Bio


I am clinically trained as a physician specializing in gastroenterology and hepatology. My research has focused on clinical research of nonalcoholic fatty liver disease (NAFLD) and obesity-related gastrointestinal diseases, focusing on a population-based study. In addition, my research was not only focused on gastroenterology and was expanded to cardiology, endocrinology, and neurology (sleep medicine). I have experience with large epidemiologic cohort studies as well as clinical trials. This work has resulted in over 250 published papers, including major journals such as Gastroenterology, Hepatology, Gut, Journal of Hepatology, American Journal of Gastroenterology, etc. (as the first and corresponding author). These publications have been cited more than 13,000 times.

Honors & Awards


  • Young Investigator Award, Korean Society of Neurogastroenterology and Motility (2006)
  • Young Investigator Travel Award, Korean Association of Study of Liver (2007, 2008)
  • Excellent Research Award, Korean College of Helicobacter and Upper Gastrointestinal Research (2009)
  • GlaxoSmithKline-KASL Academic Scholarship, Korean Association of Study of Liver (2009)
  • Excellent Research Award, Seoul National University Hospital (2009-2014)
  • Excellent Research Award, Korean Society of Gastroenterology (2011)
  • Best Reviewer Award, Korean Association of Study of Liver (2012)
  • Excellent Research Award, Korean Society of Neurogastroenterology and Motility (2012)
  • KASL-GlaxoSmithKline Excellent Research Award, Korean Association of Study of Liver (2013)

Education & Certifications


  • Pre-Medical Program, Seoul National University College of Natural Science, Pre-Medical Program (1992)
  • MD, BA, Seoul National University College of Medicine, Medicine (1996)
  • MS, Seoul National University College of Medicine, Medical Science (2005)
  • Ph.D., Seoul National University College of Medicine, Medical Science (2010)
  • Certificate, Mayo Clinic in Rochester, Clinical and Translational Science (2011)

Professional Affiliations and Activities


  • Board Certification, Korean Board of Medicine (1996 - Present)
  • Internship, Samsung Medical Center (1999 - 2000)
  • Resident, Samsung Medical Center (2000 - 2004)
  • Clinical Fellow, Samsung Medical Center (2004 - 2005)
  • Board Certification, Korean Board of Internal Medicine (2004 - Present)
  • Assistant Professor, Seoul National University Hospital (2005 - 2012)
  • Board Certification, Korean Board of Endoscopy (2005 - Present)
  • Board Certification, Korean Board of Gastroenterology (2006 - Present)
  • Member, European Association for the Study of the Liver (2009 - Present)
  • Member, Asian Pacific Association for the Study of the Liver (2009 - Present)
  • Member, American Association for the Study of Liver Diseases (2010 - Present)
  • Associate Professor, Seoul National University Hospital (2012 - 2015)
  • Member, American College of Gastroenterology (2015 - Present)

All Publications


  • Secondhand Smoke Exposure and Metabolic Dysfunction-Associated Steatotic Liver Disease in US Adolescents. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Perumpail, B. J., Danpanichkul, P., Wijarnpreecha, K., Ahmed, A. 2024

    View details for DOI 10.1016/j.cgh.2024.08.049

    View details for PubMedID 39490949

  • Long-term Outcomes and Risk Modifiers of MASLD Between Lean and Non-Lean Populations. Clinical and molecular hepatology Danpanichkul, P., Suparan, K., Prasitsumrit, V., Ahmed, A., Wijarnpreecha, K., Kim, D. 2024

    Abstract

    One-third of adults across the globe exhibit metabolic dysfunction-associated steatotic liver disease (MASLD) - formerly known as nonalcoholic fatty liver disease (NAFLD). To date, MASLD is the fastest-growing etiology of chronic liver disease and hepatocellular carcinoma (HCC). Besides the population with obesity, MASLD can also be found in lean populations, accounting for 13% of the global population, especially Asians. Notably, individuals with lean MASLD face equal or higher overall mortality rates compared to their non-lean counterparts. Risk modifiers encompass advanced age, hepatic fibrosis, and type 2 diabetes mellitus (T2DM). Moreover, the population with lean MASLD is associated with an increased risk of HCC, while their non-lean counterparts are more prone to cardiovascular outcomes and T2DM. Existing evidence indicates a similar risk of liver-related events and extrahepatic cancer between the two groups. However, MASLD-related genetic variants, such as PNPLA3 and TM6SF2, did not significantly affect mortality between the two populations. Still, underreporting alcohol consumption and regional representation limits the study's comprehensiveness. Longitudinal studies and mechanistic explorations are needed to understand differences in lean versus non-lean MASLD populations. This review highlights the need for awareness and tailored interventions in managing MASLD, considering lean individuals' unique risks.

    View details for DOI 10.3350/cmh.2024.0631

    View details for PubMedID 39439408

  • Contemporary Awareness of Viral Hepatitis between 2012 and 2022 among Korean Adults. Clinical and molecular hepatology Kim, D., Kim, W., Ahmed, A. 2024

    View details for DOI 10.3350/cmh.2024.0849

    View details for PubMedID 39376141

  • Leukocyte Telomere Shortening in MASLD and All-cause/Cause-specific Mortality. Clinical and molecular hepatology Kim, D., Danpanichkul, P., Wijarnpreecha, K., Cholankeril, G., Ahmed, A. 2024

    View details for DOI 10.3350/cmh.2024.0691

    View details for PubMedID 39188229

  • Burden of Mortality from Hepatocellular Carcinoma and Biliary Tract Cancers by Race and Ethnicity and Sex in US, 2018-2023. Clinical and molecular hepatology Kim, D., Manikat, R., Wijarnpreecha, K., Cholankeril, G., Ahmed, A. 2024

    Abstract

    The trends in mortality of hepatocellular carcinoma (HCC) and biliary tract cancers stratified by sex and race/ethnicity in the US continue to evolve. We estimated the sex- and race/ethnicity-based trends in HCC and biliary tract cancers-related mortality in US adults with a focus on disease burden.We performed a population-based analysis using the US national mortality records from 2018 to 2023. We identified HCC and biliary tract cancer using appropriate ICD-10 codes. Temporal trends in mortality were calculated by joinpoint analysis with annual percentage change (APC).Annual age-standardized mortality from HCC decreased steadily with an APC of -1.4% (95% confidence interval [CI]: -2.0% to -0.7%). While there was a linear increase in intrahepatic cholangiocarcinoma-related mortality (APC: 3.1%, 95% CI: 1.2%-4.9%) and ampulla of Vater cancer-related mortality (APC: 4.1%, 95% CI: 0.5%-7.9%), gallbladder cancer-related mortality decreased (APC: -1.9%, 95% CI: -3.8% to -0.0%). Decreasing trends in mortality from HCC were noted in males, not females. HCC-related mortality decreased more steeply in racial and ethnic minority individuals compared with non-Hispanic White individuals. Racial and ethnic differences in trends in mortality for biliary tract cancers depended on the malignancy's anatomical site.While the annual mortality for HCC- and gallbladder cancer demonstrated declining trends, ICC and AVC-related mortality continued to increase from 2018 to 2023. Although racial and ethnic minority individuals in the US experienced disproportionately higher HCC and biliary tract cancer, recent declines in HCC may be primarily due to declines among racial and ethnic minority individuals and males.

    View details for DOI 10.3350/cmh.2024.0318

    View details for PubMedID 38910110

  • Financial hardship and cost-related nonadherence to medication in patients with liver disease in the United States. Alimentary pharmacology & therapeutics Kim, D., Manikat, R., Wijarnpreecha, K., Ahmed, A. 2024

    Abstract

    Economic hardship associated with chronic liver disease (CLD) may delay timely access to healthcare.To estimate the national burden of financial hardship across the spectrum of CLD in the United States (US) during the coronavirus disease 2019 (COVID-19) pandemic.A cross-sectional analysis was performed using the 2020-2021 US National Health Interview Survey database. The questionnaire defined financial hardship from medical bills and cost-related nonadherence to medications in patients with CLD. We used weighted survey analysis to obtain the national estimates.While 6.9% (95% confidence interval [CI]: 6.7%-7.2%) out of 60,689 US adults (weighted sample: 251 million) reported financial hardship and inability to pay medical bills; 10.6% (95% CI: 8.3%-13.4%), 18.2% (95% CI: 14.5%-22.6%), 22.6% (95% CI: 11.0%-41.0%) with hepatitis, CLD/cirrhosis, and liver cancer experienced an inability to pay their medical bills due to financial hardship, respectively. 19.8% (95% CI: 15.9%-24.5%) and 23.3% (95% CI: 12.5%-39.3%) with CLD/cirrhosis and liver cancer, respectively experienced cost-related nonadherence to medications, compared to a tenth of US adults (10.7%, 95% CI: 10.3%-11.2%). CLD/cirrhosis demonstrated an independent association with financial hardship from medical bills and cost-related nonadherence to medications. Overall, these disparities were more pronounced in individuals aged <65 years old. In addition, over 40% of individuals with CLD/cirrhosis reported difficulties accessing medical care during the COVID-19 pandemic. CLD/cirrhosis showed an independent association with difficulties accessing medical care due to COVID-19.Financial hardship from medical bills and cost-related nonadherence to medication can negatively impact individuals with CLD and need further evaluation.

    View details for DOI 10.1111/apt.18122

    View details for PubMedID 38864288

  • Steatotic liver disease-associated all-cause/cause-specific mortality in the United States. Alimentary pharmacology & therapeutics Kim, D., Wijarnpreecha, K., Cholankeril, G., Ahmed, A. 2024

    Abstract

    Recently, a panel of multi-society experts proposed steatotic liver disease (SLD) as an alternative terminology for metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD).We compared the impact of SLD, subtype of SLD, MAFLD and NAFLD on all-cause and cause-specific mortality.A total of 7811 individuals in the third National Health and Nutrition Examination Survey and linked mortality through 2019 were analysed. SLD was defined based on ultrasonographic hepatic steatosis. SLD, subtype of SLD and MAFLD were defined using the proposed definitions. The Cox proportional hazard model assessed all-cause/cause-specific mortality.During a median follow-up of 27.1 years, individuals with SLD and MAFLD experienced approximately 13%-23% higher risk of all-cause mortality (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.02-1.29 for SLD; HR: 1.23, 95% CI: 1.09-1.38 for MAFLD; HR: 1.13, 95% CI: 1.01-1.27 for metabolic dysfunction-associated steatotic liver disease [MASLD]). Individuals with MetALD demonstrated a higher risk of all-cause (HR: 1.68, 95% CI: 1.10-2.57) and cancer-related mortality (HR: 2.40, 95% CI: 1.23-4.66). MASLD with advanced fibrosis had an increased risk of all-cause mortality compared to MASLD without advanced fibrosis.SLD, especially MASLD and MetALD, is associated with increased all-cause mortality among adults in the US. Given this significant association between SLD or subtype of SLD (MASLD and MetALD) and all-cause mortality, adopting the proposed SLD criteria may help identify a sub-group of individuals with SLD who are at an increased risk for all-cause mortality.

    View details for DOI 10.1111/apt.18011

    View details for PubMedID 38649335

  • Metabolic Dysfunction-Associated Steatotic Liver Disease and All-Cause/Cause-Specific Mortality among Adults in the United States. Journal of hepatology Kim, D., Wijarnpreecha, K., Cholankeril, G., Ahmed, A. 2023

    View details for DOI 10.1016/j.jhep.2023.09.014

    View details for PubMedID 37717601

  • Trends in aetiology-based hospitalisation for cirrhosis before and during the COVID-19 pandemic in the United States. Alimentary pharmacology & therapeutics Kim, D., Perumpail, B. J., Wijarnpreecha, K., Manikat, R., Cholankeril, G., Ahmed, A. 2023

    Abstract

    Patients with pre-existing cirrhosis and exposure to coronavirus disease-19 (COVID-19) may portend a poor prognosis. We evaluated the temporal trends in aetiology-based hospitalisations and potential predictors of in-hospital mortality in hospitalisation with cirrhosis before and during the COVID-19 pandemic.Based on the US National Inpatient Sample 2019-2020, we determined quarterly trends in aetiology-based hospitalisations with cirrhosis and decompensated cirrhosis and identified predictors of in-hospital mortality in hospitalisation with cirrhosis.We analysed 316,418 hospitalisations, representing 1,582,090 hospitalisations with cirrhosis. Hospitalisations for cirrhosis increased at a relatively higher rate during the COVID-19 era. Hospitalisation rates for alcohol-related liver disease (ALD)-related cirrhosis increased significantly (quarterly percentage change [QPC]: 3.6%, 95% CI: 2.2%-5.1%), with a notably higher rate during the COVID-19 era. In contrast, hospitalisation rates for hepatitis C virus (HCV)-related cirrhosis decreased steadily with a trend of -1.4% of QPC (95% CI: -2.5% to -0.1%). Quarterly trends in the proportion of ALD- (QPC: 1.7%, 95% CI: 0.9%-2.6%) and nonalcoholic fatty liver disease-related (QPC: 0.7%, 95% CI: 0.1%-1.2%) hospitalisations with cirrhosis increased significantly but declined steadily for viral hepatitis. The COVID-19 era and COVID-19 infection were independent predictors of in-hospital mortality during hospitalisation with cirrhosis and decompensated cirrhosis. Compared with HCV-related cirrhosis, ALD-related cirrhosis was associated with a 40% higher risk of in-hospital mortality.In-hospital mortality in cirrhosis was higher in the COVID-19 era than in the pre-COVID-19 era. ALD is the leading aetiology-specific cause of in-hospital mortality in cirrhosis with an independent detrimental impact of the COVID-19 infection.

    View details for DOI 10.1111/apt.17547

    View details for PubMedID 37189243

  • Trends in Etiology-based Mortality from Chronic Liver Disease before and during COVID-19 Pandemic in the United States. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Alshuwaykh, O., Dennis, B. B., Cholankeril, G., Ahmed, A. 2022

    Abstract

    BACKGROUND AIMS: During the global coronavirus disease-2019 (COVID-19) pandemic, patients with pre-existing chronic liver disease may represent a vulnerable population. We studied the etiology-based temporal trends in mortality of chronic liver disease and the underlying cause of death in the United States before and during the COVID-19 pandemic.METHODS: Population-based analyses were performed on US national mortality records (2017- 2020). Temporal trends in quarterly age-standardized mortality were obtained by joinpoint analysis with estimates of quarterly percentage change (QPC).RESULTS: Quarterly age-standardized all-cause mortality due to alcohol-related liver disease (ALD) initially increased at a quarterly rate of 1.1% before the COVID-19 pandemic, followed by a sharp increase during the COVID-19 pandemic at a quarterly rate of 11.2%. Likewise, steady increase in mortality of nonalcoholic fatty liver disease (NAFLD) before the COVID-19 pandemic (QPC: 1.9%) accelerated during the COVID-19 pandemic (QPC: 6.6%). While ALD-related mortality increased steeply compared to viral hepatitis-related mortality during the COVID-19 pandemic, the proportion of mortality due to COVID-19 among individuals with ALD was the lowest at 2.5%; more than 50% lower than viral hepatitis. The significant decline in all-cause mortality due to viral hepatitis before the COVID-19 pandemic plateaued during the COVID-19 pandemic due to increase in COVID-19-related mortality in individuals with viral hepatitis. Mortality due to cirrhosis increased markedly during the COVID-19 pandemic, mainly attributable to ALD.CONCLUSION: All-cause mortality for ALD and NAFLD rapidly accelerated during the COVID-19 pandemic compared to the pre-COVID-19 era. There has been a significant decline in viral hepatitis; however, a significant increase in COVID-related death in this population.

    View details for DOI 10.1016/j.cgh.2022.05.045

    View details for PubMedID 35811045

  • Gallstone Disease and its Association with Nonalcoholic Fatty Liver Disease, All-Cause and Cause-Specific Mortality. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Konyn, P., Alshuwaykh, O., Dennis, B. B., Cholankeril, G., Ahmed, A., Kim, D. 2022

    Abstract

    BACKGROUND AND AIMS: Presence of gallstone disease may influence outcomes in patients with nonalcoholic fatty liver disease (NAFLD). We studied the impact of gallstone disease on mortality in individuals with and without NAFLD.METHODS: Prospective cohort study using the Third National Health and Nutrition Examination Survey (1988-1994) with mortality data through 2015. Gallstone disease was defined as ultrasonographic evidence of gallstones or absence of the gallbladder (prior cholecystectomy). NAFLD was defined using standardized ultrasonographic criteria.RESULTS: Gallstone disease and cholecystectomy were independently associated with NAFLD (odds ratio [OR]: 1.75, 95% confidence interval [CI]: 1.43-2.15 for gallstone disease and OR: 2.77, 95% CI: 2.01-3.83 for cholecystectomy compared to no gallstone disease). During the median follow-up of 23 years, gallstone disease was associated with a higher risk of overall all-cause mortality (hazard ratio [HR]: 1.19, 95% CI: 1.05-1.37) and cause-specific mortality. Gallstone disease was associated with a higher risk of all-cause mortality in non-NAFLD sub-cohort (HR: 1.42, 95% CI 1.23-1.64), but not in NAFLD (HR: 1.03, 95% CI: 0.87-1.22). Gallstone disease was associated with a higher risk of cardiovascular (HR: 1.40, 95% CI 1.10-1.78) and cancer (HR: 1.71, 95% CI: 1.18-2.48)-related mortality in non-NAFLD sub-cohort. Gallstone disease was associated with increased cardiovascular mortality (HR: 1.36, 95% CI: 1.05-1.77) in NAFLD.CONCLUSION: Gallstone disease is an independent risk factor for NAFLD, but gallstone disease is not associated with all-cause mortality in individuals with NAFLD. Screening for gallstone disease in individuals at risk for developing NAFLD may help with risk stratification for all-cause mortality related to gallstone disease.

    View details for DOI 10.1016/j.cgh.2022.04.043

    View details for PubMedID 35643414

  • Trends in All-Cause and Cause-Specific Mortality Among Individuals With Diabetes Before and During the COVID-19 Pandemic in the U.S. Diabetes care Kim, D., Alshuwaykh, O., Sandhu, K. K., Dennis, B. B., Cholankeril, G., Ahmed, A. 2022

    View details for DOI 10.2337/dc22-0348

    View details for PubMedID 35446372

  • Mortality Trends in Chronic Liver Disease and Cirrhosis in the United States, before and during COVID-19 Pandemic. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Bonham, C. A., Konyn, P., Cholankeril, G., Ahmed, A. 2021

    View details for DOI 10.1016/j.cgh.2021.07.009

    View details for PubMedID 34256143

  • Physical Activity is Associated with Nonalcoholic Fatty Liver Disease and Significant Fibrosis measured by Fibroscan. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Konyn, P., Cholankeril, G., Ahmed, A. 2021

    Abstract

    BACKGROUND: /Aims: Studies evaluating the association of 2018 Physical Activity (PA) Guidelines for Americans (PA Guidelines) with nonalcoholic fatty liver (NAFLD) and significant fibrosis/cirrhosis are needed. We evaluated the association of meeting PA Guidelines with NAFLD and significant fibrosis/cirrhosis by transient elastography in the US.METHODS: A cross-sectional analysis was performed using the 2017-2018 US National Health and Nutrition Examination Survey data. NAFLD and significant fibrosis/cirrhosis were defined by transient elastography in the absence of other causes of chronic liver disease. The detailed PA questionnaire assessed the leisure-time, occupation, and transportation-related PA. PA was categorized based on the PA Guidelines.RESULTS: Of the 4,304 subjects, leisure-time PA, which met the PA Guidelines (≥150 minutes/week), was associated with 44% lower risk of NAFLD (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.46-0.67). Subjects who reported 1-2 times (150-299 minutes/week) or over 2 times (≥300 minutes/week) the recommended amount of PA Guidelines had 40% (OR: 0.60, 95% CI: 0.41-0.90) and 49% (OR: 0.51, 95% CI: 0.40-0.65) lower odds of NAFLD, respectively. Over 8 hours of sitting time had a 44% higher risk of NAFLD (OR: 1.44, 95% CI: 1.01-2.05), when we considered leisure-time PA and sitting time simultaneously. Over 2 times (≥300 minutes/week) recommended amount of PA Guidelines for leisure-time PA had 59% (OR: 0.41, 95% CI: 0.22-0.74) lower risk for significant fibrosis and 63% (OR: 0.37, 95% CI: 0.21-0.64) lower odds of cirrhosis.CONCLUSIONS: Meeting PA Guidelines for leisure-time PA has beneficial effects on NAFLD and over two times recommended amount of PA Guidelines had lower risk for significant fibrosis or cirrhosis.

    View details for DOI 10.1016/j.cgh.2021.06.029

    View details for PubMedID 34214678

  • Trends in the Mortality of Biliary Tract Cancers Based on Their Anatomical Site in the United States From 2009 to 2018. The American journal of gastroenterology Kim, D., Konyn, P., Cholankeril, G., Bonham, C. A., Ahmed, A. 2021; 116 (5): 1053–62

    Abstract

    INTRODUCTION: Recent trends in the incidence and mortality of biliary tract cancers are unknown. We estimated the trends in biliary tract cancers-related incidence and mortality stratified by anatomical site, age, sex, and race/ethnicity in the US adults.METHODS: We performed a population-based trend analysis using the US national incidence (2009-2017) and mortality records (2009-2018). We identified age-standardized incidence and mortality from intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer using appropriate ICD-10 code. Temporal mortality was calculated by joinpoint trend analysis with estimates of annual percentage change (APC) described as each trend segment.RESULTS: The incidence rates of ICC increased linearly (APC 8.9%, 95% confidence interval [CI] 7.8%-10.0%) while gallbladder cancer-related incidence rates remained stable early and decreased significantly later in the study (APC -2.8%, 95% CI -5.5% to -0.0% [2014-2017]). Age-standardized mortality from biliary tract cancers steadily increased with an annual increase of 2.0% (95% CI 1.6%-2.3%). Although there was a linear increase in the ICC-related mortality (APC 3.5%, 95% CI 3.1%-3.8%), extrahepatic cholangiocarcinoma-related mortality tended to remain stable earlier and increased later (APC 7.0%, 95% CI 4.6%-9.5% [2013-2018]). By contrast, gallbladder cancer-related mortality steadily decreased over 10 years (APC -1.6%, 95% CI -2.1% to -1.1%). Significant differences in mortality and changes in trends over time were observed in non-Hispanic blacks, Hispanics, and non-Hispanic Asians.DISCUSSION: In this analysis of nationally representative data, changing mortality trends in various biliary tract cancers was noted with a disproportionately higher burden of fatality in minorities.

    View details for DOI 10.14309/ajg.0000000000001151

    View details for PubMedID 33929380

  • Metabolic dysfunction-associated fatty liver disease is associated with increased all-cause mortality in the United States. Journal of hepatology Kim, D., Konyn, P., Sandhu, K. K., Dennis, B. B., Cheung, A. C., Ahmed, A. 2021

    Abstract

    Recently, international experts have put forward a modified criterion to redefine nonalcoholic fatty liver disease (NAFLD) as metabolic-associated fatty liver disease (MAFLD). It is suspected that outcomes such as mortality may differ for these clinical entities. We studied the impact of MAFLD and NAFLD on the all-cause and cause-specific mortality in US adults.We analyzed data from 7,761 participants in the Third National Health and Nutrition Examination Survey and their linked mortality through 2015. NAFLD was diagnosed by ultrasonographic evidence of hepatic steatosis without other known liver diseases. MAFLD was defined based on the criteria proposed by an international expert panel. The Cox proportional hazard model was used to study all-cause mortality and cause-specific mortality between MAFLD and NAFLD with adjustments for known risk factors.During a median follow-up of 23 years, individuals with MAFLD had a 17% higher risk for all-cause mortality (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.04-1.32). Furthermore, MAFLD was associated with a higher risk for cardiovascular mortality. NAFLD per se did not increase the risk of all-cause deaths. Individuals who met both definitions were noted to have a higher risk for all-cause mortality (HR: 1.13, 95% CI: 1.00-1.26). Also, MAFLD without NAFLD had 1.7-fold higher all-cause mortality (HR: 1.66, 95% CI: 1.19-2.32). Individuals with advanced fibrosis and MAFLD had higher estimates for all-cause mortality than those with advanced fibrosis and NAFLD.In this US population-based study, MAFLD was associated with increased risk of all-cause mortality, while NAFLD demonstrated no association with all-cause mortality after adjusting for metabolic risk factors.Our findings provide further support to the idea that nonalcoholic fatty liver disease (NAFLD) is a part of a broader multi-system disease that also includes obesity, diabetes, high blood pressure, and high cholesterol. Therefore, re-defining NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD) may provide a better understanding of predictors that may increase the risk of death.

    View details for DOI 10.1016/j.jhep.2021.07.035

    View details for PubMedID 34380057

  • Prevalence of Fatty Liver Disease and Fibrosis detected by Fibroscan in Adults in the United States, 2017-2018. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Cholankeril, G., Loomba, R., Ahmed, A. 2020

    View details for DOI 10.1016/j.cgh.2020.08.017

    View details for PubMedID 32801011

  • Decline in Annual Mortality of Hepatitis C Virus-related Hepatocellular Carcinoma in the United States, From 2009 to 2018. Gastroenterology Kim, D., Konyn, P., Cholankeril, G., Wong, R. J., Younossi, Z. M., Ahmed, A. 2020

    View details for DOI 10.1053/j.gastro.2020.05.007

    View details for PubMedID 32389664

  • Inadequate Physical Activity and Sedentary Behavior Are Independent Predictors of Nonalcoholic Fatty Liver Disease. Hepatology (Baltimore, Md.) Kim, D. n., Vazquez-Montesino, L. M., Li, A. A., Cholankeril, G. n., Ahmed, A. n. 2020

    Abstract

    In general, physical activity (PA) and nonalcoholic fatty liver disease (NAFLD) have an inverse association. However, studies assessing the impact of the widely accepted Physical Activity Guidelines for Americans (PA Guidelines) on NAFLD are lacking. We performed a serial, cross-sectional analysis among adults by using the 2007-2016 United States National Health and Nutrition Examination Survey. NAFLD and advanced fibrosis were defined by using various noninvasive panels. A PA questionnaire assessed the leisure-time PA, occupation-related PA, transportation-related PA, and total sitting time as sedentary behavior. PA was categorized according to the PA Guidelines. Of the 24,588 individuals (mean age 47.4 years; 47.9% males), leisure-time PA (≥150 minutes/week) demonstrated 40% lower odds of NAFLD, whereas transportation-related PA was associated with 33% risk reduction in NAFLD. Analysis of total PA and sitting times simultaneously showed a dose-response association between sitting time and NAFLD (P for trend <0.001). Compliance with the PA Guidelines was lower in NAFLD versus non-NAFLD. The trends in compliance with the PA Guidelines for any type of PA remained stable in NAFLD except for a downtrend in transportation-related PA. In contrast, an improvement in compliance with the PA Guidelines for leisure-time was noted in the non-NAFLD cohort. Although PA demonstrated 10% stronger association with risk reduction of NAFLD in women, women showed a lower tendency of meeting the PA guidelines. Trends in total sitting time increased significantly regardless of NAFLD status. Conclusion: Sedentary behavior emerged as an independent predictor of NAFLD. Overall compliance with the PA Guidelines was lower in the NAFLD cohort with sex- and ethnicity-based differences. Implementation of these observations in clinical practice may improve our understanding as well as clinical outcomes.

    View details for DOI 10.1002/hep.31158

    View details for PubMedID 32012316

  • Predictors of Outcomes of COVID-19 in Patients with Chronic Liver Disease: US Multi-center Study. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D. n., Adeniji, N. n., Latt, N. n., Kumar, S. n., Bloom, P. P., Aby, E. S., Perumalswami, P. n., Roytman, M. n., Li, M. n., Vogel, A. S., Catana, A. M., Wegermann, K. n., Carr, R. M., Aloman, C. n., Chen, V. n., Rabiee, A. n., Sadowski, B. n., Nguyen, V. n., Dunn, W. n., Chavin, K. n., Zhou, K. n., Lizaola-Mayo, B. n., Moghe, A. n., Debes, J. n., Lee, T. H., Branch, A. n., Viveiros, K. n., Chan, W. n., Chascsa, D. n., Kwo, P. n., Dhanasekaran, R. n. 2020

    Abstract

    Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19).We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD.Of the 978 patients in our cohort, 867 patients (mean age 56.9±14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29-4.55), decompensated cirrhosis (HR 2.91 [1.70-5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53-7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47-3.70]) and decompensated cirrhosis (OR 2.50 [1.20-5.21]) were independently associated with risk for severe COVID-19.The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19.

    View details for DOI 10.1016/j.cgh.2020.09.027

    View details for PubMedID 32950749

  • Physical Activity, Measured Objectively, is Associated With Lower Mortality in Patients With Nonalcoholic Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D. n., Murag, S. n., Cholankeril, G. n., Cheung, A. n., Harrison, S. A., Younossi, Z. M., Ahmed, A. n. 2020

    Abstract

    The association between physical activity (PA) and all-cause and cause-specific mortality from nonalcoholic fatty liver disease (NAFLD) requires investigation. We studied whether PA, measured by accelerometer, is associated with all-cause and cardiovascular mortality among individuals with NAFLD.We performed a longitudinal analysis using the 2003-2006 US National Health and Nutrition Examination Survey data of adults (20 years or older) and collecting mortality data through December 2015. NAFLD was defined based on hepatic steatosis index or US fatty liver index scores, in the absence of other causes of chronic liver disease. PA was measured from participants who wore accelerometers 10 hrs/day for a minimum of 4 days over a 7-day period and classified as total PA, moderate to vigorous PA (MVPA), and sedentary behavior.Over an average follow-up period of 10.6 years, increasing duration of total PA was associated with reduced risk of death, from any cause, in an age- and sex-adjusted model (hazard ratio [HR], 0.52; 95% CI, 0.32-0.86 for highest quartile vs lowest quartile; P for trend=.001) and multivariable model (HR, 0.46, 95% CI 0.28-0.75; P for trend<.001) among individuals with NAFLD. Increasing duration of MVPA was associated with a lower risk of death from any cause in individuals with NAFLD. Furthermore, longer total PA was associated with a lower risk for cardiovascular disease-related death in individuals with NAFLD (HR, 0.28; 95% CI, 0.08-0.98 for highest quartile vs lowest quartile; P for trend=.007). We did not find this association for cancer-related mortality in individuals with NAFLD. Increasing duration of sedentary behavior did not affect all-cause or cause-specific mortality in individuals with NAFLD.Longer total PA and MVPA, measured by accelerometers over a 7-day period, are associated with lower all-cause and cardiovascular mortality in individuals with NAFLD.

    View details for DOI 10.1016/j.cgh.2020.07.023

    View details for PubMedID 32683103

  • Low Thyroid Function in Nonalcoholic Fatty Liver Disease Is an Independent Predictor of All-Cause and Cardiovascular Mortality. The American journal of gastroenterology Kim, D. n., Vazquez-Montesino, L. M., Escober, J. A., Fernandes, C. T., Cholankeril, G. n., Loomba, R. n., Harrison, S. A., Younossi, Z. M., Ahmed, A. n. 2020

    Abstract

    Higher levels of thyroid-stimulating hormone (TSH) in the euthyroid state can negatively affect the metabolic health, including nonalcoholic fatty liver disease (NAFLD). We studied the effect of TSH levels in the setting of normal levels of thyroid hormone on all-cause and cause-specific mortality stratified by NAFLD status.The National Health and Nutrition Examination Survey (NHANES) III from 1988 to 1994 and NHANES III-linked mortality data through 2015 were used. NAFLD was defined as ultrasonographically diagnosed hepatic steatosis without coexisting liver diseases. Subclinical hypothyroidism was defined as a TSH level over 4.5 mIU/L and "low-normal" thyroid function as higher TSH level (2.5-4.5 mIU/L) within the euthyroid reference range. The Cox proportional hazard model analyzed the all-cause mortality and cause-specific mortality.In a multivariate logistic regression analysis, individuals with low thyroid function demonstrated an association with NAFLD in a dose-dependent manner. During a median follow-up of 23 years, low thyroid function was associated with increased all-cause mortality only in the univariate model. Low thyroid function was associated with a higher risk for all-cause mortality in individuals with NAFLD and not in those without NAFLD. Furthermore, low thyroid function was associated with a higher risk for cardiovascular mortality in the entire population and among those with NAFLD but demonstrated no association with the non-NAFLD group.In this large nationally representative sample of American adults, low thyroid function was associated with NAFLD and a predictor of higher risk for all-cause and cardiovascular mortality in individuals with NAFLD.

    View details for DOI 10.14309/ajg.0000000000000654

    View details for PubMedID 32496342

  • Longitudinal Change in Thyroid-stimulating Hormone and Risk of Nonalcoholic Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Chung, G. E., Kim, D. n., Kwak, M. S., Yim, J. Y., Ahmed, A. n., Kim, J. S. 2020

    View details for DOI 10.1016/j.cgh.2020.02.039

    View details for PubMedID 32109637

  • PNPLA3 Gene Polymorphism and Liver- and Extrahepatic Cancer-related Mortality in the United States. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Wijarnpreecha, K. n., Scribani, M. n., Raymond, P. n., Harnois, D. M., Keaveny, A. P., Ahmed, A. n., Kim, D. n. 2020

    View details for DOI 10.1016/j.cgh.2020.04.058

    View details for PubMedID 32360822

  • Depression is associated with non-alcoholic fatty liver disease among adults in the United States. Alimentary pharmacology & therapeutics Kim, D., Yoo, E. R., Li, A. A., Tighe, S. P., Cholankeril, G., Harrison, S. A., Ahmed, A. 2019

    Abstract

    BACKGROUND: Currently, the relationship between depression and non-alcoholic fatty liver disease (NAFLD) is not clearly defined.AIM: To determine whether depression is associated with NAFLD and NAFLD-related advanced fibrosis in a large population sample.METHODS: We performed a cross-sectional analysis using the 2007-2016 National Health and Nutrition Examination Survey database among adults (20years or older) in the United States (US). Depression and functional impairment due to depression were assessed with the Patient Health Questionnaire (PHQ-9). NAFLD was defined by utilising the US fatty liver index (USFLI), hepatic steatosis index (HSI) and the fatty liver index (FLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD were defined by Fibrosis-4 score.RESULTS: Of the 10484 subjects (mean age 47.0years; 48.8% men), the prevalence of depression and functional impairment due to depression was higher in subjects with NAFLD than in those without. Compared to subjects without depression, those with depression were 1.6-2.2-fold more likely to have NAFLD. In our multivariate analyses, depression_med was associated with increased risk of NAFLD using USFLI (odds ratio [OR] 1.48 95% confidence interval [CI] 1.17-1.87), HSI (OR 1.51 95% CI 1.04-2.19) and FLI (OR 2.01 95% CI 1.65-2.48), respectively. The addition of diabetes, obesity and lipid profile to the model reduced the ORs for depression, but the significance persisted. Depression was not associated with NAFLD-related advanced fibrosis.CONCLUSIONS: In a nationally representative sample of US adults, depression was independently associated with NAFLD.

    View details for DOI 10.1111/apt.15395

    View details for PubMedID 31328300

  • Trends in overall, cardiovascular and cancer-related mortality among individuals with diabetes reported on death certificates in the United States between 2007 and 2017 DIABETOLOGIA Kim, D., Li, A. A., Cholankeril, G., Kim, S. H., Ingelsson, E., Knowles, J. W., Harrington, R. A., Ahmed, A. 2019; 62 (7): 1185–94
  • Genetic Factors and Continental Ancestry Account for Some Disparities in Nonalcoholic Fatty Liver Disease Among Hispanic Subgroups. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Yoo, E. R., Ahmed, A., Kim, D. 2019

    View details for PubMedID 31009797

  • Changing Trends in Etiology-Based and Ethnicity-Based Annual Mortality Rates of Cirrhosis and Hepatocellular Carcinoma in the United States HEPATOLOGY Kim, D., Li, A. A., Perumpail, B. J., Gadiparthi, C., Kim, W., Cholankeril, G., Glenn, J. S., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019; 69 (3): 1064–74

    View details for DOI 10.1002/hep.30161

    View details for Web of Science ID 000459816500013

  • Trends in Mortality From Extrahepatic Complications in Patients With Chronic Liver Disease, From 2007 Through 2017. Gastroenterology Kim, D. n., Adejumo, A. C., Yoo, E. R., Iqbal, U. n., Li, A. A., Pham, E. A., Cholankeril, G. n., Glenn, J. S., Ahmed, A. n. 2019

    Abstract

    Trends of mortality associated with extrahepatic complications of chronic liver disease might be changing. We studied trends in mortality from extrahepatic complications of viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease in the United States (US).We performed a population-based study using US Census and the National Center for Health Statistics mortality records, from 2007 through 2017. We identified trends in age-standardized mortality using joinpoint trend analysis with estimates of annual percentage change.The liver-related mortality among patients with hepatitis C virus (HCV) infection increased from 2007 through 2013 and then decreased once patients began receiving treatment with direct-acting antiviral (DAA) agents, from 2014 through 2017. Among patients with HCV infection, the age-standardized mortality for extrahepatic cancers was 2.6%, for cardiovascular disease was 1.9%, and for diabetes was 3.3%. Among individuals with hepatitis B virus infection, liver-related mortality decreased steadily from 2007 through 2017. During the study age-standardized mortality from hepatitis B virus-related extrahepatic complications increased with an average annual percentage of 2.0%. Although liver-related mortality from ALD continued to increase, mortality from extrahepatic complications of ALD did not change significantly during the 11-year study. Among patients with nonalcoholic fatty liver disease, the cause of death was most frequently cardiovascular disease, which increased gradually over the study period, whereas liver-related mortality increased rapidly.In an analysis of US Census and the National Center for Health Statistics mortality records, we found that after widespread use of DAA agents for treatment of viral hepatitis, cause-specific mortality from extrahepatic cancers increased, whereas mortality from cardiovascular disease or diabetes increased only among patients with HCV infection. These findings indicate the need to reassess risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals successfully treated for HCV infection with DAA agents.

    View details for DOI 10.1053/j.gastro.2019.06.026

    View details for PubMedID 31251928

  • Increasing Mortality Among Patients With Diabetes and Chronic Liver Disease From 2007 Through 2017. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D. n., Cholankeril, G. n., Kim, S. H., Abbasi, F. n., Knowles, J. W., Ahmed, A. n. 2019

    View details for DOI 10.1016/j.cgh.2019.06.011

    View details for PubMedID 31220638

  • Low-Normal Thyroid Function is Associated with Advanced Fibrosis among Adults in the United States. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Yoo, E. R., Li, A. A., Fernandes, C. T., Tighe, S. P., Cholankeril, G., Hameed, B., Ahmed, A. 2018

    View details for PubMedID 30458247

  • Disparate Trends in Mortality of Etiology-specific Chronic Liver Disease Among Hispanic Sub-Populations. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Li, A. A., Perumpail, R. B., Cholankeril, G., Gonzalez, S. A., Kim, W., Ahmed, A. 2018

    Abstract

    BACKGROUND & AIMS: Little is known about trends in mortality among Hispanic subpopulations and etiologies of chronic liver disease (CLD). We investigated trends in mortality of CLD among the 3 largest Hispanic subgroups based on origin (Mexicans, Puerto Ricans, and Cubans) in the United States (US) from 2007 to 2016.METHODS: We collected data from the US Census and national mortality database, calculated age-standardized mortalities for CLD among Hispanic subgroups, and compared these with non-Hispanic whites. We determined mortality rate patterns by joinpoint analysis with estimates of annual percentage change.RESULTS: Hispanics were relatively younger with a lower likelihood of high school education than non-Hispanic whites at time of death. Puerto Ricans had the highest rates of age-standardized hepatitis C virus-related mortality in 2016, followed by non-Hispanic whites, Mexicans, and Cubans. Age-standardized mortality rates associated with hepatitis B virus infection decreased steadily among all subjects. Age-standardized mortality rates from alcoholic liver disease and nonalcoholic fatty liver disease among non-Hispanic whites and all Hispanics increased and accelerated. Mexicans had the highest rates of age-standardized alcoholic liver disease-related mortality, followed by non-Hispanic whites, Puerto Ricans, and Cubans. Cirrhosis- and hepatocellular carcinoma-related mortality rates increased steadily from 2007 to 2016, with the highest among Puerto Ricans and non-Hispanic whites and Mexicans, and lowest in Cubans.CONCLUSIONS: We found high levels of heterogeneity in CLD-related mortality patterns among the 3 largest Hispanic subgroups. Therefore, combining Hispanics as an aggregate group obscures potentially meaningful heterogeneity in etiology-specific CLD-related mortality rates among Hispanic subgroups.

