DOI 10.1016/j.jclinane.2004.06.016

  View details for Web of Science ID 000229688100005

  View details for PubMedID 15896582

• A randomized, double-blind, placebo-controlled dose-escalation trial of merimepodib (VX-497) and interferon-alpha in previously untreated patients with chronic hepatitis C ANTIVIRAL THERAPY McHutchison, J. G., Shiffman, M. L., Cheung, R. C., Gordon, S. C., Wright, T. L., Pottage, J. C., McNair, L., Ette, E., Moseley, S., Alam, J. 2005; 10 (5): 635-643

  Abstract

  Inhibition of inosine monophosphate dehydrogenase (IMPDH) is one of several proposed mechanisms of action for ribavirin (RBV), a critical component of the current treatment for chronic hepatitis C (CHC). This study was a double-blind, placebo-controlled dose-escalation study of a novel, selective, orally active small molecule inhibitor of IMPDH, merimepodib (VX-497 or MMPD) in combination with standard interferon-alpha (IFN-alpha). Fifty-four treatment-naive patients with genotype-1 CHC were randomized to receive IFN-alpha 3 MIU subcutaneously three times a week, alone or in combination with 100 mg or 300 mg (every 8 h) of MMPD for 4 weeks. At the end of 4 weeks, all patients were offered 48 weeks of treatment with IFN-alpha/RBV. The objectives of the study were to evaluate the tolerability of the IFN-alpha/MMPD combination and to evaluate whether MMPD had an on-treatment effect on HCV-RNA, similar to RBV when added to IFN-alpha. The drug combination was generally well tolerated; one patient at the higher dose discontinued because of elevated alanine aminotransferase levels. No pharmacokinetic interactions were evident between the two drugs. Analysis of covariance that adjusted for a baseline imbalance in HCV-RNA in the intent-to-treat population did not show any significant differences between the treatment groups, or between MMPD plus IFN-alpha compared with IFN-alpha alone. However, the per-protocol primary efficacy analysis based on treatment-compliant patients demonstrated a greater reduction in mean HCV-RNA in the combination of 100 mg MMPD plus IFN-alpha compared with IFN-alpha alone (-1.78 log vs -0.86 log, P=0.037). In conclusion, the addition of a selective IMPDH inhibitor to IFN-alpha was well tolerated. In a low-dose range, the addition of MMPD may have the potential to add to the antiviral efficacy of IFN-alpha. Larger, longer duration trials incorporating pegylated IFN would be required to determine whether this combination, alone or with RBV, would increase either early or sustained virological response rates.

  View details for Web of Science ID 000231963400006

  View details for PubMedID 16152757

• Expression of chemokine receptors on intrahepatic and peripheral lymphocytes in chronic hepatitis C infection: Its relationship to liver inflammation 10th International Meeting on Hepatitis C Virus and Related Viruses Wang, J. H., Holmes, T. H., Cheung, R., Greengberg, H. B., He, X. S. UNIV CHICAGO PRESS. 2004: 989–97

  Abstract

  Intrahepatic lymphocytes are believed to be directly involved in the immunopathogenesis of chronic liver diseases. Little is known about the trafficking of lymphocytes into the liver and their role in chronic hepatitis C infection.The expression of 4 chemokine receptors and an activation marker on multiple lymphocyte subsets in paired liver biopsy and peripheral blood specimens from 23 patients with chronic hepatitis C infection were analyzed by a 6-color flow-cytometric assay.CCR5, CXCR3, and CXCR6 were expressed on intrahepatic CD4+ and CD8+ T cells, natural killer (NK) T cells, NK cells, and B cells at significantly higher frequencies than on peripheral lymphocyte subsets. The expression of these receptors and the activation marker CD38 tended to increase with the severity of liver inflammation. This increase was significant for several intrahepatic lymphocytes subsets. Correlations in expression differed among pairs of these extralymphoid homing receptors on the intrahepatic T cells.The homing program for intrahepatic lymphocytes involves multiple extralymphoid chemokine receptors that are regulated by >1 pathway. The expression of homing receptors on intrahepatic lymphocytes is associated with the immunopathogenesis of chronic hepatitis C disease. These preliminary results indicate that confirmational studies with larger sample sizes are warranted.

  View details for Web of Science ID 000223114800018

  View details for PubMedID 15295707

• Hepatitis B vaccines. Clinics in liver disease Yu, A. S., Cheung, R. C., Keeffe, E. B. 2004; 8 (2): 283-300

  Abstract

  Immunization is the most effective way to prevent transmission of HBV and, hence, the development of acute or chronic hepatitis B. The national strategy to eliminate transmission of the virus in the United States includes vaccination of all newborn infants, children, adolescents, and high-risk adults. Postexposure prophylaxis is also advocated, depending on the vaccination and anti-HBs status of the exposed person. Seroprotection after vaccination, defined as anti-HBs > or = 10 mIU/mL, is achieved in over 95% of all vaccinees. The hepatitis B vaccines are very well tolerated with usually minimal adverse effects. Predictors of non-response include increasing age, male gender, obesity, tobacco smoking, and immunocompromising chronic disease. For those who remain nonresponders after the second series of vaccination, adjuvants such as GM-CSF may be considered, but their results are variable.