    View details for PubMedID 30391436

  • Longitudinal trends in renal function in chronic hepatitis B patients receiving oral antiviral treatment. Alimentary pharmacology & therapeutics Udompap, P., Kim, D., Ahmed, A., Kim, W. R. 2018

    Abstract

    BACKGROUND: Long term renal safety of antiviral agents against hepatitis B virus (HBV) has been debated.AIM: To compare longitudinal trends of renal function among HBV mono-infected patients receiving entecavir (ETV), tenofovir disoproxil fumarate (TDF), and adefovir (ADV) in comparison to untreated subjects.METHODS: A retrospective cohort consisting of 815 patients with chronic HBV infection was constructed. Serial estimated glomerular filtration rate (eGFR) was compared to the expected rate of age-dependent decline in eGFR, derived from the National Health and Nutrition Examination Survey (NHANES) data. Generalised estimating equations and linear mixed-effects models were used to compare trends in eGFR (in mL/min/1.73m2 as a "unit").RESULTS: In NHANES data (n=23051), each year of age was associated with a 0.86 unit decrease in eGFR in subjects without hypertension and 0.96 units with hypertension. The Stanford cohort consisted of patients who received ETV (n=207), TDF (n=191), ADV (n=46) or no therapy (n=371). After a median follow-up 4.0 (interquartile range: 1.9-6.5) years, there was no significant difference in the expected and observed rates of eGFR decline in untreated HBV patients. Patients receiving antiviral treatment experienced steeper reduction in renal function than expected. In the multivariable model, ETV was associated with eGFR loss at 1.81 units per year (P=0.06, compared to untreated patients). TDF- and ADV-treated patients experienced significantly higher rate of eGFR loss at 2.21 and 2.63 units per year, respectively (both P<0.01).CONCLUSION: In this longitudinal cohort study, HBV patients receiving antiviral therapy, particularly TDF and ADV, experienced more rapid loss in eGFR.

    View details for PubMedID 30370967

  • Changing Trends in Etiology-Based Annual Mortality From Chronic Liver Disease, From 2007 Through 2016 GASTROENTEROLOGY Kim, D., Li, A. A., Gadiparthi, C., Khan, M., Cholankeril, G., Glenn, J. S., Ahmed, A. 2018; 155 (4): 1154-+
  • Visceral obesity as a risk factor for colorectal adenoma occurrence in surveillance colonoscopy GASTROINTESTINAL ENDOSCOPY Im, J., Kim, D., Chung, S., Jin, E., Han, Y., Park, M., Song, J., Yang, S., Kim, Y., Yim, J., Lim, S., Kim, J. 2018; 88 (1): 119-+

    Abstract

    The aim of this study was to examine the prospective association between visceral obesity and the incidence and recurrence of colorectal adenoma.We conducted a cohort study involving 2244 participants between 2006 and 2007. The study participants were prospectively followed until 2014 according to the initial colonoscopy and histopathology findings. Incident and recurrent colorectal adenoma groups were defined as individuals with a positive follow-up colonoscopy result from the normal results and adenoma groups, respectively, at the baseline colonoscopy.Among the 1163 patients (51.8%) who received a follow-up colonoscopy, 509 (43.8%) and 654 (56.2%) were grouped into the normal and adenoma cohorts. Colorectal adenomas occurred in 592 patients (50.9%) during the median period of 43 months, with an incident adenoma prevalence of 39.1% and a recurrent adenoma prevalence of 60.1%. An increase in the visceral adipose tissue (VAT) area was associated with a higher incidence of adenoma (highest quintile vs lowest quintile of the VAT hazard ratios [HRs], 2.16; 95% confidence interval [CI], 1.26-3.71; HR 1.32 [per 1-standard deviation]; 95% CI, 1.10-1.60) in the multivariable analysis. Increases in body mass index and waist circumference were associated with recurrent adenomas (HR 1.33 [per 1 kg/m2], 95% CI, 1.18-1.46; HR 1.04 [per 1 cm], 95% CI, 1.01-1.07, respectively) in the multivariate analysis.A higher VAT area was dose-dependently associated with a higher risk of incident adenoma. Furthermore, increases in body mass index and waist circumference as surrogate markers of abdominal obesity were associated with a higher risk of recurrent adenoma.

    View details for PubMedID 29510147

  • Polycystic ovary syndrome with hyperandrogenism as a risk factor for non-obese non-alcoholic fatty liver disease ALIMENTARY PHARMACOLOGY & THERAPEUTICS Kim, J. J., Kim, D., Yim, J. Y., Kang, J. H., Han, K. H., Kim, S. M., Hwang, K. R., Ku, S. Y., Suh, C. S., Kim, S. H., Choi, Y. M. 2017; 45 (11): 1403-1412

    Abstract

    Non-alcoholic fatty liver disease (NAFLD) is known to be associated with polycystic ovary syndrome (PCOS). However, most studies investigated the prevalence of NAFLD in obese PCOS patients.To compare the prevalence of non-obese NAFLD in women with or without PCOS, and to assess an independent association between PCOS and NAFLD in a non-obese Asian cohort.This was a case-control study using a prospective PCOS cohort. After subjects with other potential causes of chronic liver disease were excluded, 275 non-obese women with PCOS and 892 non-obese controls were enrolled. NAFLD was determined by hepatic ultrasonography. Main outcomes were the prevalence of NAFLD on hepatic ultrasonography between non-obese women with or without PCOS, and an independent association between non-obese NAFLD and PCOS.Non-obese women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (5.5% vs. 2.8%, P = 0.027). PCOS was associated with non-obese NAFLD (odds ratio: 2.62, 95% confidence intervals: 1.25-5.48) after adjustment for age and body mass index (BMI). In women with PCOS, the level of androgenicity represented by free testosterone or free androgen index was associated with NAFLD after adjustment for age, BMI, lipid profile, insulin resistance or glycaemic status.Non-obese NAFLD is more prevalent in women with polycystic ovary syndrome than in those without. In non-obese patients with polycystic ovary syndrome, hyperandrogenemia may be an independent risk factor for non-obese NAFLD.

    View details for DOI 10.1111/apt.14058

    View details for Web of Science ID 000400785900003

    View details for PubMedID 28370150

  • Short Sleep Duration Is Associated With Abnormal Serum Aminotransferase Activities and Nonalcoholic Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D. n., Kim, H. J., Kushida, C. A., Heo, N. Y., Ahmed, A. n., Kim, W. R. 2017

    View details for PubMedID 28882688

  • Subclinical Hypothyroidism and Low-Normal Thyroid Function Are Associated With Nonalcoholic Steatohepatitis and Fibrosis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D. n., Kim, W. n., Joo, S. K., Bae, J. M., Kim, J. H., Ahmed, A. n. 2017

    Abstract

    Variations in level of thyroid-stimulating hormone (TSH) within the reference range of thyroid hormone could have negative health effects. We evaluated the effect of plasma TSH levels within the euthyroid range on the severity of histological damage associated with nonalcoholic fatty liver disease (NAFLD).We performed a cross-sectional study of 425 subjects with biopsy-proven NAFLD (mean age, 53 years; 52% male) who participated in the Boramae NAFLD study from January 2013 to January 2017. Each subject underwent an anthropometric assessment and laboratory and clinical evaluations. Of the subjects, 282 were assigned to a strict to normal thyroid function group (plasma level of TSH, 0.4 to 2.5 mIU/L). Patients with low thyroid function were assigned to groups of subclinical hypothyroidism (plasma level of TSH above 4.5 mIU/L within a normal thyroid hormone level; n=59) or low-normal thyroid function (higher plasma TSH level [2.5 to 4.5 mIU/L] within a normal thyroid hormone level; n=84). Multivariate logistic regression analysis was used to identify factors independently associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis.NASH and advanced fibrosis were found in higher percentages of subjects with low thyroid function vs strict-normal thyroid function (52.4% vs 37.2% for NASH and 21.0% vs 10.6% for advanced fibrosis; P < .01). Among subjects with low thyroid function, a higher proportion of patients with subclinical hypothyroidism had NASH and associated advanced fibrosis vs patients with low-normal thyroid function (57.6% vs 48.8% for NASH and 25.4% vs 17.9% for advanced fibrosis; P < .01). Subjects with low thyroid function had more extensive hepatic steatosis with greater severity of balloon degeneration and fibrosis. In multivariate analyses, low thyroid function was significantly associated with NASH (odds ratio, 1.61; 95% CI, 1.04-2.50; P = .035) and advanced fibrosis (odds ratio, 2.23; 95% CI, 1.18-4.23; P = .014). Risks of NASH and advanced fibrosis increased significantly with plasma concentration of TSH (Ptrend <.05 for each).Subclinical hypothyroidism and low-normal thyroid function are independent predictors of NASH and advanced fibrosis, confirming the relationship between these diseases. ClinicalTrials.gov, Number: NCT02206841.

    View details for PubMedID 28823829

  • Nonobese Fatty Liver Disease Clinical Gastroenterology & Hepatology Kim, D., Kim, W. 2017; 15 (4): 474-485
  • Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis. Journal of Hepatology Koo, B., Kim, D., et al 2017; 66 (1): 123-131
  • Body Fat Distribution and Risk of Incident and Regressed Nonalcoholic Fatty Liver Disease CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Kim, D., Chung, G. E., Kwak, M., Seo, H. B., Kang, J. H., Kim, W., Kim, Y. J., Yoon, J., Lee, H., Kim, C. Y. 2016; 14 (1): 132-?

    Abstract

    Some studies have examined correlations between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with nonalcoholic fatty liver disease (NAFLD) or between VAT and NAFLD. We investigated the longitudinal association between body fat distribution (VAT vs SAT) and incidence and regression of NAFLD, adjusting for risk factors, in a large population-based cohort.We collected data from adults who underwent abdominal ultrasonography (to identify liver fat), abdominal fat computed tomography scan, and blood tests from March 2007 through December 2008. Each patient underwent an anthropometric assessment and completed a questionnaire about their medical history, physical activity, and diet. Our final analysis involved 2017 subjects from the initial cohort who participated in a voluntary follow-up health screen performed in 2011 and 2013. The median follow-up time was 4.43 years.We found 288 incident cases of NAFLD; 159 patients had NAFLD regression during the follow-up period. An increasing area of VAT was associated with higher incidence of NAFLD in the multivariable analysis (highest quintile vs lowest quintile of VAT hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.28-3.89; P for trend = .002; HR, 1.36 [per 1 standard deviation]; 95% CI, 1.16-1.59). An increased area of SAT was significantly associated with regression of NAFLD (highest quintile vs lowest quintile of SAT HR, 2.30; 95% CI, 1.28-4.12; P for trend = .002; HR, 1.36 [per 1 standard deviation]; 95% CI, 1.08-1.72).In a large cohort study, larger areas of VAT were longitudinally associated with higher risk of incident NAFLD (during a period of approximately 4 years). In contrast, larger areas of SAT were longitudinally associated with regression of NAFLD. These data indicate that certain types of body fat are risk factors for NAFLD, whereas other types could reduce risk for NAFLD.

    View details for DOI 10.1016/j.cgh.2015.07.024

    View details for PubMedID 26226099

  • Comparison of detection and miss rates of narrow band imaging, flexible spectral imaging chromoendoscopy and white light at screening colonoscopy: a randomised controlled back-to-back study GUT Chung, S. J., Kim, D., Song, J. H., Kang, H. Y., Chung, G. E., Choi, J., Kim, Y. S., Park, M. J., Kim, J. S. 2014; 63 (5): 785-791

    Abstract

    Virtual chromoendoscopy (CE) is expected to enhance adenoma yield and reduce variation in performance between colonoscopists. This study aimed to compare the efficacy of narrow band imaging (NBI), flexible spectral imaging CE (FICE) and white light (WL) colonoscopy and their impact for less experienced endoscopists.We performed a randomised tandem colonoscopy trial controlling for withdrawal time and bowel preparation. Average-risk adults undergoing screening colonoscopy were enrolled and randomly assigned to first withdrawal with one of the three imaging modalities (NBI (NBI-WL group), FICE (FICE-WL group) and WL (WL-WL group)). Eight colonoscopists were categorised into expert and non-expert subgroups.1650 subjects (mean age 51.4 years, 63.9% men) were included (550 in each group). Compared with WL, neither NBI nor FICE increased the mean number of adenomas detected per patient (0.37 vs 0.35 and 0.36; p=0.591) or the percentage of patients with adenoma (25.3% vs 24.5% and 23.6%; p=0.753). For all three modalities, expert subgroups had higher yields of adenomas than non-expert subgroups. Learning curves were observed only for non-expert subgroups with all three modalities. The percentage of missed adenomas did not differ between the three groups (20.8% by WL vs 22.9% by NBI and 26.0% by FICE, p=0.300) and was not affected by endoscopists' expertise.Neither NBI nor FICE improved adenoma detection or miss rates, with no difference in diagnostic efficacy between the two systems. Virtual CE had no additional benefits over WL for non-experts.KCT0000570.

    View details for DOI 10.1136/gutjnl-2013-304578

    View details for Web of Science ID 000334393400014

    View details for PubMedID 23853211

  • An ALTer Ego of Serum ALT: Is It More Than a Marker of Liver Inflammation? GASTROENTEROLOGY Kim, D., Kim, W. R. 2013; 145 (6): 1191-1193

    View details for DOI 10.1053/j.gastro.2013.10.040

    View details for Web of Science ID 000327537600014

    View details for PubMedID 24176872

  • Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States HEPATOLOGY Kim, D., Kim, W. R., Kim, H. J., Therneau, T. M. 2013; 57 (4): 1357-1365

    Abstract

    The clinical and public health significance of nonalcoholic fatty liver disease (NAFLD) is not well established. We investigated the long-term effect of NAFLD on mortality. This analysis utilized the National Health and Nutrition Examination Survey conducted in 1988-1994 and subsequent follow-up data for mortality through December 31, 2006. NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other known liver diseases. The presence and severity of hepatic fibrosis in subjects with NAFLD was determined by the NAFLD fibrosis score (NFS), the aspartate aminotransferase to platelet ratio index (APRI), and FIB-4 score. Of 11,154 participants, 34.0% had NAFLD--the majority (71.7%) had NFS consistent with lack of significant fibrosis (NFS <-1.455), whereas 3.2% had a score indicative of advanced fibrosis (NFS >0.676). After a median follow-up of 14.5 years, NAFLD was not associated with higher mortality (age- and sex-adjusted hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 0.93-1.19). In contrast, there was a progressive increase in mortality with advancing fibrosis scores. Compared to subjects without fibrosis, those with a high probability of advanced fibrosis had a 69% increase in mortality (for NFS: HR, 1.69, 95% CI: 1.09-2.63; for APRI: HR, 1.85, 95% CI: 1.02-3.37; for FIB-4: HR, 1.66, 95% CI: 0.98-2.82) after adjustment for other known predictors of mortality. These increases in mortality were almost entirely from cardiovascular causes (for NFS: HR, 3.46, 95% CI: 1.91-6.25; for APRI: HR, 2.53, 95% CI: 1.33-4.83; for FIB-4: HR, 2.68, 95% CI: 1.44-4.99).Ultrasonography-diagnosed NAFLD is not associated with increased mortality. However, advanced fibrosis, as determined by noninvasive fibrosis marker panels, is a significant predictor of mortality, mainly from cardiovascular causes, independent of other known factors.

    View details for DOI 10.1002/hep.26156

    View details for Web of Science ID 000317363600010

    View details for PubMedID 23175136

    View details for PubMedCentralID PMC3622816

  • Nonalcoholic fatty liver disease is associated with coronary artery calcification HEPATOLOGY Kim, D., Choi, S., Park, E. H., Lee, W., Kang, J. H., Kim, W., Kim, Y. J., Yoon, J., Jeong, S. H., Lee, D. H., Lee, H., Larson, J., Therneau, T. M., Kim, W. R. 2012; 56 (2): 605-613

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is related to risk factors of coronary artery disease, such as dyslipidemia, diabetes, and metabolic syndrome, which are closely linked with visceral adiposity. The aim of this study was to investigate whether NAFLD was associated with coronary artery calcification (CAC), which is used as a surrogate marker for coronary atherosclerosis independent of computed tomography (CT)-measured visceral adiposity. Out of 5,648 subjects who visited one of our health screening centers between 2003 and 2008, we enrolled 4,023 subjects (mean age, 56.9 ± 9.4 years; 60.7% males) without known liver disease or a history of ischemic heart disease. CAC score was evaluated using the Agatston method. On univariate analysis, the presence of CAC (score >0) was significantly associated with age, sex, body mass index, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, triglycerides, and increased risk of diabetes, hypertension, smoking, and NAFLD. Increasing CAC scores (0, <10, 10-100, ≥ 100) were associated with higher prevalence of NAFLD (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.61-2.10; P<0.001). Multivariable ordinal regression analysis was adjusted for traditional risk factors, and CT-measured visceral adipose tissue area in a subgroup of subjects showed that the increased CAC scores were significantly associated with the presence of NAFLD (OR, 1.28, 95% CI, 1.04-1.59; P = 0.023) independent of visceral adiposity.Patients with NAFLD are at increased risk for coronary atherosclerosis independent of classical coronary risk factors, including visceral adiposity. These data suggest that NAFLD might be an independent risk factor for coronary artery disease.

    View details for DOI 10.1002/hep.25593

    View details for Web of Science ID 000306804500024

    View details for PubMedID 22271511

    View details for PubMedCentralID PMC3830979

  • Non-alcoholic fatty liver disease across the spectrum of hypothyroidism JOURNAL OF HEPATOLOGY Chung, G. E., Kim, D., Kim, W., Yim, J. y., Park, M. J., Kim, Y. J., Yoon, J., Lee, H. 2012; 57 (1): 150-156

    Abstract

    The aim of this study was to characterize the relationship between the broad spectrum of hypothyroidism and NAFLD.A cross-sectional study with 4648 health check-up subjects (2324 cases with hypothyroidism vs. age- and sex-matched controls) was conducted. The subjects were categorized as having either subclinical [thyroid-stimulating hormone (TSH) ≥4.1 mIU/L and normal free thyroixine (T(4)) level (0.7-1.8 ng/dl)] or overt hypothyroidism [free T(4)<0.7 ng/dl]. NAFLD was diagnosed on the basis of typical ultrasonographic findings, and alcohol consumption of less than 20 g/day in the absence of other causes of liver disease.The mean age of the subjects was 48.6±11.8 years and 62.4% were female. NAFLD was significantly associated with hypothyroidism (30.2% patients vs. 19.5% control, p<0.001). The prevalence of NAFLD and abnormal liver enzyme levels (ALT>33/25 IU/L) increased steadily with increasing grades of hypothyroidism (for NAFLD, subclinical: 29.9% and overt: 36.3%; for abnormal ALT, 20.1% and 25.9%, p<0.001, respectively). Multivariate regression analysis showed that NAFLD was statistically significantly associated with hypothyroidism (odds ratio (OR) 1.38, 95% confidence interval (CI), 1.17-1.62) and the grade of hypothyroidism in a dose-dependent manner (OR 1.36, 95% CI, 1.16-1.61 in subclinical hypothyroidism and OR 1.71, 95% CI, 1.10-2.66 in overt hypothyroidism).Subclinical hypothyroidism, even in the range of upper normal TSH levels, was found to be related to NAFLD in a dose-dependent manner. Hypothyroidism is closely associated with NAFLD independently of known metabolic risk factors, confirming a relevant clinical relationship between these two diseases.

    View details for Web of Science ID 000305811300022

    View details for PubMedID 22425701

  • Five-year risk for advanced colorectal neoplasia after initial colonoscopy according to the baseline risk stratification: a prospective study in 2452 asymptomatic Koreans GUT Chung, S. J., Kim, Y. S., Yang, S. Y., Song, J. H., Kim, D., Park, M. J., Kim, S. G., Song, S., Kim, J. S. 2011; 60 (11): 1537-1543

    Abstract

    Postpolypectomy surveillance guidelines for colorectal cancer introduced the concept of 'risk stratification'; however, few studies have been conducted for validation of its usefulness. The aim of this study was to assess the 5-year incidence of advanced neoplasia recurrence based on the risk stratification scheme of the guidelines and to identify its risk factors.A prospective study of surveillance colonoscopy after screening colonoscopy was carried out at the Seoul National University Hospital Healthcare System Gangnam Center. 3803 asymptomatic Koreans aged 50-69 were enrolled prospectively and 5-year cumulative adenoma rates were analysed according to three risk groups: normal (no baseline adenoma), low-risk (1-2 adenomas <10 mm) and high-risk (an advanced adenoma or ≥ 3 adenomas) groups. The RR was computed by HR using Cox proportional regression after multivariate adjustments. The primary outcome was the 5-year cumulative rate of recurrent advanced adenoma in each risk category and the secondary outcome was its predictive factors.Among 3803 subjects enrolled between 2003 and 2005, 2452 were followed-up within 5 years: 1242, 671 and 539 in the normal, low-risk and high-risk groups, respectively. Compared with the normal group, the low-risk group had a sufficiently low 5-year incidence and did not show an increased risk for subsequent advanced adenoma (2.4% vs 2.0%, HR=1.14, 95% CI 0.61 to 2.17). Conversely, a significantly higher 5-year rate (12.2%) and early recurrence (4.6, 7.4 and 9.6% at 1, 2 and 3 years) of advanced adenoma were revealed in the high-risk group. Among various patients and adenoma characteristics, only high-risk adenoma (HR=5.95, 95% CI 3.66 to 9.68) along with a number of ≥ 3 (HR=3.06, 95% CI 1.51 to 6.57) and size ≥ 10 mm (HR=3.02, 95% CI 1.80 to 5.06) were independent predictors.The surveillance interval for low-risk patients could be extended beyond 5 years. Colonoscopic surveillance should be targeted to high-risk patients, and 3-year follow-up after initial polypectomy may be appropriate.

    View details for DOI 10.1136/gut.2010.232876

    View details for Web of Science ID 000295399600013

    View details for PubMedID 21427200

  • Differentiating Small Polyp Histologies Using Real-Time Screening Colonoscopy With Fuji Intelligent Color Enhancement CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Kim, Y. S., Kim, D., Chung, S. J., Park, M. J., Shin, C. s., Cho, S., Kim, J. S., Song, I. S. 2011; 9 (9): 744-U57

    Abstract

    There are limited data describing the performance of Fuji Intelligent Color Enhancement (FICE, EC 590 ZW; Fujinon Inc, Saitama, Japan) for differentiating polyp histologies during screening colonoscopy. We evaluated the ability of an endoscopist to diagnose small polyp histology during a screening colonoscopy using FICE.A prospective study was performed on 763 consecutive, asymptomatic subjects who were undergoing screening colonoscopy. Pit patterns and vascular patterns were used to predict the histology of 525 polyps (mean size, 4.5 ± 2.2 mm, 315 adenomas) of less than 10 mm using FICE with high magnification and without. The performances of the FICE analyses were calculated and compared with the results from the histopathology.The overall accuracy achieved by FICE with high magnification in the diagnosis of adenomas of less than 10 mm (87.0%) was significantly greater than that achieved without high magnification (80.4%; P < .05). Moreover, the improvement of accuracy attained when using high-magnification FICE was most pronounced and significant compared without using high-magnification FICE in the diagnosis for diminutive polyps (≤5 mm; 85.4% vs 79.1%; P < .05). Among all types of adenomas, the sensitivity of FICE was lowest for sessile serrated adenomas (38.5% vs 89.4%; P < .01), even when FICE was used with high magnification.FICE with high magnification is better for differentiating the histology of small polyps during screening colonoscopy than FICE without high magnification, especially for diminutive polyps. Large-scale studies are needed to improve the identification of serrated adenomas and small diminutive polyps using FICE.

    View details for DOI 10.1016/j.cgh.2011.05.021

    View details for Web of Science ID 000294678400013

    View details for PubMedID 21699809

  • Sagittal Abdominal Diameter Is a Strong Anthropometric Measure of Visceral Adipose Tissue in the Asian General Population DIABETES CARE Yim, J. y., Kim, D., Lim, S. H., Park, M. J., Choi, S. H., Lee, C. H., Kim, S. S., Cho, S. 2010; 33 (12): 2665-2670

    Abstract

    Finding the anthropometric measure of visceral obesity is essential to clinical practice, because it predicts cardiovascular and metabolic risks. Sagittal abdominal diameter (SAD) has been proposed as an estimate of visceral adipose tissue (VAT). The aim of the present study was to evaluate the usefulness of SAD in predicting visceral obesity by comparing SAD to other anthropometric measures.Estimation of subcutaneous and visceral adipose tissue and measurement of SAD and transverse abdominal diameter using computed tomography at the umbilical level were obtained in 5,257 men and women who were enrolled in a health checkup program in Korea. To compare SAD to other anthropometric measures, linear regression analyses were used to determine correlations between anthropometrics and visceral obesity.SAD showed a stronger correlation to VAT than waist circumference, BMI, and transverse abdominal diameter in the both sexes (men: r = 0.804, women: r = 0.724). Waist circumference showed generally stronger associations to subcutaneous adipose tissue (SAT) than to VAT (men: r = 0.789 vs. 0.705, women: r = 0.820 vs. 0.636). Even after subdividing according to age or BMI in both sexes and analyzing multiple regressions, SAD showed the strongest correlation to VAT.SAD showed the strongest correlation to VAT irrespective of age, sex, and the degree of obesity compared with other anthropometric measures, whereas waist circumference may have a stronger correlation to SAT than to VAT. The clinical use of SAD has advantages over other anthropometric measures in predicting VAT.

    View details for DOI 10.2337/dc10.0606

    View details for Web of Science ID 000285666200034

    View details for PubMedID 20843976

    View details for PubMedCentralID PMC2992209

  • Visceral Obesity and Insulin Resistance as Risk Factors for Colorectal Adenoma: A Cross-Sectional, Case-Control Study AMERICAN JOURNAL OF GASTROENTEROLOGY Kang, H. W., Kim, D., Kim, H. J., Kim, C. H., Kim, Y. S., Park, M. J., Kim, J. S., Cho, S., Sung, M., Jung, H. C., Lee, H., Song, I. S. 2010; 105 (1): 178-187

    Abstract

    Colorectal adenoma is known to be associated with obesity, but the association between colorectal adenoma and visceral adipose tissue (VAT) area measured by abdominal computed tomography (CT) has not been documented clearly. In addition, the relationship between insulin resistance and colorectal adenomas, which underlies the mechanism that links obesity and colorectal adenoma, has not been studied extensively. The aim of this study was to examine VAT area and insulin resistance as risk factors of colorectal adenoma.A cross-sectional, case-control study was conducted in Koreans that presented for health check-ups. Subjects underwent various laboratory tests, abdominal CT, and colonoscopy. VAT, subcutaneous adipose tissue (SAT), and homeostatic metabolic assessment (HOMA) index were evaluated as potential risk factors of colorectal adenoma in 2,244 age- and sex-matched subjects.According to univariate analysis, the prevalences of smoking, hypertension, metabolic syndrome, and family history of colorectal cancer were higher in the adenoma group than in the normal control group. In addition, body mass index, waist circumference, triglyceride, high-density lipoprotein cholesterol, and VAT and SAT areas were significantly different in the two groups. According to the multivariate analysis adjusted for multiple confounders, VAT area was independently associated with the risk of colorectal adenoma (odds ratio (OR)=3.09, 95% confidence interval (CI): 2.19-4.36, highest quintile vs. lowest quintile). Mean HOMA index was higher in the adenoma group than in the control group (OR=1.99, 95% CI: 1.35-2.92, highest vs. lowest quintile).Visceral obesity was found to be an independent risk factor of colorectal adenoma, and insulin resistance was associated with the presence of colorectal adenoma.

    View details for DOI 10.1038/ajg.2009.541

    View details for Web of Science ID 000273996200025

    View details for PubMedID 19755965

  • The Relation Between Non-Alcoholic Fatty Liver Disease and the Risk of Coronary Heart Disease in Koreans AMERICAN JOURNAL OF GASTROENTEROLOGY Choi, S., Kim, D., Kim, H. J., Kang, J. H., Chung, S. J., Park, M. J., Kim, Y. S., Kim, C. H., Choi, S. H., Kim, W., Kim, Y. J., Yoon, J., Lee, H., Cho, S., Sung, M., Oh, B. 2009; 104 (8): 1953-1960

    Abstract

    Non-alcoholic fatty liver disease (NAFLD) is known to be related to factors that predict the development of coronary heart disease (CHD), such as dyslipidemia, central obesity, and metabolic syndrome (MS). The aim of this study was to determine whether individuals with NAFLD have an elevated risk of CHD, as estimated using the Framingham risk score (FRS).A total of 21,130 individuals who underwent a voluntary general health examination were recruited. NAFLD was diagnosed among these individuals on the basis of typical sonographic findings and a level of alcohol consumption of <20 g/day. Of the 21,130 individuals, 3,780 were excluded because they had known causes of liver disease (1,690 were alcoholics, 975 had hepatitis B virus, 242 had hepatitis C virus, 91 had other hepatitis history, and 593 were taking medication known to produce fatty liver) or a history of heart disease (189).NAFLD was diagnosed in 5,769 of the 17,350 individuals (33.3%). The 11,581 normal individuals constituted the control group. The 5,769 individuals with NAFLD were split into two groups on the basis of ultrasonographic findings, that is, into a mild NAFLD group (n=3,278) and a moderate-severe NAFLD group (n=2,491). Individuals with NAFLD had an elevated risk of CHD, as estimated using FRS. Multivariable regression analysis, adjusted for confounding factors, showed a strong association between a higher FRS and NAFLD.Individuals with ultrasonographically detected NAFLD have an elevated 10-year risk of developing CHD as estimated using FRS. Furthermore, NAFLD was found to be independently related to the risk of developing CHD, regardless of classical risk factors and other components of MS.

    View details for DOI 10.1038/ajg.2009.238

    View details for Web of Science ID 000268965300010

    View details for PubMedID 19491838

  • Metabolic syndrome and visceral obesity as risk factors for reflux oesophagitis: a cross-sectional case-control study of 7078 Koreans undergoing health check-ups GUT Chung, S. J., Kim, D., Park, M. J., Kim, Y. S., Kim, J. S., Jung, H. C., Song, I. S. 2008; 57 (10): 1360-1365

    Abstract

    Obesity has been associated with reflux oesophagitis. However, the relationship between metabolic syndrome characterised by visceral obesity and reflux oesophagitis is unclear.To investigate whether metabolic syndrome or visceral obesity is a risk factor for reflux oesophagitis.A cross-sectional study of 7078 subjects undergoing upper endoscopy during health check-ups was conducted (3539 patients with reflux oesophagitis vs age- and sex-matched controls). We further analysed according to categories of visceral adipose tissue and subcutaneous adipose tissue area with 750 cases and age-, sex- and waist circumference-matched controls who underwent abdominal CT scan.The prevalence of metabolic syndrome was higher in cases than controls (26.9% vs 18.5%, p<0.001). Multivariate analysis demonstrated that metabolic syndrome is associated with reflux oesophagitis (odds ratio (OR) = 1.42; 95% confidence interval (CI), 1.26 to 1.60). Among the individual components of metabolic syndrome, waist circumference (OR = 1.47; 95% CI, 1.30 to 1.65) and triglyceride (OR = 1.20; 95% CI, 1.05 to 1.36) independently increased the risk for reflux oesophagitis. On sub-analysis, cases showed higher mean visceral adipose tissue area (cm(2)) (136.1 (SD 57.8) vs 124.0 (SD 54.7), p<0.001) and subcutaneous adipose tissue area (cm(2)) (145.9 (SD 56.8) vs 133.5 (SD 50.7), p<0.001). However, only visceral adipose tissue area was an independent risk factor for reflux oesophagitis after adjusting for multiple confounders including smoking, alcohol, body mass index (BMI) and subcutaneous adipose tissue area (OR = 1.60; 95% CI, 1.03 to 2.48, lowest quartile vs highest quartile).Metabolic syndrome was associated with reflux oesophagitis. Abdominal obesity, especially visceral obesity, was an important risk factor for reflux oesophagitis.

    View details for DOI 10.1136/gut.2007.147090

    View details for Web of Science ID 000259198800010

    View details for PubMedID 18441006

  • Association between Body Fat Distribution and Nonalcoholic Fatty Liver Disease/Fibrosis Based on Race/Ethnicity. Journal of obesity & metabolic syndrome Kim, D., Cholankeril, G., Ahmed, A. 2024

    Abstract

    Body fat distribution may impact nonalcoholic fatty liver disease (NAFLD) and significant fibrosis differently according to race/ethnicity. We determined the relationship between body fat distribution and NAFLD/significant fibrosis according to race/ethnicity.A cross-sectional study of 2,395 participants used the National Health and Nutrition Examination Survey 2017 to 2018. NAFLD and significant fibrosis (≥F2) were defined by controlled attenuation parameter scores and liver stiffness measurements on transient elastography, respectively. Visceral and subcutaneous fat volumes were defined by dual-energy X-ray absorptiometry.The odds ratio (OR) for NAFLD per 1-standard deviation in visceral fat volume and subcutaneous fat volume was 2.31 (95% confidence interval [CI], 1.50 to 3.39) and 1.93 (95% CI, 1.43 to 2.61) in total population, respectively. Visceral fat in non-Hispanic Blacks had the highest odds for NAFLD (OR, 2.86; 95% CI, 1.45 to 5.62), and non-Hispanic Whites (OR, 2.29; 95% CI, 1.19 to 4.40) and non-Hispanic Asians (OR, 1.61; 95% CI, 1.13 to 2.29) were in order. Significant associations between subcutaneous fat volume (OR, 2.10; 95% CI, 1.34 to 3.29; P=0.003) or visceral fat volume (OR, 1.35; 95% CI, 1.05 to 1.73; P=0.023) and significant fibrosis were noted among individuals with NAFLD. Hispanics had the highest odds for NAFLD-associated significant fibrosis (OR, 2.74; 95% CI, 1.32 to 5.70), and non-Hispanic Whites (OR, 2.35; 95% CI, 1.11 to 4.98) and non-Hispanic Asians (OR, 2.01; 95% CI, 1.01 to 4.01) were in order.Visceral adiposity was associated with NAFLD and significant fibrosis despite the association of subcutaneous adiposity in NAFLD and significant fibrosis. Racial/ethnic differences in the association between body fat distribution on NAFLD and significant fibrosis were noted.

    View details for DOI 10.7570/jomes24005

    View details for PubMedID 39428122

  • Health service utilization, substance use treatment response, and death in patients with opioid use disorder and comorbid hepatitis C findings from prospective cohort study with administrative database linkage. Journal of substance use and addiction treatment Dennis, B. B., Babe, G., Gayowsky, A., Rosic, T., Rodrigues, M., Bach, P., Perez, R., de Oliveira, C., Samet, J., Weaver, V., Young, S., Dionne, J., Ahmed, A., Kim, D., Thabane, L., Samaan, Z. 2024: 209524

    Abstract

    Among patients with opioid use disorder (OUD), high rates of overdose and death have been reported in subgroups with Hepatitis C Virus (HCV). Evidence on the comorbid effect of HCV on clinical and substance use trajectories has been limited by small sample sizes, short follow-up, and heavy reliance on administrative data which lacks granularity on important prognostic factors. Additionally, few studies include populations on substance use treatment.To establish the impact of HCV exposure (antibody positivity) on health care utilization patterns, substance use treatment response, and death in a cohort of patients with OUD on opioid agonist therapy (OAT).This multi-center prospective cohort study recruited adult patients with OUD on OAT from 57 substance use treatment centers in Ontario, Canada. The study collected substance use outcomes, and classified patients with ≥50 % positive opioid urine screens over one year of follow-up as having poor treatment response. Additional data obtained via linkage with ICES administrative databases evaluated the relationship between HCV status, healthcare service utilization, and death over 3 years of follow-up. Multiple logistic regression models established the adjusted impact of HCV on various outcomes.Among recruited participants (n = 3430), 44.10 % were female with a mean age of 38.64 years (Standard deviation: 10.96). HCV was prevalent in 10.6 % of the cohort (n = 365). Methadone was used most often (83.9 %, n = 2876), followed by sublingual buprenorphine (16.2 %, n = 554). Over the three-year follow-up, 5.3 % of patients died (n = 181). Unadjusted results reveal rates of hospitalization (all-cause, mental-health related, critical care) and emergency department visits (mental health-related), were significantly higher among HCV patients. Associations diminished in adjusted models. Active injection drug use exhibited the highest predictive risk for all outcomes.A high degree of acute physical and mental illness and its resulting health service utilization burden is concentrated among patients with OUD and comorbid HCV. Future research should explore the role for targeted interventions and how best to implement integrated healthcare models to better address the complex health needs of HCV populations who inject drugs.

    View details for DOI 10.1016/j.josat.2024.209524

    View details for PubMedID 39341602

  • Mortality outcomes in individuals with MASLD versus MASLD and increased alcohol intake. Journal of gastroenterology and hepatology Aboona, M. B., Danpanichkul, P., Chen, V. L., Rangan, P., Kim, D., Alkhouri, N., Fallon, M. B., Noureddin, M., Arab, J. P., Wijarnpreecha, K. 2024

    Abstract

    BACKGROUND AND AIM: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of chronic liver disease worldwide. A new entity termed MetALD has also been described and is defined as individuals with MASLD and increased alcohol intake. However, the natural history of MetALD compared with MASLD is unknown. We aimed to compare longitudinal outcomes in patients with MASLD versus MetALD.METHODS: This study was performed using data from the National Health and Nutrition Examination Survey from 2011 to 2018. MASLD patients (defined by the United States Fatty Liver Index >30) who met cardiometabolic criteria including body mass index (BMI) >25 (BMI>23 in Asians), hypertension, diabetes mellitus, dyslipidemia, and hypertriglyceridemia were included. MetALD was defined as MASLD with increased alcohol intake (3-6 standard drinks per day in males; 2-5 standard drinks per day in females). A comparison of overall, cardiovascular, cancer-related, and other causes of mortality in patients with MASLD versus MetALD was performed.RESULTS: A total of 2838 individuals with MASLD and 2557 individuals with MetALD were included with a median follow-up time of 56months. MetALD patients were at increased risk of cancer-related mortality compared with patients with MASLD (hazard ratio 1.32; 95% confidence interval 1.14-1.53; P<0.01). However, there was no significant difference in overall, cardiovascular, and other causes of mortality.CONCLUSIONS: Patients with MetALD were at higher risk for cancer-related mortality than MASLD. Close attention to regular cancer surveillance and accurate classification of alcohol consumption in individuals with diagnosed MASLD is warranted to help improve patient care and outcome.

    View details for DOI 10.1111/jgh.16726

    View details for PubMedID 39175201

  • Contemporary Awareness of Nonalcoholic Fatty Liver Disease and Viral Hepatitis Based on the Stage. The American journal of the medical sciences Kim, D., Manikat, R., Wijarnpreecha, K., Cholankeril, G., Ahmed, A. 2024

    View details for DOI 10.1016/j.amjms.2024.08.014

    View details for PubMedID 39159751

  • Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: systematic analysis from the global burden of disease study 2019. Metabolism: clinical and experimental Danpanichkul, P., Suparan, K., Dutta, P., Kaeosri, C., Sukphutanan, B., Pang, Y., Kulthamrongsri, N., Jaisa-Aad, M., Ng, C. H., Teng, M., Nakano, M., Morishita, A., Alkhouri, N., Yang, J. D., Chen, V. L., Kim, D., Fallon, M. B., Diaz, L. A., Arab, J. P., Mantzoros, C. S., Noureddin, M., Lazarus, J. V., Wijarnpreecha, K. 2024: 155958

    Abstract

    Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary.From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data.Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase (+134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average.The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions.

    View details for DOI 10.1016/j.metabol.2024.155958

    View details for PubMedID 38942169

  • Current epidemiology of chronic liver disease. Gastroenterology report Manikat, R., Ahmed, A., Kim, D. 2024; 12: goae069

    Abstract

    Chronic liver disease presents a significant global health burden, characterized by several etiologies, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), chronic hepatitis B virus infection, and chronic hepatitis C virus infection. This review explored current epidemiological trends and projections for each etiology, looking into their respective burdens and challenges. MASLD, formerly known as nonalcoholic fatty liver disease, is the most prevalent cause of chronic liver disease, and its global incidence and prevalence are steadily rising. ALD, fueled by increased alcohol consumption, is also on the rise, with concerning implications for future mortality rates. Chronic hepatitis B and C infections remain major public health concerns, particularly in specific regions of the world, necessitating concerted efforts for screening and treatment. The coronavirus disease 2019 (COVID-19) pandemic has impacted the epidemiology of chronic liver disease, exacerbating mortality rates and disrupting healthcare services. Mental health issues arising from the pandemic further complicate the treatment of chronic liver disease, making comprehensive healthcare strategies essential. Despite advancements in treatment, chronic liver disease continues to impose a substantial economic burden, emphasizing the importance of preventive measures and early intervention. In conclusion, ongoing surveillance and research efforts are crucial for understanding and addressing the evolving landscape of chronic liver disease. Comprehensive strategies that encompass prevention, screening, and treatment of its different etiologies are essential for mitigating its impact and improving patient outcomes.

    View details for DOI 10.1093/gastro/goae069

    View details for PubMedID 38915345

    View details for PubMedCentralID PMC11194530

  • Estimated pulse wave velocity in metabolic dysfunction-associated steatotic liver disease and all-cause/cause-specific mortality. Journal of gastroenterology and hepatology Kim, D., Manikat, R., Wijarnpreecha, K., Cholankeril, G., Ahmed, A. 2024

    Abstract

    Several reports show a significant association between metabolic dysfunction-associated steatotic liver disease (MASLD) and arterial stiffness (estimated pulse wave velocity [ePWV]) as a surrogate marker of vascular age. We investigate whether ePWV as arterial stiffness in MASLD is associated with all-cause/cause-specific mortality.This cohort study was based on the third National Health and Nutrition Examination Survey (NHANES, 1988-1994) and NHANES 2007-2014 and linked mortality datasets through 2019. Cox regression models assessed the association between ePWV categorized by quartile and all-cause/cause-specific mortality among individuals with MASLD.During the follow-up of a median of 26.3 years (interquartile range: 19.9-27.9), higher levels of ePWV among individuals with MASLD were associated with increased all-cause mortality, which remained significant after adjusting for demographic, lifestyle, clinical, and metabolic risk factors. Furthermore, higher ePWV in MASLD was associated with higher cardiovascular mortality. There was a 44% (hazard ratio: 1.44, 95% confidence interval: 1.32-1.58) increase in all-cause mortality and a 53% (hazard ratio: 1.53, 95% confidence interval: 1.32-1.77) increase in cardiovascular mortality for every 1 m/s increase in ePWV in MASLD. However, there was no significant association between ePWV and cancer-related mortality. Sensitivity analyses using the NHANES 2007-2014 dataset showed results identical to the original analysis.Higher ePWV in MASLD was associated with a higher risk of all-cause and cardiovascular mortality beyond traditional cardiovascular risk factors. Screening for ePWV in individuals with MASLD may be an effective and beneficial approach to reducing all-cause and cardiovascular mortality.

    View details for DOI 10.1111/jgh.16608

    View details for PubMedID 38740513

  • The prevalence and predictors of metabolic dysfunction-associated steatotic liver disease and fibrosis/cirrhosis among adolescents/young adults. Journal of pediatric gastroenterology and nutrition Perumpail, B. J., Manikat, R., Wijarnpreecha, K., Cholankeril, G., Ahmed, A., Kim, D. 2024

    Abstract

    We investigated the current prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and fibrosis/cirrhosis and identified at-risk populations for MASLD and MASLD-related fibrosis among US adolescents and young adults in the United States.Utilizing the National Health and Nutrition Examination Survey 2017-2020, the prevalence of MASLD and fibrosis/cirrhosis was assessed via controlled attenuation parameter (CAP) score and liver stiffness measurements by transient elastography in participants aged 12-29 years with at least one cardiometabolic criteria and absence of other chronic liver disease. Multivariable logistic regression was performed to determine predictors of MASLD and MASLD-related fibrosis.The overall prevalence of MASLD was 23.9% (95% CI: 21.3-26.5 for CAP ≥ 263 dB/m) and 17.3% (95% CI: 14.7-20.0 for ≥285 dB/m), respectively. The prevalence of fibrosis and cirrhosis in MASLD was 11.0% and 3.1%, respectively. When categorized by age, the prevalence of MASLD varied from 16.8% (of which 6.2% [fibrosis], 1.8% [cirrhosis]) in early and middle adolescents (12-17 years), to 25.5% (11.8% [fibrosis], 4.8% [cirrhosis]) in late adolescents and young adults (18-24 years), and to 30.4% (of which 13.2% [fibrosis] and 2.1% [cirrhosis]) in older young adults (25-29 years). The independent predictors for MASLD included male sex, Hispanic, non-Hispanic Asian, body mass index, and low HDL-cholesterol. In contrast, diabetes and body mass index were associated with an increased risk of fibrosis in individuals with MASLD.The prevalence of MASLD and related fibrosis in adolescents and young adults in the United States has reached a significant level, with a substantial proportion of cirrhosis.

    View details for DOI 10.1002/jpn3.12219

    View details for PubMedID 38623942

  • Incidence of liver cancer in young adults according to the global burden of disease database 2019. Hepatology (Baltimore, Md.) Danpanichkul, P., Aboona, M. B., Sukphutanan, B., Kongarin, S., Duangsonk, K., Ng, C. H., Muthiah, M. D., Huang, D. Q., Seko, Y., Diaz, L. A., Arab, J. P., Yang, J. D., Chen, V. L., Kim, D., Noureddin, M., Liangpunsakul, S., Wijarnpreecha, K. 2024

    Abstract

    OBJECTIVE: The worldwide burden of cancer is increasing in younger populations. However, the epidemiology of primary liver cancer remains understudied in young adults compared to other cancer forms.METHODS: This study analyzed data from the Global Burden of Disease (GBD) study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years (DALYs) associated with primary liver cancer in the young (15-49y), stratified by region, nation, sociodemographic index, and sex.RESULTS: The study found a global estimate of 78,299 primary liver cancer cases, 60,602 deaths, and 2.90 million DALYs in the young population. The Western Pacific region exhibited the highest burden in 2019, showing the most significant increase compared to other regions between 2010-2019. More than half of countries worldwide have undergone an increase in primary liver cancer incidence rates in young adults. Around 12.51% of deaths due to primary liver cancer occur in young individuals. Throughout the study period, there was a significant decline in primary liver cancer mortality due to most etiologies, except for metabolic dysfunction-associated steatotic liver disease (MASLD)-attributable primary liver cancer (annual percentage change [APC] +0.87%, 95% confidence interval 0.70-1.05%) and alcohol-attributable primary liver cancer (APC +0.21%, 95% confidence interval 0.01-0.42%). Limitations of the GBD database include reliance on the quality of primary data and possible underestimation of alcohol consumption.CONCLUSION: Over the past decade, there has been a marked increase in the burden of primary liver cancer, especially that originating from steatotic liver disease. This trend calls for the development of urgent and comprehensive strategies to mitigate this rising burden globally.

    View details for DOI 10.1097/HEP.0000000000000872

    View details for PubMedID 38598364

  • Editorial: Using machine learning to predict significant fibrosis in metabolic dysfunction-associated steatotic liver disease. Alimentary pharmacology & therapeutics Manikat, R., Ahmed, A., Kim, D. 2024; 59 (7): 893-895

    View details for DOI 10.1111/apt.17902

    View details for PubMedID 38462684

  • Editorial: Updated epidemiology of steatotic liver disease in people with HIV in the United States. Alimentary pharmacology & therapeutics Manikat, R., Kim, S. U., Ahmed, A., Kim, D. 2024; 59 (6): 789-790

    View details for DOI 10.1111/apt.17871

    View details for PubMedID 38401138

  • Disparities among ethnic groups in mortality and outcomes among adults with MASLD: A multicenter study. Liver international : official journal of the International Association for the Study of the Liver Aboona, M. B., Faulkner, C., Rangan, P., Ng, C. H., Huang, D. Q., Muthiah, M., Nevah Rubin, M. I., Han, M. A., Fallon, M. B., Kim, D., Chen, V. L., Wijarnpreecha, K. 2024

    Abstract

    BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and 10%-20% occurs in lean individuals. There is little data in the literature regarding outcomes in an ethnically-diverse patient populations with MASLD. Thus, we aim to investigate the natural history and ethnic disparities of MASLD patients in a diverse population, and stratified by body mass index categories.METHODS: We conducted a retrospective multicenter study on patients with MASLD at the Banner Health System from 2012 to 2022. Main outcomes included mortality and incidence of cirrhosis, cardiovascular disease, diabetes mellitus (DM), liver-related events (LREs), and cancer. We used competing risk and Cox proportional hazard regression analysis for outcome modelling.RESULTS: A total of 51452 (cross-sectional cohort) and 37027 (longitudinal cohort) patients were identified with 9.6% lean. The cohort was 63.33% European ancestry, 27.96% Hispanic ancestry, 3.45% African ancestry, and 2.31% Native American/Alaskan ancestry. Median follow-up was 45.8months. After adjusting for confounders, compared to European individuals, Hispanic and Native American/Alaskan patients had higher prevalence of cirrhosis and DM, and individuals of Hispanic, African, and Native American/Alaskan ancestry had higher mortality and incidence of LREs and DM. Lean patients had higher mortality and incidence of LREs compared with non-lean patients.CONCLUSION: Native American/Alaskan, Hispanic, and African patients had higher mortality and incidence of LREs and DM compared with European patients. Further studies to explore the underlying disparities and intervention to prevent LREs in lean patients, particularly several ethnic groups, may improve clinical outcomes.

    View details for DOI 10.1111/liv.15880

    View details for PubMedID 38407554

  • Impact of the COVID-19 pandemic on hospitalizations with hepatocellular carcinoma in the United States. Expert review of gastroenterology & hepatology Konyn, P., Perumpail, B. J., Wijarnpreecha, K., Cholankeril, G., Ahmed, A., Kim, D. 2024

    Abstract

    BACKGROUND: We studied the temporal trends of hepatocellular carcinoma (HCC)-related hospitalizations and potential predictors of in-hospital mortality around the COVID-19 pandemic.RESEARCH DESIGN AND METHODS: Using the International Classification of Diseases code, we used the National Inpatient Sample 2019-2020 and defined HCC and its underlying etiology. To assess the impact of the COVID-19 pandemic on hospitalization and in-hospital mortality, the study period was divided into the pre-COVID-19 era (2019 Q1-2020 Q1) and the COVID-19 era (2020 Q2-2020 Q4). Quarterly trends in etiology-based hospitalizations with HCC and predictors of in-hospital mortality among hospitalizations with HCC were determined.RESULTS: Hospitalization rates for HCC, as well as viral hepatitis-related HCC hospitalization rates, remained stable, while hospitalizations with alcohol-related liver disease (ALD, quarterly percentage change [QPC]: 2.1%; 95% confidence interval [CI]: 0.1%-4.2%) increased steadily. Hospitalization related to nonalcoholic fatty liver disease (NAFLD)-related HCC increased significantly steeper in the COVID-19 era (QPC: 6.6%; 95% CI: 4.0%-9.3%) than in the pre-COVID-19 era (QPC: 0.7%; 95% CI: 0.2%-1.3%). COVID-19 infection was independently associated with in-hospital mortality among hospitalizations with HCC (odds ratio: 1.94, 95% CI: 1.30-2.88).CONCLUSION: Hospitalization rates for viral hepatitis-related HCC remained stable, while those for HCC due to ALD and NAFLD increased during the COVID-19 pandemic.

    View details for DOI 10.1080/17474124.2024.2319580

    View details for PubMedID 38353612

  • 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

  • Association between food insecurity and metabolic dysfunction-associated steatotic liver disease/significant fibrosis measured by fibroscan. European journal of nutrition Kim, D., Perumpail, B. J., Cholankeril, G., Ahmed, A. 2024

    Abstract

    PURPOSE: Studies evaluating food insecurity and metabolic dysfunction-associated steatotic liver disease (MASLD) and significant hepatic fibrosis are currently scarce. We evaluated the characteristics of food insecure individuals and whether food insecurity was associated with MASLD and significant hepatic fibrosis in the US population.METHODS: In this cross-sectional study from the National Health and Nutrition Examination Survey 2017-2018, 3441 participants with complete data were enrolled. We defined MASLD and significant hepatic fibrosis (≥F2) by transient elastography in the absence of other causes of liver disease. The detailed questionnaire assessed and categorized food security as high, marginal, low, and very low food security.RESULTS: Food-insecure subjects were more likely to be female, younger, more impoverished, non-Hispanic blacks, Hispanics, and less likely to be educated, married, and physically active. Food insecurity increased the odds of the prevalence of MASLD by 42% (odds ratio [OR]: 1.42, 95% confidence interval [CI]: 1.12-1.78) after adjustment for demographic, lifestyle, and metabolic risk factors. The addition of diabetes and obesity did not change this association (OR: 1.36, 95% CI: 1.03-1.78). The multivariable model showed an independent relationship between food insecurity and significant hepatic fibrosis (OR: 1.40, 95% CI: 1.04-1.88) after adjustment for demographic, lifestyle, and metabolic risk factors, although the association was attenuated and changed insignificantly after adjustment for diabetes and obesity.CONCLUSIONS: Food insecurity was associated with higher odds for MASLD. While there is a relationship between food insecurity and significant hepatic fibrosis, this relationship changed insignificantly after adjustment of diabetes and obesity.

    View details for DOI 10.1007/s00394-024-03327-9

    View details for PubMedID 38260997

  • What Is New in Metabolic Dysfunction-Associated Steatotic Liver Disease in Lean Individuals: From Bench to Bedside. Journal of clinical medicine Danpanichkul, P., Suparan, K., Kim, D., Wijarnpreecha, K. 2024; 13 (1)

    Abstract

    Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world's adult population. While it is associated with obesity and metabolic syndrome, emerging evidence has shown that a substantial number of MASLD patients have a normal body mass index ("lean individuals with MASLD"). In this article, we provide an overview of the definition, epidemiology, pathogenesis, and clinical outcomes associated with lean individuals with MASLD and updates on current management.

    View details for DOI 10.3390/jcm13010278

    View details for PubMedID 38202285

  • Up-to-date global epidemiology of nonalcoholic fatty liver disease. Hepatobiliary surgery and nutrition Manikat, R., Ahmed, A., Kim, D. 2023; 12 (6): 956-959

    View details for DOI 10.21037/hbsn-23-548

    View details for PubMedID 38115930

    View details for PubMedCentralID PMC10727827

  • Endogenous sex hormones and nonalcoholic fatty liver disease in US adults. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Manikat, R., Cholankeril, G., Ahmed, A. 2023

    Abstract

    Sex steroid hormones and sex hormone-binding globulin (SHBG) have a role in predisposing individuals to nonalcoholic fatty liver disease (NAFLD), but their effects are known to differ between men and women. The testosterone-to-estradiol ratio (T/E2 ratio) and free androgen index (FAI) were known biomarkers for the hormonal milieu. We investigated whether sex steroid hormones, T/E2 ratio, FAI, and SHBG were associated with NAFLD in US adults.A cross-sectional analysis using the 2013-2016 National Health and Nutrition Examination Survey (NHANES) was performed. NAFLD was defined by utilizing the Hepatic Steatosis Index (HSI) and the US fatty liver index (USFLI) without other causes of chronic liver disease.Out of 8687 subjects (49.5% male), low total testosterone levels were associated with progressively higher odds of NAFLD in men. Increasing T/E2 ratio was inversely associated with higher odds of NAFLD in men. Low serum SHBG levels were independently associated with an increased risk of NAFLD regardless of sex and menopausal status. Increasing FAI was independently associated with NAFLD. When we additionally adjusted for SHBG, T/E2 ratio, not total testosterone, was inversely associated with NAFLD in a dose-dependent manner. Increasing FAI was associated with higher odds of NAFLD in premenopausal women and marginally associated with NAFLD in postmenopausal women.The T/E2 ratio and SHBG were inversely associated with an increased risk of NAFLD in men. In women, increasing FAI was associated with NAFLD, whereas SHBG was inversely associated with NAFLD.

    View details for DOI 10.1111/liv.15786

    View details for PubMedID 38010926

  • Up-to-date global epidemiology of nonalcoholic fatty liver disease HEPATOBILIARY SURGERY AND NUTRITION Manikat, R., Ahmed, A., Kim, D. 2023
  • The Surreptitious Burden of Nonalcoholic Fatty Liver Disease in the Elderly in the Asia-Pacific Region: An Insight from the Global Burden of Disease Study 2019. Journal of clinical medicine Danpanichkul, P., Kongarin, S., Permpatdechakul, S., Polpichai, N., Duangsonk, K., Manosroi, W., Chaiyakunapruk, N., Mousa, O. Y., Kim, D., Chen, V. L., Wijarnpreecha, K. 2023; 12 (20)

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) represents a significant health threat worldwide. The aging population and a rise in metabolic syndrome in Asia might influence the epidemiology of NAFLD among the elderly. However, there is a lack of understanding of the burden and recommendations for NAFLD in this group. Our study sought to investigate the trends in the NAFLD burden among the elderly in the Asia-Pacific region. We employed data from the Global Burden of Disease 2019 study for an in-depth analysis of the prevalence and disability-adjusted life years (DALYs) along with age-standardized rate (ASR) associated with NAFLD in elderly populations (age 65-89 years) across the Asia-Pacific region, including the Southeast Asia (SEA) and Western Pacific (WP) regions, from 2010 to 2019. This study also examined the trends and disparities in NAFLD burden across different nations and sexes. In 2019, there were over 120 million cases of NAFLD in the elderly in the Asia-Pacific region. The ASR of prevalence was higher in SEA compared to WP (36,995.37 vs. 32,821.78 per 100,000). ASR of prevalence increased with annual percentage change (APC) +0.95% in the WP while it increased by +0.87% in SEA. During the study period, the ASR of DALYs decreased in SEA (APC -0.41%) but remained stable in the WP region. The burden of NAFLD in the elderly population in Asia-Pacific has increased, underscoring the timely intervention to tackle this high and rising burden.

    View details for DOI 10.3390/jcm12206456

    View details for PubMedID 37892594

    View details for PubMedCentralID PMC10607093

  • STATIN USE IN NONALCOHOLIC FATTY LIVER DISEASE AND EFFECTS ON VIBRATION-CONTROLLED TRANSIENT ELASTOGRAPHY-DERIVED SCORES - A POPULATION-BASED INVERSE PROBABILITY TREATMENT WEIGHTING ANALYSIS Polpichai, N., Saowapa, S., Jaroenlapnopparat, A., Fangsaard, P., Danpanichkul, P., Wattanachayakul, P., Chen, V., Wong, Y., Kim, D., Wijarnpreecha, K. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1182
  • RACIAL DISPARITIES IN PREVALENCE AND INCIDENCE OF CIRRHOSIS AND EXTRAHEPATIC MANIFESTATIONS IN NONALCOHOLIC FATTY LIVER DISEASE Aboona, M., Faulkner, C., Rangan, P., Chen, V., Ng, C., Huang, D. Q., Muthiah, M., Kim, D., Rubin, M., Han, M., Fallon, M., Wijarnpreecha, K. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1038-S1039
  • INCREASED MORTALITY AND LIVER- RELATED COMPLICATIONS IN LEAN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE COMPARED TO NON- LEAN Faulkner, C., Aboona, M., Rangan, P., Chen, V., Ng, C., Huang, D. Q., Muthiah, M., Kim, D., Rubin, M., Han, M., Fallon, M., Wijarnpreecha, K. LIPPINCOTT WILLIAMS & WILKINS. 2023: S986
  • PREVALENCE OF NONALCOHOLIC FATTY LIVER DISEASE AND FIBROSIS IN PATIENTS WITH PREDIABETES/DIABETES BASED ON BODY MASS INDEX Alshuwaykh, O., Ahmed, A., Cholankeril, G., Kim, D. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1033-S1034
  • EVALUATING INTENTION- TO- TREAT SURVIVAL FOR LIVER TRANSPLANTATION IN ALCOHOL- ASSOCIATED HEPATITIS COMPARED TO STATUS 1A FROM ACUTE LIVER FAILURE Patel, A., Mathew, C., Lee, T., Hernaez, R., Lymberopoulos, P., Bhatnagar, A., Shaikh, A., Tran, V., Kim, D., Ahmed, A., Goss, J. A., Rana, A., Kanwal, F., Im, G. Y., Cholankeril, G. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1600
  • OUTCOMES OF LIVER TRANSPLANTATION IN PATIENTS WITH ACUTE ALCOHOLIC HEPATITIS BASED ON WAITLIST DURATION Alshuwaykh, O., Cholankeril, G., Kim, D., Ahmed, A. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1632
  • The Impact of Alcohol Consumption and Addiction on Liver Transplantation Programs in the COVID-19 Era. Hepatic medicine : evidence and research Manikat, R., Ahmed, A., Kim, D. 2023; 15: 141-149

    Abstract

    The coronavirus disease 2019 (COVID-19) pandemic has caused significant shifts in alcohol consumption patterns in the United States, with potential long-term implications for liver transplantation (LT) programs. Alcohol consumption has increased, particularly in women, leading to a rise in alcohol-related liver disease (ALD) and alcohol use disorder. Psychological distress associated with the pandemic may further exacerbate alcohol addiction. ALD is now the most common indication for LT, with higher disease severity and complex clinical presentations, demanding a fundamental transformation in LT programs. Multidisciplinary cooperation among medical specialists, telemedicine, and remote healthcare are essential strategies to address these challenges. However, barriers to telemedicine and costs must be overcome. Curbing alcohol consumption at the societal level and bolstering mental health programs to mitigate healthcare workforce moral injury are recommended to optimize patient care in the post-COVID-19 era. Adequate planning and compassionate management of finite resources will be crucial for the successful continuation of LT programs amidst the concerning trends in alcohol consumption and addiction.

    View details for DOI 10.2147/HMER.S384070

    View details for PubMedID 37794854

    View details for PubMedCentralID PMC10546995

  • Total Bilirubin Levels in Nonalcoholic Fatty Liver Disease and All- cause and Cause-specific Mortality in US Adults. Journal of gastrointestinal and liver diseases : JGLD Moss, K., Dennis, B. B., Naji, L., Ahmed, A., Kim, D. 2023; 32 (3): 323-331

    Abstract

    Nonalcoholic Fatty Liver Disease (NAFLD) is a chronic progressive illness with a spectrum of disease severity from steatosis to end-stage liver disease. Emerging evidence suggests total serum bilirubin levels are inversely related to the prevalence of metabolic syndrome including NAFLD. We investigated the effects of bilirubin on all-cause and cause-specific mortality stratified by NAFLD status.We used the third National Health and Nutrition Examination Survey Cohort (1988-1994) and linked mortality dataset through 2019. Cox-regression models were constructed to assess the association between bilirubin levels categorized by quartile with all-cause and cause-specific mortality.During the median follow-up of 324 months (n=11,078), higher bilirubin levels were associated with a reduction in risk of all-cause mortality in the multivariate model (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.71-0.97 for quarter 4 [highest bilirubin levels] vs. quarter 1 [lowest bilirubin levels], p for trend=0.033). Higher bilirubin levels were associated with a lower risk for all-cause mortality in individuals with NAFLD (HR; 0.68, 95% CI: 0.55-0.86 for quarter 4, p for trend=0.010); however, this protective association with higher bilirubin levels was not noted in those without NAFLD. Higher bilirubin levels were associated with a lower risk for cardiovascular and cancer-related mortality in individuals with NAFLD.In this large nationally representative sample of American adults, higher bilirubin levels in NAFLD were associated with a lower risk of all-cause mortality, which may be derived from a lower risk of cardiovascular/cancer-related mortality.

    View details for DOI 10.15403/jgld-4732

    View details for PubMedID 37774224

  • Chronic liver disease-related mortality during the COVID-19 pandemic. European journal of internal medicine Kim, D., Manikat, R., Wijarnpreecha, K., Cholankeril, G., Ahmed, A. 2023

    View details for DOI 10.1016/j.ejim.2023.09.024

    View details for PubMedID 37777423

  • Rising incidence and impact of early-onset colorectal cancer in the Asia-Pacific with higher mortality in females from Southeast Asia: a global burden analysis from 2010 to 2019. Journal of gastroenterology and hepatology Danpanichkul, P., Moolkaew, P., Kanjanakot, Y., Polpichai, N., Jaroenlapnopparat, A., Kim, D., Lukens, F. J., Wassef, W., Fallon, M. B., Chen, V. L., Lui, R., Wijarnpreecha, K. 2023

    Abstract

    BACKGROUND AND AIM: Early-onset colorectal cancer (CRC) is a growing global health concern, especially in the Asia-Pacific region. However, comprehensive research on this topic from the region is lacking. Our study aims to investigate trends in early-onset CRC in Asia over 10years, filling this research gap.METHODS: This study utilized data from the Global Burden of Disease Study 2019 to assess temporal trends in early-onset CRC in the Asia-Pacific. The analysis included estimating annual frequencies and age-standardized rates (ASRs) of early-onset CRC incidence, death, and disability-adjusted life-years (DALYs) by gender.RESULTS: The incidence of early-onset CRC significantly increased in both regions with higher increase and in the Western Pacific region. Notable increases were observed among males in the Western Pacific and females in Southeast Asia (SEA). Mortality rates remained stable in the Western Pacific but increased by 10.6% in SEA, especially among females. DALYs due to CRC also increased significantly in SEA, with a greater rise among females. The Western Pacific had the highest CRC incidence, and in SEA, the mortality rate was higher in females than males.CONCLUSIONS: Our study reveals a substantial increase in early-onset CRC in the Asia-Pacific underscoring the urgency for effective interventions. Thus, a comprehensive approach comprising controlled risk reduction, health promotion to heightened disease awareness, and implementation of effective screening strategies should be executed timely to mitigate the burden of early-onset CRC.

    View details for DOI 10.1111/jgh.16331

    View details for PubMedID 37644698

  • Depression in nonalcoholic fatty liver disease and all-cause/cause-specific mortality. European journal of clinical investigation Kim, D., Manikat, R., Shaikh, A., Cholankeril, G., Ahmed, A. 2023: e14087

    Abstract

    Depression has been associated with nonalcoholic fatty liver disease (NAFLD). Data addressing the impact of depression on NAFLD-related mortality are evolving. We aim to study the association of depression in NAFLD and all-cause/cause-specific mortality in the United States.A total of 11,877 individuals with NAFLD in the 2007-2016 National Health and Nutrition Examination Survey with the availability of linked mortality through 2019 were analysed. NAFLD was defined by utilizing the hepatic steatosis index in the absence of known causes of chronic liver disease. Depression and functional impairment due to depression were assessed using the Patient Health Questionnaire.During the median follow-up of 7.6 years, individuals with depression among individuals with NAFLD had a 35% higher all-cause mortality than those without depression (hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.03-1.75) after adjusting for demographic, lifestyle and clinical risk factors. NAFLD with functional impairment due to depression had a 62% higher all-cause mortality than NAFLD without functional impairment (HR: 1.62, 95% CI: 1.10-2.39). Depression in NAFLD was associated with an approximately 50% increase in the risk for cardiovascular mortality, with a 2-fold higher cardiovascular mortality in those with functional impairment compared to those without (HR: 2.07, 95% CI: 1.30-3.30). However, there was no significant difference in cancer- and accident-related mortalities in NAFLD with or without depression.Depression among individuals with NAFLD was associated with a higher risk for all-cause and cardiovascular mortality in the United States.

    View details for DOI 10.1111/eci.14087

    View details for PubMedID 37638383

  • Transplanting hepatitis B surface antigen-positive livers in the United States: Outcomes and opportunities AMERICAN JOURNAL OF TRANSPLANTATION Bhatnagar, A., Prakash, S., Lymberopoulos, P., Goff, C., Shaikh, A., Kim, D., Ahmed, A., Berg, C., Naggie, S., Kanwal, F., Cholankeril, G., Lee, T. 2023; 23 (8): 1221-1226
  • Trends in mortality of liver cancer before and during the COVID-19 pandemic, 2017-2021. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Manikat, R., Cholankeril, G., Ahmed, A. 2023

    Abstract

    We studied the trends in liver cancer-related mortality before and during the COVID-19 pandemic. Quarterly age-standardized mortality and quarterly percentage change (QPC) for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) were estimated using the US national mortality database 2017-2021. Quarterly age-standardized mortality from HCC decreased steadily with an average QPC of -0.4% (95% confidence interval [CI]: -0.6% to -0.2%). A decrease in hepatitis C virus and hepatitis B virus-related HCC mortality of -2.2% (95% CI: -2.4% to -1.9%) and -1.1% (95% CI: -2.0% to -0.3%) was noted. In contrast, mortality for HCC from nonalcoholic fatty liver disease (3.0%, 95% CI: 2.0%-4.0%) and alcohol-related liver disease (1.3%, 95% CI: 0.8%-1.9%) demonstrated a linear increase. There was a linear increase in the quarterly age-standardized ICC-related mortality (0.8%, 95% CI: 0.5%-1.0%). While ICC-related mortality continued to increase, HCC-related mortality tended to decline mainly due to a decline in mortality due to viral hepatitis.

    View details for DOI 10.1111/liv.15668

    View details for PubMedID 37387517

  • Survival following liver transplantation for hepatocellular carcinoma after implementation of MMaT-3 policy. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Shaikh, A., Lee, T., Rich, N. E., Benhammou, J. N., Lymberopoulos, P., Agopian, V. G., Kim, D., Ahmed, A., Hernaez, R., Berg, C. L., Goss, J., Rana, A., Kanwal, F., Cholankeril, G. 2023

    View details for DOI 10.1097/LVT.0000000000000167

    View details for PubMedID 37129867

  • Transplanting Hepatitis B Surface Antigen Positive Livers in the U.S.: Outcomes and Opportunities. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Bhatnagar, A., Prakash, S., Lymberopoulos, P., Goff, C., Shaikh, A., Kim, D., Ahmed, A., Berg, C., Naggie, S., Kanwal, F., Cholankeril, G., Lee, T. H. 2023

    Abstract

    Livers from donors with positive hepatitis B surface antigen (HBsAg+) have been used to expand the donor pool, but outcome data are limited. We aim to evaluate survival following liver transplant (LT) from HBsAg+ donors. Using the United Network for Organ Sharing registry, we identified HBsAg+ donors utilized for LT from 2009 to 2020. We used Kaplan-Meier survival and Cox proportional hazards regression to compare post-LT survival in HBV- recipients who utilized HBsAg+ donors to propensity-matched cohorts who utilized other types of donors. From 2009-2020, 70 patients received HBsAg+ livers, and 58 of them did not carry a diagnosis of chronic hepatitis B (HBV-). The 1 and 3-year post-LT survival for HBV- patients who received livers from HBsAg+ donors were 96.6% and 91.4%, respectively, with no statistical differences compared to patients received livers from HCV viremic donors (96.5%/93.0%, P=0.961/0.427), donation after cardiac death (DCD) donors (93.0%/86.0%, p=0.651/0.598), average risk donors (89.5%/86.0%, P=0.264/0.617), and combination of extended criteria donors, including DCD, donor age over 70, and graft with greater than 30% steatosis (93.0%/91.2%, P=0.621/0.785). Recipients of HBsAg+ livers have similar post-LT survival compared to those received other types of grafts. Increase utilization of HBsAg+ livers could safely expand the donor pool.

    View details for DOI 10.1016/j.ajt.2023.04.024

    View details for PubMedID 37116583

  • The current trends in the health burden of primary liver cancer across the globe. Clinical and molecular hepatology Konyn, P., Ahmed, A., Kim, D. 2023

    View details for DOI 10.3350/cmh.2023.0092

    View details for PubMedID 36916167

  • Post-transplant outcomes for alcohol-associated liver disease during the COVID-19 pandemic. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Goli, K., Lymberopoulos, P., Samuel, R., Shaikh, A., Parakadavil, N., Kim, D., Ahmed, A., Goss, J. A., Rana, A., Lee, T., Kanwal, F., Cholankeril, G. 2023

    Abstract

    ■■■■. Karthik Goli, Peter Lymberopoulos: Authors contributed equally.

    View details for DOI 10.1097/LVT.0000000000000113

    View details for PubMedID 36872590

  • Types of Physical Activity in Nonalcoholic Fatty Liver Disease and All-Cause and Cardiovascular Mortality. Journal of clinical medicine Kim, D., Wijarnpreecha, K., Dennis, B. B., Cholankeril, G., Ahmed, A. 2023; 12 (5)

    Abstract

    The impact of different types of physical activity (PA) on mortality in the context of nonalcoholic fatty liver disease (NAFLD) is not clearly defined and was investigated. This prospective study was performed using the 2007-2014 US National Health and Nutrition Examination Survey with mortality follow-up through 2019. Over a median follow-up of 8.6 years, leisure-time and transportation-related PA that fulfilled the criteria outlined in the PA guidelines (≥150 min/week) in NAFLD were associated with a risk reduction in all-cause mortality (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.59-0.98 for leisure-time PA; HR: 0.62, 95% CI: 0.45-0.86 for transportation-related PA). Leisure-time and transportation-related PA in NAFLD were inversely associated with all-cause mortality in a dose-dependent manner (p for trends <0.01). Furthermore, the risk for cardiovascular mortality was lower in those meeting the PA guidelines for leisure-time PA (HR: 0.63, 95% CI: 0.44-0.91) and transportation-related PA (HR: 0.38, 95% CI: 0.23-0.65). Increasing sedentary behavior was linked to an increased risk of all-cause and cardiovascular mortality (p for trend <0.01). Meeting PA guidelines (≥150 min/week) for leisure-time and transportation-related PA has beneficial health effects on all-cause and cardiovascular mortality among individuals with NAFLD. Sedentary behavior in NAFLD showed harmful effects on all-cause and cardiovascular mortality.

    View details for DOI 10.3390/jcm12051923

    View details for PubMedID 36902707

  • Association between depression and metabolic dysfunction-associated fatty liver disease/significant fibrosis. Journal of affective disorders Kim, D., Dennis, B. B., Cholankeril, G., Ahmed, A. 2023

    Abstract

    BACKGROUND: An association between depression and metabolic dysfunction-associated fatty liver disease (MAFLD) appears logical on the basis of previous observations linking depression to nonalcoholic fatty liver disease. We aim to investigate the association between depression and MAFLD and significant fibrosis.METHODS: This cross-sectional study was conducted on data from National Health and Nutrition Examination Survey, 2017 to March 2020 Pre-pandemic dataset. Depression and depression-related functional impairment were assessed using the Patient Health Questionnaire (PHQ-9). MAFLD, based on the criteria proposed by an international expert panel, and significant fibrosis were defined by transient elastography.RESULTS: Of the 3327 individuals (mean age: 46.9 years, 50.2 % men), the prevalence of depression and functional impairment due to depression was higher among individuals with MAFLD or significant fibrosis than among those without. Individuals with depression were approximately 70 % more likely to have MAFLD than those without. In multivariable analyses, depression was associated with an increased risk of MAFLD (odds ratio [OR]: 1.77, 95 % confidence interval [CI]:1.33-2.36 for ≥263 dB/m and OR: 1.70, 95 % CI: 1.20-2.41 for ≥285 dB/m). These associations were more pronounced in postmenopausal women than premenopausal women. In terms of significant fibrosis, depression remained an independent predictor of significant fibrosis; however, it attenuated after adjustment for body mass index.LIMITATIONS: Temporal causality and residual confounders could not be entirely investigated due to the study design.CONCLUSIONS: Depression was independently associated with MAFLD and significant fibrosis in a nationally representative sample of adults in the US.

    View details for DOI 10.1016/j.jad.2023.02.101

    View details for PubMedID 36841305

  • Lean or diabetic subtypes predict increased all-cause and disease-specific mortality in metabolic-associated fatty liver disease. BMC medicine Chung, G. E., Yu, S. J., Yoo, J. J., Cho, Y., Lee, K. N., Shin, D. W., Kim, D., Kim, Y. J., Yoon, J. H., Han, K., Cho, E. J. 2023; 21 (1): 4

    Abstract

    Metabolic-associated fatty liver disease (MAFLD) encompasses diverse disease groups with potentially heterogeneous clinical outcomes. We investigated the risk of all-cause and disease-specific mortality in MAFLD subgroups.Using the Korean National Health Insurance Service database, participants were divided into four subgroups: no MAFLD, MAFLD-diabetes, MAFLD-overweight/obese, and MAFLD-lean. Hazard ratios (HRs) and 95% confidence interval (CI) values for all-cause and disease-specific mortality according to MAFLD subgroups were analyzed using Cox proportional hazards models.Among 9,935,314 participants, those with MAFLD-diabetes showed the highest risk of all-cause and disease-specific mortality. The HRs (95% CI) for all-cause mortality were 1.61 (1.59-1.63), 1.36 (1.34-1.38), and 1.19 (1.18-1.20) in the MAFLD-diabetes, MAFLD-lean, and MAFLD-overweight/obese groups, respectively. The magnitude of cardiovascular disease and cancer-related risk showed the same pattern. The risk of liver-related mortality in the MAFLD-lean group (HR: 2.84, 95% CI: 2.72-2.97) was comparable with that in the MAFLD-diabetes group (HR: 2.85, 95% CI: 2.75-2.95). When stratified by body mass index, liver-related mortality was the highest in MAFLD-lean individuals in the underweight group (HR, 5.03, 95% CI: 4.23-5.97).The MAFLD-lean and MAFLD-diabetes groups had a higher risk of all-cause and disease-specific mortality than did the MAFLD-overweight/obese group. Classifying MAFLD subgroups based on metabolic phenotypes might help risk stratification of patients with MAFLD.

    View details for DOI 10.1186/s12916-022-02716-3

    View details for PubMedID 36600263

  • Muscle Strength in Nonalcoholic Fatty Liver Disease and All-cause and Cause-specific Mortality. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Dennis, B. B., Wijarnpreecha, K., Cholankeril, G., Ahmed, A. 2022

    View details for DOI 10.1111/liv.15498

    View details for PubMedID 36520009

  • Reduction in racial and ethnic disparity in survival following liver transplant for hepatocellular carcinoma in DAA era. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Shaikh, A., Goli, K., Lee, T., Rich, N. E., Benhammou, J. N., Keeling, S., Kim, D., Ahmed, A., Goss, J., Rana, A., Singal, A. G., Kanwal, F., Cholankeril, G. 2022

    Abstract

    BACKGROUND & AIMS: Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct acting antivirals (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for HCC candidates.METHODS: Using the United Network for Organ Sharing (UNOS) registry, we identified HCC patients who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into two era-based cohorts: the pre-DAA era (LT between 2009-2011) and DAA era (LT between 2015-2017, with follow-up through 2020). Kaplan Meir and Cox proportional hazards analyses were used to compare post-LT survival, stratified by era and race and ethnicity.RESULTS: Annual wait list additions for HCV-related HCC decreased significantly in White and Hispanic patients during the DAA era, with no change (P=0.14) in Black patients. Black patients had lower 3-year survival than White patients in the pre-DAA era (70.6% vs.80.1%, respectively, P<0.001) but comparable survival in the DAA era (82.1%, vs. 85.5%, respectively, P= 0.16). 0n multivariable analysis, Black patients in the pre-DAA era had a 53% higher risk (adjusted HR, 1.53, 95% CI:1.28-1.84), for mortality than White patients, but mortality was comparable in the DAA era (aHR, 1.23, 95% CI:0.99-1.52). In a stratified analysis in Black patients, HCV-related HCC carried more than a two-fold higher risk of mortality in the pre-DAA era (aHR 2.86, 95% CI:1.50-5.43) which was reduced in DAA era (aHR 1.34, 95%CI:0.78-2.30).CONCLUSIONS: With the availability of DAA therapy, racial disparities in post-LT survival have improved.

    View details for DOI 10.1016/j.cgh.2022.11.038

    View details for PubMedID 36521738

  • Causes and Risk Profiles of Mortality among Individuals with Nonalcoholic Fatty Liver. Clinical and molecular hepatology Konyn, P., Ahmed, A., Kim, D. 2022

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and worldwide. Though nonalcoholic fatty liver per se may not be independently associated with an increased risk for all-cause mortality, it is associated with a number of harmful metabolic risk factors, such as type 2 diabetes mellitus, hyperlipidemia, obesity, a sedentary lifestyle, and an unhealthy diet. The fibrosis stage is a predictor of all-cause mortality in NAFLD. Mortality in individuals with NAFLD has been steadily increasing, and the most common cause-specific mortality for NAFLD is cardiovascular disease, followed by extra-hepatic cancer, liver-related mortality, and diabetes. High-risk profiles for mortality in NAFLD include PNPLA3 I148M polymorphism, low thyroid function and hypothyroidism, and sarcopenia. Achieving weight loss through adherence to a high-quality diet and sufficient physical activity is the most important predictor of improvement in NAFLD severity and the benefit of survival. Given the increasing health burden of NAFLD, future studies with more long-term mortality data may demonstrate an independent association between NAFLD and mortality.