  View details for PubMedID 15481341

• The use of class-I HLA tetramers for the detection of hepatitis C virus NS3-specific CD8+ T cells in patients with chronic infection JOURNAL OF IMMUNOLOGICAL METHODS Lopez-Labrador, F. X., He, X. S., Berenguer, M., Cheung, R. C., Wright, T. L., Greenberg, H. B. 2004; 287 (1-2): 91-99

  Abstract

  New methods to detect virus-specific T-cell responses have recently been developed. Several human leukocyte antigen (HLA)-peptide tetramers for the detection of hepatitis C virus (HCV)-specific CD8(+) T cells are under evaluation.Evaluation of one HLA class I-tetramer (HCVNS3-2) for the detection of HCV NS3-specific CD8(+) T cells in a series of 38 HLA-A2(+) chronically infected patients.Almost half (42%) of the patients had detectable NS3-specific CD8(+) T cells. The frequencies of such cells ranged from 0.01% to 0.22% of total CD8(+) T cells. No significant differences in clinical features or mean viral load were detected between patients with or without tetramer + CD8(+) T cells.The tetramer HCVNS3-2 may be very useful for the study of the HCV-specific CD8(+) immune response. Combination of this reagent with other tetramers based on other HCV peptides may help in the understanding of the immune response to the virus. However, a panel of tetramers based on several parts of the HCV polyprotein may be a mandatory requirement to explore the whole breadth of the CD8(+) T-cell response against HCV and to detect that response in the majority of patients with chronic infection.

  View details for DOI 10.1016/j.jim.2004.01.023

  View details for Web of Science ID 000221148800008

  View details for PubMedID 15099758

• Genetic variability of hepatitis C virus non-structural protein 3 and virus-specific CD8+response in patients with chronic hepatitis C JOURNAL OF MEDICAL VIROLOGY Lopez-Labrador, F. X., He, X. S., Berenguer, M., Cheung, R. C., Gonzalez-Candelas, F., Wright, T. L., Greenberg, H. B. 2004; 72 (4): 575-585

  Abstract

  Hepatitis C virus (HCV) variation in specific T-cell epitopes may represent a mechanism of viral persistence in chronic infection. We examined the HCV non-structural protein 3 (NS3), including the immunologically relevant epitopes HCV NS3-2 KLVALGINAV (human leukocyte antigen [HLA]-A2-restricted) and HCV NS3-1391 LIFCHSKKK (HLA-A3-restricted), in 22 HLA-A2+ patients with chronic infection. Significant amino acid variation was found in HCV NS3-2 epitope sequences when compared to the HCV-1 prototype virus. Six of the nine different HCV NS3-2 peptide variants were identified in patients with HCV NS3-2-specific CD8+ cells, detected with an HLA-A2 tetramer made with the HCV-1 prototype peptide. Phylogenetic analysis, including HCV reference sequences other than HCV-1, suggested however that most of the variations in the HCV NS3-2 epitope could be related to genetic heterogeneity between HCV reference subtypes. Variation was less common when comparing HCV NS3-2 epitope sequences from the clinical isolates to the most-closely related HCV reference subtype in each case. Some subtype-independent variations were found in epitopic residues probably important for T-cell receptor interaction. In contrast, no significant variation was found in HLA primary anchor sites, flanking regions, or in the contiguous HLA A3-restricted CD8+ T-cell epitope. Ongoing variation was not evident in two selected patients with follow-up. In conclusion, (i) the HCV NS3-2 epitope is not conserved between different HCV strains/subtypes, and (ii) an HLA-A2 tetramer loaded with the HCV-1 prototype NS3-2 peptide may still detect NS3-specific CD8+ cells in some patients with variant viruses. These data may be useful to improve T-cell assays using HCV NS3 peptides, taking into account the genetic diversity of this virus.

  View details for DOI 10.1002/jmv.20036

  View details for Web of Science ID 000220046100010

  View details for PubMedID 14981760

• Polychromatic flow cytometric and functional analysis of intrahepatic lymphocytes in chronic HCV infection. Wang, J. H., Cheung, R., Hansch, E., Greenberg, H. B., He, X. S. W B SAUNDERS CO. 2003: 355A

  View details for Web of Science ID 000185816700406

• The impact of hepatitis C status on postoperative outcome ANESTHESIA AND ANALGESIA Cheung, R. C., Hsieh, F., Wang, Y. J., Pollard, J. B. 2003; 97 (2): 550-554

  Abstract

  The impact of the hepatitis C virus (HCV) infection on the postoperative complication rate is unknown. We identified a population of surgical patients (n = 2457) for whom the HCV antibody (anti-HCV) had been measured and compared after surgical complications and mortality between those who were positive (17.9%) versus negative. The complication rates were 10% in the anti-HCV positive and 13% in the negative group (P = 0.125), whereas the mortality rates were 0.7% and 2.5%, respectively (P = 0.017). The anti-HCV positive patients were younger, had lower ASA physical status, and underwent shorter procedures. In the univariate analysis, emergent surgery and high ASA physical status but not anti-HCV positivity were associated with a more frequent complication. In the multivariate analysis, the urgency of surgery, age, ASA physical status, length of surgery, and preoperative hematocrit (but not platelet count) were associated with complications. Anti-HCV positivity was associated with an odds ratio for having a complication of 1.08 (95% confidence interval, 0.90-1.30), which was not statistically significant (P = 0.405). In conclusion, we were unable to show HCV antibody status to be an independent risk factor for postoperative complications when other co-factors were considered.In this large study at a Veterans Administration medical center, the urgency of surgery, age, ASA physical status, length of surgery, and preoperative hematocrit were all independently associated with postoperative complications. However, hepatitis C infection was not an independent risk factor for postoperative complications.