    View details for DOI 10.3350/cmh.2022.0351

    View details for PubMedID 36417893

  • Improved Survival after Liver Transplantation for Patients with HIV and HIV/HCV Coinfection in the INSTI and DAA eras. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Jacob, J. S., Shaikh, A., Goli, K., Rich, N. E., Benhammou, J. N., Ahmed, A., Kim, D., Rana, A., Goss, J. A., Naggie, S., Lee, T. H., Kanwal, F., Cholankeril, G. 2022

    Abstract

    BACKGROUND: Patients with human immunodeficiency virus (HIV) with and without hepatitis C virus (HCV) coinfection had poor outcomes after liver transplant (LT). Integrase strand transfer inhibitors (INSTI) and direct-acting antivirals (DAA) changed the treatment landscape for HIV and HCV, respectively; their impact on LT outcomes remains unclear.METHODS: This retrospective analysis of adults with HIV monoinfection (n=246) and HIV/HCV coinfection (n=286) who received LT compared mortality in patients with HIV who received LT before vs. after approval of INSTI and in patients with HIV/HCV coinfection who received LT before vs after approval of DAA. In secondary analysis, we compared the outcomes in the different eras with those of propensity score (PS) matched control cohorts of LT recipients without HIV or HCV infection.RESULTS: HIV monoinfected LT recipients did not experience a significant improvement in survival between the pre-INSTI and INSTI recipients with HIV (aHR 0.70 [0.36-1.34). However, recipients with HIV/HCV coinfection in the DAA era had a 47% reduction (aHR 0.53 [0.31-9.2] in one-year mortality than co-infected recipients in the pre-DAA era. Compared to non-HIV or HCV recipients, HIV monoinfected recipients had higher mortality during the pre-INSTI era (aHR, ), but survival was comparable between groups during the INSTI era (aHR, ). HIV/HCV coinfected recipients also experienced comparable survival during the DAA era compared to non-HIV or HCV recipients (aHR, ).CONCLUSIONS: Post-LT survival for patients with HIV monoinfection and HIV/HCV coinfection has improved with the introduction of INSTI and DAA therapy, suggesting that LT has become safer in these populations.

    View details for DOI 10.1093/cid/ciac821

    View details for PubMedID 36221143

  • Body fat distribution: a crucial target for intervention in nonalcoholic fatty liver disease and fibrosis. Hepatobiliary surgery and nutrition Wijarnpreecha, K., Ahmed, A., Kim, D. 2022; 11 (5): 738-742

    View details for DOI 10.21037/hbsn-22-366

    View details for PubMedID 36268244

    View details for PubMedCentralID PMC9577990

  • POST-TRANSPLANT OUTCOMES FOR HEPATITIS B CORE ANTIBODY OR SURFACE ANTIGEN POSITIVE DONORS - OPPORTUNITY TO EXPAND DONOR POOL Bhatnagar, A., Prakash, S., Cholankeril, R., Lymberopoulos, P., Ahmed, A., Goff, C., Kim, D., Kim, H., Flores, A. G., Goss, J. A., Rana, A., Kanwal, F., Cholankeril, G., Lee, T. WILEY. 2022: S520-S521
  • CLINICAL IMPACT OF METABOLIC-ASSOCIATED FATTY LIVER DISEASE ON LIVER TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA Shaikh, A., Lymberopoulos, P., Benhammou, J. N., Rich, N. E., Patel, A., Bhatnagar, A., Kim, D., Ahmed, A., Rana, A., Lee, T., Cholankeril, G. WILEY. 2022: S879
  • POST-TRANSPLANT OUTCOMES FOR ALCOHOL-ASSOCIATED LIVER DISEASE DURING THE COVID-19 PANDEMIC Goli, K., Lymberopoulos, P., Shaikh, A., Parakadavil, N., Kim, D., Ahmed, A., Goss, J. A., Rana, A., Lee, T., Kanwal, F., Cholankeril, G. WILEY. 2022: S532-S533
  • RACIAL AND ETHNIC DISPARITIES IN CURE RATES FOR HCV INFECTION AT LIVER TRANSPLANTATION IN THE UNITED STATES Lymberopoulos, P., Shaikh, A., Cholankeril, R., Parakadavil, N., Poche, M., Ahmed, A., Kim, D., Lee, T., Kanwal, F., Cholankeril, G. WILEY. 2022: S523-S524
  • Chronic liver disease-related mortality in diabetes before and during the COVID-19 in the United States. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver Kim, D., Alshuwaykh, O., Dennis, B. B., Cholankeril, G., Knowles, J. W., Ahmed, A. 2022

    Abstract

    BACKGROUND: Global pandemic of COVID-19 represents an unprecedented challenge. COVID-19 has predominantly targeted vulnerable populations with pre-existing chronic medical diseases, such as diabetes and chronic liver disease.AIMS: We estimated chronic liver disease-related mortality trends among individuals with diabetes before and during the COVID-19 pandemic.METHODS: Utilizing the US national mortality database and Census, we determined the quarterly age-standardized chronic liver disease-related mortality and quarterly percentage change (QPC) among individuals with diabetes.RESULTS: The quarterly age-standardized mortality for chronic liver disease and/or cirrhosis among individuals with diabetes remained stable before the COVID-19 pandemic and sharply increased during the COIVD-19 pandemic at a QPC of 8.5%. The quarterly mortality from nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) increased markedly during the COVID-19 pandemic. Mortality for hepatitis C virus (HCV) infection declined with a quarterly rate of -3.3% before the COVID-19 pandemic and remained stable during the COVID-19 pandemic. While ALD- and HCV-related mortality was higher in men than in women, NAFLD-related mortality in women was higher than in men.CONCLUSIONS: The sharp increase in mortality for chronic liver disease and/or cirrhosis among individuals with diabetes during the COVID-19 pandemic was associated with increased mortality from NAFLD and ALD.

    View details for DOI 10.1016/j.dld.2022.09.006

    View details for PubMedID 36182570

  • Body fat distribution: a crucial target for intervention in nonalcoholic fatty liver disease and fibrosis HEPATOBILIARY SURGERY AND NUTRITION Wijarnpreecha, K., Ahmed, A., Kim, D. 2022
  • Reply: Does Fatty Liver Play a Role in the Risk of All-Cause and Cause-Specific Mortality in Patients with Gallstone Disease? Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Konyn, P., Ahmed, A. 2022

    View details for DOI 10.1016/j.cgh.2022.08.002

    View details for PubMedID 35963540

  • Changing Trends in Etiology-Based Hospitalizations with End-Stage Liver Disease in the United States from 2016 to 2019. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Perumpail, B. J., Alshuwaykh, O., Dennis, B. B., Cholankeril, G., Ahmed, A. 2022

    Abstract

    BACKGROUNDS AND AIMS: A potent and safe antiviral agent may impact chronic hepatitis C (HCV)-related end-stage liver disease (ESLD). We assess etiology-based hospitalizations for ESLD in the United States, 2016-2019.METHODS: We utilized the National Inpatient Sample (NIS) from 2016 to 2019. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma, criteria obtained from the International Classification of Diseases, Tenth Revision.RESULTS: National hospitalization rates for nonalcoholic fatty liver disease (NAFLD) increased significantly from 67.1/100,000 persons in 2016 to 93.6 in 2019 with an average annual percentage change (AAPC) of 12.1%, while chronic hepatitis C (HCV) decreased significantly from 71.2/100,000 persons in 2016 to 58.5 in 2019 (-6.5% AAPC). Hospitalizations for ESLD in alcohol-related liver disease (ALD) increased as well.CONCLUSIONS: Hospitalization rates for NAFLD-and ALD-related ESLD increased steadily, while those for HCV-related ESLD decreased during the direct-acting antivirals era.

    View details for DOI 10.1111/liv.15381

    View details for PubMedID 35906461

  • Early Impact of MMaT-3 Policy on Liver Transplant Waitlist Outcomes for Hepatocellular Carcinoma. Transplantation direct Shaikh, A., Goli, K., Rich, N. E., Benhammou, J. N., Khaderi, S., Hernaez, R., Agopian, V. G., Vierling, J. M., Kim, D., Ahmed, A., Goss, J. A., Rana, A., Kanwal, F., Cholankeril, G. 2022; 8 (5): e1313

    Abstract

    To reduce the disparity in access to liver transplant (LT), United Network for Organ Sharing implemented an exception policy in May 2019, which capped hepatocellular carcinoma (HCC) exception score to the median Model for End-Stage Liver Disease (MELD) at transplant within the donor service area minus 3 points (MMaT-3) after the 6-mo wait period. We aimed to evaluate how this policy affected HCC waitlist outcomes.Methods: Using United Network for Organ Sharing data, we analyzed waitlist outcomes in HCC patients at the time they received exception points from in the pre-MMaT era (August 15, 2017, to November 15, 2018) and MMaT era (June 1, 2019, to August 30, 2020). Comparisons were made within the HCC group and HCC versus non-HCC (at time of listing) groups in the pre-MMaT and MMaT eras and regions were grouped as low, medium, and high MELD based on MMaT.Results: HCC group: LT probability within HCC patients decreased by 20% (subhazard ratio [sHR], 0.78; 95% confidence interval [CI], 0.74-0.85) between the eras and decreased by 41% in low MELD regions (sHR, 0.59; 95% CI, 0.52-0.66). Waitlist dropout was unchanged. Matched HCC versus non-HCC groups: HCC patients had 80% higher LT probability (sHR, 1.84; 95% CI, 1.71-1.99) than non-HCC patients in the pre-MMaT era; which decreased to a 14% higher LT probability in MMaT era. In low and medium regions, HCC patients had over twofold higher LT probability in the pre-MMaT era, which decreased to a ~20% higher probability (sHR, 1.14; 95% CI, 1.06-1.23) in the MMaT era. After implementation of the acuity circle policy, HCC patients had lower LT probability (sHR, 0.84; 95% CI, 0.74-0.94) than non-HCC patients.Conclusions: The geographic disparity between HCC and non-HCC patients has improved with the MMaT-3 policy. Despite lower LT probability for HCC patients, waitlist dropout was not adversely impacted.

    View details for DOI 10.1097/TXD.0000000000001313

    View details for PubMedID 35434283

  • Nonalcoholic fatty liver disease in early life and all-cause and cause-specific mortality. Hepatobiliary surgery and nutrition Kim, D., Ahmed, A. 2022; 11 (2): 317-319

    View details for DOI 10.21037/hbsn-21-571

    View details for PubMedID 35464284

    View details for PubMedCentralID PMC9023838

  • Comparable survival for hepatitis C-related hepatocellular carcinoma after liver transplantation irrespective of viremic status. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Lymberopoulos, P., Shaikh, A., Rich, N. E., Benhammou, J. N., Kanwal, F., Cholankeril, G., Liver Cancer Investigator Working Group, Lee, T., Goss, J., Rana, A., Kim, D., Ahmed, A. 2022

    View details for DOI 10.1016/j.cgh.2022.03.021

    View details for PubMedID 35346850

  • Nonalcoholic fatty liver disease in early life and all-cause and cause-specific mortality HEPATOBILIARY SURGERY AND NUTRITION Kim, D., Ahmed, A. 2022
  • The association of weight gain with nonalcoholic fatty liver disease and fibrosis detected by FibroScan in the United States. Annals of gastroenterology Wijarnpreecha, K., Aby, E. S., Ahmed, A., Kim, D. 2022; 35 (2): 194-202

    Abstract

    Studies have reported the association between weight gain and nonalcoholic fatty liver disease (NAFLD) in the Asian population. We investigated the association between weight gain, NAFLD and significant fibrosis measured by transient elastography in a representative Unites States sample.A cross-sectional study of 2849 participants was performed using the 2017-2018 National Health and Nutrition Examination Survey. We defined NAFLD by controlled attenuation parameter (CAP) scores and significant fibrosis (≥F2) by liver stiffness measurements using transient elastography, in the absence of other causes of chronic liver disease. A questionnaire that assessed weight change over 1 (short term) and 10 years (long term) was utilized.Age- and sex-adjusted odds ratios (OR) for NAFLD, comparing the third and fourth quartiles (weight-gain group) with the second quartile (weight-stable group, reference), were 1.61 (95% confidence interval [CI] 1.07-2.43) and 3.58 (95%CI 2.19-5.86), respectively. The association between weight gain and NAFLD remained significant after adjustment for demographic and metabolic risk factors (OR 1.87, 95%CI 1.19-2.95 for CAP score ≥263 dB/m; OR 2.23, 95%CI 1.48-3.35 for CAP ≥285 dB/m). In terms of significant fibrosis, multivariate-adjusted OR for significant fibrosis were 1.99 (95%CI 1.05-3.79 for the third quartile) and 3.12 (95%CI 1.46-6.65 for the fourth quartile), respectively. A statistically significant association between weight gain over 1 year and NAFLD was noted, whereas no such association was found between weight gain and significant fibrosis.Weight gain over 10 years was associated with increased odds of NAFLD and significant fibrosis.

    View details for DOI 10.20524/aog.2022.0687

    View details for PubMedID 35479585

    View details for PubMedCentralID PMC8922259

  • The association of weight gain with nonalcoholic fatty liver disease and fibrosis detected by FibroScan in the United States ANNALS OF GASTROENTEROLOGY Wijarnpreecha, K., Aby, E. S., Ahmed, A., Kim, D. 2022
  • Extrahepatic causes of death in cirrhosis compared to other chronic conditions in the United States, 1999-2017. Annals of hepatology Shankar, N., Ramani, A., Griffin, C., Agbim, U., Kim, D., Ahmed, A., Asrani, S. K. 2021: 100565

    Abstract

    INTRODUCTION AND OBJECTIVES: Cirrhosis- related mortality is underestimated and is increasing; extrahepatic factors may contribute. We examined trends in cirrhosis mortality from 1999-2017 in the United States attributed to liver-related (varices, peritonitis, hepatorenal syndrome, hepatic encephalopathy, hepatocellular carcinoma sepsis) or extrahepatic (cardiovascular disease, influenza and pneumonia, diabetes, malignancy) causes, and compared mortality trends with congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) populations.MATERIALS AND METHODS: A national mortality database was used. Changes in age-standardized mortality over time were determined by joinpoint analysis. Average annual percentage change (AAPC) was estimated.RESULTS: Cirrhosis cohort: From 1999-2017, both liver-related (AAPC 1.3%; 95% confidence interval [CI] 0.7-1.9) and extrahepatic mortality (AAPC 1.0%; 95% CI 0.7-1.2) increased. Cirrhosis vs other chronic disease cohorts: changes in all-cause mortality were higher in cirrhosis (AAPC 1.0%; 95% CI 0.7-1.4) than CHF (AAPC 0.1%; 95% CI -0.5- 0.8) or COPD (AAPC -0.4%; 95% CI -0.6- -0.2). Sepsis mortality was highest in cirrhosis (AAPC 3.6%, 95% 3.2- 4.1) compared to CHF (AAPC 0.6%, 95% CI -0.5- 1.7) or COPD (AAPC 0.8%, 95% CI 0.5- 1.2). Cardiovascular mortality increased in cirrhosis (AAPC 1.3%, 95% CI 1.1- 1.5), declined in CHF (AAPC -2.0%, 95% CI -5.3- 1.3) and remained unchanged in COPD (AAPC 0.1%, 95% CI -0.2- 0.4). Extrahepatic mortality was higher among women, rural populations, and individuals >65 years with cirrhosis.CONCLUSIONS: Extrahepatic causes of death are important drivers of mortality and differentially impact cirrhosis compared to other chronic diseases.

    View details for DOI 10.1016/j.aohep.2021.100565

    View details for PubMedID 34728419

  • Management of Cardiometabolic Complications in Patients With Nonalcoholic Fatty Liver Disease: A Review of the Literature With Recommendations. Journal of clinical gastroenterology Dennis, B. B., Sallam, S., Perumpail, B. J., Shah, N. D., Kim, D., Cholankeril, G., Ahmed, A. 2021; 55 (9): 747-756

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of liver conditions characterized by significant lipid deposition within hepatocytes. As an overarching diagnosis, NAFLD contains a continuum of progressive liver diseases ranging from isolated liver steatosis to necroinflammatory states leading to end-stage liver disease. Nonalcoholic fatty liver and nonalcoholic steatohepatitis are distinguished by their histologic patterns, with the former exhibiting steatosis without fibrosis or inflammation. This important distinction provides clinicians a timeline within the NAFLD staging to target appropriate interventions against modifiable risk factors. NAFLD is likely formed in response to metabolic imbalances that damage the livers adaptive capacity. Metabolic conditions leading to steatosis mirror common cardiovascular risk factors, including dyslipidemia, diabetes mellitus, and obesity. Acknowledging the common risk factors for development and progression of NAFLD, it is unsurprising the first-line management focuses on the treatment of metabolic syndrome with an emphasis on weight reduction in obese populations. The purpose of this review is to provide a detailed summary of the literature as well as outline the current treatment recommendations for patients with NAFLD with a detailed focus on pharmacologic antiobesity interventions.

    View details for DOI 10.1097/MCG.0000000000001555

    View details for PubMedID 34469404

  • IMPROVED SURVIVAL AFTER LIVER TRANSPLANTATION FOR HIV POSITIVE AND HIV/HCV CO-INFECTION IN THE INSTI AND DAA ERAS Jacob, J., Shaikh, A., Goli, K., Rich, N. E., Benhammou, J. N., Kim, D., Rana, A., Goss, J. A., Kanwal, F., Cholankeril, G. WILEY. 2021: 41A-42A
  • THE STEATOSIS-ASSOCIATED FIBROSIS ESTIMATOR (SAFE) SCORE: A TOOL FOR PRIMARY CARE TO TRIAGE LOW-RISK NON-ALCOHOLIC FATTY LIVER DISEASE PATIENTS Sripongpun, P., Mannalithara, A., Kim, D., Kwong, A. J., Kim, W. WILEY. 2021: 53A-54A
  • WEIGHT GAIN AND NONALCOHOLIC FATTY LIVER DISEASE AND FIBROSIS DETECTED BY FIBROSCAN IN THE UNITED STATES Wijarnpreecha, K., Aby, E., Ahmed, A., Kim, D. WILEY. 2021: 1051A-1052A
  • SURVIVAL OUTCOMES AND PROGNOSTIC FACTORS ASSOCIATED WITH LIVER TRANSPLANTATION FOR HEMOCHROMATOSIS Lymberopoulos, P., Cholankeril, G., Jalal, P. K., Alshuwaykh, O., Goli, K., Kim, D., Ahmed, A. WILEY. 2021: 926A
  • New hope for hepatitis C virus: Summary of global epidemiologic changes and novel innovations over 20 years. World journal of gastroenterology Dennis, B. B., Naji, L., Jajarmi, Y., Ahmed, A., Kim, D. 2021; 27 (29): 4818-4830

    Abstract

    Hepatitis C virus (HCV) is a global health concern associated with significant morbidity and mortality. Before the approval of second-generation direct-acting antiviral agents (DAAs), interferon therapy and liver transplantation constituted the mainstay of treatment. The introduction of well-tolerated oral DAAs in late 2013 has revolutionized HCV management with over 95% cure rates. The predominance of HCV-related liver transplantations has declined following the widespread approval of DAAs. Despite the unparallel efficacy observed among these novel therapies, pharmaceutical costs continue to limit equitable access to healthcare and likely contribute to the differential HCV infection rates observed globally. To reduce the burden of disease worldwide, essential agenda items for all countries must include the prioritization of integrated care models and access to DAAs therapies. Through transparent negotiations with the pharmaceutical industry, the consideration for compassionate release of medications to promote equitable division of care is paramount. Here we provide a literature review of HCV, changes in epidemiologic trends, access issues for current therapies, and global inequities in disease burden.

    View details for DOI 10.3748/wjg.v27.i29.4818

    View details for PubMedID 34447228

  • Current Trends in Liver Transplantation for Alcoholic Hepatitis. Clinics in liver disease Bhatti, S., Kim, D., Ahmed, A., Cholankeril, G. 2021; 25 (3): 625-634

    Abstract

    Liver transplantation (LT) for alcohol-related or alcoholic hepatitis (AH) remains a controversial treatment option. However, recent studies have shown promising outcomes for LT in a subgroup of patients with AH. Considering these emerging data, LT as definitive therapy for severe AH refractory to medical management is gaining recognition. However, concerns of alcohol recidivism pose a significant barrier to perform LT for this indication. Predictive models can be utilized to develop a selection criterion to identify suitable candidates for LT. Hence, carefully selected patients with severe AH and low risk of alcohol relapse can be considered for LT.

    View details for DOI 10.1016/j.cld.2021.04.002

    View details for PubMedID 34229844

  • Impact of COVID-19 pandemic on liver transplantation and alcohol-associated liver disease in the United States. Hepatology (Baltimore, Md.) Cholankeril, G., Goli, K., Rana, A., Hernaez, R., Podboy, A., Jalal, P., Da, B. L., Satapathy, S. K., Kim, D., Ahmed, A., Goss, J., Kanwal, F. 2021

    Abstract

    BACKGROUND & AIMS: The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the US. We evaluated the impact of the pandemic on temporal trends for LT including ALD.APPROACH & RESULTS: Utilizing data from United Network for Organ Sharing, we analyzed waitlist outcomes in the US through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019 and February 29, 2020 were defined as the "pre-COVID" era and after April 1, 2020 were defined as the "COVID" era. Interrupted time-series analyses utilizing monthly count data from 2016-2020 were constructed to evaluate rate change for listing and LT prior to and during the COVID-19 pandemic. Rates for listings (P=0.19) and LT (P=0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P <0.001) and NASH (-13.18%; P <0.001). There was a significant increase in ALD listing (+7.26%; P <0.001) and LT (10.67%; P <0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcoholic hepatitis (+50%). ALD patients presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a MELD-Na ≥ 30.CONCLUSIONS: Since the start of COVID-19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on healthcare resources.

    View details for DOI 10.1002/hep.32067

    View details for PubMedID 34310738

  • Association between sarcopenic obesity and non-alcoholic fatty liver disease and fibrosis detected by fibroscan Wijarnpreecha, K., Aby, E., Ahmed, A., Kim, D. ELSEVIER. 2021: S532-S533
  • Association between Sarcopenic Obesity and Nonalcoholic Fatty Liver Disease and Fibrosis detected by Fibroscan. Journal of gastrointestinal and liver diseases : JGLD Wijarnpreecha, K., Aby, E. S., Ahmed, A., Kim, D. 2021

    Abstract

    BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) and sarcopenic obesity share several pathophysiologic backgrounds. No prior studies have determined a plausible association between sarcopenic obesity and NAFLD and NAFLD-associated fibrosis. We aim to investigate the association between sarcopenic obesity and NAFLD, and NAFLD-associated fibrosis detected by transient elastography.METHODS: In a cross-sectional study from the 2017-2018 National Health and Nutrition Examination Survey, 1,925 participants were identified. NAFLD was defined by controlled attenuation parameter (CAP) scores and significant fibrosis (≥F2)/cirrhosis by liver stiffness measurements on transient elastography. Sarcopenic obesity was defined by appendicular lean mass and body fat.RESULTS: Individuals with sarcopenic obesity had a significantly higher odds of having NAFLD [CAP score ≥263 dB/m, odds ratio (OR): 2.88, 95% confidence interval (CI): 1.82-4.57, and CAP score ≥285, OR: 3.71, 95%CI: 2.24-6.14] after adjusting for age, gender, and race/ethnicity. The association remained statistically significant after adjustment for socioeconomic status, lifestyle and behavioral risk factors, and metabolic conditions (CAP score ≥263, OR: 2.61, 95%CI: 1.51-4.50, and CAP score ≥285, OR: 3.31, 95%CI: 1.85-5.96). Sarcopenic obesity was also associated with higher odds of having NAFLD-associated significant fibrosis (OR 2.22, 95% CI: 1.03-4.80) in the multivariate model. While those with sarcopenic obesity had a higher prevalence of NAFLD-associated cirrhosis, this association did not reach statistical significance.CONCLUSIONS: Sarcopenic obesity was independently associated with an increased risk of NAFLD and NAFLD- associated significant fibrosis independent of well-defined risk factors. Targeted interventions to improve sarcopenic obesity may reduce the risk of NAFLD and NAFLD-associated siginificant fibrosis.

    View details for DOI 10.15403/jgld-3323

    View details for PubMedID 33951121

  • Prevalence of Nonalcoholic Fatty Liver Disease and Hepatic Fibrosis Among US Adults with Prediabetes and Diabetes, NHANES 2017-2018. Journal of general internal medicine Kim, D., Cholankeril, G., Loomba, R., Ahmed, A. 2021

    View details for DOI 10.1007/s11606-021-06677-w

    View details for PubMedID 33674915

  • Sarcopenia in Nonalcoholic Fatty Liver Disease and All-Cause and Cause-Specific Mortality in the United States. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Wijarnpreecha, K., Sandhu, K. K., Cholankeril, G., Ahmed, A. 2021

    Abstract

    BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) has been associated with sarcopenia. However, mortality in the setting of NAFLD-related sarcopenia remains undefined. We aim to determine the all-cause and cause-specific mortality from sarcopenia among adults with NAFLD in the United States (US).METHODS: 11,065 individuals in the Third National Health and Nutrition Examination Survey were studied and linked mortality through 2015 was analyzed. NAFLD was diagnosed based on presence of ultrasonographic hepatic steatosis without other known liver diseases. Sarcopenia was defined as skeletal muscle index determined by bioelectrical impedance analysis. The Cox proportional hazard model was used to assess all-cause mortality and cause-specific mortality, and hazard ratio (HR) adjusted for known risk factors.RESULTS: During a median follow-up of 23 years or more, sarcopenia was associated with increased all-cause mortality (HR 1.27, 95% confidence interval [CI] 1.11-1.44). Only in individuals with NAFLD, sarcopenia was associated with a higher risk for all-cause mortality, while this association was absent in those without NAFLD. Individuals with both sarcopenia and NAFLD had a higher risk for all-cause mortality (HR 1.28 95% CI 1.06-1.55) compared with those without sarcopenia and NAFLD. Furthermore, sarcopenia was associated with a higher risk for cancer- and diabetes-related mortality among those with NAFLD. This association was not noted in those without NAFLD.CONCLUSION: In this nationally representative sample of US adults, sarcopenia was associated with a higher risk for all-cause, cancer- and diabetes-related mortality in individuals with NAFLD.

    View details for DOI 10.1111/liv.14852

    View details for PubMedID 33641244

  • Current Epidemiology in Hepatocellular Carcinoma. Expert review of gastroenterology & hepatology Konyn, P., Ahmed, A., Kim, D. 2021

    Abstract

    IntroductionHepatocellular carcinoma (HCC) is the sixth most common cancer and the third-leading cause of cancer-related mortality in the world.Areas coveredThis review will discuss risk factors, demographic differences, global trends, and the economic burden of HCC. Viral hepatitis, particularly hepatitis B virus (HBV) infection, is the most common underlying liver disease leading to HCC in those with cirrhosis. Other important risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, metabolic syndrome, etc. With the introduction of direct-acting antiviral agents for hepatitis C virus infection, routine vaccination against HBV, and increasing support for robust public screening programs, the incidence rates for HCC due to viral hepatitis is falling in many countries. Meanwhile, the prevalence of obesity and metabolic syndrome are on the rise, as is NAFLD-related HCC incidence. Asia and Africa have the highest incidence rates of HCC. In multiethnic countries, racial and ethnic minorities experience disparities in HCC incidence as well as mortality, representing an essential area for improvement in terms of healthcare inequity.Expert opinionInterventions to minimize the global burden of HCC aim to reduce rates of the most common risk factors and implement effective treatment of underlying etiology and comprehensive screening programs for HCC.

    View details for DOI 10.1080/17474124.2021.1991792

    View details for PubMedID 34624198

  • Trends in the Prevalence of Hepatitis C Virus Infection based on the Insurance Status in the United States from 2013 to 2018. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Cholankeril, G., Dennis, B. B., Alshuwaykh, O., Kumari, R., Wong, R. J., Ahmed, A. 2021

    Abstract

    With the recent improvement in the treatment of hepatitis C virus (HCV) infection, a better understanding of the infection burden is needed. We aimed to (1) estimate the trends in the national prevalence of HCV infection based on the type of health insurance coverage and (2) identify at-risk populations for HCV infection in the United States (US) general population.Population-based analyses using the National Health and Nutrition Examination Survey (2013-2018) were performed with a focus on HCV infection. We analyzed the prevalence of HCV infection based on the health insurance status before the direct-acting antiviral (DAA) era (2013-2014) and during the DAA era (2015-2018).The age-adjusted prevalence of active HCV infection (HCV RNA [+]) was 0.92% (95% confidence interval [CI], 0.71%-1.19%) in the US non-institutionalized civilian population. While the prevalence of active HCV infection has remained stable, the prevalence of resolved HCV infection has increased after the introduction of DAA. In terms of health insurance coverage, the prevalence of active HCV infection decreased, and the prevalence of resolved HCV infection increased among individuals who had health insurance, especially private health insurance. The independent risk factors of active HCV infection were 40-69 years group, male, less than high school education, unmarried, below poverty status, being born in the US, history of blood transfusion, and not having private health insurance.The burden of active HCV infection has decreased among individuals who had health insurance, especially private health insurance, during the DAA era.

    View details for DOI 10.1111/liv.15113

    View details for PubMedID 34817925

  • Sex-specific Risk Factors and Health Disparity Among Hepatitis C Positive Patients Receiving Pharmacotherapy for Opioid Use Disorder: Findings From a Propensity Matched Analysis. Journal of addiction medicine Dennis, B. B., Martin, L. J., Naji, L., Akhtar, D., Cholankeril, G., Kim, D., Sanger, N., Hillmer, A., Chawar, C., D'Elia, A., Panesar, B., Worster, A., Marsh, D. C., O'Shea, T., Bawor, M., Thabane, L., Samaan, Z., Ahmed, A. 2021

    Abstract

    The incidence of opioid-related fatality has reached unparalleled levels across North America. Patients with comorbid hepatitis C virus (HCV) remain the most vulnerable and difficult to treat. Considering the unique challenges associated with this population, we aimed to re-examine the impact of HCV on response to medication assistant treatment for opioid use disorder and establish sex-specific risk factors affecting care.This study employs a multi-center prospective cohort design, with 1-year follow-up. Patients aged ≥18, receiving methadone for opioid use disorder were recruited from a network of out-patient opioid addiction treatment centers across Southern Ontario, Canada. Patients with ≥50% positive opioid urine screens over 1 year of follow-up were classified as poor responders. The prognostic impact of HCV on response was established using a propensity score matched analysis. Sex-specific regression models were constructed to evaluate risk factors for treatment response.Among participants eligible for inclusion (n = 1234), HCV was prevalent in 25% (n = 307). HCV patients exhibited significantly higher rates of high-risk opioid consumption patterns 35.29% (standard deviation 0.478). Sex-specific examination revealed females with HCV incur a 2 times increased risk for high-risk opioid consumption behaviors (female odds ratio: 1.95, 95% confidence interval 1.23, 3.10; P = 0.01).Findings from this study establish the link between HCV and poor treatment response, with differentially higher risk among female patients. In light of the high potential for overdose among this population, concerted efforts are required for distinguishing the source for sex-based disparities, in addition to establishing trauma and gender informed treatment protocols.

    View details for DOI 10.1097/ADM.0000000000000937

    View details for PubMedID 34799492

  • Reply: NAFLD Vs MAFLD - It is not the name but the disease that decides the outcome in fatty liver. Journal of hepatology Kim, D., Ahmed, A. 2021

    View details for DOI 10.1016/j.jhep.2021.10.023

    View details for PubMedID 34748894

  • Increasing changes in visceral adiposity is associated with higher risk for colorectal adenoma: multilevel analysis in a prospective cohort. Journal of gastroenterology and hepatology Moon, J. M., Im, J. P., Kim, D., Han, Y. M., Soh, H., Song, J. H., Yang, S. Y., Kim, Y. S., Yim, J. Y., Lim, S. H., Kim, J. S. 2020

    Abstract

    Background & Aims While many studies demonstrated an association between visceral adiposity and colorectal adenoma (CRA), the effect of longitudinal changes in body fat composition on CRA is unclear. We investigated the longitudinal association between changes in visceral adiposity and CRA occurrence.METHODS: Between 2006 and 2018, 732 (62.8%) of 1165 subjects in a prospective cohort voluntarily underwent follow-up abdominal fat computed tomography and colonoscopy. We defined incident and recurrent CRA as adenoma detected at follow-up colonoscopy from negative and positive adenoma at baseline colonoscopy, respectively. Multilevel survival analysis examined the longitudinal association between changes in visceral fat and CRA.RESULTS: During a median follow-up of 7.4 years, 400 (54.6%) subjects developed CRA. In multivariable analysis, increasing changes in visceral adipose tissue (VAT) area were associated with higher risk of incident adenoma (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.00-1.46 for change per 10 cm2 increase; HR 1.79, 95% CI 1.08-2.97 for highest vs. lowest quartile, p values for trend= 0.045). Likewise, increasing changes in VAT area were independently associated with a higher risk of recurrent adenoma (HR 1.35, 95% CI 1.13-1.62 for change per 10 cm2 increase; HR 1.62, 95% CI 1.04-2.52 for highest vs. lowest quartile, p values for trend= 0.001). Changes in subcutaneous adipose tissue area were not independently associated with CRA.CONCLUSION: Increasing changes in VAT area were longitudinally associated with a higher risk of incident and recurrent CRA, independent of risk factors, suggesting that visceral adiposity may be an important target in CRA prevention.

    View details for DOI 10.1111/jgh.15364

    View details for PubMedID 33300216

  • Evaluation and Management of Extrahepatic Manifestations of Nonalcoholic Fatty Liver Disease. Clinical and molecular hepatology Wijarnpreecha, K., Aby, E. S., Ahmed, A., Kim, D. 2020

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is a multisystemic disease and a rapidly growing cause of chronic liver disease in children and adults worldwide. Diagnosis and management of extrahepatic manifestations of NAFLD, including cardiovascular disease (CVD), type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, obstructive sleep apnea, polycystic ovarian syndrome, hypothyroidism, psoriasis, and extrahepatic malignancy are crucial for the treatment of patients with NAFLD. The leading cause of death in NAFLD is primarily from CVD, followed by liver-related mortality, extrahepatic cancer, liver cancer, and diabetes-related mortality. Therefore, clinicians need to identify high-risk patients earlier in the disease course and be aware of the extrahepatic manifestations of NAFLD to improve liver disease outcomes. In this review, we focus on the monitoring and management of the extrahepatic manifestations of NAFLD.

    View details for DOI 10.3350/cmh.2020.0239

    View details for PubMedID 33317243

  • PREDICTORS OF OUTCOMES OF COVID-19 IN PATIENTS WITH CHRONIC LIVER DISEASE: US MULTI-CENTER STUDY Adeniji, N., Kim, D., Latt, N. L., Kumar, S., Bloom, P. P., Aby, E. S., Perumalswami, P. V., Roytman, M., Li, M., Vogel, A. S., Catana, A. M., Wegermann, K., Carr, R. M., Aloman, C., Chen, V., Moghe, A., Nguyen, V., Sadowski, B., Rabiee, A., Dunn, W., Chavin, K. D., Zhou, K., Lizaola-Mayo, B., Debes, J. D., Lee, T., Branch, A. D., Viveiros, K., Chan, W. W., Chascsa, D. M., Kwo, P. Y., Dhanasekaran, R. WILEY. 2020: 7A
  • A MACHINE LEARNING MODEL TO SAFELY TRIAGE LOW-RISK NON-ALCOHOLIC FATTY LIVER DISEASE PATIENTS: THE STEATOSIS-ASSOCIATED FIBROSIS ESTIMATOR (SAFE) SCORE Sripongpun, P., Mannalithara, A., Kim, D., Kim, W. WILEY. 2020: 888A–889A
  • COVID-19 AND LIVER INJURY: A META-ANALYSIS Zaver, H., Wijarnpreecha, K., Ungprasert, P., Panjawatanan, P., Hamois, D. M., Ahmed, A., Kim, D. WILEY. 2020: 265A–266A
  • Patients with hepatocellular carcinoma from more rural and lower income households have more advanced tumor stage at diagnosis and significantly higher mortality. Cancer Wong, R. J., Kim, D., Ahmed, A., Singal, A. K. 2020

    Abstract

    BACKGROUND: Patients from rural and low-income households may have suboptimal access to liver disease care, which may translate into worse HCC outcomes. The authors provide a comprehensive update of HCC incidence and outcomes among US adults, focusing on the effect of rural geography and household income on tumor stage and mortality.METHODS: The authors retrospectively evaluated adults with HCC using Surveillance, Epidemiology, and End Results data from 2004 to 2017. HCC incidence was reported per 100,000 persons and was compared using z-statistics. Tumor stage at diagnosis used the Surveillance, Epidemiology, and End Results staging system and was evaluated with multivariate logistic regression. HCC mortality was evaluated using Kaplan-Meier and multivariate Cox proportional hazards methods.RESULTS: HCC incidence plateaued for most groups, with the exception of American Indians/Alaska Natives (2004-2017: APC, 4.17%; P < .05) and patients in the lowest household income category (<$40,000; 2006-2017: APC, 2.80%; P < .05). Compared with patients who had HCC in large metropolitan areas with a population >1 million, patients in more rural regions had higher odds of advanced-stage HCC at diagnosis (odds ratio, 1.10; 95% CI, 1.00-1.20; P = .04) and higher mortality (hazard ratio, 1.05; 95% CI, 1.01-1.08; P = .02). Compared with the highest income group (≥$70,000), patients with HCC who earned <$40,000 annually had higher odds of advanced-stage HCC (odds ratio, 1.15; 95% CI, 1.01-1.32; P = .03) and higher mortality (hazard ratio, 1.23; 95% CI, 1.16-1.31; P < .001).CONCLUSIONS: Patients from rural regions and lower income households had more advanced tumor stage at diagnosis and significantly higher HCC mortality. These disparities likely reflect suboptimal access to consistent high-quality liver disease care, including HCC surveillance.

    View details for DOI 10.1002/cncr.33211

    View details for PubMedID 33103243

  • Liver Injury in Liver Transplant Recipients with Coronavirus Disease 2019 (COVID-19): US Multicenter Experience. Hepatology (Baltimore, Md.) Rabiee, A., Sadowski, B., Adeniji, N., Perumalswami, P., Nguyen, V., Moghe, A., Latt, N., Kumar, S., Aloman, C., Catana, A. M., Bloom, P. P., Chavin, K., Carr, R. M., Dunn, W., Chen, V., Aby, E. S., Debes, J., Dhanasekaran, R., COLD Consortium, Kim, D., Roytman, M., Viveiros, K., Chan, W., Li, M., Vogel, A., Wegerman, K., Lee, T., Zhou, K. 2020

    Abstract

    BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with liver injury, but the prevalence and patterns of liver injury in liver transplant (LT) recipients with COVID-19 is not defined.APPROACH AND RESULTS: We conducted a multicenter study in the US of 112 adult LT recipients with COVID-19. The median age was 61 years (IQR 20), 54.5% (n=61) were male, and 39.3% (n=44) Hispanic. The mortality rate was 22.3% (n=25); 72.3% (n=81) were hospitalized and 26.8% (n=30) admitted to the ICU. Analysis of peak values of alanine aminotransferase (ALT) during COVID-19 showed moderate liver injury (ALT 2-5x ULN) in 22.2% (n= 18) and severe liver injury (ALT > 5x ULN) in 12.3% (n= 10). Compared to age and gender matched non-transplant patients with CLD and COVID-19 (n=375), the incidence of acute liver injury was lower in LT recipients (47.5% vs. 34.6%; p=0.037). Variables associated with liver injury in LT recipients were younger age (p= 0.009, odds ratio (OR) 2.06 [1.20-3.54]), Hispanic ethnicity (p= 0.011; OR 6.01 [1.51-23.9]), metabolic syndrome (p= 0.016; OR 5.87 [1.38-24.99]), vasopressor use (p= 0.018; OR 7.34 [1.39-38.52]) and antibiotic use (p= 0.046; OR 6.93 [1.04-46.26]). Reduction in immunosuppression (49.4%) was not associated with liver injury (p= 0.156) or mortality (p= 0.084). Liver injury during COVID-19 was significantly associated with mortality (p= 0.007; OR 6.91 [95% CI: 1.68-28.48]) and ICU admission (p=0.007; OR 7.93[1.75-35.69]) in LT recipients.CONCLUSION: Liver injury is associated with higher mortality and ICU admission in LT recipients with COVID-19. Hence, monitoring liver enzymes closely can help in early identification of patients at risk for adverse outcomes. Reduction of immunosuppression during COVID-19 did not increase risk for mortality or graft failure.