  View details for DOI 10.1213/01.ANE.0000068984.22840.FE

  View details for Web of Science ID 000184354600044

  View details for PubMedID 12873952

• Determination of hepatitis C virus genotype by Pyrosequencing JOURNAL OF VIROLOGICAL METHODS Elahi, E., Pourmand, N., Chaung, R., Rofoogaran, A., Boisver, J., Samimi-Rad, K., Davis, R. W., Ronaghi, M. 2003; 109 (2): 171-176

  Abstract

  A simple sequencing-based assay is described for genotyping of hepatitis C virus (HCV). RT-PCR was employed to amplify a 237-nucleotide-long fragment from the 5' untranslated region (UTR) of the genome using one biotinylated and one normal primer. Subsequent to capture of the PCR products on streptavidin-coated beads, single-stranded DNA separation, and hybridization of sequencing primer, Pyrosequencing was performed. The genotype of 98 samples out of which 77 samples were from American veterans and 21 samples were from Iran was determined. The samples from the American veterans contained six different subtypes, while five subtypes were found in Iranian samples. For rapid population-specific HCV subtyping, a multiplex assay was developed. This study demonstrates the suitability of this technology for low-cost, high throughput and accurate microbial genotyping.

  View details for DOI 10.1016/S0166-0934(03)00068-5

  View details for Web of Science ID 000183092800009

  View details for PubMedID 12711060

• Interferon alfa regulated gene expression in patients initiating interferon treatment for chronic hepatitis C HEPATOLOGY Ji, X. H., Cheung, R., Cooper, S., Li, Q. Q., Greenberg, H. B., He, X. S. 2003; 37 (3): 610-621

  Abstract

  Interferon alfa (IFN-alpha) is an approved therapeutic agent for chronic hepatitis C. To directly characterize the effects of IFN-alpha in humans, we used microarrays to profile gene expression in peripheral blood mononuclear cells (PBMCs) from hepatitis C patients treated with IFN-alpha. Seven patients were studied using two strategies: (1) in vivo: PBMCs were collected immediately before the first dose of IFN-alpha, and 3 and 6 hours after the dose; (2) ex vivo: PBMCs that were collected before the first IFN-alpha dose were incubated with IFN-alpha for 3 and 6 hours. The microarray datasets were analyzed with significance analysis of microarrays (SAM) to identify genes regulated by IFN-alpha. We identified 516 named genes up-regulated at least 2-fold, at a false discovery rate (FDR) of less than 1%. In vivo and ex vivo studies generated similar results. No genes were identified as regulated differently between these 2 experimental conditions. The up-regulated genes belonged to a broad range of functional pathways and included multiple genes thought to be involved in the direct antiviral effect of IFN-alpha. Of particular interest, 88 genes directly relating to functions of immune cells were up-regulated, including genes involved in antigen processing and presentation, T-cell activation, lymphocyte trafficking, and effector functions, suggesting that IFN-alpha up-regulates multiple genes involving different aspects of immune responses to enhance immunity against hepatitis C virus. In conclusion, IFN-alpha-inducible genes can be identified in human PBMCs in vivo as well as ex vivo. Signature changes associated with different treatment outcomes may be found among these genes.

  View details for DOI 10.1053/jhep.2003.50105

  View details for Web of Science ID 000181276800017

  View details for PubMedID 12601359

• Depression, anxiety, post-traumatic stress, and alcohol-related problems among veterans with chronic hepatitis C AMERICAN JOURNAL OF GASTROENTEROLOGY Lehman, C. L., Cheung, R. C. 2002; 97 (10): 2640-2646

  Abstract

  The aim of this study was to determine the incidence of psychiatric comorbidities among veterans with chronic hepatitis C.Depression, anxiety sensitivity, post-traumatic stress symptoms, and alcohol use were assessed using standardized questionnaires in 120 consecutive veterans with chronic hepatitis C referred to the Liver Clinic.Using well-established scoring criteria of the questionnaires, clinically significant levels of depression (44.2%), anxiety (38.1%), post-traumatic stress disorder (20.8%), and alcohol-related problems (26.7%) were observed. The majority of patients had a clinically significant score for at least one questionnaire, whereas 37.2% had significant scores in two or more questionnaires. Positive correlations were found between post-traumatic symptoms and depressive symptoms, anxiety sensitivity, and alcohol use problems. Depressive symptoms were also correlated with anxiety. Responses to the questionnaires, in general, correlated poorly with psychiatric histories documented in the medical record. Overall, 79 (65.8%) patients had one or more possible contraindications to antiviral therapy: coexisting unstable psychiatric disorders and/or recent substance use was found in 73.4% of these patients.Psychiatric comorbidities were very common among veterans with chronic hepatitis C and correlated poorly with diagnoses documented in the medical record. We recommend a multidisciplinary approach that includes psychological assessment using standardized questionnaires in the evaluation of these patients for antiviral therapy.

  View details for Web of Science ID 000178504800028

  View details for PubMedID 12385453

• Role of chronic hepatitis C on postoperative complications. Cheung, R., Hsieh, F., Wang, Y. J., Pollard, J. W B SAUNDERS CO. 2002: 532A

  View details for Web of Science ID 000178301701460

• Microarray analysis of leukocyte gene expression in Hepatitis C patients treated with interferon-alpha He, X. S., Ji, X. H., Cheung, R., Cooper, S., Brown, P., Greenberg, H. W B SAUNDERS CO. 2002: 79

  View details for Web of Science ID 000176684400395

• Viral hepatitis and other infectious diseases in a homeless population JOURNAL OF CLINICAL GASTROENTEROLOGY Cheung, R. C., Hanson, A. K., Maganti, K., Keeffe, E. B., Matsui, S. M. 2002; 34 (4): 476-480

  Abstract

  To determine the prevalence of four common infectious diseases-hepatitis B, hepatitis C, human immunodeficiency virus (HIV), and tuberculosis-as well as co-infection rates and risk factors in a homeless population.The prevalence of infectious diseases, especially viral hepatitis, among the homeless population is largely unknown.This study consists of a retrospective analysis of the history and laboratory data collected from all homeless veterans admitted to a Veterans Administration (VA) domiciliary from May 1995 to March 2000.Of the homeless veterans admitted to a VA domiciliary program, 597 of 829 were screened for markers of all four infectious diseases. The overall prevalence of anti-hepatitis C virus (HCV) antibody, and positive result for purified protein derivative (PPD), anti-HIV antibody, and hepatitis B surface antigen (HbsAg) were 41.7%, 20.6%, 1.84% and 1.17%, respectively. At least one of the four markers was positive in 52.6% and more than one in 12%. Co-infection with HCV occurred commonly in veterans who were positive for anti-HIV (72.7%) and HBsAg (57.1%). Four self-reported major risk factors (intravenous drug use, alcohol abuse, previous imprisonment, and prior stay in a shelter) were evaluated. Multivariate analysis indicates that intravenous drug use and anti-HBs reactivity are independent risk factors for HCV infection, HCV infection for anti-hepatitis B surface antibody reactivity, and older age for PPD positivity.Chronic hepatitis C and co-infections are common among the homeless population. Patients infected with HIV and hepatitis B virus frequently are co-infected with HCV. Infections frequently are associated with certain identifiable risk factors.

  View details for Web of Science ID 000174716100021

  View details for PubMedID 11907367

• Quantitative analysis of hepatitis C virus in peripheral blood and liver: Replication detected only in liver 10th International Symposium on Viral Hepatitis and Liver Disease Boisvert, J., He, X. S., Cheung, R., Keeffe, E. B., Wright, T., Greenberg, H. B. UNIV CHICAGO PRESS. 2001: 827–35

  Abstract

  Prior studies seeking evidence of viral replication in peripheral lymphocytes of hepatitis C virus (HCV)-infected patients have yielded conflicting results. This study sought to quantitatively determine whether a permissive HCV cell interaction could be detected in leukocytes from infected patients. Peripheral leukocytes from chronically infected patients were purified and were tested for HCV RNA. The results show that virus load is highest in B cells. Other subsets of peripheral leukocytes consistently had very low levels of viral RNA or were negative. Negative-strand HCV was found only in hepatocytes. To determine whether HCV replication could be induced by activation, B cells from HCV-infected patients were stimulated in vitro. No HCV replicating in peripheral leukocytes was detected by a highly sensitive assay. If HCV replication occurs in the leukocyte subsets analyzed here, it is at extremely low levels or occurs under alternate physiological conditions.

  View details for Web of Science ID 000171228400003

  View details for PubMedID 11550124

• Treating chronic hepatitis C patients with psychiatric disorders: An uphill battle AMERICAN JOURNAL OF GASTROENTEROLOGY Cheung, R., Ahmed, A. 2001; 96 (1): 3-4

  View details for Web of Science ID 000166435400003

  View details for PubMedID 11197283

• Endoscopic gastrointestinal manifestations of liver disease. Gastrointestinal endoscopy clinics of North America Cheung, R. C., Cooper, S., Keeffe, E. B. 2001; 11 (1): 15-44

  Abstract

  Esophageal and gastric varices are common manifestations of advanced chronic liver disease, but other endoscopic gastrointestinal manifestations of portal hypertension may occur. In the upper gastrointestinal tract, portal hypertensive gastropathy, particularly when severe, and gastric antral vascular ectasias are important alternative causes of gastrointestinal bleeding. Portal hypertensive enteropathy is an uncommon source of gastrointestinal bleeding, and its overall clinical significance remains unknown. In the lower gastrointestinal tract, portal hypertension may be associated with hemorrhoids, anorectal varices, and portal hypertensive colopathy, all of which are occasional causes of gastrointestinal bleeding.

  View details for PubMedID 11175973

• Delayed fatal hemorrhage from pseudoaneurysm of the hepatic artery after percutaneous liver biopsy AMERICAN JOURNAL OF GASTROENTEROLOGY Ahmed, A., Samuels, S. L., Keeffe, E. B., Cheung, R. C. 2001; 96 (1): 233-237

  Abstract

  Hemorrhage is the most common serious complication of percutaneous liver biopsy. Liver biopsy is usually done in an outpatient setting because most significant hemorrhage is evident within a few hours after biopsy. Delayed hemorrhage occurs much less frequently but carries a much higher mortality. We present a 41-yr-old man with chronic hepatitis C who underwent a percutaneous liver biopsy uneventfully but was found to have a pseudoaneurysm of the hepatic artery 5 days later. Shortly after admission, the patient experienced bleeding into the liver from the pseudoaneurysm, which was controlled initially by angiographic embolization. However, recurrent bleeding could not be controlled by repeat angiography and surgical intervention, and the patient expired. The diagnosis and management of pseudoaneurysm of the hepatic artery complicating liver biopsy is reviewed.

  View details for Web of Science ID 000166435400039

  View details for PubMedID 11197259

• Management of gallstones and their complications AMERICAN FAMILY PHYSICIAN Ahmed, A., Cheung, R. C., Keeffe, E. B. 2000; 61 (6): 1673-1680

  Abstract

  The accurate differentiation of gallstone-induced biliary colic from other abdominal disease processes is the most crucial step in the successful management of gallstone disease. Despite the availability of many imaging techniques to demonstrate the presence of gallstones, clinical judgment ultimately determines the association of symptoms with cholelithiasis and its complications. Adult patients with silent or incidental gallstones should be observed and managed expectantly, with few exceptions. In symptomatic patients, the intervention varies with the type of gallstone-induced complication. In this article, we review the salient clinical features, diagnostic tests and therapeutic options employed in the management of gallstones and their complications.