    View details for DOI 10.1002/hep.31574

    View details for PubMedID 32964510

  • Recent Epidemiology of Nonalcoholic Fatty Liver Disease. Gut and liver Murag, S., Ahmed, A., Kim, D. 2020

    Abstract

    The ongoing obesity epidemic and the increasing recognition of metabolic syndrome have contributed to the growing prevalence of nonalcoholic fatty liver disease (NAFLD), the most common form of liver disease worldwide. It is imperative to understand the incidence and prevalence of NAFLD as it is associated with a profound economic burden of hospitalizations, including the shifting trends in liver transplantation. The long-term cumulative healthcare cost of NAFLD patients has been shown to be 80% higher than that of non-NAFLD patients. We explore diagnostic challenges in identifying those with NAFLD who have a higher predilection to progress to end-stage liver disease. We aim to assess all-cause and cause-specific mortality as it relates to NAFLD.

    View details for DOI 10.5009/gnl20127

    View details for PubMedID 32921636

  • Circulating lipidomic alterations in obese and non-obese subjects with non-alcoholic fatty liver disease. Alimentary pharmacology & therapeutics Jung, Y., Lee, M. K., Puri, P., Koo, B. K., Joo, S. K., Jang, S. Y., Lee, D. H., Jung, Y. J., Kim, B. G., Lee, K. L., Park, T., Kang, K., Ryu, D. H., Kang, S. W., Kim, D., Oh, S., Kim, W., Hwang, G. 2020

    Abstract

    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects obese and non-obese individuals. However, mechanisms underlying non-obese non-alcoholic steatohepatitis (NASH) remain unclear.AIMS: To attempt to identify metabolic perturbations associated with non-obese and obese NAFLD using a lipidomics approach.METHODS: A cross-sectional analysis of 361 subjects with biopsy-proven NAFLD (157 NAFL and 138 NASH) and healthy controls (n=66) was performed. Individuals were categorised as obese or non-obese based on the Asian cut-off for body mass index. Circulating lipidomic profiling of sera was performed based on the histological severity of NAFLD. Circulating lipidomic alterations were validated with an independent validation set (154 NAFLD subjects [93 NAFL and 61 NASH] and 21 healthy controls).RESULTS: Saturated sphingomyelin (SM) species were significantly associated with visceral adiposity in non-obese NAFLD (SM d38:0; P<0.001) but not in obese NAFLD. Additionally, SM levels were significantly associated with systemic and adipose tissue insulin resistance (SM d38:0; P=0.002 and <0.001, respectively). Five potential lipid metabolites for non-obese subjects and seven potential lipids for obese subjects were selected to predict NAFLD and NASH. These lipid combinations showed good diagnostic performance for non-obese (area under the curve [AUC] for NAFLD/NASH=0.916/0.813) and obese (AUC for NAFLD/NASH=0.967/0.812) subjects. Moreover, distinctly altered patterns of diacylglycerol (DAG), triacylglycerol (TAG) and SM levels were confirmed in the validation set depending on the histological severity of NAFLD.CONCLUSION: Non-obese and obese NAFLD subjects exhibit unique circulating lipidomic signatures, including DAGs, TAGs and SMs. These lipid combinations may be useful biomarkers for non-obese and obese NAFLD patients.

    View details for DOI 10.1111/apt.16066

    View details for PubMedID 32892365

  • Association of Sarcopenia and NAFLD: An Overview. Clinical liver disease Li, A. A., Kim, D., Ahmed, A. 2020; 16 (2): 73–76

    View details for DOI 10.1002/cld.900

    View details for PubMedID 32922754

  • PNPLA3 gene polymorphism and overall and cardiovascular mortality among non-alcoholic fatty liver disease in the United States Wijarnpreecha, K., Scribani, M., Raymond, P., Ahmed, A., Kim, D., Harnois, D. ELSEVIER. 2020: S146-S147
  • The FIB-8 score: validation of a model to screen patients with non-alcoholic fatty liver disease for significant fibrosis Sripongpun, P., Kim, D., Mannalithara, A., Kim, W. ELSEVIER. 2020: S435-S436
  • Early Impact of COVID-19 on Solid Organ Transplantation in the United States. Transplantation Cholankeril, G., Podboy, A., Alshuwaykh, O. S., Kim, D., Kanwal, F., Esquivel, C. O., Ahmed, A. 2020

    Abstract

    BACKGROUND: The regional impact of COVID-19 on solid organ transplantation in the United States (US) has not been fully evaluated.METHODS: A retrospective analysis of month-to-month trends on waitlist additions, waitlist deaths, and transplant surgeries between all United Network for Organ Sharing (UNOS) regions was performed. A linear regression model trained on historical data was used to estimate anticipated transplantation volume.RESULTS: All UNOS Regions reported a decrease in total waitlist additions and transplant surgeries. The largest decreases in total transplants were identified in Regions 1,2,6 and 9; with Regions 2, 7, 8 and 9 noting the largest decrease in waitlist additions. Six of the 11 regions noted increases in waitlist deaths, with UNOS Regions 9, 1, and 2, all located within the Northeast, noting the highest percent increase in waitlist deaths at 170%, 89%, and 54%, respectively. The largest reductions in SOT and waitlist deaths were seen in kidney and lung transplantation. Current transplantation volume is significantly lower than the low range of the 95% CI derived from the linear regression model (2182 vs 3110, p<0.05) CONCLUSIONS:: Significant decreases in total waitlist additions and transplant surgeries with increases in waitlist deaths were noted in the majority of US transplant domains. The impact was especially prevalent in areas with high burden of COVID-19 infection. National and regional strategies aimed at minimizing disruptions in transplantation are needed.

    View details for DOI 10.1097/TP.0000000000003391

    View details for PubMedID 32675741

  • The burden of Clostridioides difficile infection in patients with history of liver transplant and during index admission. European journal of gastroenterology & hepatology Wijarnpreecha, K., Aby, E. S., Kim, D., Ungprasert, P., Cheungpasitporn, W., Thongprayoon, C., Lukens, F. J., Harnois, D. M., Kroner, P. T. 2020

    Abstract

    BACKGROUND/OBJECTIVES: Liver transplant recipients have an increased risk of Clostridioides difficile infection (CDI) which associated with higher morbidity and mortality. CDI in liver transplant has been argued to increase hospital costs, charges, and length of stay (LOS) in small studies. However, no recent nationwide analysis determines these outcomes.METHODS: This is a retrospective cohort study using the National Inpatient Sample 2016. All patients with ICD10CM diagnostic codes for CDI were included. The cohort was stratified for the history of liver transplant and liver transplant index admission. The primary outcome was the odds of CDI in both patient cohorts to patients without liver transplant. Secondary outcomes were inpatient morbidity, mortality, resource utilization, colectomy rates, LOS, and total hospital costs and charges.RESULTS: A total of 360364 patients with CDI were identified, 1665 had a history of liver transplant and 155 had liver transplant during that admission. Patients with a history of liver transplant had increased odds of CDI compared to patients with no history of liver transplant (adjusted odds ratio 2.78; 95% confidence interval, 2.44-3.16). Patients with CDI had greater odds of shock, acute kidney injury, ICU stay, organ failure and significantly higher costs, charges and LOS.CONCLUSIONS: Patients with a history of liver transplant increased odds of CDI. CDI with history of liver transplant and the index admission for liver transplant had higher odds of morbidity and resource utilization. Clinicians must maintain a high index of suspicion for CDI for early diagnosis and appropriate initiation of treatment.

    View details for DOI 10.1097/MEG.0000000000001812

    View details for PubMedID 32541243

  • Association of Digestive Symptoms and Hospitalization in Patients with SARS-CoV-2 Infection. medRxiv : the preprint server for health sciences Cholankeril, G., Podboy, A., Aivaliotas, V., Pham, E. A., Tarlow, B., Spencer, S., Kim, D., Hsing, A., Ahmed, A. 2020

    Abstract

    High rates of concurrent gastrointestinal manifestations have been noted in patients with COVID- 19, however the association between these digestive manifestations and need for hospitalization has not been established.Following expedited approval from our Institutional Review Board, we analyzed retrospectively collected data from consecutive patients with confirmed COVID-19 based on a positive polymerase chain reaction testing at our institution from March 03, 2020 to April 7, 2020. Baseline demographic, clinical, laboratory and patient-reported symptom data were collected at presentation in the emergency room. Multivariable logistic regression analyses were performed to evaluate the association between hospitalization and presence of gastrointestinal symptoms.During this study period, we identified 207 consecutive patients with confirmed COVID-19. 34.5% noted concurrent gastrointestinal symptoms; of which 90% of gastrointestinal symptoms were mild. In a multivariate regression model controlled for demographics and disease severity, an increased risk for hospitalization was noted in patients with any gastrointestinal symptom (adjusted OR 4.84 95% CI: 1.68-13.94]. Diarrhea was associated with a seven-fold higher likelihood for hospitalization (adjusted OR=7.58, 95% CI: 2.49-20.02, P <0.001) and nausea or vomiting had a four times higher odds (adjusted OR 4.39, 95% CI: 1.61-11.4, P = 0.005).We demonstrate that a significant portion of COVID19 patients have concurrent mild gastrointestinal symptoms and that the presence of these digestive symptoms is associated with a need for hospitalization. With the current focus on streamlining triaging efforts, first responders and frontline providers should consider assessing for digestive symptoms in their initial clinical evaluation and decision-making.

    View details for DOI 10.1101/2020.04.23.20076935

    View details for PubMedID 32511634

    View details for PubMedCentralID PMC7276990

  • High Prevalence of Concurrent Gastrointestinal Manifestations in Patients with SARS-CoV-2: Early Experience from California. Gastroenterology Cholankeril, G., Podboy, A., Aivaliotis, V. I., Tarlow, B., Pham, E. A., Spencer, S., Kim, D., Hsing, A., Ahmed, A. 2020

    View details for DOI 10.1053/j.gastro.2020.04.008

    View details for PubMedID 32283101

  • Road to identifying endpoint biomarkers in the treatment of nonalcoholic steatohepatitis: are we there yet? Hepatobiliary surgery and nutrition Kim, D., Vazquez-Montesino, L. M., Ahmed, A. 2020; 9 (2): 244-246

    View details for DOI 10.21037/hbsn.2019.10.02

    View details for PubMedID 32355692

    View details for PubMedCentralID PMC7188524

  • Road to identifying endpoint biomarkers in the treatment of nonalcoholic steatohepatitis: are we there yet? HEPATOBILIARY SURGERY AND NUTRITION Kim, D., Vazquez-Montesino, L., Ahmed, A. 2020; 9 (2): 244–46
  • Trends in Hospitalizations for Clostridioides difficile Infection in End-Stage Liver Disease, 2005-2014. Digestive diseases and sciences Kim, D., Yoo, E. R., Li, A. A., Tighe, S. P., Cholankeril, G., Ahmed, A. 2020

    Abstract

    BACKGROUND: Data on the current estimates of the disease burden of Clostridioides difficile (C. difficile) infection in the setting of end-stage liver disease (ESLD) are emerging.AIMS: We examined the recent trends and predictors of hospitalizations and in-hospital mortality from C. difficile infection among hospitalizations with ESLD in the USA.METHODS: We performed a retrospective analysis using the National Inpatient Sample, 2005-2014. We defined ESLD and C. difficile infection using the International Classification of Diseases, Ninth Revision, Clinical Modification. Multivariable logistic regression was used to determine the risk factors that impacted hospitalization and mortality.RESULTS: The prevalence of coding for C. difficile infection in decompensated cirrhosis increased from 1.3% in 2005 to 2.7% in 2014, with an annual rate of 7.8%. In hospitalizations with hepatocellular carcinoma, C. difficile infection increased steadily from 1.0 to 1.7% with an annual incremental rate of 6.4%. Among hospitalizations with ESLD, each passing 2-year period, increasing age, female, higher Charlson index, accompanying infection, hepatorenal syndrome, and ascites were associated with C. difficile infection. Although C. difficile infection was an independent predictor of in-hospital mortality during hospitalization with decompensated cirrhosis (odds ratio 1.53, 95% confidence interval 1.44-1.63), the proportion of in-hospital mortality during hospitalization with C. difficile infection and decompensated cirrhosis decreased from 15.4% in 2005 to 11.1% in 2014, with an annual rate of -3.1% (95% CI -5.7% to -0.3%).CONCLUSIONS: While the prevalence of C. difficile infection in hospitalized patients with ESLD increased approximately twofold, the in-hospital mortality decreased significantly during the past decade.

    View details for DOI 10.1007/s10620-020-06162-0

    View details for PubMedID 32124196

  • Development and Validation of a Scoring System, Based on Genetic and Clinical Factors, to Determine Risk of Steatohepatitis in Asian Patients with Nonalcoholic Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Koo, B. K., Joo, S. K., Kim, D., Lee, S., Bae, J. M., Park, J. H., Kim, J. H., Chang, M. S., Kim, W. 2020

    Abstract

    BACKGROUND & AIMS: There are no biomarkers of nonalcoholic steatohepatitis (NASH) that are ready for routine clinical use. We investigated whether an analysis of PNPLA3 and TM6SF2 genotypes (rs738409 and rs58542926) can be used to identify patients with nonalcoholic fatty liver disease (NAFLD), with and without diabetes, who also have NASH.METHODS: We collected data from the Boramae registry in Korea on 453 patients with biopsy-proven NAFLD with sufficient clinical data for calculating scores. Patients enrolled from May 2011 through March 2016 were assigned to cohort 1 (n = 302; discovery cohort) and patients enrolled thereafter were assigned to cohort 2 (n = 151; validation cohort). DNA samples were obtained from all participants and analyzed for the PNPLA3 rs738409 C>G, TM6SF2 rs58542926 C>T, SREBF2 rs133291 C>T, MBOAT7-TMC4 rs641738 C>T, and HSD17B13 rs72613567 adenine insertion (A-INS) polymorphisms. We used multivariable logistic regression analyses with stepwise backward selection to build a model to determine patients' risk for NASH (NASH PT) using the genotype and clinical data from cohort 1 and tested its accuracy in cohort 2. We used the receiver operating characteristic (ROC) curve to compare the diagnostic performances of the NASH PT and the NASH scoring systems.RESULTS: We developed a NASH PT scoring system based on PNPLA3 and TM6SF2 genotypes, diabetes status, insulin resistance, and levels of aspartate aminotransferase and high-sensitivity C-reactive protein. NASH PT scores identified patients with NASH with an area under the ROC (AUROC) of 0.859 (95% CI, 0.817-0.901) in cohort 1. In cohort 2, NASH PT scores identified patients with NASH with an AUROC of 0.787 (95% CI, 0.715-0.860), which was significantly higher than the AUROC of the NASH score (AUROC, 0.729; 95% CI, 0.647-0.812; P=.007). The AUROC of the NASH PT score for detecting NASH in patients with NAFLD with diabetes was 0.835 (95% CI, 0.776-0.895) and in patients without diabetes was 0.809 (95% CI, 0.757-0.861). The negative predictive value of the NASH PT score <-0.785 for NASH in patients with NAFLD with diabetes reached 0.905.CONCLUSIONS: We developed a scoring system, based on polymorphisms in PNPLA3 and TM6SF2 and clinical factors that identifies patients with NAFLD, with or without diabetes, who have NASH, with an AUROC value of 0.787. This system might help clinicians better identify NAFLD patients at risk for NASH.

    View details for DOI 10.1016/j.cgh.2020.02.011

    View details for PubMedID 32062042

  • Diet Quality and its Association with Nonalcoholic Fatty Liver Disease and All-cause and Cause-specific Mortality. Liver international : official journal of the International Association for the Study of the Liver Yoo, E. R., Kim, D. n., Vazquez-Montesino, L. M., Escober, J. A., Li, A. A., Tighe, S. P., Fernandes, C. T., Cholankeril, G. n., Ahmed, A. n. 2020

    Abstract

    Healthy diet has been recommended for nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent mortality. We aim to assess the impact of quality of diet on NAFLD and mortality in subjects with and without NAFLD.We performed cohort study using the Third National Health and Nutrition Examination Survey from 1988 to 1994 and linked mortality data through 2015. We used the Healthy Eating Index (HEI) scores to define diet quality, with higher HEI scores (Q4) indicating better adherence to dietary recommendations. NAFLD was defined as ultrasonographic hepatic steatosis.Multivariate analysis showed that subjects with higher diet quality were inversely associated with NAFLD in a dose-dependent manner. During the median follow-up of 23 years, having a higher diet quality was associated with reduction in risk of all-cause mortality in the age, sex, Race/ethnicity-adjusted hazard ratio (HR) (Q4, HR:0.60 95% CI: 0.52-0.68) and the multivariate model (Q4, HR:0.81 95% CI: 0.71-0.92). Higher diet quality was associated with a lower risk for all-cause mortality in subjects without NAFLD; however, this protective association with diet quality was not noted in those with NAFLD. Furthermore, a high diet quality was associated with a lower risk for cancer-related mortality in the total population and among those without NAFLD. This association was not noted in those with NAFLD.High diet quality was inversely associated with NAFLD and was positively associated with a lower risk for cancer-related and all-cause mortality in those without NAFLD.

    View details for DOI 10.1111/liv.14374

    View details for PubMedID 31910319

  • Trends in Mortality in Hepatitis C Infection and Alcoholic Liver Disease based on Drug Overdose in the United States. Journal of viral hepatitis Kim, D. n., Alshuwaykh, O. S., Cholankeril, G. n., Wong, R. J., Ahmed, A. n. 2020

    Abstract

    We examined trends in mortality from hepatitis C virus (HCV) and alcoholic liver disease (ALD) in the setting of drug overdose. Using US Census and national mortality records (2009-2018), we identified deaths with HCV infection, ALD, and drug overdose. HCV-related mortality without drug overdose increased up to 2014, followed by a marked decrease. Mortality from HCV and drug overdose increased significantly. Whereas ALD-related mortality without drug overdose continued to rise, no significant trend from ALD with drug overdose was noted. HCV-related mortalities reduced after the introduction of DAA agents, while drug overdose-related mortality was constantly increased.

    View details for DOI 10.1111/jvh.13435

    View details for PubMedID 33147365

  • COVID-19 and liver injury: a meta-analysis. European journal of gastroenterology & hepatology Wijarnpreecha, K. n., Ungprasert, P. n., Panjawatanan, P. n., Harnois, D. M., Zaver, H. B., Ahmed, A. n., Kim, D. n. 2020

    Abstract

    The number of cases with coronavirus disease 2019 (COVID-19) has exceeded seven million worldwide. However, the data describing the global prevalence of liver injury associated with COVID-19 is lacking secondary to the novelty of this ongoing pandemic. Therefore, we conducted a meta-analysis to determine the association between COVID-19 and liver injury.A systematic literature search of indexed databases including, PubMed, Medline, and Embase databases from inception to 14 April 2020, was used to identify studies that reported data of liver chemistry in patients diagnosed with COVID 19. The overall prevalence of abnormal liver chemistry and relevant 95% confidence interval was used to estimate the pooled results studies.Sixty-four studies with 11 245 patients with COVID-19 were included. The pattern of abnormal liver enzymes was notable for higher aspartate aminotransferase (AST) than alanine aminotransferase (ALT) levels. The overall global prevalence of elevated AST, ALT, total bilirubin, gamma-glutamyltransferase (GGT), and alkaline phosphatase was 23.2, 21.2, 9.7, 15.0, and 4.0%, respectively. The prevalence of elevated AST was substantially higher among those with severe cases (45.5%) compared to non-severe cases (15.0%). Co-existing chronic liver disease presented up to 37.6% of patients with COVID-19.A fourth of COVID-19 patients had elevated liver enzymes and associated with disease severity. Our study may be used as a guide for clinicians and epidemiologists to proactively identify other sources of injury and illness in patients diagnosed with COVID-19. Intensive monitoring for liver injury may be needed in cases with severe COVID-19.

    View details for DOI 10.1097/MEG.0000000000001817

    View details for PubMedID 32639420

  • Association of Digestive Symptoms and Hospitalization in Patients With SARS-CoV-2 Infection. The American journal of gastroenterology Cholankeril, G. n., Podboy, A. n., Aivaliotis, V. I., Pham, E. A., Spencer, S. P., Kim, D. n., Ahmed, A. n. 2020; 115 (7): 1129–32

    Abstract

    High rates of concurrent gastrointestinal manifestations have been noted in patients with corona virus disease 2019 (COVID-19); however, the association between these digestive manifestations and need for hospitalization has not been established.This is a retrospective review of consecutive patients diagnosed with COVID-19. A total of 207 patients were identified; 34.5% of patients noted concurrent gastrointestinal symptoms, with 90% of gastrointestinal symptoms being mild.In a multivariate regression model controlled for demographics and disease severity, an increased risk of hospitalization was noted in patients with any digestive symptom (adjusted odds ratio 4.84, 95% confidence interval: 1.68-13.94).The presence of digestive symptoms in COVID-19 is associated with a need for hospitalization.

    View details for DOI 10.14309/ajg.0000000000000712

    View details for PubMedID 32618665

    View details for PubMedCentralID PMC7302101

  • Gender and Racial Differences in Hospitalizations for Primary Biliary Cholangitis in the USA. Digestive diseases and sciences Adejumo, A. C., Akhtar, D. H., Dennis, B. B., Cholankeril, G. n., Alayo, Q. n., Ogundipe, O. A., Kim, D. n., Ahmed, A. n. 2020

    Abstract

    The prevalence, characteristics, burden and trends of primary biliary cholangitis (PBC) hospitalizations in the USA remain unclear.We identified primary PBC hospitalizations from the National Inpatient Sample (NIS) 2007 through 2014 using ICD-9-CM codes. We calculated the rates and trends of hospitalization for PBC per 100,000 US population among each gender (males and females) and racial categories (Whites, Blacks, Hispanics and other racial minorities), and measured the predictors of hospitalization, and of mortality, charges and length of stay (LOS) among PBC hospitalizations.There were 8460 (weighted: 41,191) PBC hospitalizations between 2007 and 2014. The mean national PBC hospitalization rate was 2.2 cases per 100,000 population (2.2/100,000), increasing from 1.7/100,000 (2007) to 2.5/100,000 (2014). From 2007 to 2014, the in-hospital mortality and LOS were unchanged while the charges increased from $65,993 to $73,093 ($225 million to $447 million overall expenses). Compared to Whites, the PBC hospitalization rate was 12% higher among Hispanics (RR: 1.12 [1.09-1.16]), 53% lower in Blacks (RR: 0.47 [0.45-0.49]) and 5% lower among other racial minorities (0.95 [0.91-0.99]). The rate was higher among females (RR:4.02 [3.93-4.12]) compared to males. On multivariate analysis, Blacks and other racial minorities, respectively, had higher odds of mortality (AOR: 1.47 [1.03-2.10] and 1.33 [0.96-1.84]), while other racial minorities had longer LOS (7.0 vs. 5.6 days) and higher hospital charges ($48,984 vs. $41,495) when compared to Whites.The hospitalization rate and burden of PBC in the USA have increased disproportionately among females and Hispanics with higher mortality in Blacks.

    View details for DOI 10.1007/s10620-020-06402-3

    View details for PubMedID 32535779

  • Nonalcoholic Fatty Liver Disease Is Associated with Benign Prostate Hyperplasia. Journal of Korean medical science Chung, G. E., Yim, J. Y., Kim, D. n., Kwak, M. S., Yang, J. I., Park, B. n., An, S. J., Kim, J. S. 2020; 35 (22): e164

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is associated with a wide spectrum of metabolic abnormalities. This study aimed to evaluate whether NAFLD is associated with benign prostatic hyperplasia (BPH) independent of other risk factors.A total of 3,508 subjects who underwent prostate and hepatic ultrasonography were enrolled. NAFLD was diagnosed and graded by ultrasonographic findings. BPH was defined by total prostate volume.The prevalence of BPH was significantly increased according to NAFLD severity (P < 0.001). The multivariate analysis showed that NAFLD was associated with a 22% increase in the risk of BPH (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.02-1.45). In non-obese subjects, NAFLD was associated with a 41% increase in the risk of BPH (OR, 1.41; 95% CI, 1.14-1.73), and an incremental increase in the risk of BPH according to NAFLD severity was pronounced (adjusted OR [95% CI], 1.32 [1.05-1.68] for mild NAFLD, 1.55 [1.15-2.10] for moderate to severe NAFLD vs. no NAFLD, P for trend = 0.004). However, in the obese population, the association of NAFLD in the risk of BPH was insignificant (P = 0.208).NAFLD is associated with an increased risk of BPH regardless of metabolic syndrome, especially in non-obese subjects. An incrementally increased risk of BPH according to NAFLD severity is prominent in non-obese subjects with NAFLD. Thus, physicians caring for non-obese patients with NAFLD may consider assessing the risk of BPH and associated urologic conditions.

    View details for DOI 10.3346/jkms.2020.35.e164

    View details for PubMedID 32508064

  • PNPLA3 Gene Polymorphism and Overall and Cardiovascular Mortality in the United States. Journal of gastroenterology and hepatology Wijarnpreecha, K. n., Scribani, M. n., Raymond, P. n., Harnois, D. M., Keaveny, A. P., Ahmed, A. n., Kim, D. n. 2020

    Abstract

    The association between palatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) polymorphism and mortality is not well understood. We investigated the impact of PNPLA3 I148M (rs738409) polymorphism on overall and cardiovascular mortality based on the presence of NAFLD.The Third National Health and Nutrition Examination Survey (NHANES) from 1991 to 1994 and NHANES III-linked mortality data through 31 December 2015 were utilized in this study.Of 4,814 participants, 50.7% were homozygous for the C-allele and 12.6% were homozygous for the G-allele. During a follow-up of 20 years, there were a total of 1,255 deaths, 422 attributed to cardiovascular disease. There was a significant association with overall mortality among those with the PNPLA3 I148M (rs738409) GG genotype (hazard ratio [HR] 1.34; 95% confidence interval [CI] 1.02-1.77) or G-allele (HR 1.22 95% CI 1.09-1.36) in the general population NAFLD with homozygous PNPLA3 I148M (rs738409) GG genotype had higher overall mortality after adjusting for multiple metabolic risk factors (hazard ratio [HR] 1.45; 95% confidence interval [CI] 1.01-2.08). The PNPLA3 I148M (rs738409) G-allele had a tendency of increased cardiovascular mortality in the total population. This association was not noted in those with NAFLD.The homozygous PNPLA3 I148M (rs738409) GG genotype showed an increase in overall mortality in the general population and NAFLD independent of multiple metabolic risk factors.

    View details for DOI 10.1111/jgh.15045

    View details for PubMedID 32220085

  • The impact of chronic liver disease in patients receiving active pharmacological therapy for opioid use disorder: One-year findings from a prospective cohort study. Drug and alcohol dependence Dennis, B. B., Akhtar, D. n., Cholankeril, G. n., Kim, D. n., Sanger, N. n., Hillmer, A. n., Chawar, C. n., D'Elia, A. n., Panesar, B. n., Worster, A. n., Marsh, D. C., Thabane, L. n., Samaan, Z. n., Ahmed, A. n. 2020; 209: 107917

    Abstract

    Despite the demonstrated benefit of methadone, the incidence opioid-related overdose, and its associated mortality continues to rise at an alarming rate. The impact of high prevalence comorbid features such as chronic liver disease (CLD) on methadone treatment response remain unclear.To determine whether CLD is associated with poor response to methadone treatment.Using a well-established multi-center cohort from the Genetics of Opioid Addiction Study (GENOA), we evaluated if presence of CLD among 1234 eligible patients with opioid use disorder receiving methadone treatment impacted health and behavioural responses to treatment. CLD was classified as any liver disorder/dysfunction present for a minimum period of six months. Serial urine toxicology assessments were used to determine treatment response. The effect of CLD was determined using a multi-variable logistic regression model.CLD was present in 25 % (n = 314) of the population. On average, patients with CLD were found to be older (mean age 44 vs 36 years, p < 0.0001), unemployed (81.8 % vs 61 %, p < 0.0001), and receiving government disability benefits at significantly higher rates (21.9 % vs 11 %, p < 0.0001). Increased levels of physical craving, emotional stress, as well as health risk behaviors were noted in CLD patients. Findings from the multi-variable model demonstrate a 68 % increased risk for dangerous opioid consumption behaviors (Odds Ration [OR]: 1.68, 95 % Confidence Interval [CI] 1.22, 2.31, p = 0.001) among patients with CLD. Methadone dose (OR: 0.76, 95 % CI 0.70, 0.81, p < 0.0001) was shown to be protective with a significant risk reduction of 24 % per 20 mg increase in methadone. Duration in treatment was also found to be protective (OR: 0.99, 95 % CI 0.97, 0.99, p < 0.0001).CLD poses a distinct risk for patients with opioid addiction. Closer drug monitoring, and substance use contingency management should be considered to reduce mortality risk in these patients.

    View details for DOI 10.1016/j.drugalcdep.2020.107917

    View details for PubMedID 32088589

  • Regional Trends in Mortality from Alcohol-Induced Causes in the United States, 2000-2017. Journal of general internal medicine Cholankeril, G., Dennis, B. B., Kim, D., Ahmed, A. 2019

    View details for DOI 10.1007/s11606-019-05442-4

    View details for PubMedID 31792862

  • Skeletal muscle mass and sarcopenia in nonalcoholic fatty liver disease. Translational gastroenterology and hepatology Panjawatanan, P., Wijarnpreecha, K., Kim, D. 2019; 4: 77

    View details for DOI 10.21037/tgh.2019.11.03

    View details for PubMedID 31872141

    View details for PubMedCentralID PMC6917548

  • Skeletal muscle mass and sarcopenia in nonalcoholic fatty liver disease TRANSLATIONAL GASTROENTEROLOGY AND HEPATOLOGY Panjawatanan, P., Wijarnpreecha, K., Kim, D. 2019; 4
  • Low-Normal Thyroid Function Is Associated With Advanced Fibrosis Among Adults in the United States CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Kim, D., Yoo, E. R., Li, A. A., Fernandes, C. T., Tighe, S. P., Cholankeril, G., Hameed, B., Ahmed, A. 2019; 17 (11): 2379–81
  • FIB-8 SCORE: A MODEL INCORPORATING ADDITIONAL COMMON VARIABLES INTO THE FIB-4 SCORE AFFORDS BETTER PREDICTION OF SIGNIFICANT FIBROSIS IN NONALCOHOLIC FATTY LIVER DISEASE Sripongpun, P., Mannalithara, A., Kim, D., Touros, A., Kim, W. WILEY. 2019: 1037A–1038A
  • PNPLA3 GENE POLYMORPHISM AND OVERALL AND CARDIOVASCULAR MORTALITY IN THE UNITED STATES Wijarnpreecha, K., Scribani, M., Raymond, P., Harnois, D. M., Keaveny, A., Ahmed, A., Kim, D. WILEY. 2019: 727A
  • NATIONAL ESTIMATE OF THE FREQUENCY, TRENDS AND HEALTHCARE BURDEN OF CARE FRAGMENTATION IN READMISSIONS FOR END-STAGE LIVER DISEASE IN THE US Adejumo, A., Dennis, B., Cholankeril, G., Wong, R. J., Kim, D., Younossi, Z. M., Ahmed, A. WILEY. 2019: 449A
  • TRENDS AND OUTCOMES ASSOCIATED WITH ALCOHOL-RELATED HOSPITALIZATIONS IN THE UNITED STATES: A RETROSPECTIVE COHORT STUDY Murag, S., Yoo, E., Dennis, B. B., Adejumo, A., Hu, M., Kim, D., Ahmed, A., Cholankeril, G. WILEY. 2019: 392A–393A
  • HOSPITALIZATION OUTCOMES AND READMISSION RATES ASSOCIATED WITH NONALCOHOLIC FATTY LIVER DISEASE IN THE US: A NATIONAL COHORT STUDY UTILIZING ICD-10 ADMINISTRATIVE DATA Murag, S., Yoo, E., Dennis, B., Adejumo, A., Hu, M., Kim, D., Ahmed, A., Cholankeril, G. WILEY. 2019: 745A–746A
  • Genetic Factors and Continental Ancestry Account for Some Disparities in Nonalcoholic Fatty Liver Disease Among Hispanic Subgroups CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Yoo, E. R., Ahmed, A., Kim, D. 2019; 17 (11): 2176–78
  • DIET QUALITY AND ITS ASSOCIATION WITH NONALCOHOLIC FATTY LIVER DISEASE AND MORTALITY - A POPULATION-BASED STUDY Yoo, E., Li, A., Cholankeril, G., Kim, D., Ahmed, A. WILEY. 2019: 726A
  • Association between body size-metabolic phenotype and nonalcoholic steatohepatitis and significant fibrosis. Journal of gastroenterology Kim, D., Kim, W., Joo, S. K., Han, J., Kim, J. H., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019

    Abstract

    BACKGROUND AND AIMS: Body size-metabolic phenotype may help predict whether or not individuals with nonalcoholic fatty liver disease (NAFLD) develop advanced liver disease. We studied the association of body size-metabolic phenotype with nonalcoholic steatohepatitis (NASH) and significant fibrosis.METHODS: Our cross-sectional study included 559 subjects (mean age of 53years; women 51%) with biopsy-proven NAFLD. Clinical, genetic, and histological characteristic features of NAFLD were evaluated. The metabolically unhealthy phenotype was defined by the presence of two or more metabolic components, while body size was categorized based on body mass index: obese (≥ 25kg/m2) or non-obese (< 25kg/m2). Body size-metabolic phenotypes were divided into four study groups: (1) non-obese metabolic syndrome (MS)-, (2) non-obese MS+, (3) obese MS-, and (4) obese MS+.RESULTS: Obese MS- and non-obese MS+groups demonstrated comparable levels of insulin resistance, adipose tissue insulin resistance indexes, and visceral adipose tissue (VAT) areas. The VAT area was significantly higher in the obese MS+group versus obese MS- group. However, the VAT to subcutaneous adipose tissue (SAT) ratio was highest in the non-obese MS+group. There was no difference in histology between the non-obese MS+, obese MS-, and obese MS+groups. Multivariate analyses adjusted for age, sex, smoking status, PNPLA3, TM6SF2, and VAT/SAT areas demonstrated an independent and dose-dependent relationship between the body size-metabolic phenotype and NASH or significant fibrosis.CONCLUSION: The non-obese MS+group displayed similar degree of hepatic histological severity compared to their obese MS- counterparts. Metabolic milieu beyond obesity may play a pathogenic role in non-obese MS+individuals who develop NASH with significant hepatic fibrosis.CLINICAL TRIAL NUMBER: NCT02206841.

    View details for DOI 10.1007/s00535-019-01628-z

    View details for PubMedID 31535207

  • Trends in hospitalizations for chronic liver disease-related liver failure in the United States, 2005-2014 LIVER INTERNATIONAL Kim, D., Cholankeril, G., Li, A. A., Kim, W., Tighe, S. P., Hameed, B., Kwo, P. Y., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019; 39 (9): 1661–71

    View details for DOI 10.1111/liv.14135

    View details for Web of Science ID 000485292200008

  • Associations between sarcopenia and nonalcoholic fatty liver disease and advanced fibrosis in the USA EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY Wijarnpreecha, K., Kim, D., Raymond, P., Scribani, M., Ahmed, A. 2019; 31 (9): 1121–28
  • Suboptimal Use of Inpatient Palliative Care Consultation May Lead to Higher Readmissions and Costs in End-Stage Liver Disease. Journal of palliative medicine Adejumo, A. C., Kim, D., Iqbal, U., Yoo, E. R., Boursiquot, B. C., Cholankeril, G., Wong, R. J., Kwo, P. Y., Ahmed, A. 2019

    Abstract

    Background/Aims: Patients with end-stage liver disease (ESLD) have a high risk for readmission. We studied the role of palliative care consultation (PCC) in ESLD-related readmissions with a focus on health care resource utilization in the United States. Methods: We performed a retrospective longitudinal analysis on patients surviving hospitalizations with ESLD from January 2010 to September 2014 utilizing the Nationwide Readmissions Database with a 90-day follow-up after discharge. We analyzed annual trends in PCC among patients with ESLD. We matched PCC to no-PCC (1:1) using propensity scores to create a pseudorandomized clinical study. We estimated the impact of PCC on readmission rates (30- and 90-day), and length of stay (LOS) and cost during subsequent readmissions. Results: Of the 67,480 hospitalizations with ESLD, 3485 (5.3%) received PCC, with an annual increase from 3.6% to 6.7% (p for trend <0.01). The average 30- and 90-day annual readmission rates were 36.2% and 54.6%, respectively. PCC resulted in a lower risk for 30- and 90-day readmissions (hazard ratio: 0.42, 95% confidence interval [CI]: 0.38-0.47 and 0.38, 95% CI: 0.34-0.42, respectively). On subsequent 30- and 90-day readmissions, PCC was associated with decreased LOS (5.6- vs. 7.4 days and 5.7- vs. 6.9 days, p<0.01) and cost (US $48,752 vs. US $75,810 and US $48,582 vs. US $69,035, p<0.01). Conclusion: Inpatient utilization of PCC for ESLD is increasing annually, yet still remains low in the United States. More importantly, PCC was associated with a decline in readmission rates resulting in a lower burden on health care resource utilization and improvement in cost savings during subsequent readmissions.

    View details for DOI 10.1089/jpm.2019.0100

    View details for PubMedID 31397615

  • Disparate Trends in Mortality of Etiology-Specific Chronic Liver Diseases Among Hispanic Subpopulations CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Kim, D., Li, A. A., Perumpail, R. B., Cholankeril, G., Gonzalez, S. A., Kim, W., Ahmed, A. 2019; 17 (8): 1607-+
  • The interaction of nonalcoholic fatty liver disease and smoking on mortality among adults in the United States LIVER INTERNATIONAL Wijarnpreecha, K., Scribani, M., Kim, D., Kim, W. 2019; 39 (7): 1202–6

    View details for DOI 10.1111/liv.14058

    View details for Web of Science ID 000475387700005

  • Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States LIVER INTERNATIONAL Kim, D., Yoo, E. R., Li, A. A., Cholankeril, G., Tighe, S. P., Kim, W., Harrison, S. A., Ahmed, A. 2019; 39 (7): 1335–42

    View details for DOI 10.1111/liv.14110

    View details for Web of Science ID 000475387700019

  • Increasing Trends in Transplantation of HCV-Positive Livers Into Uninfected Recipients CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Cholankeril, G., Li, A. A., Dennis, B. B., Toll, A. E., Kim, D., Bonham, C., Nair, S., Ahmed, A. 2019; 17 (8): 1634–36
  • Impact of sarcopenia on the progression of nonalcoholic fatty liver disease: a frequently forgotten association HEPATOBILIARY SURGERY AND NUTRITION Li, A. A., Ahmed, A., Kim, D. 2019; 8 (3): 260–61
  • Impact of sarcopenia on the progression of nonalcoholic fatty liver disease: a frequently forgotten association. Hepatobiliary surgery and nutrition Li, A. A., Ahmed, A., Kim, D. 2019; 8 (3): 260-261

    View details for DOI 10.21037/hbsn.2018.12.10

    View details for PubMedID 31245407

    View details for PubMedCentralID PMC6561878

  • Nonalcoholic fatty liver disease in the over-60s: Impact of sarcopenia and obesity MATURITAS Wijampreecha, K., Panjawatanan, P., Aby, E., Ahmed, A., Kim, D. 2019; 124: 48–54
  • Potential Mechanisms Influencing the Inverse Relationship Between Cannabis and Nonalcoholic Fatty Liver Disease: A Commentary NUTRITION AND METABOLIC INSIGHTS Dibba, P., Li, A. A., Cholankeril, G., Khan, M., Kim, D., Ahmed, A. 2019; 12
  • Potential Mechanisms Influencing the Inverse Relationship Between Cannabis and Nonalcoholic Fatty Liver Disease: A Commentary. Nutrition and metabolic insights Dibba, P., Li, A. A., Cholankeril, G., Ali Khan, M., Kim, D., Ahmed, A. 2019; 12: 1178638819847480

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) develops when the liver is unable to oxidize or export excess free fatty acids generated by adipose tissue lipolysis, de novo lipogenesis, or dietary intake. Although treatment has generally been centered on reversing metabolic risk factors that increase the likelihood of NAFLD by influencing lifestyle modifications, therapeutic modalities are being studied at the cellular and molecular level. The endocannabinoid system has been of recent focus. The agonism and antagonism of cannabinoid receptors play roles in biochemical mechanisms involved in the development or regression of NAFLD. Exocannabinoids and endocannabinoids, the ligands which bind cannabinoid receptors, have been studied in this regard. Exocannabinoids found in cannabis (marijuana) may have a therapeutic benefit. Our recent study demonstrated an inverse association between marijuana use and NAFLD among adults in the United States. This commentary combines knowledge on the role of the endocannabinoid system in the setting of NAFLD with the findings in our article to hypothesize different potential mechanisms that may influence the inverse relationship between cannabis and NAFLD.