  View details for Web of Science ID 000086196400009

  View details for PubMedID 10750875

• Differential diagnosis of gallstone-induced complications SOUTHERN MEDICAL JOURNAL Ahmad, M., Cheung, R. C., Keeffe, E. B., Ahmed, A. 2000; 93 (3): 261-264

  Abstract

  Early recognition and prompt intervention are the most crucial steps in the management of gallstone-induced biliary disease. Many conditions can mimic the presentation of gallstone-induced complications. Therefore, participation of a clinically astute physician is essential in evaluating symptoms and interpreting diagnostic data in patients with symptomatic gallstones.

  View details for Web of Science ID 000085880200002

  View details for PubMedID 10728510

• Quantitative analysis of hepatitis C virus-specific CD8(+) T cells in peripheral blood and liver using peptide-MHC tetramers PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA He, X. S., Rehermann, B., Lopez-Labrador, F. X., Boisvert, J., Cheung, R., Mumm, J., Wedemeyer, H., Berenguer, M., Wright, T. L., DAVIS, M. M., Greenberg, H. B. 1999; 96 (10): 5692-5697

  Abstract

  It is believed that the hepatitis C virus (HCV)-specific CD8(+) cytotoxic T lymphocytes (CTLs) play a role in the development of liver cell injury and in the clearance of the virus. To develop a direct binding assay for HCV-specific CTLs, we generated two peptide-MHC tetramers by using the recombinant HLA A2.1 molecule and A2-restricted T cell epitopes of the HCV NS3 protein. With these reagents we are able to detect specific CD8(+) cells in the blood of 15 of 20 HLA-A2(+), HCV-infected patients, at a frequency ranging from 0.01% to 1.2% of peripheral CD8(+) T cells. Phenotypic analysis of these specific cells indicated that there is a significant variation in the expression of the CD45 isoforms and CD27 in different patients. A 6-hour incubation of one patient's blood with NS3 peptides resulted in the activation of the epitope-specific CD8(+) cells, as indicated by their expression of CD69 and IFN-gamma. We also detected NS3-specific CD8(+) T cells in the intrahepatic lymphocyte population isolated from liver biopsies of two HCV-infected patients. The frequency of these specific CD8(+) cells in the liver was 1-2%, at least 30-fold higher than in the peripheral blood. All of the intrahepatic NS3-specific CD8(+) T cells were CD69(+), suggesting that they were activated CTLs. Direct quantitation and characterization of HCV-specific CTLs should extend our understanding of the immunopathogenesis and the mechanism of clearance or persistence of HCV.

  View details for Web of Science ID 000080246500068

  View details for PubMedID 10318946

• Utilization of H2RA in the era of proton pump inhibitor and H-pylori infection. Cheung, R., Alto, P., Yella, M. W B SAUNDERS CO-ELSEVIER INC. 1999: A51

  View details for Web of Science ID 000079778400215

• Quantitative analysis of hepatitis C virus-specific CD8(+) T cells using peptide-MHC tetramers. He, X. S., Lopez, Boisvert, J., Cheung, R., Davis, M. M., Wright, T. L., Rehermann, B., Wedemeyer, H., Greenberg, H. B. W B SAUNDERS CO-ELSEVIER INC. 1999: A735

  View details for Web of Science ID 000079778403190

• Finding the iron in the melting pot - Practical use of a new genetic assay for hereditary hemochromatosis WESTERN JOURNAL OF MEDICINE Glenn, J. S., Cheung, R. C. 1998; 168 (6): 525-527

  View details for Web of Science ID 000074374100010

  View details for PubMedID 9655998

• Seroprevalence of viral hepatitis B and C: A study based on bloodborne pathogen exposure accidents. Cheung, R. C. W B SAUNDERS CO. 1998: A1225

  View details for Web of Science ID 000073089604971

• Hepatitis G virus: Clinical relevance and responsiveness to interferon AMERICAN JOURNAL OF GASTROENTEROLOGY Cheung, R. C., Keeffe, E. B. 1997; 92 (11): 1957-1959

  View details for Web of Science ID A1997YE27000001

  View details for PubMedID 9362171

• Hepatitis G virus: Is it a hepatitis virus? WESTERN JOURNAL OF MEDICINE Cheung, R. C., Keeffe, E. B., Greenberg, H. B. 1997; 167 (1): 23-33

  Abstract

  Hepatitis G virus (HGV) and GB virus C (GBV-C) are two newly discovered viral agents, different isolates of a positive-sense RNA virus that represents a new genus of Flaviviridae. The purpose of this review is to analyze new data that have recently been published on the epidemiology and associations between HGV and liver diseases such as posttransfusion hepatitis, acute and chronic non-A-E hepatitis, fulminant hepatitis, cryptogenic cirrhosis, and hepatocellular carcinoma. The role of HGV in coinfection with other hepatitis viruses, the response to antiviral therapy, and the impact of HGV on liver transplantation are also discussed. HGV is a transmissible blood-borne viral agent that frequently occurs as a coinfection with other hepatitis viruses due to common modes of transmission. The prevalence of HGV ranges from 0.9 to 10% among blood donors throughout the world and is found in 1.7% of volunteer blood donors in the United States. The majority of patients infected with HGV by blood transfusion do not develop chronic hepatitis, but hepatitis G viremia frequently persists without biochemical evidence of hepatitis. Serum HGV RNA has been found in 0 to 50% of patients with fulminant hepatitis of unknown etiology and 14 to 36% of patients with cryptogenic cirrhosis. The association between HGV and chronic non-A-E hepatitis remains unclear. Although HGV appears to be a hepatotrophic virus, its role in independently causing acute and chronic liver diseases remains uncertain.

  View details for Web of Science ID A1997XQ01100004

  View details for PubMedID 9265860

• Hepatitis C virus detection by single-round PCR specific for the terminal 3' noncoding region JOURNAL OF CLINICAL MICROBIOLOGY Umlauft, F., WONG, D. T., Oefner, P. J., Underhill, P. A., Cheung, R. C., Wright, T. L., Kolykhalov, A. A., Gruenewald, K., Greenberg, H. B. 1996; 34 (10): 2552-2558

  Abstract

  A single-round PCR method with primers specific for the 3' noncoding region (NCR) of hepatitis C virus (HCV) has been developed. Using a double RNAzol-B extraction, a high-temperature reverse-transcription step with SuperScript II reverse transcriptase, and a 40-cycle two-temperature PCR with a TaqStart antibody hot-start procedure, we were able to detect a 92-nucleotide fragment of the recently discovered 98-nucleotide highly conserved sequence at the 3' terminus of the HCV genome. Direct sequencing of the PCR products confirmed the specificity of the PCR and demonstrated conservation in this region. Only one nucleotide change in 14 specimens was found. End point dilution titration of sera with known viral RNA titers showed the sensitivity of the single-round 3' NCR PCR to be comparable to those of the established nested 5' NCR assays (fewer than 25 HCV genome equivalents). To evaluate specificity and sensitivity, a panel of 116 serum samples characterized by nested 5'-end PCR, genotyping, and quantitative assays was tested. A high degree of concordance (96%) between the 3' NCR and 5' NCR PCR results was found. The sequence conservation at the 3' end of the HCV genome among common genotypes and the savings in time, labor, and reagents from a single-round PCR make this assay a useful addition to the detection systems available to identify and monitor HCV infection.

  View details for Web of Science ID A1996VK78700043

  View details for PubMedID 8880519

• DETECTION OF HEPATITIS-C VIRUS-RNA BY METHODS USING PHENOL-CHLOROFORM OR SILICA PARTICLES - REPLY JOURNAL OF CLINICAL MICROBIOLOGY Cheung, R. C., Matsui, S. M., Greenberg, H. B. 1995; 33 (9): 2522-2523

  View details for Web of Science ID A1995RP75500062

• RAPID AND SENSITIVE METHOD FOR DETECTION OF HEPATITIS-C VIRUS-RNA BY USING SILICA PARTICLES JOURNAL OF CLINICAL MICROBIOLOGY Cheung, R. C., Matsui, S. M., Greenberg, H. B. 1994; 32 (10): 2593-2597

  Abstract

  We describe a rapid, sensitive, and economic method for detection of hepatitis C virus (HCV) RNA. This method uses silica particles for purification of nucleic acid and then a modified reverse transcription-PCR that minimizes the risk of contamination and reduces the amount of reagents used. We found purification by silica particles to be at least as sensitive and in certain circumstances more sensitive than that by traditional phenol-chloroform extraction. This improved sensitivity may be due to more efficient recovery of HCV RNA by silica particles. HCV RNA appears to bind to silica particles in a saturable fashion, and the addition of extraneous nucleic acids (salmon sperm DNA or tRNA) decreases the binding in a dose-related fashion. The reverse transcription-PCR is performed by using a modified single tube method which further simplifies and reduces the cost of this assay. Finally, this method may be applied to clinical specimens such as liver tissue.

  View details for Web of Science ID A1994PG91200050

  View details for PubMedID 7529243

  View details for PubMedCentralID PMC264112

• FORMATION AND INTRACELLULAR-LOCALIZATION OF HEPATITIS-C VIRUS ENVELOPE GLYCOPROTEIN COMPLEXES EXPRESSED BY RECOMBINANT VACCINIA AND SINDBIS VIRUSES JOURNAL OF VIROLOGY Dubuisson, J., Hsu, H. H., Cheung, R. C., Greenberg, H. B., Russell, D. G., Rice, C. M. 1994; 68 (10): 6147-6160

  Abstract

  Hepatitis C virus (HCV) encodes two putative virion glycoproteins (E1 and E2) which are released from the polyprotein by signal peptidase cleavage. In this report, we have characterized the complexes formed between E1 and E2 (called E1E2) for two different HCV strains (H and BK) and studied their intracellular localization. Vaccinia virus and Sindbis virus vectors were used to express the HCV structural proteins in three different cell lines (HepG2, BHK-21, and PK-15). The kinetics of association between E1 and E2, as studied by pulse-chase analysis and coprecipitation of E2 with an anti-E1 monoclonal antibody, indicated that formation of stable E1E2 complexes is slow. The times required for half-maximal association between E1 and E2 were 60 to 85 min for the H strain and more than 165 min for the BK strain. In the presence of nonionic detergents, two forms of E1E2 complexes were detected. The predominant form was a heterodimer of E1 and E2 stabilized by noncovalent interactions. A minor fraction consisted of heterogeneous disulfide-linked aggregates, which most likely represent misfolded complexes. Posttranslational processing and localization of the HCV glycoproteins were examined by acquisition of endoglycosidase H resistance, subcellular fractionation, immunofluorescence, cell surface immunostaining, and immunoelectron microscopy. HCV glycoproteins containing complex N-linked glycans were not observed, and the proteins were not detected at the cell surface. Rather, the proteins localized predominantly to the endoplasmic reticular network, suggesting that some mechanism exists for their retention in this compartment.