    View details for DOI 10.1177/1178638819847480

    View details for PubMedID 31308686

    View details for PubMedCentralID PMC6612909

  • Economic burden and healthcare utilization in nonalcoholic fatty liver disease HEPATOBILIARY SURGERY AND NUTRITION Yoo, E. R., Ahmed, A., Kim, D. 2019; 8 (2): 181–83
  • Economic burden and healthcare utilization in nonalcoholic fatty liver disease. Hepatobiliary surgery and nutrition Yoo, E. R., Ahmed, A., Kim, D. 2019; 8 (2): 181-183

    View details for DOI 10.21037/hbsn.2018.12.11

    View details for PubMedID 31098375

    View details for PubMedCentralID PMC6503245

  • Association between advanced fibrosis in fatty liver disease and overall mortality in terms of body size and body fat distribution Chung, G., Heo, N., Yim, J., Kwak, M., Kim, J., Ahmed, A., Kim, D. ELSEVIER SCIENCE BV. 2019: E293
  • Predictors of outcomes for patients with non-alcoholic steatohepatitis undergoing liver transplantation in the United States Stepanova, M., Mishra, A., Younossi, I., Kim, D., Ahmed, A., Younossi, Z. ELSEVIER SCIENCE BV. 2019: E573
  • Association between body size-metabolic phenotype and non-alcoholic steatohepatitis and significant fibrosis Kim, W., Kim, D., Harrison, S., Younossi, Z., Ahmed, A. ELSEVIER SCIENCE BV. 2019: E300–E301
  • Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States Kim, D., Yoo, E., Li, A., Cholankeril, G., Tighe, S., Kim, W., Harrison, S., Ahmed, A. ELSEVIER SCIENCE BV. 2019: E300
  • Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Yoo, E. R., Li, A. A., Cholankeril, G., Tighe, S. P., Kim, W., Harrison, S. A., Ahmed, A. 2019

    Abstract

    BACKGROUND AND AIMS: The relationship between bisphenol A (BPA) and non-alcoholic fatty liver disease (NAFLD) is undefined. We studied the impact of BPA on NAFLD.METHODS: We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) 2005-2014 among adults in the United States (US). NAFLD was diagnosed using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver diseases. The first sample using HSI consisted of 7605 adults. The second sample using USFLI consisted of 3631 participants with availability of fasting data.RESULTS: Of the first 7605 participants (mean age 47years, 48.4% male), the prevalence of NAFLD and abnormally elevated alanine aminotransferase (ALT) levels was correlated with urinary BPA levels (P<0.05). Compared to the reference group with lowest quartile of urinary BPA levels, those with the third and fourth quartiles were 81% and 53% more likely to develop NAFLD defined by HSI. In a multivariate model, the ORs for NAFLD in the third and fourth quartiles were 1.69 (95% CI 1.39-2.04) and 1.44 (95% CI 1.19-1.76) respectively (P for trend <0.001). In the second sample using USFLI, high BPA levels (fourth quartile) remained an independent predictor of NAFLD (OR 1.44, 95% CI 1.05-1.98, P for trend=0.012).CONCLUSIONS: High levels of urinary BPA were associated with NAFLD in a nationally representative sample of adults in the US. The pathophysiology remains unclear and warrants further investigation.

    View details for PubMedID 30924602

  • The Epidemiology, Risk Profiling and Diagnostic Challenges of Nonalcoholic Fatty Liver Disease. Medicines (Basel, Switzerland) Iqbal, U., Perumpail, B. J., Akhtar, D., Kim, D., Ahmed, A. 2019; 6 (1)

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver damage from the more prevalent (75%⁻80%) and nonprogressive nonalcoholic fatty liver (NAFL) category to its less common and more ominous subset, nonalcoholic steatohepatitis (NASH). NAFLD is now the most common cause of chronic liver disease in the developed world and is a leading indication for liver transplantation in United States (US). The global prevalence of NAFLD is estimated to be 25%, with the lowest prevalence in Africa (13.5%) and highest in the Middle East (31.8%) and South America (30.4%). The increasing incidence of NAFLD has been associated with the global obesity epidemic and manifestation of metabolic complications, including hypertension, diabetes, and dyslipidemia. The rapidly rising healthcare and economic burdens of NAFLD warrant institution of preventative and treatment measures in the high-risk sub-populations in an effort to reduce the morbidity and mortality associated with NAFLD. Genetic, demographic, clinical, and environmental factors may play a role in the pathogenesis of NAFLD. While NAFLD has been linked with various genetic variants, including PNPLA-3, TM6SF2, and FDFT1, environmental factors may predispose individuals to NAFLD as well. NAFLD is more common in older age groups and in men. With regards to ethnicity, in the US, Hispanics have the highest prevalence of NAFLD, followed by Caucasians and then African-Americans. NAFLD is frequently associated with the components of metabolic syndrome, such as type 2 diabetes mellitus (T2DM), obesity, hypertension, and dyslipidemia. Several studies have shown that the adoption of a healthy lifestyle, weight loss, and pro-active management of individual components of metabolic syndrome can help to prevent, retard or reverse NAFLD-related liver damage. Independently, NAFLD increases the risk of premature cardiovascular disease and associated mortality. For this reason, a case can be made for screening of NAFLD to facilitate early diagnosis and to prevent the hepatic and extra-hepatic complications in high risk sub-populations with morbid obesity, diabetes, and other metabolic risk factors.

    View details for PubMedID 30889791

  • Associations between sarcopenia and nonalcoholic fatty liver disease and advanced fibrosis in the USA. European journal of gastroenterology & hepatology Wijarnpreecha, K., Kim, D., Raymond, P., Scribani, M., Ahmed, A. 2019

    Abstract

    BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) may be associated with sarcopenia. This study aims to determine whether sarcopenia is independently associated with NAFLD and advanced fibrosis.PARTICIPANTS AND METHODS: Cross-sectional data from 11325 participants in the third National Health and Nutrition Examination Survey were analyzed. NAFLD was defined as the presence of hepatic steatosis from the ultrasound. Sarcopenia was defined as the skeletal muscle index.RESULTS: NAFLD was more common in participants with sarcopenia than in those without (46.7 vs. 27.5%). Univariate analysis showed that sarcopenia was associated with NAFLD [odds ratio (OR): 2.31; 95% confidence interval (CI): 2.01-2.64], which remained significant after adjustment for age, sex, ethnicity, metabolic risk factors (OR: 1.24; 95% CI: 1.03-1.48). This finding persisted after adjustment for C-reactive protein as a marker of chronic inflammation. NAFLD-associated advanced fibrosis was more common in participants with sarcopenia than in those without (7.8 vs. 1.6%). Sarcopenia was associated with NAFLD-associated advanced fibrosis independent of metabolic risk factors (OR: 1.79; 95% CI: 1.18-2.72).CONCLUSION: Sarcopenia was independently associated with increased odds of NAFLD and NAFLD-associated advanced fibrosis independent of well-defined risk factors. Interventions to strengthen muscle mass may reduce the burden of NAFLD and advanced fibrosis.

    View details for PubMedID 30888971

  • Race/ethnicity-based temporal changes in prevalence of NAFLD-related advanced fibrosis in the United States, 2005-2016 HEPATOLOGY INTERNATIONAL Kim, D., Kim, W., Adejumo, A. C., Cholankeril, G., Tighe, S. P., Wong, R. J., Gonzalez, S. A., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019; 13 (2): 205–13
  • The Therapeutic Implications of the Gut Microbiome and Probiotics in Patients with NAFLD DISEASES Perumpail, B. J., Li, A. A., John, N., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2019; 7 (1)
  • The Therapeutic Implications of the Gut Microbiome and Probiotics in Patients with NAFLD. Diseases (Basel, Switzerland) Perumpail, B. J., Li, A. A., John, N., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2019; 7 (1)

    Abstract

    Recent breakthrough in our understanding pertaining to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) has pointed to dysregulation or derangement of the gut microbiome, also known as dysbiosis. This has led to growing interest in probiotic supplementation as a potential treatment method for NAFLD due to its ability to retard and/or reverse dysbiosis and restore normal gut flora. A thorough review of medical literature was completed from inception through July 10, 2018 on the PubMed database by searching for key terms such as NAFLD, probiotics, dysbiosis, synbiotics, and nonalcoholic steatohepatitis (NASH). All studies reviewed indicate that probiotics had a beneficial effect in patients with NAFLD and its subset NASH. Results varied between studies, but there was evidence demonstrating improvement in liver enzymes, hepatic inflammation, hepatic steatosis, and hepatic fibrosis. No major adverse effects were noted. Currently, there are no guidelines addressing the use of probiotics in the setting of NAFLD. In conclusion, probiotics appear to be a promising option in the treatment of NAFLD. Future research is necessary to assess the efficacy of probiotics in patients with NAFLD.

    View details for PubMedID 30823570

  • Marijuana is not associated with progression of hepatic fibrosis in liver disease: a systematic review and meta-analysis EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY Farooqui, M. T., Khan, M. A., Cholankeril, G., Khan, Z., Abdul, M., Li, A. A., Shah, N., Wu, L., Haq, K., Solanki, S., Kim, D., Ahmed, A. 2019; 31 (2): 149–56
  • A Comparison Between Community and Academic Practices in the USA in the Management of Chronic Hepatitis B Patients Receiving Entecavir: Results of the ENUMERATE Study DIGESTIVE DISEASES AND SCIENCES Lee, H. M., Ahn, J., Kim, W., Lim, J. K., Nguyen, M., Pan, C. Q., Kim, D., Mannalithara, A., Te, H., Huy Trinh, Chu, D., Tram Tran, Woog, J., Lok, A. S. 2019; 64 (2): 358–66
  • Predictors of nonalcoholic steatohepatitis and significant fibrosis in non-obese nonalcoholic fatty liver disease LIVER INTERNATIONAL Kim, D., Kim, W., Joo, S., Kim, J., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019; 39 (2): 332–41

    View details for DOI 10.1111/liv.13983

    View details for Web of Science ID 000457468000013

  • Race/ethnicity-based temporal changes in prevalence of NAFLD-related advanced fibrosis in the United States, 2005-2016. Hepatology international Kim, D., Kim, W., Adejumo, A. C., Cholankeril, G., Tighe, S. P., Wong, R. J., Gonzalez, S. A., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019

    Abstract

    BACKGROUND AND AIM: Advanced fibrosis associated with nonalcoholic fatty liver disease (NAFLD) has been reported to have a higher risk of hepatic and non-hepatic mortality. We aim to study the recent trends in the prevalence of NAFLD-related advanced fibrosis in a large population sample.METHODS: Cross-sectional data from 28,739 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2016 were utilized. NAFLD was defined using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD was determined by the NAFLD fibrosis score, FIB-4 score, and aspartate aminotransferase-to-platelet ratio index.RESULTS: The prevalence of NAFLD-related advanced fibrosis increased from 2.6% [95% confidence interval (CI) 2.1-3.1] in 2005-2008 and 4.4% (95% CI 3.7-5.1) in 2009-2012, to 5.0% (95% CI 4.2-5.9) in 2013-2016 using HSI as the NAFLD prediction model; and from 3.3% (95% CI 2.5-4.5) in 2005-2008 and 6.4% (95% CI 3.7-5.1) in 2009-2012, to 6.8% (95% 5.3-8.7) in 2013-2016 using USFLI (p<0.01). A similar trend was observed in entire NHANES cohort regardless of NAFLD status. While the prevalence of advanced fibrosis increased steadily in non-Hispanic whites through the duration of the study, it leveled off during 2013-2016 in non-Hispanic blacks.CONCLUSIONS: Prevalence of advanced fibrosis associated with NAFLD increased steadily from 2005 to 2016. More importantly, race/ethnicity-based temporal differences were noted in the prevalence of NAFLD-related advanced fibrosis during the study.

    View details for PubMedID 30694445

  • The interaction of nonalcoholic fatty liver disease and smoking on mortality among adults in the United States. Liver international : official journal of the International Association for the Study of the Liver Wijarnpreecha, K., Scribani, M., Kim, D., Kim, W. R. 2019

    Abstract

    BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in Western countries. Smoking and diabetes mellitus (DM) have been shown to increase mortality, however, whether NAFLD adds to the detrimental effect of smoking in DM and non-DM patients is unknown. We evaluated the possible interactive effect of NAFLD and smoking on mortality risk in a U.S. population-based sample.METHODS: Cross-sectional data from 11,205 participants in the third National Health and Nutrition Examination Survey were analyzed. NAFLD was defined as ultrasonographic hepatic steatosis without evidence of other liver diseases. Proportional hazards regresionn modeling was used to test for the multiplicative interaction of NAFLD and smoking on overall mortality, controlling for DM.RESULTS: 36.5% of the participants had NAFLD of whom 21.1% were current smokers, while among non-NAFLD subjects, 26.2% reported current smoking. Smoking was associated with a hazard ratio (HR) of 2.23 (95% confidence interval (CI): 1.87-2.65) among non-NAFLD subjects, and 2.31 (95% CI: 1.33-2.92, p<0.01) among NAFLD patients.In contrast, the HR for NAFLD was 1.01 (95% CI: 0.78-1.31, p=0.96) among smokers and 0.98 (95% CI: 0.87-1.10, p=0.73) among non-smokers. There was no evidence of interaction between NAFLD and smoking (HR=1.01, 95% CI: 0.74-1.38, p=0.94) in the combined model.CONCLUSION: We found that smoking increased mortality by two-fold among the U.S.POPULATION: Although the magnitude of the increase in mortality did not differ from that in non-NAFLD subjects, smoking represents a modifiable determinant of long-term outcomes in NAFLD patients. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30697898

  • Trends in Hospitalizations for Chronic Liver Disease-related Liver Failure in the United States, 2005-2014. Liver international : official journal of the International Association for the Study of the Liver Kim, D. n., Cholankeril, G. n., Li, A. A., Kim, W. n., Tighe, S. P., Hameed, B. n., Kwo, P. Y., Harrison, S. A., Younossi, Z. M., Ahmed, A. n. 2019

    Abstract

    Current estimates of the population-based disease burden of liver failure or end-stage liver disease (ESLD) are lacking. We investigated recent trends in hospitalizations and in-hospital mortality among patients with ESLD in the United States (US).A retrospective analysis was performed utilizing the National Inpatient Sample (NIS) from 2005 to 2014. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma (HCC), criteria obtained from the International Classification of Diseases, Ninth Revision. Nationwide rates of hospitalization and in-hospital mortality were analyzed from 2005 to 2014.Hospitalization rates for decompensated cirrhosis during this period increased from 105.3/100,000 persons to 159.9/100,000 persons. In terms of HCC, hospitalization rates increased from 13.6/100,000 to 22.1/100,000. In patients with nonalcoholic fatty liver disease (NAFLD)-related decompensated cirrhosis, the hospitalization rate increased from 13.4/100,000 to 32.1/100,000 with an annual incremental increase of 10.6%, a magnitude two-fold higher than other etiologies. The proportion of NAFLD among hospitalizations with ESLD steadily increased from 12.7% to 20.1% for decompensated cirrhosis while the proportion of chronic hepatitis C (HCV) and alcoholic liver disease (ALD) declined (29.3% to 27.6% for HCV; 39.0% to 37.4% for ALD). Although the overall in-hospital mortality rates for ESLD declined during the study, mortality rates for NAFLD-related decompensated cirrhosis showed no significant change.Among etiologies of chronic liver disease, NAFLD demonstrated the fastest growing rate of hospitalizations in non-HCC patients with ESLD in the US. Our study highlights the need for a focus on NAFLD-related hospitalizations and its impact on resource utilization. This article is protected by copyright. All rights reserved.

    View details for PubMedID 31081997

  • Recent advances in liver transplantation with HCV seropositive donors. F1000Research Murag, S. n., Dennis, B. B., Kim, D. n., Ahmed, A. n., Cholankeril, G. n. 2019; 8

    Abstract

    The paradigm shift from interferon-based to direct-acting antiviral (DAA) therapy for the treatment of hepatitis C virus (HCV) infection has revolutionized the field of liver transplantation. These advances in effective HCV treatment, along with the persistent shortage in available liver grafts, have encouraged investigators to assess the need for adopting more inclusive donor policies. Owing to the poor outcomes following liver transplantation with recurrent HCV infection, liver transplantation using HCV seropositive donors (non-viremic and viremic) had been restricted. However, as a result of the growing supply of HCV seropositive donors from the recent opioid epidemic along with the advent of efficacious DAA therapy to treat HCV recurrence, there has been an increasing trend to use HCV seropositive donors for both HCV seropositive and seronegative recipients. The review aims to discuss recent advances and associated outcomes related to the use of HCV seropositive grafts for liver transplantation.

    View details for DOI 10.12688/f1000research.20387.1

    View details for PubMedID 31942236

    View details for PubMedCentralID PMC6944251

  • Association Between a Polymorphism in MBOAT7 and Chronic Kidney Disease in Patients With Biopsy-confirmed Nonalcoholic Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Koo, B. K., An, J. N., Joo, S. K., Kim, D. n., Lee, S. n., Bae, J. M., Park, J. H., Kim, J. H., Chang, M. S., Kim, W. n. 2019

    View details for DOI 10.1016/j.cgh.2019.09.017

    View details for PubMedID 31546054

  • Use of anti-platelet agents in the prevention of hepatic fibrosis in patients at risk for chronic liver disease: a systematic review and meta-analysis HEPATOLOGY INTERNATIONAL Iqbal, U., Dennis, B. B., Li, A. A., Cholankeril, G., Kim, D., Khan, M., Ahmed, A. 2019; 13 (1): 84–90
  • Readmission Rates and Associated Outcomes for Alcoholic Hepatitis: A Nationwide Cohort Study. Digestive diseases and sciences Adejumo, A. C., Cholankeril, G. n., Iqbal, U. n., Yoo, E. R., Boursiquot, B. C., Concepcion, W. C., Kim, D. n., Ahmed, A. n. 2019

    Abstract

    Alcoholic hepatitis (AH) can lead to sudden and severe hepatic decompensation necessitating recurrent hospitalizations. We evaluated the trends, predictors, and healthcare cost burden of AH-related readmissions in the USA.Utilizing the National Readmissions Database 2010-2014, we performed a retrospective longitudinal analysis to identify the index readmission with AH for up to 90 days after discharge. Annual trends of 30- and 90-day AH-related readmissions were calculated. Predictors of 30- and 90-day readmission were determined by multivariate logistic regression. Annual healthcare cost burden associated with AH-linked readmissions was estimated.Of the 21,572 (unweighted: 50,769) AH-related hospitalizations, 4917 (22.8%) and 7890 (36.6%) were readmitted in 30 and 90 day, respectively, with rates that were statistically unchanged from 2010 to 2014. Predictors of 30-day readmissions included female gender, hepatitis C virus infection, cirrhosis, ascites, acute kidney injury, urinary tract infection, history of bariatric surgery, chronic pancreatitis, and high medical comorbidity index. Acute pancreatitis and palliative care consultation were associated with a lower risk of 30-day readmission. Predictors of 90-day readmission were similar to risk factors for 30-day readmission. From 2010 to 2014, the annual cost (and total hospitalization days) burden increased in 2014 to $164 million (22,244 days) and $321 million (42,772 days) for 30- and 90-day AH-related readmissions, respectively.Despite relatively stable trends in AH-related readmission, the total LOS and cost has been rising. A target-directed approach with a focus on high-risk subpopulations may help understand the unique challenges associated with the rising cost of AH-related readmissions.

    View details for DOI 10.1007/s10620-019-05759-4

    View details for PubMedID 31372912

  • Association between Advanced Fibrosis in Fatty Liver Disease and Overall Mortality based on Body Fat Distribution. Journal of gastroenterology and hepatology Chung, G. E., Heo, N. J., Kim, D. n., Kwak, M. S., Yim, J. Y., Kim, J. S., Ahmed, A. n. 2019

    Abstract

    Studies on association between fatty liver disease and overall mortality have yielded conflicting results. We evaluated the impact of fatty liver disease and advanced fibrosis on overall morality with a focus on body size and abdominal fat distribution measured by computed tomography (CT).We performed a prospective cohort study including 34,080 subjects (mean age, 51.4 years; 58.6% men) who underwent abdominal ultrasonography and fat CT, from 2007 to 2015. Fatty liver was diagnosed by ultrasonography, and advanced fibrosis was defined as high probability of advanced fibrosis based on three noninvasive methods, aspartate aminotransferase-to-platelet ratio index, nonalcoholic fatty liver disease fibrosis score, and FiB-4 score. Body size was categorized by body mass index into obese (≥25 kg/m2 ) or nonobese (<25 kg/m2 ). Multivariate proportional Cox hazard regression analyses were performed.The prevalence of fatty liver disease was 37.5%, while the prevalence of advanced fibrosis in fatty liver disease was 1.8%. During a median follow-up of 87 months (interquartile range, 62-110), 296 deaths occurred. Fatty liver disease was not associated with higher overall mortality (multivariate-adjusted hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.77-1.34), while increased subcutaneous adiposity was associated with decreased mortality (HR 0.72, 95% CI 0.60-0.88). Advanced fibrosis resulted in a 3.5-fold increase in overall mortality (adjusted HR 3.52, 95% CI, 1.86-6.65), which was more pronounced in the nonobese.While fatty liver disease did not impact overall mortality, subcutaneous adiposity was associated with reduced overall mortality. Advanced fibrosis was an independent predictor of increase in overall mortality.

    View details for DOI 10.1111/jgh.14778

    View details for PubMedID 31272131

  • Hepatocellular carcinoma is leading in cancer-related disease burden among hospitalized baby boomers. Annals of hepatology Gadiparthi, C. n., Yoo, E. R., Are, V. S., Charilaou, P. n., Kim, D. n., Cholankeril, G. n., Pitchumoni, C. n., Ahmed, A. n. 2019

    Abstract

    Three fourths of chronic hepatitis C virus (HCV) infected adult patients in the United States (US) are born between 1945 and 1965, also known as baby boomers (BB). Prevalence of hepatocellular carcinoma (HCC) is raising in BB due to their advancing age and prolonged HCV infection. We evaluated inpatient hospitalization and mortality in BB associated with HCC.It is a retrospective cohort study utilizing the Healthcare Utilization Project-National Inpatient Sample (HCUP-NIS) database. From 2003 to 2012, top five primary cancer related hospitalization and mortality among BB were studied.Among 48,733 hospitalizations related to HCC in HCUP-NIS database from 2003 to 2012, BB accounted for 49.6% (24,210) whereas non-BB 50.4% (24,523). Within BB cohort, the top five cancers with the highest proportion of hospitalizations were HCC (46%), prostate (43%), kidney (41%), pancreas (33%), and bladder (21%). From 2003 to 2012, the proportion of HCC related hospitalizations represented by BB almost doubled (33.5 to 57.8%) whereas there was one-third reduction (66.4 to 42.1%) among non-BB. Similarly, HCC-related inpatient mortality in BB decreased by 28% (6.1 to 2.7 per 100,000 hospitalization) but it remained unchanged in non-BB (11.1 to 10.6). HCC accounted for 2nd highest mortality (4960 total deaths) among hospitalized BB behind pancreatic cancer. HCC related to HCV was disproportionately higher in BB compared to non-BB (50.6% vs. 19%; P<0.001).HCC ranks number one among the top five cancers with highest proportion of inpatient burden. Future studies should focus on understanding the underlying reasons for this ominous trend.

    View details for DOI 10.1016/j.aohep.2019.04.014

    View details for PubMedID 31164267

  • Nonalcoholic steatohepatitis is associated with a higher risk of advanced colorectal neoplasm. Liver international : official journal of the International Association for the Study of the Liver Cho, Y. n., Lim, S. K., Joo, S. K., Jeong, D. H., Kim, J. H., Bae, J. M., Park, J. H., Chang, M. S., Lee, D. H., Jung, Y. J., Kim, B. G., Kim, D. n., Lee, K. L., Kim, W. n. 2019

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is known to increase the risk of adenomatous colonic polyps. However, the role of screening colonoscopy in patients with biopsy-proven NAFLD in detecting advanced colorectal neoplasm is not clearly evidence-based. Therefore, we investigated whether the histological severity of NAFLD is associated with advanced colorectal neoplasm.This study included patients ≥18 years old who underwent screening colonoscopy between 2013 and 2018 within a biopsy-evaluated prospective NAFLD cohort. Advanced colorectal neoplasm was defined as an adenomatous polyp greater than 10 mm in diameter and/or with villous histology and/or with high-grade dysplasia or adenocarcinoma.Among the 476 patients with clinically suspected NAFLD, 379 patients diagnosed as biopsy-proven NAFLD and 97 patients had no evidence of NAFLD histologically, who were analyzed as healthy controls. The prevalence of advanced colorectal neoplasm was 11.1% (n=53). Patients with advanced colorectal neoplasm had higher grade of steatosis (P=.004) and higher stage of hepatic fibrosis (P=.044) than those with normal colonoscopic findings or low-grade adenomatous polyp. Multivariable logistic regression analysis revealed that the presence of nonalcoholic steatohepatitis (NASH) was an independent risk factor for both colorectal polyp (odds ratio [OR], 2.08; 95% confidential interval [CI], 1.12-3.86; P=.020) and advanced colorectal neoplasm (OR, 2.81; 95% CI, 1.01-7.87; P=.049).The presence of biopsy-proven NASH was significantly associated with an increased risk of advanced colorectal neoplasm among patients with NAFLD. This finding may alert physicians to conduct screening colonoscopy in patients with NASH to detect advanced colorectal neoplasm early. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/liv.14163

    View details for PubMedID 31162812

  • Nonalcoholic fatty liver disease in the over-60s: Impact of sarcopenia and obesity. Maturitas Wijarnpreecha, K. n., Panjawatanan, P. n., Aby, E. n., Ahmed, A. n., Kim, D. n. 2019; 124: 48–54

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adults of all ethnicities. NAFLD is commonly seen in individuals with metabolic abnormalities, such as obesity and insulin resistance, which are closely associated with sarcopenia. Sarcopenia, defined as low muscle mass and impaired muscle function, is associated with NAFLD and worse outcomes in patients with NAFLD. As the world's elderly population and the prevalence of obesity continues to grow at an unprecedented rate, NAFLD and sarcopenia are projected to increase. Given that there are no approved pharmacologic treatments for NAFLD, it is imperative to gain a better understanding of the disease pathophysiology, to guide treatment options. Recent studies have given new insight into sarcopenic obesity, but there is no consensus on its definition. In this review, we attempt to address the impact of sarcopenia and obesity on NAFLD, especially in the elderly population.

    View details for PubMedID 31097179

  • Nonalcoholic fatty liver disease is associated with breast cancer in nonobese women. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver Kwak, M. S., Yim, J. Y., Yi, A. n., Chung, G. E., Yang, J. I., Kim, D. n., Kim, J. S., Noh, D. Y. 2019

    Abstract

    Growing evidence supports that nonalcoholic fatty liver disease (NAFLD) is associated with extrahepatic cancers. Nonalcoholic fatty liver disease (NAFLD) and breast cancer share similar risk factors, including obesity.The aim of this case-control study was to investigate the association between NAFLD and breast cancer.Subjects who received health screening, including mammography and breast and hepatic ultrasonography simultaneously, were included. Subjects diagnosed with breast cancer were matched with controls. Conditional logistic regression analyses were performed.Among 270 breast cancer patients and 270 controls, 81 cancer patients (30.0%) and 54 controls (20.0%) had NAFLD (P = 0.008). NAFLD was significantly associated with breast cancer in multivariate analysis (P = 0.046). When the interaction between obesity (BMI < 25 kg/m2 vs. ≥25 kg/m2) and NAFLD in breast cancer patients was examined, a significant effect modification between obesity and NAFLD in breast cancer was noted (P = 0.021). The subgroup analysis showed that NAFLD was significantly associated with breast cancer in the nonobese subgroup (odds ratio 3.04, 95% confidence interval 1.37-4.32, P = 0.002) but not in the obese group (P = 0.163).NAFLD was significantly associated with breast cancer independent of traditional risk factors, and this association existed in the nonobese subgroup but not in the obese subgroup.

    View details for PubMedID 30686716

  • Extrahepatic Manifestations of Nonalcoholic Fatty Liver Disease. Gut and liver Li, A. A., Ahmed, A. n., Kim, D. n. 2019

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and encompasses a spectrum of pathology from simple steatosis to inflammation and significant fibrosis that leads to cirrhosis. NAFLD and its comorbid conditions extend well beyond the liver. It is a multisystemic clinical disease entity with extrahepatic manifestations such as cardiovascular disease, type 2 diabetes, chronic kidney disease, hypothyroidism, polycystic ovarian syndrome, and psoriasis. Indeed, the most common causes of mortality in subjects with NAFLD are cardiovascular disease, followed by malignancies and then liver-related complications as a distant third. This review focuses on several of the key extrahepatic manifestations of NAFLD and areas for future investigation. Clinicians should learn to screen and initiate treatment for these extrahepatic manifestations in a prompt and timely fashion before they progress to end-organ damage.

    View details for DOI 10.5009/gnl19069

    View details for PubMedID 31195434

  • Pre-Operative Delta-MELD is an Independent Predictor of Higher Mortality following Liver Transplantation. Scientific reports Cholankeril, G. n., Li, A. A., Dennis, B. B., Gadiparthi, C. n., Kim, D. n., Toll, A. E., Maliakkal, B. J., Satapathy, S. K., Nair, S. n., Ahmed, A. n. 2019; 9 (1): 8312

    Abstract

    Clinical decompensation immediately prior to liver transplantation may affect post-liver transplant (LT) outcomes. Using the serial Model for End-Stage Liver Disease (MELD) scores recorded in the United Network for Organ Sharing national registry (2010-2017), we analyzed post-LT mortality among adult LT recipients based on the degree of fluctuation in MELD score during the 30-day period prior to LT surgery. Delta-MELD (D-MELD) was defined as recipient MELD score at LT minus lowest MELD score within the preceding 30 days. Impact of D-MELD as a continuous and categorical variable (D-MELD 0-4, 5-10, >10) on early, 30-day post-LT mortality was assessed. Overall, a total of 12,785 LT recipients were analyzed, of which 8,862 (67.9%) had a pre-operative D-MELD 0-4; 2,574 (20.1%) with a D-MELD 5-10; and 1,529 (12.0%) with a D-MELD > 10. One-point incremental increase in pre-operative D-MELD (adjusted HR, 1.07, 95% CI: 1.04-1.10) was associated with higher 30-day post-LT mortality. Moreover, pre-operative D-MELD > 10 was associated with nearly a two-fold increased risk for 30-day post-LT mortality (adjusted HR, 1.89, 95% CI: 1.30-2.77) compared to D-MELD 0-4. The increased risk of pre-LT mortality associated with severity of clinical decompensation assessed by the magnitude of pre-operative D-MELD persists in the early post-LT period.

    View details for DOI 10.1038/s41598-019-44814-y

    View details for PubMedID 31165776

  • Temporal Trends Associated With the Rise in Alcoholic Liver Disease-related Liver Transplantation in the United States TRANSPLANTATION Cholankeril, G., Gadiparthi, C., Yoo, E. R., Dennis, B. B., Li, A. A., Hu, M., Wong, K., Kim, D., Ahmed, A. 2019; 103 (1): 131–39
  • Nonalcoholic Fatty Liver Disease: Epidemiology, Liver Transplantation Trends and Outcomes, and Risk of Recurrent Disease in the Graft. Journal of clinical and translational hepatology Liu, A., Galoosian, A., Kaswala, D., Li, A. A., Gadiparthi, C., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (4): 420–24

    Abstract

    In parallel with the rising prevalence of metabolic syndrome globally, nonalcoholic fatty liver (NAFL) disease is the most common chronic liver disease in Western countries and nonalcoholic steatohepatitis (NASH) has become increasingly associated with hepatocellular carcinoma. Recent studies have identified NASH as the most rapidly growing indication for liver transplantation (LT). As a hepatic manifestation of the metabolic syndrome, NAFL disease can be histologically divided into NAFL and NASH. NAFL is considered a benign condition, with histological changes of hepatocyte steatosis but without evidence of hepatocellular injury or fibrosis. This is distinct from NASH, which is characterized by hepatocyte ballooning and inflammation, and which can progress to fibrosis and cirrhosis, hepatocellular carcinoma, and liver failure. As for any other end-stage liver disease, LT is a curative option for NASH after the onset of decompensated cirrhosis or hepatocellular carcinoma. Although some studies have suggested increased rates of sepsis and cardiovascular complications in the immediate postoperative period, the long-term posttransplant survival of NASH cases is similar to other indications for LT. Recurrence of NAFL following LT is common and can be challenging, although recurrence rates of NASH are lower. The persistence or progression of metabolic syndrome components after LT are likely responsible for NASH recurrence in transplanted liver. Therefore, while maintaining access to LT is important, concerted effort to address the modifiable risk factors and develop effective screening strategies to identify early stages of disease are paramount to effectively tackle this growing epidemic.

    View details for PubMedID 30637220

  • Use of anti-platelet agents in the prevention of hepatic fibrosis in patients at risk for chronic liver disease: a systematic review and meta-analysis. Hepatology international Iqbal, U., Dennis, B. B., Li, A. A., Cholankeril, G., Kim, D., Khan, M. A., Ahmed, A. 2018

    Abstract

    BACKGROUND AND AIMS: While the association between platelet activation and hepatic fibrosis has been previously demonstrated in animal studies; the utility of anti-platelet agents in reversing the progression of hepatic fibrosis requires further review. Utilizing systematic review methods, we provide to our knowledge the first meta-analysis combining evidence from all studies aimed to establish the effect of anti-platelet agents in the prevention of hepatic fibrosis.METHODS: We searched Medline, EMBASE and PubMed databases from inception to October 2018 to identify all studies aimed at evaluating the role of anti-platelet agents in the prevention of hepatic fibrosis. The primary outcome was hepatic fibrosis. The initial title, abstract, and full-text screening were performed in duplicate. Risk of bias was evaluated using the Newcastle-Ottawa Scale. A fixed-effect generic inverse variance method was used to create a pooled estimate of the odds of hepatic fibrosis in patients with anti-platelet agents versus without anti-platelet agents.RESULTS: Among the 2310 unique articles identified during the title screening, 4 studies with a combined population of 3141 patients were deemed eligible for inclusion into the meta-analysis establishing the effect of anti-platelet agents on hepatic fibrosis. One study failed to report their findings in the entire cohort, electing to instead summarize the effects of anti-platelets within subgroups categorized by fibrotic risk factors. Use of anti-platelets was associated with 32% decreased odds of hepatic fibrosis, (adjusted pooled OR 0.68; CI 0.56-0.82, p≤0.0001). The statistical heterogeneity among the studies was insignificant.CONCLUSION: Use of anti-platelet agents is associated with the decreased odds of hepatic fibrosis. Due to limited evidence, future high-quality randomized controlled trials with larger comparative samples are required to further delineate the potential beneficial effects of these drugs in preventing hepatic fibrosis.

    View details for PubMedID 30539518

  • Disparities in mortality for chronic liver disease among Asian subpopulations in the United States from 2007 to 2016 JOURNAL OF VIRAL HEPATITIS Li, A. A., Kim, D., Kim, W., Dibba, P., Wong, K., Cholankeril, G., Jacobson, I. M., Younossi, Z. M., Ahmed, A. 2018; 25 (12): 1608–16

    View details for DOI 10.1111/jvh.12981

    View details for Web of Science ID 000451117100023

  • Longitudinal trends in renal function in chronic hepatitis B patients receiving oral antiviral treatment ALIMENTARY PHARMACOLOGY & THERAPEUTICS Udompap, P., Kim, D., Ahmed, A., Kim, W. 2018; 48 (11-12): 1282–89

    View details for DOI 10.1111/apt.15020

    View details for Web of Science ID 000451550300010

  • Temporal Trends Associated with the Rise in Alcoholic Liver Disease Related Liver Transplantation in the United States. Transplantation Cholankeril, G., Gadiparthi, C., Yoo, E. R., Dennis, B. B., Li, A. A., Hu, M., Wong, K., Kim, D., Ahmed, A. 2018

    Abstract

    BACKGROUND: In the United States, alcoholic liver disease (ALD) has recently become the leading indication for liver transplantation (LT).METHODS: Using the United Network for Organ Sharing registry, we examined temporal trends in adult liver transplant waitlist registrants and recipients with chronic liver disease (CLD) due to ALD from 2007 to 2016.RESULTS: From 2007 to 2016, ALD accounted for 20.4% (18 399) of all CLD waitlist (WL) additions. The age-standardized ALD WL addition rate was 0.459 per 100 000 US population in 2007; nearly doubled to 0.872 per 100 000 US population in 2016 and increased with an average annual percent change of 47.56% (95% CI: 30.33% to 64.72%).The ALD WL addition rate increased over twofold among young (18-39 years) and middle-aged (40-59 years) adults during the study period. Young adult ALD WL additions presented with a higher severity of liver disease including Model for End-Stage Liver Disease score compared to middle aged and older adults (> 60 years). The number of annual ALD WL deaths readily rose from 2014 to 2016, despite an overall annual decline in all CLD WL deaths. Severe hepatic encephalopathy, low BMI (< 18.5) and diabetes mellitus were significant predictors for 1-year waitlist mortality.CONCLUSION: ALD-related WL registrations and LT have increased over the past decade with a disproportionate increase in young and middle-aged adults. These subpopulations within the ALD cohort need to be evaluated in future studies to improve our understanding of factors associated with these alarming trends.

    View details for PubMedID 30300285

  • Predictors of Nonalcoholic Steatohepatitis and Significant Fibrosis in Non-Obese Nonalcoholic Fatty Liver Disease. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Kim, W., Joo, S. K., Kim, J. H., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2018

    Abstract

    AIMS: We compared (1) demographic and clinical characteristics, and (2) determinants of nonalcoholic steatohepatitis (NASH) and significant fibrosis in non-obese and obese NAFLD.METHODS: A cross-sectional study of 664 Asian subjects (mean age 53.1 years; men 50.3%) with biopsy-proven NAFLD and controls was conducted. Subjects were divided by their body mass index (BMI) into obese (BMI ≥25 kg/m2 ) and non-obese (BMI <25 kg/m2 ).RESULTS: Observations in subjects with non-obese NAFLD were in between non-obese controls and obese NAFLD subjects for BMI, sagittal abdominal diameter (SAD), aminotransferase levels, insulin resistance, and abdominal visceral adipose tissue (VAT) area. There was no significant difference in histology between non-obese and obese subjects with NAFLD except for lower grade of hepatic steatosis in non-obese NAFLD and higher severity of hepatic fibrosis in non-obese NASH. Predictors of NASH in non-obese subjects included females (odds ratio [OR] 2.49), higher alanine aminotransferase (OR 1.03), lower high density lipoprotein-cholesterol (OR 0.96), higher prevalence of diabetes (OR 3.65) and higher VAT area (OR 1.63 per SD increase of VAT), while age (OR 1.04), higher aspartate aminotransferase (OR 1.02), diabetes (OR 2.76,), and higher VAT area (OR 1.57 per SD increase) were associated with significant fibrosis in the non-obese. SAD was independently associated with NASH or significant fibrosis among non-obese NAFLD subjects.CONCLUSION: While there were a few phenotypic differences from obese subjects, non-obese subjects with NAFLD displayed a similar severity of histological liver damage. Potential factor(s) beyond obesity may play a role as non-obese NAFLD advances to more severe disease. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30298568

  • Anti-Diabetic Medications for the Pharmacologic Management of NAFLD. Diseases (Basel, Switzerland) Cholankeril, R., Patel, V., Perumpail, B. J., Yoo, E. R., Iqbal, U., Sallam, S., Shah, N. D., Kwong, W., Kim, D., Ahmed, A. 2018; 6 (4)

    Abstract

    As a chronic disease encompassing a wide spectrum of liver-related histologic damage, nonalcoholic fatty liver disease (NAFLD) is becoming a global epidemic with significant impacts on all-cause morbidity and mortality. Insulin resistance and type 2 diabetes mellitus predispose individuals to NAFLD and related complications. Therefore, timely intervention with anti-diabetic medications may prevent and delay the development of NAFLD or have a therapeutic implication. The focus of this review is to evaluate the evidence supporting the efficacy of anti-diabetic medications in the treatment of NAFLD. While many of these anti-diabetic agents have shown to improve biochemical parameters, their effect on hepatic histology is limited. Among anti-diabetic medications, only thiazolidinediones and glucagon-like peptide-1 receptor agonists demonstrate significant improvement in hepatic histology.