  View details for Web of Science ID A1994PG54100002

  View details for PubMedID 8083956

  View details for PubMedCentralID PMC237034

• SCREENING AND CONFIRMATORY TESTING OF CADAVER ORGAN DONORS FOR HEPATITIS-C VIRUS-INFECTION - A US NATIONAL COLLABORATIVE STUDY KIDNEY INTERNATIONAL Pereira, B. J., Wright, T. L., Schmid, C. H., Bryan, C. F., Cheung, R. C., Cooper, E. S., Hsu, H., HEYNLAMB, R., Light, J. A., Norman, D. J., VANTHIEL, D. H., Werner, B. G., Wright, C. E., Levey, A. S. 1994; 46 (3): 886-892

  Abstract

  Hepatitis C virus (HCV) can be transmitted by organ transplantation. Cadaver organ donors are screened for HCV infection by testing for antibodies to HCV (anti-HCV). The prevalence of HCV infection and performance of anti-HCV tests in detecting HCV infection in organ donors are unknown. Sera from 3078 cadaver organ donors were tested for anti-HCV by a first generation enzyme-linked immunosorbent assay (ELISA1). Sera from all 137 ELISA1 positive donors and a random sample of 92 ELISA1 negative donors were tested for anti-HCV by a second generation ELISA (ELISA2) and for HCV RNA by the polymerase chain reaction. Organ bank records were reviewed for risk factors associated with HCV infection. Follow-up was available on 70 recipients of organs from 42 ELISA2 positive donors. The prevalence of HCV RNA, extrapolated to all 3078 donors, was 2.4%. Liver disease, anti-HCV and HCV RNA were detected more frequently among recipients of organs from ELISA2 positive donors with HCV RNA than from ELISA2 positive donors without HCV RNA. Among donors, the sensitivity and negative predictive value of the ELISA2 for HCV RNA were 100%. However, despite a specificity of 98.1%, the positive predictive value was only 55.1%. Clinical and laboratory characteristics did not distinguish ELISA2 positive donors with and without HCV RNA. The presence of serum HCV RNA in organ donors predicts the risk of transmission of HCV infection. Discarding organs from ELISA2 positive donors would eliminate transmission, but organs from 1.88 percent of donors would be wasted.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1994PC21700036

  View details for PubMedID 7527878

• A CELL-SURFACE PROTEIN THAT BINDS AVIAN HEPATITIS-B VIRUS-PARTICLES JOURNAL OF VIROLOGY Kuroki, K., Cheung, R., Marion, P. L., Ganem, D. 1994; 68 (4): 2091-2096

  Abstract

  We have identified a 180-kDa cellular glycoprotein (gp180) that binds with high affinity to duck hepatitis B virus (DHBV) particles. The protein was detected by coprecipitating labeled duck hepatocyte proteins with virions or recombinant DHBV envelope proteins, using nonneutralizing monoclonal antibodies to the virion envelope. Binding of gp180 requires only the pre-S region of the viral large envelope protein, since recombinant fusion proteins bearing only this region efficiently coprecipitate gp180. The DHBV-gp180 interaction is blocked by two independent neutralizing monoclonal antibodies. The protein is found on both internal and surface membranes of the cell, and the species distribution of gp180 binding activity mirrors the known host range of DHBV infection. Functional gp180 is expressed in a wide variety of tissues in susceptible ducks.

  View details for Web of Science ID A1994NA30700007

  View details for PubMedID 8138993

  View details for PubMedCentralID PMC236683

• LONGITUDINAL-STUDY OF HEPATITIS-C VIREMIA IN CHRONIC HEPATITIS-C JOURNAL OF MEDICAL VIROLOGY Cheung, R. C., Chan, R. T., Lok, A. S. 1993; 41 (4): 338-342

  Abstract

  Serial serum samples from 20 untreated patients with chronic hepatitis C virus (HCV) infection were tested for HCV RNA by a nested polymerase chain reaction assay using primers from the highly conserved 5' noncoding region to determine the relationship between hepatitis C viremia and the activity of liver disease during the natural course of chronic HCV infection. Semiquantitation of serum HCV RNA level was achieved by testing serial 10-fold dilutions of RNA extracts to determine the end-point titer. All the patients were HCV RNA positive at presentation. There was a poor correlation between the initial HCV RNA titer and serum transaminase levels. All patients except one were persistently HCV RNA positive during a follow-up period of 1.5-15 years, although 17 (85%) had periods of normal or near-normal transaminase levels. There was no correlation between changes in the serum transaminase levels and HCV RNA titer. Patients with chronic HCV infection have persistent viremia despite fluctuations in ALT levels.

  View details for Web of Science ID A1993MJ71700014

  View details for PubMedID 8106870

• HCV INFECTION AMONG VETERANS - CLINICAL CORRELATION WITH VIREMIA AND ANTIBODY-RESPONSE CHEUNG, R., CARLSON, T., HSU, H., HOLODNIY, M., SALEM, P., GREENBERG, H. W B SAUNDERS CO. 1993: A84

  View details for DOI 10.1016/0270-9139(93)91864-O

  View details for Web of Science ID A1993LY99500111

• HEPATITIS-C VIREMIA IN PATIENTS WITH HEPATITIS-C VIRUS-INFECTION HEPATOLOGY Lok, A. S., Cheung, R., Chan, R., Liu, V. 1992; 15 (6): 1007-1012

  Abstract

  Sera from 103 patients were tested for hepatitis C virus RNA by nested polymerase chain reaction assay. Using primers from the highly conserved 5'-untranslated region, we detected hepatitis C virus RNA in 67 (88.2%) of 76 patients positive for antibody to hepatitis C virus by both second-generation and neutralization enzyme immunoassays. Hepatitis C virus RNA was detected in 93% of patients who had been infected for 10 yr or less and in 89% of those who had been infected for longer than 10 yr. Hepatitis C virus RNA was detected in all patients with chronic hepatitis, active cirrhosis or hepatocellular carcinoma and in 50% of those with nonspecific reactive hepatitis or inactive cirrhosis. Hepatitis C virus RNA was not detected in sera from 22 patients negative for antibody to hepatitis C virus or in 5 patients positive for antibody to hepatitis C virus by second-generation but not by neutralization enzyme immunoassay. Using primers from the less conserved nonstructural region 4, we detected hepatitis C virus RNA at a lower frequency, in 66% of patients who were positive for antibody to hepatitis C virus by both second-generation and neutralization enzyme immunoassays. The detection rate was higher in patients with frequent parenteral exposure. Our study showed that hepatitis C viremia can be detected in most patients with hepatitis C virus infection, including those with long-standing infection or advanced liver disease.

  View details for Web of Science ID A1992HX53200005

  View details for PubMedID 1317337

• PEPTIDE-MAPPING OF NEUTRALIZING AND NONNEUTRALIZING EPITOPES OF DUCK HEPATITIS-B VIRUS PRE-S POLYPEPTIDE VIROLOGY Yuasa, S., Cheung, R. C., Pham, Q., Robinson, W. S., Marion, P. L. 1991; 181 (1): 14-21

  Abstract

  Antibodies to the envelope proteins of duck hepatitis B virus neutralize viral infection in vitro. Using a library of murine monoclonal antibodies (Mabs) against the envelope proteins, we previously identified four neutralizing and two non-neutralizing epitopes on the pre-S region of the large envelope proteins. In this study we report the localization of all but one of these epitopes at the amino acid level. All but 28 nucleotides of the pre-S and S genes were cloned in pUC vectors and expressed in Escherichia coli. All Mabs in this study reacted with the expressed gene products in Western blots. Deletion mutants of the pre-S region were generated and their expressed products tested on Western blots for reactivity with the Mabs. Of the three epitopes involved in neutralization, the epitope found to be immunodominant in convalescent ducks was localized to nine amino acids of the middle portion of the pre-S gene product, while a second epitope was mapped to nine amino acids upstream of the immunodominant epitope and the third epitope to seven amino acids adjacent to the S gene. One of the two non-neutralizing epitopes was located between the two groups of neutralizing epitopes while the other mapped to the same region as one of the neutralizing epitopes. Our data indicate that several regions of the pre-S polypeptide may play a role in neutralization of hepadnaviruses.

  View details for Web of Science ID A1991EW94200002

  View details for PubMedID 1704654

• EPITOPE-SPECIFIC ANTIBODY-RESPONSE TO THE SURFACE-ANTIGEN OF DUCK HEPATITIS-B VIRUS IN INFECTED DUCKS VIROLOGY Cheung, R. C., TRUJILLO, D. E., Robinson, W. S., Greenberg, H. B., Marion, P. L. 1990; 176 (2): 546-552

  Abstract

  In order to investigate the immune response to duck hepatitis B virus (DHBV) infection, newly hatched DHBV DNA negative ducklings were injected with infectious serum of sufficiently low DHBV-DNA titer to allow clearance of viremia. Of 20 injected ducklings, 13 (65%) became viremic. Of these, 6 (46%) cleared virus from the serum 3 to 22 weeks postinjection. The convalescent sera of these 6 animals were tested for an epitope-specific antibody response in a highly specific competitive inhibition assay using a panel of monoclonal antibodies against duck hepatitis B surface antigen (DHBsAg) that had been well-characterized. All 6 animals recovering from DHBV infection developed antibodies to epitopes on the preS and S proteins of DHBV. Antibody responses were highly variable with marked differences between animals in the extent and specificity of the antibody response. The humoral response to DHBsAg was prolonged in some animals but transient in others. No antibody to preS or S was detected in either preimmune sera or sera of control animals from an uninfected flock. Infected animals that did not clear viremia also remained antibody negative. The humoral responses to neutralizing preS epitopes III and V were weak but antibodies to two immunodominant epitopes on the preS region (II and B) were present in all 6 animals. The humoral response to the two epitopes in the S region was transient and of lower titer when compared to the two immunodominant preS epitopes. The two immunodominant preS epitopes may play an important role in clearance of DHBV infection in ducks.

  View details for Web of Science ID A1990DF12300025

  View details for PubMedID 1693247

• EPITOPE MAPPING OF NEUTRALIZING MONOCLONAL-ANTIBODIES AGAINST DUCK HEPATITIS-B VIRUS JOURNAL OF VIROLOGY Cheung, R. C., Robinson, W. S., Marion, P. L., Greenberg, H. B. 1989; 63 (6): 2445-2451

  Abstract

  In this article we report the first topological mapping of neutralizing epitopes of a hepadnavirus. Duck hepatitis B virus is the only hepadnavirus that can replicate and spread from cell to cell in tissue culture. As a result, it is possible to study hepadnaviral neutralization in vitro with this system. To accomplish this goal, we produced a library of monoclonal antibodies against duck hepatitis B virus and identified 12 neutralizing monoclonal antibodies by using an in vitro neutralization assay. The characteristics of six of the neutralizing monoclonal antibodies were further studied by epitope mapping. From the results of competitive binding studies, three distinct neutralizing epitopes were identified on the pre-S polypeptides and one was identified on the S polypeptide. Our findings suggest that antibodies to both the pre-S and S gene products of duck hepatitis B virus can neutralize viral infection in vitro. The pre-S gene product is at least as important as the S gene product in eliciting neutralizing antibodies.

  View details for Web of Science ID A1989U609600005

  View details for PubMedID 2470915