    View details for PubMedID 30282916

  • Pre-Operative Magnitude in the Rise of Meld Score Is a Predictor of Survival Following Liver Transplantation Cholankeril, G., Yoo, E. R., Li, A. A., Kim, D., Ahmed, A. WILEY. 2018: 690A–691A
  • Leucocyte telomere shortening is associated with nonalcoholic fatty liver disease-related advanced fibrosis LIVER INTERNATIONAL Kim, D., Li, A. A., Ahmed, A. 2018; 38 (10): 1839–48

    View details for DOI 10.1111/liv.13886

    View details for Web of Science ID 000445622400017

  • Subclinical Hypothyroidism and Low-Normal Thyroid Functionare Associated with Nonalcoholic Steatohepatitis and Fibrosis Han, J., Kim, W., Kim, D., Joo, S., Lee, D., Jung, Y. WILEY. 2018: 1327A
  • Predictors of Nonalcoholic Steatohepatitis and Significant Fibrosis in Non-Obese Population Kim, W., Kim, D., Joo, S., Lee, D., Jung, Y. WILEY. 2018: 989A–990A
  • Nonalcoholic Fatty Liver Disease: Epidemiology, Liver Transplantation Trends and Outcomes, and Risk of Recurrent Disease in the Graft JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY Liu, A., Galoosian, A., Kaswala, D., Li, A. A., Gadiparthi, C., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (4): 420–24
  • Use of Antiplatelet Agents for the Prevention of Hepatic Fibrosis: A Systematic Review and Meta-Analysis Iqbal, U., Li, A. A., Dibba, P., Yoo, E. R., Cholankeril, G., Khan, M., Kim, D., Ahmed, A. WILEY. 2018: 1141A
  • Trends in Causes of Mortality in Liver Transplantation Recipients: Comparison Among Nash, ALD, and HCV Cohorts Yoo, E. R., Cholankeril, G., Li, A. A., Dibba, P., Iqbal, U., Khan, M., Gadiparthi, C., Kim, D., Ahmed, A. WILEY. 2018: 966A–967A
  • When to Initiate Weight Loss Medications in the NAFLD Population. Diseases (Basel, Switzerland) Yoo, E. R., Sallam, S., Perumpail, B. J., Iqbal, U., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (4)

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is characterized by histological evidence of hepatic steatosis, lobular inflammation, ballooning degeneration and hepatic fibrosis in the absence of significant alcohol use and other known causes of chronic liver diseases. NAFLD is subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is generally benign but can progress to NASH, which carries a higher risk of adverse outcomes including cirrhosis, end-stage liver disease, hepatocellular carcinoma and death if liver transplantation is not pursued in a timely fashion. Currently, lifestyle modifications including healthy diet and increased physical activity/exercise culminating in weight loss of 5% to >10% is the cornerstone of treatment intervention for patients with NAFLD. Patients with NAFLD who fail to obtain this goal despite the help of dietitians and regimented exercise programs are left in a purgatory state and remain at risk of developing NASH-related advance fibrosis. For such patients with NAFLD who are overweight and obese, healthcare providers should consider a trial of FDA-approved anti-obesity medications as adjunct therapy to provide further preventative and therapeutic options as an effort to reduce the risk of NAFLD-related disease progression.

    View details for PubMedID 30274326

  • Increasing Trends in Transplantation of HCV-positive Livers into Uninfected Recipients. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Cholankeril, G., Li, A. A., Dennis, B. B., Toll, A. E., Kim, D., Bonham, C. A., Nair, S., Ahmed, A. 2018

    View details for PubMedID 30268562

  • The Role of Vitamin E in the Treatment of NAFLD. Diseases (Basel, Switzerland) Perumpail, B. J., Li, A. A., John, N., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (4)

    Abstract

    There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect.

    View details for PubMedID 30249972

  • Disparities in Mortality for Chronic Liver Disease among Asian Sub-Populations in the United States from 2007 to 2016. Journal of viral hepatitis Li, A. A., Kim, D., Kim, W., Dibba, P., Wong, K., Cholankeril, G., Jacobson, I. M., Younossi, Z. M., Ahmed, A. 2018

    Abstract

    The Asian-American population is characterized by remarkable diversity. Studying Asians as an aggregate group may obscure clinically-meaningful heterogeneity. We performed a population-based study using data from the United States (US) National Vital Statistics System. We determined the trends in age-standardized mortality rates for chronic liver disease stratified by etiology among the most populous US-based Asian subgroups (Asian Indians, Chinese, Filipino, Japanese, Korean, and Vietnamese) and compared it to non-Hispanic whites. Annual percentage change was calculated to determine temporal mortality patterns using joinpoint analysis.Hepatitis C virus-related mortality rates were higher in non-Hispanic whites compared to individual Asian subgroups, but a sharp decline in mortality rates was noted in 2014 among non-Hispanic whites and all Asian subgroups. Age-standardized hepatitis B virus-related mortality rates were higher in all Asian subgroups as compared to non-Hispanic whites in 2016, with the highest mortality among Vietnamese followed by Chinese. Mortality rates for alcoholic liver disease have been steadily trending upwards in all Asian subgroups, with the highest mortality in Japanese. Overall, age-standardized cirrhosis-related mortality rates were highest in non-Hispanic whites, followed by Japanese, and more distantly by Vietnamese and other subgroups. However, hepatocellular carcinoma-related mortality rates were higher in most Asian subgroups led by Vietnamese, Japanese and Koreans compared to non-Hispanic whites. In this population-based study utilizing a nationally representative database, we demonstrated a marked heterogeneity in the mortality rates of etiology-specific chronic liver disease among Asian subgroups in the US. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30112849

  • Continuous Positive Airway Pressure Therapy on Nonalcoholic Fatty Liver Disease in Patients With Obstructive Sleep Apnea. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine Kim, D., Ahmed, A., Kushida, C. 2018; 14 (8): 1315–22

    Abstract

    STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD) and related advanced fibrosis. We studied the treatment of OSA with continuous positive airway pressure (CPAP) in a population with NAFLD.METHODS: Using an institutional database (2010-2014), we identified patients with NAFLD and OSA and studied changes in serum aminotransferases before and after CPAP use. We defined suspected NAFLD (sNAFLD) as serum alanine aminotransferase (ALT) > 30 U/L for men and > 19 U/L for women in the absence of known causes of chronic liver disease. The aspartate aminotransferase (AST) to platelet ratio index (APRI) was used to determine significant fibrosis. Consistent CPAP use for more than 3 months with adequate adherence parameters defined good adherence.RESULTS: Of 351 patients with OSA on CPAP treatment, majority (mean age 57.6 years, 59.3% male) had abnormal ALT, and 89.4% met the criteria for sNAFLD. The prevalence of sNAFLD was higher among patients with moderate to severe OSA (90.6%) versus mild OSA (86.3%). There was a statistically significant improvement in AST, ALT, and APRI with CPAP therapy (all P < .01). There was an apparent dose-response relationship: patients with good adherence to CPAP showed a significantly larger decrease in AST and ALT than did those with poor adherence (P < .01). Multivariable logistic regression analysis showed CPAP treatment with adequate adherence (odds ratio = 3.93, 95% confidence interval = 1.29-11.94) was an independent predictor of regression of sNAFLD after adjusting for obesity class and severity of OSA.CONCLUSIONS: OSA treatment with CPAP was associated with significant biochemical improvement and reduction in NAFLD-related fibrosis.

    View details for PubMedID 30092894

  • Association between cagA negative Helicobacter pylori status and nonalcoholic fatty liver disease among adults in the United States PLOS ONE Kang, S., Kim, H., Kim, D., Ahmed, A. 2018; 13 (8): e0202325

    Abstract

    We investigated the relationship of H. pylori stratified by cytotoxin-associated gene A (cagA) status with nonalcoholic fatty liver disease (NAFLD) in the general population of the United States (US). We utilized the Third National Health and Nutrition Examination Survey from 1988 to 1994 in this study. NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other known causes of liver diseases and significant alcohol consumption. Hepatic steatosis was assessed by parenchymal brightness, liver to kidney contrast, deep beam attenuation, bright vessel walls and gallbladder wall definition. Antibodies to H. pylori and cagA of participants were measured using H. pylori IgG and anti-cagA IgG enzyme-linked immunosorbent assays. Among 5,404 participants, the prevalence of NAFLD was higher in H. pylori positive subjects (33.5±1.8%) compared to H. pylori negative subjects (26.1±1.7%, p <0.001). In terms of cagA protein status stratification, while cagA positive H. pylori group did not demonstrate an association with NAFLD (OR: 1.05; 95% CI: 0.81-1.37), cagA negative H. pylori group was noted to have a significant association with NAFLD in a multivariable analysis (OR: 1.30; 95% CI: 1.01-1.67). In conclusion, our study demonstrated that cagA negative H. pylori infection was an independent predictor of NAFLD in the US general population.

    View details for PubMedID 30110395

  • Expanding Donor Pool for Liver Transplantation by Utilizing Hepatitis C Virus-Infected Donors for Uninfected Recipients HEPATOLOGY Cholankeril, G., Gadiparthi, C., Kim, D., Ahmed, A. 2018; 68 (2): 792–93

    View details for DOI 10.1002/hep.30043

    View details for Web of Science ID 000441244400043

  • Changing Trends in Etiology- and Ethnicity-Based Annual Mortality Rates of Cirrhosis and Hepatocellular Carcinoma in the United States. Hepatology (Baltimore, Md.) Kim, D., Li, A. A., Perumpail, B. J., Gadiparthi, C., Kim, W., Cholankeril, G., Glenn, J. S., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2018

    Abstract

    With recent improvements in the treatment of end-stage liver disease (ESLD), a better understanding of the burden of cirrhosis and hepatocellular carcinoma (HCC) is needed in the United States (US). A population-based study using the US Census and national mortality database was performed. We identified the age-standardized etiology-specific mortality rates for cirrhosis and HCC among US adults aged ≥ 20 years from 2007 to 2016. We determined temporal mortality rate patterns by joinpoint analysis with estimates of annual percentage change (APC). Age-standardized cirrhosis-related mortality rates increased from 19.77/100,000 persons in 2007 to 23.67 in 2016 with an annual increase of 2.3% (95% CI 2.0-2.7). The APC in mortality rates for hepatitis C virus (HCV)-cirrhosis shifted from a 2.9% increase per year during 2007-2014 to a 6.5% decline per year during 2014-2016. Meanwhile, mortality for cirrhosis from alcoholic liver disease (ALD, APC 4.5%) and nonalcoholic fatty liver disease (NAFLD, APC 15.4%) increased over the same period, while mortality for hepatitis B virus (HBV)-cirrhosis decreased with an average APC of -1.1%. HCC-related mortality increased from 3.48/100,000 persons in 2007 to 4.41 in 2016 at an annual rate of 2.0% (95% CI 1.3-2.6). Etiology-specific mortality rates of HCC were largely consistent with cirrhosis-related mortality. Minority populations had a higher burden of HCC-related mortality.CONCLUSION: Cirrhosis- and HCC-related mortality rates increased between 2007 and 2016 in the US. However, mortality rates in HCV-cirrhosis demonstrated a significant decline from 2014-2016, during the direct-acting antiviral era. Mortality rates for ALD/NAFLD-cirrhosis and HCC have continued to increase, while HBV-cirrhosis-related mortality declined during the 10-year period. Importantly, minorities had a disproportionately higher burden of ESLD-related mortality. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30014489

  • Changing Trends in Etiology-based Annual Mortality From Chronic Liver Disease, From 2007 Through 2016. Gastroenterology Kim, D., Li, A. A., Gadiparthi, C., Khan, M. A., Cholankeril, G., Glenn, J. S., Ahmed, A. 2018

    Abstract

    BACKGROUND & AIMS: Although treatment of hepatitis C virus (HCV) infection has improved, the prevalence of alcoholic liver disease (ALD) has been increasing, so we need an updated estimate of the burden and etiology-specific mortality of chronic liver diseases. We studied the trends in age-standardized mortality of chronic liver diseases among adults 20 years or older in the United States (US), from 2007 through 2016.METHODS: We collected data from the US Census and National Center for Health Statistics mortality records, identifying individuals with HCV infection, ALD, nonalcoholic fatty liver disease (NAFLD), or hepatitis B virus (HBV) infection using ICD-10 codes. We obtained temporal mortality rate patterns using joinpoint trend analysis with estimates of annual percentage change (APC).RESULTS: Age-standardized HCV-related mortality increased from 7.17/100,000 persons in 2007 to 8.14/100,000 persons in 2013, followed by a marked decrease in the time period at which patients began receiving treatment with direct-acting antiviral agents (from 8.09/100,000 persons in 2014 to 7.15/100,000 persons in 2016). The APC in HCV mortality increased 2.0%/year from 2007 through 2014, but decreased 6.4%/year from 2014 through 2016. In contrast, age-standardized mortality increased for ALD (APC of 2.3% from 2007 through 2013 and APC of 5.5% from 2013 through 2016) and NAFLD (APC of 6.1% from 2007 through 2013 and APC of 11.3% from 2013 through 2016). HBV-related mortality decreased steadily from 2007 through 2016, with an average APC of -2.1% (95% CI, -3.0 to -1.2). Etiology-based mortality in minority populations were higher. HCV-related mortality (per 100,000 persons) was highest among non-Hispanic blacks (10.28) and whites (6.92), followed by Hispanics (5.94), and lowest among non-Hispanic Asians (2.33). Non-Hispanic Asians had higher mortality for HBV infection (2.82 per 100,000 vs 1.02 for non-Hispanic blacks, and 0.47 for non-Hispanic whites).CONCLUSION: In our population-based analysis of chronic liver disease mortality in the US, the decline in HCV-related mortality coincided with the introduction of direct-acting antiviral therapies, while the mortality from ALD and NAFLD increased during the same period. Minorities in the US have disproportionately higher chronic liver disease-related mortality.

    View details for PubMedID 30009816

  • Underutilization of Hepatitis C Virus Seropositive Donor Kidneys in the United States in the Current Opioid Epidemic and Direct-Acting Antiviral Era. Diseases (Basel, Switzerland) Li, A. A., Cholankeril, G., Cheng, X. S., Tan, J. C., Kim, D., Toll, A. E., Nair, S., Ahmed, A. 2018; 6 (3)

    Abstract

    In recent years, the opioid epidemic and new hepatitis C virus (HCV) treatments have changed the landscape of organ procurement and allocation. We studied national trends in solid organ transplantation (2000⁻2016), focusing on graft utilization from HCV seropositive deceased donors in the pre-2014 (2000⁻2013) versus current (2014⁻2016) eras with a retrospective analysis of the United Network for Organ Sharing database. During the study period, HCV seropositive donors increased from 181 to 661 donors/year. The rate of HCV seropositive donor transplants doubled from 2014 to 2016. Heart and lung transplantation data were too few to analyze. A higher number of HCV seropositive livers were transplanted into HCV seropositive recipients during the current era: 374 versus 124 liver transplants/year. Utilization rates for liver transplantation reached parity between HCV seropositive and non-HCV donors. While the number of HCV seropositive kidneys transplanted to HCV seropositive recipients increased from 165.4 to 334.7 kidneys/year from the pre-2014 era to the current era, utilization rates for kidneys remained lower in HCV seropositive than in non-HCV donors. In conclusion, relative underutilization of kidneys from HCV seropositive versus non-HCV donors has persisted, in contrast to trends in liver transplantation.

    View details for PubMedID 29996536

  • Increased Waitlist Mortality and Lower Rate for Liver Transplantation in Hispanic Patients With Primary Biliary Cholangitis CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Cholankeril, G., Gonzalez, H. C., Satapathy, S. K., Gonzalez, S. A., Hu, M., Khan, M., Yoo, E. R., Li, A. A., Kim, D., Nair, S., Wong, R. J., Kwo, P. Y., Harrison, S. A., Younossi, Z. M., Lindor, K. D., Ahmed, A. 2018; 16 (6): 965-+
  • Leukocyte Telomere Shortening Is Associated With Nonalcoholic Fatty Liver Disease-Related Advanced Fibrosis. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Li, A. A., Ahmed, A. 2018

    Abstract

    BACKGROUND AND AIM: Telomere length and telomerase has been linked with cirrhosis and hepatocellular carcinoma. However, the impact of telomere length on nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis is in a large national population sample is not well understood.METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 were utilized. Suspected NAFLD was diagnosed if serum alanine aminotransferase was > 30 IU/L for men and > 19 IU/L for women in the absence of other causes of chronic liver disease. Presence of advanced fibrosis was determined by the NAFLD fibrosis score, aspartate aminotransferase to platelet ratio index, and FIB-4 score.RESULTS: Of the 6,738 participants (mean age 46.3 years, 48.4% male), suspected NAFLD prevalence was inversely associated with leukocyte telomere length in young adults aged 20-39 years, though this was not seen in the overall population. Percentage of participants with advanced fibrosis increased corresponding with leukocyte telomere length (longest to shortest). The shortest quartile of leukocyte telomere length was associated with a significantly higher odds ratio (95% confidence interval) of advanced fibrosis of 2.36 (1.32-4.24) in a univariate model compared to the longest quartile, and 2.01 (1.13-3.58) in a multivariate model adjusted for age, gender, ethnicity, waist circumference, smoking, diabetes, hypertension, total cholesterol, and high-density lipoprotein cholesterol (P for trend < 0.05, respectively).CONCLUSIONS: In this large nationally-representative sample of American adults, leukocyte telomere shortening was associated with increased risk of advanced fibrosis in the setting of suspected NAFLD independent of other known risk factors. This article is protected by copyright. All rights reserved.

    View details for PubMedID 29797393

  • Case Report of Isoniazid-Related Acute Liver Failure Requiring Liver Transplantation. Diseases (Basel, Switzerland) Li, A. A., Dibba, P., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (2)

    Abstract

    The prevalence of latent tuberculosis infection (LTBI) in the United States in 2011 and 2012 was estimated at 4.4⁻4.8%. As of 2015, 12.4 million people still possessed LTBI. Isoniazid, or isonicotinic acid hydrazine (INH), is the most commonly used medication among varying regimens that exist in the treatment of tuberculosis and LTBI. INH-related hepatotoxicity is a well-known adverse effect of its use, often causing asymptomatic elevations in serum aminotransferase levels. These elevations are typically transient and reversible, but can cause acute, clinically-significant liver injury in rare cases. We report a case of a 67-year old male who developed subacute hepatic injury secondary to INH treatment for LTBI, and ultimately underwent liver transplantation due to the progression to hepatic decompensation, despite withdrawal of the medication. Because symptoms of INH hepatotoxicity are nonspecific and prognosis can be variable, clinicians must maintain a high index of suspicion for this adverse effect. As exemplified by this case, early recognition may be life-saving.

    View details for PubMedID 29783726

  • Nonalcoholic fatty liver disease and advanced fibrosis are associated with left ventricular diastolic dysfunction ATHEROSCLEROSIS Chung, G., Lee, J., Lee, H., Kim, M., Yim, J., Choi, S., Kim, Y., Yoon, J., Kim, D. 2018; 272: 137–44

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) may be associated with a wide spectrum of cardiac abnormalities, which share many metabolic risk factors. This study aimed to evaluate whether NAFLD is associated with left ventricular (LV) diastolic dysfunction independent of other classical risk factors.A total of 3300 subjects (mean age, 54.1 years; 62.9% men), who underwent echocardiography and hepatic ultrasonography, were enrolled. LV diastolic dysfunction was diagnosed and graded using conventional and Doppler echocardiographic assessments. NAFLD was diagnosed by ultrasonographic findings without any evidence of significant alcohol consumption or viral hepatitis, other liver diseases, or medication provoking fatty liver. Advanced fibrosis was defined as having intermediate-high probability for advanced fibrosis using the NAFLD fibrosis score.The prevalence of LV diastolic dysfunction was 35.1%. NAFLD had a higher prevalence and severity of LV diastolic dysfunction. The prevalence rates of LV diastolic dysfunction were significantly increased according to the NAFLD fibrosis grade (30.4% for no-NAFLD, 35.2% for NAFLD without advanced fibrosis and 57.4% for NAFLD with advanced fibrosis, p < 0.001). Multivariable analysis showed that NAFLD was associated with a 29% increase in the risk of diastolic dysfunction compared with controls (odds ratio [OR] 1.29; 95% confidence interval [CI] 1.07-1.60). There was significant interaction between obesity (BMI < 25 kg/m2vs. ≥ 25 kg/m2) and advanced fibrosis for LV diastolic dysfunction. A significant, incrementally increased risk of diastolic dysfunction according to the fibrosis grade was more pronounced in the non-obese population [adjusted OR (95% CI), 1.40 (1.06-1.84) for NAFLD without advanced fibrosis, 1.44 (0.95-2.17) for NAFLD with advanced fibrosis vs. no NAFLD, P for trend = 0.022] compared with the obese population (p for trend = 0.081), independent of other well-defined risk factors.NAFLD was associated with increased risk for LV diastolic dysfunction. In addition, an incrementally increased risk for LV diastolic dysfunction according to fibrosis grade was prominent in the non-obese population.

    View details for PubMedID 29604480

  • Expanding Donor Pool for Liver Transplantation by Utilizing Hepatitis C Virus-Infected Donors for Uninfected Recipients. Hepatology (Baltimore, Md.) Cholankeril, G., Gadiparthi, C., Kim, D., Ahmed, A. 2018

    View details for PubMedID 29672899

  • Increased Waitlist Mortality and Lower Rate for Liver Transplantation in Hispanic Patients With Primary Biliary Cholangitis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Cholankeril, G., Gonzalez, H. C., Satapathy, S., Gonzalez, S. A., Hu, M., Khan, M. A., Yoo, E. R., Li, A. A., Kim, D., Nair, S., Wong, R. J., Kwo, P. Y., Harrison, S. A., Younossi, Z. M., Lindor, K. D., Ahmed, A. 2018

    Abstract

    BACKGROUND & AIMS: Data on the differences in ethnicity and race among patients with primary biliary cholangitis (PBC) awaiting liver transplantation (LT) are limited. We evaluated liver transplant waitlist trends and outcomes based on ethnicity and race in patients with PBC in the United States.METHODS: Using the United Network for Organ Sharing (UNOS) registry, we collected data on patients with PBC on the liver transplant waitlist, and performed analysis with a focus on ethnicity and race-based variations clinical manifestations, waitlist mortality and LT rates from 2000 to 2014. Outcomes were adjusted for demographics, complications of portal hypertension, and Model for End-stage Liver Disease score at time of waitlist registration.RESULTS: Although the number of white PBC waitlist registrants and additions decreased from 2000 to 2014, there were no significant changes in the number of Hispanic PBC waitlist registrants and additions each year. The proportion of Hispanic patients with PBC on the liver transplant waitlist increased from 10.7% in 2000 to 19.3% in 2014. Hispanics had the highest percentage of waitlist deaths (20.8%) of any ethnicity or race evaluated. After adjusting for demographic and clinical characteristics, Hispanic patients with PBC had the lowest overall rate for undergoing LT (adjusted hazard ratio, 0.71; 95% CI, 0. 60-0.83; P < .001) and a significantly higher risk of death while on the waitlist, compared to whites (adjusted hazard ratio, 1.41; 95% CI, 1.15-1.74; P < .001). Furthermore, Hispanic patients with PBC had the highest proportion of waitlist removals due to clinical deterioration.CONCLUSIONS: In an analysis of data from UNOS registry focusing on outcomes, we observed differences in rates of LT and liver transplant waitlist mortality of Hispanic patients compared with white patients with PBC. Further studies are needed to improve our understanding of ethnicity and race-based differences in progression of PBC.

    View details for PubMedID 29427734

  • Steatosis severity affects the diagnostic performances of noninvasive fibrosis tests in nonalcoholic fatty liver disease LIVER INTERNATIONAL Joo, S., Kim, W., Kim, D., Kim, J., Oh, S., Lee, K., Chang, M., Jung, Y., So, Y., Lee, M., Bae, J., Kim, B. 2018; 38 (2): 331–41

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of heterogeneous metabolic subtypes. This study compared the diagnostic performances of noninvasive fibrosis tests in predicting advanced fibrosis among patients with NAFLD and examined the effects of the subgroups on their diagnostic performances.Three hundred fifteen patients with biopsy-proven NAFLD were prospectively enrolled. Acoustic radiation force impulse imaging (ARFI) was performed to obtain liver stiffness measurements (LSMs). The aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis 4 index (FIB-4), NAFLD fibrosis score (NFS) and BARD score were calculated. The diagnostic performances of noninvasive fibrosis tests were evaluated using the area under the receiver operating characteristic curve (AUROC).Fibrosis 4 index (FIB-4) showed the highest AUROC for advanced fibrosis (0.866; 95% CI, 0.811-0.922). AUROC subgroup analyses were performed to assess the effects of the subgroups on diagnostic performance. For patients with advanced fibrosis, the APRI, BARD, FIB-4 and NFS AUROCs were significantly different among the radiological steatosis grades. Additionally, the AUROC of ARFI tended to decrease with increasing radiological steatosis severity. FIB-4 and NFS showed significantly lower AUROCs for advanced fibrosis in obese NAFLD than in nonobese NAFLD (P = .002 and P < .001 respectively). However, only radiological steatosis severity was independently associated with advanced fibrosis in multivariable analysis.Steatosis severity may affect the diagnostic performances of noninvasive fibrosis tests in patients with NAFLD. The application of different tools should be tailored for various NAFLD subgroups to optimize noninvasive fibrosis assessments.

    View details for PubMedID 28796410

  • The Role of Cannabinoids in the Setting of Cirrhosis. Medicines (Basel, Switzerland) Dibba, P. n., Li, A. A., Cholankeril, G. n., Iqbal, U. n., Gadiparthi, C. n., Khan, M. A., Kim, D. n., Ahmed, A. n. 2018; 5 (2)

    Abstract

    Although the mortality rates of cirrhosis are underestimated, its socioeconomic burden has demonstrated a significant global impact. Cirrhosis is defined by the disruption of normal liver architecture after years of chronic insult by different etiologies. Treatment modalities are recommended primarily in decompensated cirrhosis and specifically tailored to the different manifestations of hepatic decompensation. Antifibrogenic therapies are within an active area of investigation. The endocannabinoid system has been shown to play a role in liver disease, and cirrhosis specifically, with intriguing possible therapeutic benefits. The endocannabinoid system comprises cannabinoid receptors 1 (CB1) and cannabinoid receptor 2 (CB2) and their ligands, endocannabinoids and exocannabinoids. CB1 activation enhances fibrogenesis, whereas CB2 activation counteracts progression to fibrosis. Conversely, deletion of CB1 is associated with an improvement of hepatic fibrosis and steatosis, and deletion of CB2 results in increased collagen deposition, steatosis, and enhanced inflammation. CB1 antagonism has also demonstrated vascular effects in patients with cirrhosis, causing an increase in arterial pressure and vascular resistance as well as a decrease in mesenteric blood flow and portal pressure, thereby preventing ascites. In mice with hepatic encephalopathy, CB1 blockade and activation of CB2 demonstrated improved neurologic score and cognitive function. Endocannabinoids, themselves also have mechanistic roles in cirrhosis. Arachidonoyl ethanolamide (AEA) exhibits antifibrogenic properties by inhibition of HSC proliferation and induction of necrotic death. AEA induces mesenteric vasodilation and hypotension via CB1 induction. 2-arachidonoyl glycerol (2-AG) is a fibrogenic mediator independent of CB receptors, but in higher doses induces apoptosis of HSCs, which may actually show antifibrotic properties. 2-AG has also demonstrated growth-inhibitory and cytotoxic effects. The exocannabinoid, THC, suppresses proliferation of hepatic myofibroblasts and stellate cells and induces apoptosis, which may reveal antifibrotic and hepatoprotective mechanisms. Thus, several components of the endocannabinoid system have therapeutic potential in cirrhosis.

    View details for PubMedID 29890719

  • Noninvasive Response Prediction in Prophylactic Carvedilol Therapy for Cirrhotic Patients with Esophageal Varices. Journal of hepatology Kim, H. Y., So, Y. H., Kim, W. n., Ahn, D. W., Jin Jung, Y. n., Woo, H. n., Kim, D. n., Kim, M. Y., Baik, S. K. 2018

    Abstract

    Nonselective beta-blockers (NSBBs) are the mainstay of primary prophylaxis of esophageal variceal bleeding in patients with liver cirrhosis. We investigated whether noninvasive markers of portal hypertension correlate with hemodynamic responses to NSBBs in cirrhotic patients with esophageal varices.In this prospective cohort study, 106 cirrhotic patients with high-risk esophageal varices in the derivation cohort received carvedilol prophylaxis, and completed paired measurements of hepatic venous pressure gradient (HVPG), liver stiffness (LS), and spleen stiffness (SS) at the beginning and end of dose titration. LS and SS were measured using acoustic radiation force impulse imaging. A prediction model for hemodynamic response was derived, and subject to an external validation in the validation cohort (63 patients).Hemodynamic response occurred in 59 patients (55.7%) in the derivation cohort, and in 33 patients (52.4%) in the validation cohort, respectively. Multivariate logistic regression analysis identified that ΔSS was the only significant predictor of hemodynamic response (odds ratio, 0.039; 95% confidence interval, 0.008-0.135; P<.0001). The response prediction model (ModelΔSS=0.0490-2.8345×ΔSS; score=(exp[ModelΔSS])/(1+exp[ModelΔSS]) showed good predictive performance (area under the receiver-operating characteristic curve [AUC]=0.803) using 0.530 as the threshold value. The predictive performance of the ModelΔSS in the validation set improved using the same threshold value (AUC=0.848).This new model including dynamic changes in SS exhibited good performance in predicting hemodynamic response to NSBBs as primary prophylaxis of esophageal variceal hemorrhage.This prospective study showed that a prediction model based on changes in spleen stiffness before vs. after dose titration might be a noninvasive marker for hemodynamic response to prophylactic carvedilol therapy in patients with cirrhosis and high-risk esophageal varices.

    View details for PubMedID 30389550

  • Judicious Use of Lipid Lowering Agents in the Management of NAFLD. Diseases (Basel, Switzerland) Iqbal, U. n., Perumpail, B. J., John, N. n., Sallam, S. n., Shah, N. D., Kwong, W. n., Cholankeril, G. n., Kim, D. n., Ahmed, A. n. 2018; 6 (4)

    Abstract

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world. NAFLD encompasses a spectrum of histological features, including steatosis, steatohepatitis with balloon degeneration, and hepatic fibrosis leading to cirrhosis. In patients with advanced liver damage, NAFLD is associated with an increased risk of hepatocellular carcinoma. Diabetes mellitus, hypertension, and dyslipidemia are components of metabolic syndrome and are commonly associated with NAFLD. Cardiovascular disease is the leading cause of mortality in patients with NAFLD. Therefore, it is important to pre-emptively identify and proactively treat conditions like hyperlipidemia in an effort to favorably modify the risk factors associated with cardiovascular events in patients with NAFLD. The management of hyperlipidemia has been shown to reduce cardiovascular mortality and improve histological damage/biochemical abnormalities associated with non-alcoholic steatohepatitis (NASH), a subset of NAFLD with advance liver damage. There are no formal guidelines available regarding the use of anti-hyperlipidemic drugs, as prospective data are lacking. The focus of this article is to discuss the utility of lipid-lowering drugs in patients with NAFLD.

    View details for PubMedID 30249980

  • A Comparison Between Community and Academic Practices in the USA in the Management of Chronic Hepatitis B Patients Receiving Entecavir: Results of the ENUMERATE Study. Digestive diseases and sciences Lee, H. M., Ahn, J. n., Kim, W. R., Lim, J. K., Nguyen, M. n., Pan, C. Q., Kim, D. n., Mannalithara, A. n., Te, H. n., Trinh, H. n., Chu, D. n., Tran, T. n., Woog, J. n., Lok, A. S. 2018

    Abstract

    The management of chronic hepatitis B patients is not well characterized in real-world practice. We compared baseline characteristics of CHB patients on entecavir, the frequency of on-treatment monitoring, and the effectiveness of ETV treatment between academic and community practices.Treatment-naïve CHB patients ≥18 years old, treated with ETV for ≥12 months from 2005 to 2013, in 26 community and academic practices throughout the USA were retrospectively evaluated.Of 841 patients enrolled, 658 (65% male, 83% Asian, median age 47, 9% with cirrhosis) met inclusion criteria. Half of the patients (52%) were from community practices. A lower percentage of patients in community practices had cirrhosis or liver cancer (5 vs. 14%). Community practices more often treated patients with baseline ALT < 2 × ULN. Over a median follow-up of 4 years, community practices were more likely to discontinue ETV with less frequent laboratory monitoring compared to academic practices. The 5-year cumulative probability of ALT normalization was greater among patients treated in community practices (70 vs. 50%, p < 0.001), but the 5-year cumulative probability of undetectable HBV DNA was lower (45 vs. 70%, p < 0.001) than those treated in academic practices.Academic practices saw CHB patients with more advanced liver disease, more often followed AASLD guidelines, and monitored patients on ETV treatment more frequently than community practices. While patients in community practices were less likely to achieve undetectable HBV DNA and more likely to achieve ALT normalization, the rates of HBeAg loss and seroconversion as well as HBsAg loss were similar.

    View details for PubMedID 30238203

  • Effect of longitudinal changes of body fat on the incidence and regression of nonalcoholic fatty liver disease. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver Kim, D. n., Chung, G. E., Kwak, M. S., Kim, Y. J., Yoon, J. H. 2018; 50 (4): 389–95

    Abstract

    To investigate the longitudinal association between changes in body fat amount and the incidence and regression of nonalcoholic fatty liver disease (NAFLD).We performed a cohort study of 2017 subjects without liver disease or significant alcohol consumption from 2007 to 2008 and participated in a voluntary follow-up between 2011 and 2013. Of the 2017 subjects, we enrolled 956 (47.4%) subjects who had available abdominal fat data in both 2007-2008 and 2011-2013. NAFLD was diagnosed on the basis of ultrasonographic findings. Adipose tissue area was evaluated by computed tomography.We observed 145 incident cases of NAFLD (22.6% of 642), and 79 subjects experienced a regression of NAFLD (25.2% of 314) during a median of 4.64 years. An increasing change in visceral adipose tissue (VAT) area was associated with a higher incidence of NAFLD (highest tertile vs. lowest tertile of VAT hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.56-3.85, P for trend <0.001) in the multivariable analysis. An increasing change in VAT area was inversely associated with the regression of NAFLD (highest tertile vs. lowest tertile of VAT HR 0.40, 95% CI 0.20-0.80, P for trend = 0.008).An increasing change in VAT area was longitudinally associated with a higher risk of incident NAFLD and inversely associated with the regression of NAFLD.

    View details for PubMedID 29373238

  • Serum testosterone and non-alcoholic fatty liver disease in men and women in the US. Liver international : official journal of the International Association for the Study of the Liver Yim, J. Y., Kim, J. n., Kim, D. n., Ahmed, A. n. 2018

    Abstract

    Testosterone plays a role in predisposing individuals to cardiovascular and metabolic diseases, but its effects differ between men and women. We investigated the association between serum total testosterone and non-alcoholic fatty liver disease in adults in the US.A cross-sectional analysis of data from participants in the 2011-2012 National Health and Nutrition Examination Survey was performed. Subjects with significant alcohol consumption and those with viral hepatitis were excluded. We used the highest sex-specific quartiles of serum total testosterone as references. Suspected non-alcoholic fatty liver disease was diagnosed when serum alanine aminotransferase was >30 IU/L for men and >19 IU/L for women.Of the 4758 subjects (49.4% men), the prevalence of suspected non-alcoholic fatty liver disease was inversely correlated with the sex-specific quartiles of testosterone in men and women. In a multivariate model, low total testosterone levels were associated with progressively higher odds of suspected non-alcoholic fatty liver disease in men after adjusting for age, obesity and other metabolic risk factors (P values for trends <.01). When the women were divided into 2 groups according to menopausal status, a significant correlation was observed only in the post-menopausal women (P values for trends <.01). The adjusted odds ratios for suspected non-alcoholic fatty liver disease were 1.72-1.99 in men and 2.15-2.26 in post-menopausal women (lowest quartile vs highest quartile).In this nationally representative sample of adults in the US, low total testosterone levels were associated with suspected non-alcoholic fatty liver disease in men and post-menopausal women independent of known risk factors.

    View details for PubMedID 29517842

  • Nonalcoholic Fatty Liver Disease and Metabolic Syndrome Clinics in Liver Disease Kim, D., Touros, A., Kim, W. 2018; 22 (1): 133-140

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are highly prevalent, affecting approximately one-third of the US population. The relationship between NAFLD and MS is complex and may be bidirectionally associated. NAFLD is strongly associated with MS, the components of which include abdominal obesity, hyperglycemia, hypertension, and dyslipidemia. NAFLD associated with certain genetic factors such as the PNPLA3 G allele variant is not accompanied by insulin resistance and MS. Lifestyle modification, including diet and physical activity targeting visceral adiposity, remains the standard of care for patients with NAFLD and MS.

    View details for DOI 10.1016/j.cld.2017.08.010

  • Continuous Positive Airway Pressure Therapy on Nonalcoholic Fatty Liver Disease in Patients With Obstructive Sleep Apnea JOURNAL OF CLINICAL SLEEP MEDICINE Kim, D., Ahmed, A., Kushida, C. 2018; 14 (8): 1315–22

    View details for DOI 10.5664/jcsm.7262

    View details for Web of Science ID 000458332400005

  • Potential Therapeutic Benefits of Herbs and Supplements in Patients with NAFLD. Diseases (Basel, Switzerland) Perumpail, B. J., Li, A. A., Iqbal, U. n., Sallam, S. n., Shah, N. D., Kwong, W. n., Cholankeril, G. n., Kim, D. n., Ahmed, A. n. 2018; 6 (3)

    Abstract

    Our aim is to review the efficacy of various herbs and supplements as a possible therapeutic option in the treatment and/or prevention of nonalcoholic fatty liver disease (NAFLD). We performed a systematic review of medical literature using the PubMed Database by searching the chemical names of many common herbs and supplements with "AND (NAFLD or NASH)". Studies and medical literature that discussed the roles and usage of herbs and supplements in NAFLD and nonalcoholic steatohepatitis (NASH) from inception until 20 June 2018 were reviewed. Many studies have claimed that the use of various herbs and supplements may improve disease endpoints and outcomes related to NAFLD and/or NASH. Improvement in liver function tests were noted. Amelioration or reduction of lobular inflammation, hepatic steatosis, and fibrosis were also noted. However, well-designed studies demonstrating improved clinical outcomes are lacking. Furthermore, experts remain concerned about the lack of regulation of herbs/supplements and the need for further research on potential adverse effects and herb⁻drug interactions. In conclusion, preliminary data on several herbs have demonstrated promising antioxidant, anti-inflammatory, anti-apoptotic, and anti-adipogenic properties that may help curtail the progression of NAFLD/NASH. Clinical trials testing the safety and efficacy must be completed before widespread can be recommended.

    View details for PubMedID 30201879

  • Marijuana is not associated with progression of hepatic fibrosis in liver disease: a systematic review and meta-analysis. European journal of gastroenterology & hepatology Farooqui, M. T., Khan, M. A., Cholankeril, G. n., Khan, Z. n., Mohammed Abdul, M. K., Li, A. A., Shah, N. n., Wu, L. n., Haq, K. n., Solanki, S. n., Kim, D. n., Ahmed, A. n. 2018

    Abstract

    An estimated 22 million adults use marijuana in the USA. The role of marijuana in the progression of hepatic fibrosis remains unclear.We carried out a systematic review and meta-analysis to evaluate the impact of marijuana on prevalence and progression of hepatic fibrosis in chronic liver disease.We searched several databases from inception through 10 November 2017 to identify studies evaluating the role of marijuana in chronic liver disease. Our main outcome of interest was prevalence/progression of hepatic fibrosis. Adjusted odds ratios (ORs) and hazards ratios (HRs) were pooled and analyzed using random-effects model.Nine studies with 5 976 026 patients were included in this meta-analysis. Prevalence of hepatic fibrosis was evaluated in nonalcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis C and HIV coinfection by two, four, and one studies. Progression of hepatic fibrosis was evaluated by two studies. Pooled OR for prevalence of fibrosis was 0.91 (0.72-1.15), I=75%. On subgroup analysis, pooled OR among NAFLD patients was 0.80 (0.75-0.86), I=0% and pooled OR among HCV patients was 1.96 (0.78-4.92), I=77%. Among studies evaluating HR, pooled HR for progression of fibrosis in HCV-HIV co-infected patients was 1.03 (0.96-1.11), I=0%.Marijuana use did not increase the prevalence or progression of hepatic fibrosis in HCV and HCV-HIV-coinfected patients. On the contrary, we noted a reduction in the prevalence of NAFLD in marijuana users. Future studies are needed to further understand the therapeutic impact of cannabidiol-based formulations in the management of NAFLD.

    View details for PubMedID 30234644

  • Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD. Diseases (Basel, Switzerland) Dibba, P. n., Li, A. A., Perumpail, B. J., John, N. n., Sallam, S. n., Shah, N. D., Kwong, W. n., Cholankeril, G. n., Kim, D. n., Ahmed, A. n. 2018; 6 (3)

    Abstract

    The two main subsets of nonalcoholic fatty liver disease (NAFLD) include: (1) nonalcoholic fatty liver (NAFL), the more common and non-progressive subtype; and (2) nonalcoholic steatohepatitis (NASH), the less common subtype, which has the potential to progress to advanced liver damage. Current treatment strategies have focused on lifestyle management of modifiable risk factors, namely weight, and on the optimization of the management of individual components of metabolic syndrome. Various hypothetical pathogenic mechanisms have been proposed, leading to the development of novel drugs with the potential to effectively treat patients with NASH. Numerous clinical trials are ongoing, utilizing these experimental drugs and molecules targeting specific mechanistic pathway(s) to effectively treat NASH. Some of these mechanistic pathways targeted by experimental pharmacologic agents include chemokine receptor 2 and 5 antagonism, inhibition of galectin-3 protein, antagonism of toll-like receptor 4, variation of fibroblast growth factor 19, agonism of selective thyroid hormone receptor-beta, inhibition of apoptosis signal-regulating kinase 1, inhibition of acetyl-coenzyme A carboxylase, agonism of farnesoid X receptor, antibodies against lysl oxidase-like-2, and inhibition of inflammasomes. Emerging data are promising and further updates from ongoing clinical trials are eagerly awaited.

    View details for PubMedID 30235807

  • Mechanistic Potential and Therapeutic Implications of Cannabinoids in Nonalcoholic Fatty Liver Disease. Medicines (Basel, Switzerland) Dibba, P. n., Li, A. n., Cholankeril, G. n., Iqbal, U. n., Gadiparthi, C. n., Khan, M. A., Kim, D. n., Ahmed, A. n. 2018; 5 (2)

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is comprised of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). It is defined by histologic or radiographic evidence of steatosis in the absence of alternative etiologies, including significant alcohol consumption, steatogenic medication use, or hereditary disorders. NAFLD is now the most common liver disease, and when NASH is present it can progress to fibrosis and hepatocellular carcinoma. Different mechanisms have been identified as contributors to the physiology of NAFLD; insulin resistance and related metabolic derangements have been the hallmark of physiology associated with NAFLD. The mainstay of treatment has classically involved lifestyle modifications focused on the reduction of insulin resistance. However, emerging evidence suggests that the endocannabinoid system and its associated cannabinoid receptors and ligands have mechanistic and therapeutic implications in metabolic derangements and specifically in NAFLD. Cannabinoid receptor 1 antagonism has demonstrated promising effects with increased resistance to hepatic steatosis, reversal of hepatic steatosis, and improvements in glycemic control, insulin resistance, and dyslipidemia. Literature regarding the role of cannabinoid receptor 2 in NAFLD is controversial. Exocannabinoids and endocannabinoids have demonstrated some therapeutic impact on metabolic derangements associated with NAFLD, although literature regarding direct therapeutic use in NAFLD is limited. Nonetheless, the properties of the endocannabinoid system, its receptors, substrates, and ligands remain a significant arena warranting further research, with potential for a pharmacologic intervention for a disease with an anticipated increase in economic and clinical burden.

    View details for PubMedID 29843404

  • Inverse association of marijuana use with nonalcoholic fatty liver disease among adults in the United States PLOS ONE Kim, D., Kim, W., Kwak, M., Chung, G., Yim, J., Ahmed, A. 2017; 12 (10): e0186702

    Abstract

    The impact of marijuana on nonalcoholic fatty liver disease (NAFLD) is largely unknown. We studied the association between marijuana and NAFLD utilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2005-2014 and NHANES III (1988-1994).Suspected NAFLD was diagnosed if serum alanine aminotransferase (ALT) was > 30 IU/L for men and > 19 IU/L for women in the absence of other liver diseases (NHANES 2005-2014). In NHANES III cohort, NAFLD was defined based on ultrasonography.Of the 14,080 (NHANES 2005-2014) and 8,286 (NHANES III) participants, prevalence of suspected NAFLD and ultrasonographically-diagnosed NAFLD were inversely associated with marijuana use (p < 0.001). Compared to marijuana-naïve participants, marijuana users were less likely to have suspected NAFLD (odds ratio [OR]: 0.90, 95% confidence interval [CI]: 0.82-0.99 for past user; OR: 0.68, 95% CI: 0.58-0.80 for current user) and ultrasonographically-diagnosed NAFLD (OR: 0.75, 95% CI: 0.57-0.98 for current user) in the age, gender, ethnicity-adjusted model. On multivariate analysis, the ORs for suspected NAFLD comparing current light or heavy users to non-users were 0.76 (95% CI 0.58-0.98) and 0.70 (95% CI 0.56-0.89), respectively (P for trend = 0.001) with similar trends in ultrasonographically-diagnosed NAFLD (OR: 0.77, 95% CI: 0.59-1.00 for current user; OR: 0.71, 95% CI: 0.51-0.97 for current light user). In insulin resistance-adjusted model, marijuana use remained an independent predictor of lower risk of suspected NAFLD.In this nationally representative sample, active marijuana use provided a protective effect against NAFLD independent of known metabolic risk factors. The pathophysiology is unclear and warrants further investigation.

    View details for PubMedID 29049354

  • Alcohol Liver Disease is now the most rapidly rising Indication for Liver Transplant Waitlist Registration in the United States Rahim, U., Cholankeril, G., Yoo, E. R., Liu, A., Li, A. A., Kim, D., Kwo, P. Y., Ahmed, A., Goel, A. WILEY. 2017: 708A
  • Non-obese fatty liver disease is independently associated with lacunar infarct Kwak, M., Chung, G., Yim, J., Kim, D. WILEY. 2017: 1163A
  • Rapidly Rising Burden of Portopulmonary Hypertension in the United States Rahim, U., Mannalithara, A., Kim, D., Zamanian, R., Kim, W. WILEY. 2017: 253A–254A
  • Hepatocellular Carcinoma results in Highest Number of Malignancy-related Hospitalizations in Baby Boomers Gadiparthi, C., Yoo, E. R., Liu, A., Hu, M., Kim, D., Cholankeril, G., Howden, C. W., Ahmed, A. WILEY. 2017: 774A
  • Demographics and Clinical Characteristics of Hepatitis C Virus-Positive Donors and Recipients Li, A. A., Yoo, E. R., Sandhu, K., Perumpail, R. B., Cholankeril, G., Kim, D., Ahmed, A. WILEY. 2017: 894A–895A
  • National Drug Overdose Epidemic is a Significant Contributor to Deceased Donor Liver Organ Pool Cholankeril, G., Li, A. A., Cholankeril, R., Sandhu, J., Kim, D., Ahmed, A. WILEY. 2017: 397A
  • Need to Improve Organs Transplanted Per Donor Despite the Rising Utilization of Hepatitis C Virus-Positive Donors in the United States Li, A. A., Rahim, U., Yoo, E. R., Cholankeril, G., Kim, D., Ahmed, A. WILEY. 2017: 887A
  • Nonalcoholic Steatohepatitis Remains the Fastest Growing Indication for Liver Transplantation in Patients with Hepatocellular Carcinoma in the United States Li, A. A., Yoo, E. R., Cholankeril, G., Kim, D., Puri, P., Harrison, S. A., Younossi, Z. M., Ahmed, A. WILEY. 2017: 749A
  • Optimal Timing for Hepatitis C Antiviral Therapy in the Peri-Transplant Period? Hepatology (Baltimore, Md.) Cholankeril, G., Wong, R. J., Kim, D., Ahmed, A. 2017

    View details for DOI 10.1002/hep.29300

    View details for PubMedID 28586088

  • Racial/ethnic disparities in the prevalence and awareness of Hepatitis B virus infection and immunity in the United States. Journal of viral hepatitis Kim, H., Rotundo, L., Yang, J. D., Kim, D., Kothari, N., Feurdean, M., Ruhl, C., Unalp-Arida, A. 2017

    Abstract

    Hepatitis B virus (HBV) infection in the United States is the most common among Asians followed by non-Hispanic blacks. However, there have been few studies that describe HBV infection and immunity by racial group. Our study aimed to assess racial/ethnic disparities in the prevalence and awareness of HBV infection and immunity using nationally representative data. In the National Health and Nutrition Examination Survey 2011-2014, 14 722 persons had HBV serology testing. We estimated the prevalence of HBV infection, past exposure, and immunity by selected characteristics and calculated adjusted odds ratios using survey-weighted generalized logistic regression. Awareness of infection and vaccination history was also investigated. The overall prevalence of chronic HBV infection, past exposure and vaccine-induced immunity was 0.34% [95%CI 0.24-0.43], 4.30% [95%CI 3.80-4.81], and 24.4% [95%CI 23.4-25.4], respectively. The prevalence of chronic infection was 2.74% [95% CI 1.72-3.76] in Asians, 0.64% [95% CI 0.35-0.92] in non-Hispanic blacks, and 0.15% [95% CI 0.06-0.24] in non-Asian, non-blacks. Only 26.2% of those with chronic infection were aware of their infection. The prevalence of the past exposure was 21.5% [95%CI 19.3-23.7] in Asians, 8.92% [95%CI 7.84-9.99] in non-Hispanic blacks, 2.05% [95%CI 1.49-2.63] in non-Hispanic whites and 4.47% [95%CI 3.25-5.70] in Hispanics. Prevalence of vaccine-induced immunity by each race was 34.1% [95%CI: 32.0-36.2] in Asians, 25.5% [95%CI: 24.0-27.0] in non-Hispanic blacks, 24.0% [95%CI: 22.6-25.4] in non-Hispanic whites and 22.2% [95%CI: 21.3-23.3] in Hispanics. There are considerable racial/ethnic disparities in HBV infection, exposure and immunity. More active and sophisticated healthcare policies on HBV management may be warranted.

    View details for DOI 10.1111/jvh.12735

    View details for PubMedID 28581638

  • PERSPECTIVES IN CLINICAL GASTROENTEROLOGY AND HEPATOLOGY CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Kim, D., Kim, W. R. 2017; 15 (4): 474-485

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) refers to a group of conditions characterized by hepatic steatosis in the absence of significant alcohol consumption. NAFLD is seen commonly in patients with metabolic abnormalities associated with obesity, such as type II diabetes, dyslipidemia, and metabolic syndrome. Evidently, however, not all obese subjects develop NAFLD and, more importantly, NAFLD can be found in nonobese individuals. Although NAFLD occurring in nonobese subjects has been reported in children and adults of all ethnicities, it appears to be recognized more frequently in Asians, even when strict ethnicity-specific body mass index criteria are used to define obesity. Studies based on liver biopsies suggest that the prevalence of nonalcoholic steatohepatitis and fibrosis does not differ significantly between nonobese NAFLD and NAFLD in obese patients. Visceral obesity as opposed to general obesity, high fructose and cholesterol intake, and genetic risk factors (eg, palatin-like phospholipase domain-containing 3) may be associated with nonobese NAFLD. In general, nonalcoholic steatohepatitis is associated with increased mortality, primarily from cardiovascular causes, independent of other metabolic factors. Although data regarding the mortality impact of nonobese NAFLD are not as mature, it may be important to identify high-risk nonobese NAFLD patients and manage their metabolic profile. Currently, lifestyle modification to reduce visceral adiposity, including dietary changes and physical activity, remains the standard of care in patients with nonobese NAFLD.

    View details for DOI 10.1016/j.cgh.2016.08.028

    View details for Web of Science ID 000397247000008

  • Impact of direct-acting antiviral agents-induced SVR on the long-term burden of hepatocellular carcinoma in chronic hepatitis C cirrhosis. Udompap, P., Mannalithara, A., Kim, D., Kim, W. AMER SOC CLINICAL ONCOLOGY. 2017
  • Visceral obesity is associated with white matter hyperintensity and lacunar infarct. International journal of obesity (2005) Kim, K. W., Seo, H., Kwak, M. S., Kim, D. 2017

    Abstract

    The presences of white matter hyperintensity (WMH) and lacunar infarct are recognized as risk factors of dementia, stroke, and mortality. It is undetermined whether visceral adipose tissue (VAT) area is associated with an increased risk of cerebral small vessel disease. We explored whether VAT area was responsible for cerebral small vessel disease through the identification of WMH and lacunar infarct.A total of 2046 subjects free of cerebrovascular disease who underwent brain magnetic resonance imaging (MRI) and abdominal fat computed tomography (CT) during a general health check-up were enrolled.The prevalence of cerebral WMH was 37.7%. Subjects with WMH had greater VAT area and higher BMI and waist circumference than those without WMH, although significant differences in subcutaneous adipose tissue (SAT) area were not shown. Subjects with lacunar infarct also had significantly greater VAT area and higher waist circumference and BMI than those without. Multivariate analyses adjusted for age, sex, diabetes, hypertension, smoking, and alcohol, showed VAT area was an independent risk factor of cerebral WMH (OR 1.13, 95% CI 1.02-1.24, P=0.016), whereas waist circumference and SAT area were not significantly associated with the risk of WMH. Likewise, VAT area was also independently associated with lacunar infarct (OR 1.38, 95% CI 1.06-1.81, P=0.018), whereas the other anthropometric measures were not related with lacunar infarct.VAT has a significant association with cerebral small vessel disease, which was defined as WMH or lacunar infarct. Visceral obesity can be a potential therapeutic target for the prevention of cerebral small vessel disease.International Journal of Obesity accepted article preview online, 20 January 2017. doi:10.1038/ijo.2017.13.

    View details for DOI 10.1038/ijo.2017.13

    View details for PubMedID 28104915

  • Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis JOURNAL OF HEPATOLOGY Koo, B. K., Kim, D., Joo, S. K., Kim, J. H., Chang, M. S., Kim, B. G., Lee, K. L., Kim, W. 2017; 66 (1): 123-131

    Abstract

    We explored whether sarcopenia is associated with the histological severity of non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) and significant fibrosis.In a biopsy-proven NAFLD cohort, the appendicular skeletal muscle mass (ASM) was measured. Sarcopenia was defined as a ASM/body weight (ASM%) value beyond two standard deviations below the mean for healthy young adults.Among the entire set of 309 subjects, the prevalences of sarcopenia in subjects without NAFLD, with non-alcoholic fatty liver (NAFL), and with NASH were 8.7%, 17.9%, and 35.0%, respectively (P < 0.001). ASM% was inversely correlated with the severity of fibrosis (P < 0.001), and the prevalence of significant fibrosis (⩾F2) was higher in subjects with sarcopenia than in those without (45.7% vs. 24.7%; P < 0.001). A crude analysis revealed that sarcopenia was associated with NAFLD (odds ratio [OR], 3.82; 95% confidence interval [CI], 1.58 - 9.25), which became insignificant after adjustment for body mass index (BMI), diabetes, and hypertension. Among NAFLD subjects, subjects with sarcopenia were more likely to have NASH than those without sarcopenia through a multivariate analysis adjusted for age, gender, BMI, hypertension, diabetes, and smoking status (OR, 2.28; 95% CI, 1.21 - 4.30), and this finding was obtained even after adjustment for insulin resistance (OR, 2.30; 95% CI, 1.08 - 4.93). Sarcopenia was also associated with significant fibrosis independent of BMI and insulin resistance (OR, 2.05; 95% CI, 1.01 - 4.16).In this large biopsy-proven NAFLD cohort, sarcopenia was significantly associated with NASH and significant fibrosis.Low muscle mass was found to be associated with histological severity in non-alcoholic fatty liver disease, and sarcopenia was significantly associated with non-alcoholic steatohepatitis and significant fibrosis, independent of obesity, inflammation, and insulin resistance.

    View details for DOI 10.1016/j.jhep.2016.08.019

    View details for Web of Science ID 000390642900015

  • An Overview of Dietary Interventions and Strategies to Optimize the Management of Non-Alcoholic Fatty Liver Disease. Diseases (Basel, Switzerland) Perumpail, B. J., Cholankeril, R. n., Yoo, E. R., Kim, D. n., Ahmed, A. n. 2017; 5 (4)

    Abstract

    Aim: To investigate the efficacy of lifestyle adjustment strategies as a preventive measure and/or treatment of obesity-related non-alcoholic fatty liver disease in adults. Method: A systematic review of literature through 1 July 2017 on the PubMed Database was performed. A comprehensive search was conducted using key terms, such as non-alcoholic fatty liver disease (NAFLD), combined with lifestyle intervention, diet, and exercise. All of the articles and studies obtained from the search were reviewed. Redundant literature was excluded. Results: Several types of dietary compositions and exercise techniques were identified. Most studies concluded and recommended reduction in the intake of saturated and trans fatty acids, carbohydrates, and animal-based protein, and increased intake of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), plant-based proteins, antioxidants, and other nutrients was recommended. The Mediterranean and Paleo diet both seem to be promising schemes for NAFLD patients to follow. Exercise was also encouraged, but the type of exercise did not affect its efficacy as a NAFLD treatment when the duration is consistent. Conclusions: Although these different dietary strategies and exercise regimens can be adopted to treat NAFLD, current literature on the topic is limited in scope. Further research should be conducted to truly elucidate which lifestyle adjustments individually, and in combination, may facilitate patients with obesity-related NAFLD.

    View details for PubMedID 29065499

  • Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World journal of gastroenterology Perumpail, B. J., Khan, M. A., Yoo, E. R., Cholankeril, G. n., Kim, D. n., Ahmed, A. n. 2017; 23 (47): 8263–76

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.

    View details for PubMedID 29307986

    View details for PubMedCentralID PMC5743497

  • Additive effects of PNPLA3 and TM6SF2 on the histological severity of non-alcoholic fatty liver disease. Journal of gastroenterology and hepatology Koo, B. K., Joo, S. K., Kim, D. n., Bae, J. M., Park, J. H., Kim, J. H., Kim, W. n. 2017

    Abstract

    We investigated the effects of PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7-TMC4 rs641738 variants on metabolic phenotypes and their combined effects on the histological severity of non-alcoholic fatty liver disease (NAFLD).We genotyped rs738409, rs58542926, and rs641738 in biopsy-proven NAFLD patients (n = 416) and healthy controls (n = 109). Homeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance (adipo-IR) were calculated.The rs738409 and rs58542926 variants, but not rs641738, were associated with not only NASH (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.46-2.73 and OR, 1.91; 95% CI, 1.04-3.51) but also with significant fibrosis (≥F2) (OR, 1.53; 95% CI, 1.11-2.11 and OR, 1.88; 95% CI, 1.02-3.46) in NAFLD, even after adjustment for metabolic risk factors. Of both variants, only rs738409 was associated with HOMA-IR and adipo-IR even in healthy controls (P = 0.046 and 0.002, respectively) as well as in the entire study cohort (P = 0.016 and 0.048, respectively). PNPLA3 and TM6SF2 risk variants additively increased the risk of NASH and significant fibrosis (OR per risk allele, 2.03; 95% CI, 1.50-2.73 and 1.61; 95% CI, 1.19-2.17). Even in subjects with low insulin resistance, the risk of NASH or significant fibrosis increased as the number of risk alleles increased (P = 0.008 and 0.020, respectively).PNPLA3 and TM6SF2 determine the risk of NASH and significant fibrosis, even after adjustment for insulin resistance, and exert an additive effect on NASH and significant fibrosis.

    View details for PubMedID 29193269

  • Non-alcoholic fatty liver disease and lifestyle modifications, focusing on physical activity. The Korean journal of internal medicine Kwak, M. S., Kim, D. n. 2017

    Abstract

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and the prevalence of non-alcoholic steatohepatitis (NASH) with fibrosis is increasing as the population with NAFLD ages. To date, lifestyle modifications including weight loss, increased physical activity, and dietary changes remain the treatment of choice for NAFLD because there are no approved effective pharmacologic agents. Increased physical activity has therapeutic effects on NAFLD by reducing hepatic fat independent of weight reduction. Indeed, even minimal physical activity below the recommended threshold may have a beneficial impact on NAFLD. Aerobic activity and resistance training have similar effects on NAFLD. Universal recommendations for the optimal intensity and dose of physical activity have not been established. Therefore, physical activity should be tailored based on a patient's clinical characteristics, comorbidities, and fitness capacity. Physical activity also prevents the development of NAFLD and may represent a valuable strategy for reducing the public health burden. However, there are insufficient data supporting the effects of physical activity on the progression of non-alcoholic fatty liver to NASH with advanced fibrosis, and on extrahepatic disease-related morbidity and mortality. In this paper, we review the role of physical activity in the management of NAFLD.

    View details for PubMedID 29202557

  • Non-obese fatty liver disease is associated with lacunar infarct. Liver international : official journal of the International Association for the Study of the Liver Kwak, M. S., Kim, K. W., Seo, H. n., Chung, G. E., Yim, J. Y., Kim, D. n. 2017

    Abstract

    Lacunar infarct, a small subcortical ischemic lesion, is a known risk factor for future cognitive impairment, dementia, and stroke. We evaluated the relationship between fatty liver disease(FLD) and lacunar infarct in a healthy general population.Subjects who underwent brain magnetic resonance imaging(MRI) and abdominal ultrasonography(US) during health check-ups from 2007-2009 were included. FLD was diagnosed by US. Subjects with a history of cerebrovascular disease, radiological findings consistent with cerebrovascular stenosis, or cerebral small vessel disease were excluded.Of 1277 subjects, 54 (4.2%) exhibited lacunar infarct, and 514 (40.3%) had FLD. Subjects with lacunar infarct had a higher prevalence of FLD. (59.3% vs. 39.4%, P=0.004). There was significant interaction between obesity (BMI<25 kg/m2 vs. ≥25 kg/m2 ) and FLD for lacunar infarct (P for interaction=0.024). Subgroup analysis revealed that non-obese FLD was more common in the subjects with lacunar infarct than those without (51.7% vs. 23.5%, P=0.001). However, there was no significant difference in the obese FLD prevalence between these two groups. In multivariate models adjusted by age, sex, smoking, alcohol, hypertension and diabetes, FLD was significantly associated with lacunar infarct (odds ratio[OR] 1.97; 95% confidence interval[CI] 1.08-3.58; P=0.027). Non-obese FLD was associated with the lacunar infarct (OR 3.58; 95% CI 1.63-7.89; P=0.002); however, this association remained insignificant in obese fatty liver disease. Instead, aging and hypertension were independent risk factors for lacunar infarct in the obese population.FLD is significantly associated with lacunar infarct, independent of traditional risk factors. This association was prominent in the non-obese population. This article is protected by copyright. All rights reserved.

    View details for PubMedID 29220869

  • Steatosis severity affects the diagnostic performances of noninvasive fibrosis tests in nonalcoholic fatty liver disease. Liver International Joo, S., Kim, W., Kim, D., Kim, J., Oh, S., Chang, M., Jung, Y., So, Y., Lee, M., Bae, J., Kim, B. 2017
  • Inverse association of marijuana use with nonalcoholic fatty liver disease among adults in the United States PLoS One Kim, D., Kim, W., Kwak, M., Chung, G., Yim, J., Ahmed, A. 2017; 12 (10): e0186702
  • An Overview of Dietary Interventions and Strategies to Optimize the Management of Non-Alcoholic Fatty Liver Disease Diseases Perumpail, B., Cholankeril, R., Yoo, E., Kim, D., Ahmed, A. 2017; 5 (4): pii: E23
  • Decreasing Mortality and Disease Severity in Hepatitis C Patients Awaiting Liver Transplantation in the United States. Liver Transplantation Kwong, A., Kim, W., Mannalithara , A., Heo, N., Udompap, P., Kim, D. 2017

    View details for DOI 10.1002/lt.24973

  • Long-term Patient and Graft Survival of Kidney Transplant Recipients with Hepatitis C Virus Infection in the United States. Transplantation Heo, N. Y., Mannalithara, A. n., Kim, D. n., Udompap, P. n., Tan, J. C., Kim, W. R. 2017

    Abstract

    Hepatitis C virus (HCV) infection is common among kidney transplant (KTx) recipients. However, the impact of HCV infection on long-term graft and recipient survival after KTx from the large-scale data remains to be determined.We used the Organ Procurement and Transplantation Network (OPTN) database to identify all adults undergoing KTx in 2004-2006 in the United States. A propensity score (PS) was created to match each HCV-positive recipient with a HCV-negative control for unbiased comparisons. Survival analysis was conducted to evaluate recipient and death-censored graft survival.Out of 33,357 adult primary KTx recipients, 1470 (4.4%) were HCV-positive. 1,364 HCV-positive and -negative pairs were selected based on PS-matching. Based on the multivariable regression models, HCV is associated with a higher risk of death (hazard ratio [HR]=1.50, 95% confidence interval [95% CI=1.28-1.75) and graft failure (HR=1.26, 95% CI=1.08-1.47). Infection was a more common cause of death in HCV-positive patients than in HCV-negative recipients (HR=1.64, 95% CI=1.12-2.42). The incidence of death due to liver failure was 0.23% per year among HCV-positive recipients, whereas no HCV-negative recipients died from liver failure. Graft failure due to recurrent disease was higher in HCV-positive than in HCV-negative recipients (HR=2.00; 95% CI=1.06-3.78).HCV infection is associated with decreased long-term recipient and graft survival. Future studies are needed to examine whether recently available, safe and effective antiviral therapy improves the long-term clinical outcome in these patients.

    View details for PubMedID 28976413

  • Polycystic ovary syndrome with hyperandrogenism as a risk factor for non-obese non-alcoholic fatty liver disease Alimentary Pharmacology & Therapeutics Kim, J., Kim, D., et al 2017; 45 (11): 1403-1412

    View details for DOI 10.1111/apt.14058

  • Associations between hemoglobin concentrations and the development of incidental metabolic syndrome or nonalcoholic fatty liver disease DIGESTIVE AND LIVER DISEASE Chung, G. E., Yim, J. Y., Kim, D., Kwak, M., Yang, J. I., Chung, S. J., Yang, S. Y., Kim, J. S. 2017; 49 (1): 57-62

    Abstract

    Hemoglobin (Hb) is known to be associated with both nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS). We evaluated the relationship between serum Hb levels and the development of MS or NAFLD.A retrospective cohort study was conducted. We recruited participants who underwent abdominal ultrasonography and blood samplings in both 2005 and 2010.Graded independent relationships were observed between higher Hb levels and the incidence of MS and NAFLD. After adjusting for age, body mass index, and fasting glucose, high-density lipoprotein cholesterol and triglyceride levels, the risk of developing MS was significantly higher according to the Hb quartiles in men (P for trend=0.027). The adjusted odds ratio (OR) and 95% confidence intervals (CIs) for the highest Hb quartile was 1.81 (1.06-3.10) for women and 1.43 (1.00-2.05) for men. The risk of developing NAFLD was also significantly higher according to the Hb quartiles in men (P for trend=0.03). The adjusted OR and 95% CI for the highest Hb quartile was 1.18 (0.73-1.91) in women and 1.76 (1.16-2.66) in men.The risk of developing either MS or NAFLD was significantly associated with serum Hb levels in men. These findings have implications in the clinical availability of serum Hb as a predictor of MS and NAFLD.

    View details for DOI 10.1016/j.dld.2016.10.004

    View details for Web of Science ID 000392633600011

  • Body Fat Distribution and the Risk of Incident Metabolic Syndrome: A Longitudinal Cohort Study. Scientific reports Kwon, H. n., Kim, D. n., Kim, J. S. 2017; 7 (1): 10955

    Abstract

    The effect of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area on metabolic syndrome (MS) has been debated. We aimed to evaluate the effects of VAT and SAT on the incidence of MS and its components in a large and apparently healthy Asian population. We performed a longitudinal cohort study of 1,964 subjects who received health screenings over a 5-year follow-up period; 317 incidents of MS (16.1%) were observed during a median follow-up of 4.5 years. The VAT area was significantly associated with a higher incidence of MS; the adjusted HR for incident MS per 1 SD of VAT was 1.50 (95% CI 1.29-1.74), and the adjusted HR of the 5(th) VAT quintile compared with the 1(st) quintile was 3.73 (95% CI 2.22-6.28). However, the SAT area was not associated with incident MS. Although the VAT area was longitudinally associated with the incidence of each component of MS, the SAT area was inversely associated with the risk of high blood pressure, fasting blood sugar, and triglycerides, with marginal significance. In conclusion, the VAT area is longitudinally associated with an increased risk of incident MS, while SAT may have a protective effect against the incidence of individual MS components.

    View details for PubMedID 28887474

    View details for PubMedCentralID PMC5591218

  • Improved Outcomes in HCV Patients Following Liver Transplantation During the Era of Direct Acting Antiviral Agents. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Cholankeril, G. n., Li, A. A., March, K. L., Yoo, E. R., Kim, D. n., Snyder, H. n., Gonzalez, S. A., Younossi, Z. M., Ahmed, A. n. 2017

    View details for PubMedID 28838786

  • Correction: Spontaneous Evolution in Bilirubin Levels Predicts Liver-Related Mortality in Patients with Alcoholic Hepatitis. PloS one Lee, M., Kim, W., Choi, Y., Kim, S., Kim, D., Yu, S. J., Lee, J. H., Kim, H. Y., Jung, Y. J., Kim, B. G., Kim, Y. J., Yoon, J. H., Lee, K. L., Lee, H. S. 2016; 11 (11): e0167184

    Abstract

    [This corrects the article DOI: 10.1371/journal.pone.0100870.].

    View details for DOI 10.1371/journal.pone.0167184

    View details for PubMedID 27861575

    View details for PubMedCentralID PMC5115856

  • Associations between hemoglobin concentrations and the development of incidental metabolic syndrome or nonalcoholic fatty liver disease. Digestive and liver disease Chung, G. E., Yim, J. y., Kim, D., Kwak, M., Yang, J. I., Chung, S. J., Yang, S. Y., Kim, J. S. 2016

    Abstract

    Hemoglobin (Hb) is known to be associated with both nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS). We evaluated the relationship between serum Hb levels and the development of MS or NAFLD.A retrospective cohort study was conducted. We recruited participants who underwent abdominal ultrasonography and blood samplings in both 2005 and 2010.Graded independent relationships were observed between higher Hb levels and the incidence of MS and NAFLD. After adjusting for age, body mass index, and fasting glucose, high-density lipoprotein cholesterol and triglyceride levels, the risk of developing MS was significantly higher according to the Hb quartiles in men (P for trend=0.027). The adjusted odds ratio (OR) and 95% confidence intervals (CIs) for the highest Hb quartile was 1.81 (1.06-3.10) for women and 1.43 (1.00-2.05) for men. The risk of developing NAFLD was also significantly higher according to the Hb quartiles in men (P for trend=0.03). The adjusted OR and 95% CI for the highest Hb quartile was 1.18 (0.73-1.91) in women and 1.76 (1.16-2.66) in men.The risk of developing either MS or NAFLD was significantly associated with serum Hb levels in men. These findings have implications in the clinical availability of serum Hb as a predictor of MS and NAFLD.

    View details for DOI 10.1016/j.dld.2016.10.004

    View details for PubMedID 27810399

  • Reply to: "The association between sarcopenia and non-alcoholic fatty liver disease". Journal of hepatology Koo, B. K., Kim, D., Joo, S. K., Kim, J. H., Chang, M. S., Kim, B. G., Lee, K. L., Kim, W. 2016

    View details for DOI 10.1016/j.jhep.2016.10.005

    View details for PubMedID 27743988

  • Impact of Antiviral Nucleotide Analogues on Age-Dependent Decline in Renal Function Udompap, P., Mannalithara, A., Kim, D., Kim, W. WILEY. 2016: 925A–926A
  • Polycystic Ovary Syndrome as Risk Factor for Non-alcoholic Fatty Liver Disease in Non-obese Asian Cohort Kim, J., Kim, D. NATURE PUBLISHING GROUP. 2016: S387
  • The Preventive Effect of Sustained Physical Activity on Incident Nonalcoholic Fatty Liver Disease Kim, D., Kwak, M., Chung, G. NATURE PUBLISHING GROUP. 2016: S397
  • Nonalcoholic Fatty Liver Disease in the Non-obese: Insights from the PIVENS and FLINT Trials Kim, D., Mannalithara, A., Udompap, P., Kim, W. WILEY. 2016: 537A
  • Decreasing Mortality in Hepatitis C Patients Awaiting Liver Transplantation in the Direct Acting Antiviral Era Kim, D., Kwong, A., Mannalithara, A., Heo, N., Udompap, P., Kim, W. WILEY. 2016: 29A
  • Nonalcoholic Fatty Liver Disease Is Associated With Coronary Artery Calcification Development: A Longitudinal Study. journal of clinical endocrinology and metabolism Park, H. E., Kwak, M., Kim, D., Kim, M., Cha, M., Choi, S. 2016; 101 (8): 3134-3143

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery calcification (CAC) in cross-sectional studies. However, whether NAFLD itself affects CAC development or progression remains unknown.This study investigated the longitudinal association between NAFLD and CAC score.This study is a longitudinal cohort study performed in a healthcare center.Among 1732 subjects who underwent serial CAC evaluation, we evaluated 846 subjects with NAFLD and 886 subjects without NAFLD, as diagnosed via ultrasonography.CAC score was compared at baseline and follow-up. In subjects without calcification (CAC score = 0) at baseline, any incidental calcification (CAC score >0) at follow-up was defined as development of CAC. In subjects with CAC (CAC score > 0) at baseline, confirmed CAC aggravation was defined as progression. Logistic regression analysis was performed.More subjects with NAFLD than without showed CAC development or progression (48.8 vs 38.4%; P < .001). The impact of NAFLD on a change in CAC score significantly differed according to the CAC score at baseline. In subjects without calcification at baseline, NAFLD significantly affected the development of calcification (odds ratio, 1.49; 95% confidence interval, 1.01-2.21; P = .045) after adjusting for traditional metabolic risk factors. However, in subjects with baseline CAC, NAFLD did not significantly affect progression (P = .734). Additionally, the severity of NAFLD was important. The severity of NAFLD was dose-dependently associated with the development of CAC (P for trend = .043).NAFLD plays a role in the early development of CAC, but not the progression. Ultrasonographic severity of NAFLD is dose-dependently associated with CAC development in subjects with a CAC score of 0 at baseline, independent of traditional risk factors.

    View details for DOI 10.1210/jc.2016-1525

    View details for PubMedID 27253666

  • Increasing prevalence of cirrhosis among U.S. adults aware or unaware of their chronic hepatitis C virus infection. Journal of hepatology Udompap, P., Mannalithara, A., Heo, N., Kim, D., Kim, W. R. 2016; 64 (5): 1027-1032

    Abstract

    Cirrhosis from hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and hepatocellular carcinoma worldwide. We determine the prevalence of cirrhosis among HCV-infected American adults including those unaware of their infection.Using the National Health and Nutrition Examination Survey (NHANES) data, we identified participants aged⩾20 years with detectable serum HCV RNA. The prevalence of advanced fibrosis and cirrhosis was determined for Eras 1 (1988-94), 2 (1999-2006) and 3 (2007-12) by using FIB-4 > 3.25 and APRI > 2.0, respectively.Out of 52,644 NHANES examinees, 49,429 were tested for HCV, of whom 725 met the inclusion criteria (positive HCV RNA with available data for FIB-4 and APRI). Based on APRI, 6.6% (95% confidence interval [CI]:2.2-11.0) of HCV-infected adults in Era 1, 7.6% (95%CI:3.4-11.8) in Era 2 and 17.0% (95%CI:8.0-26.0) in Era 3 had cirrhosis. In the multivariable regression analysis, this era effect was attributable to increasing age (odds ratio [OR]:1.04, 95%CI:1.02-1.07), diabetes (OR:2.33, 95%CI:1.01-5.40) and obesity (OR:2.96, 95%CI:1.15-7.57). Cirrhosis was as common among respondents who were unaware of their infection as those who were aware (both 11%). Results were identical when FIB-4 was used.Among HCV-infected American adults, the proportion with cirrhosis has increased rapidly. Cirrhosis prevalence remains high in individuals unaware of their HCV infection. These data highlight the urgency for HCV screening regardless of symptoms, systematic assessment for liver fibrosis in those with HCV infection and institution of antivirals to prevent advanced liver disease.Chronic hepatitis C virus (HCV) infection is a major cause of cirrhosis, creatingalarge public health burden. Based on the US National Health and Nutrition Examination Survey sample, we found the proportion of patients with cirrhosis among Americans with HCV infection increased from 6.6% to 17.0% over the past two decades. Patients who wereunaware of their infection was just as likely to have cirrhosis as those who knew about their infection,which highlights the need for screening and treatment for HCV at the population level.

    View details for DOI 10.1016/j.jhep.2016.01.009

    View details for PubMedID 26809112

  • The serum vitamin D level is inversely correlated with nonalcoholic fatty liver disease. Clinical and molecular hepatology Chung, G. E., Kim, D., Kwak, M., Yang, J. I., Yim, J. y., Lim, S. h., Itani, M. 2016; 22 (1): 146-151

    Abstract

    A low vitamin D level has been associated with metabolic syndrome and diabetes. However, an association between a low vitamin D level and nonalcoholic fatty liver disease (NAFLD) has not yet been definitively established. This study aimed to characterize the relationship between a vitamin D level and NAFLD in Korea.A cross-sectional study involving 6,055 health check-up subjects was conducted. NAFLD was diagnosed on the basis of typical ultrasonographic findings and a history of alcohol consumption.The subjects were aged 51.7 ± 10.3 years (mean ± SD) and 54.7% were female. NAFLD showed a significant inverse correlation with the vitamin D level after adjusting for age and sex [odds ratio (OR)=0.85, 95% confidence interval (CI)=0.75-0.96]. The age- and sex-adjusted prevalence of NAFLD decreased steadily with increasing vitamin D level [OR=0.74, 95% CI=0.60-0.90, lowest quintile (≤14.4 ng/mL) vs highest quintile (≥28.9 ng/mL), p for trend <0.001]. Multivariate regression analysis after adjusting for other metabolic factors revealed that NAFLD showed a significant inverse correlation with both the vitamin D level (>20 ng/mL) [OR=0.86, 95% CI=0.75-0.99] and the quintiles of the vitamin D level in a dose-dependent manner (p for trend=0.001).The serum level of vitamin D, even when within the normal range, was found to be inversely correlated with NAFLD in a dose-dependent manner. Vitamin D was found to be inversely correlated with NAFLD independent of known metabolic risk factors. These findings suggest that vitamin D exerts protective effects against NAFLD.

    View details for DOI 10.3350/cmh.2016.22.1.146

    View details for PubMedID 27044765

    View details for PubMedCentralID PMC4825160

  • Characterization of acute-on-chronic liver failure and prediction of mortality in Asian patients with active alcoholism JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Kim, H. Y., Chang, Y., Park, J. Y., Ahn, H., Cho, H., Han, S. J., Oh, S., Kim, D., Jung, Y. J., Kim, B. G., Lee, K. L., Kim, W. 2016; 31 (2): 427-433

    Abstract

    Alcoholic liver diseases often evolve to acute-on-chronic liver failure (ACLF), which increases the risk of (multi-)organ failure and death. We investigated the development and characteristics of alcohol-related ACLF and evaluated prognostic scores for prediction of mortality in Asian patients with active alcoholism.A total of 205 patients who were hospitalized with severe alcoholic liver disease were included in this retrospective cohort study, after excluding those with serious cardiovascular diseases, malignancy, or co-existing viral hepatitis. The Chronic Liver Failure (CLIF) Consortium Organ Failure score was used in the diagnosis and grading of ACLF, and the CLIF Consortium ACLF score (CLIF-C ACLFs) was used to predict mortality.Patients with ACLF had higher Maddrey discriminant function, model for end-stage liver disease (MELD), and MELD-sodium scores than those without ACLF. Infections were more frequently documented in patients with ACLF (33.3% vs 53.0%; P = 0.004). Predictive factors for ACLF development were systemic inflammatory response syndrome (odds ratio [OR], 2.239; P < 0.001), serum sodium level (OR, 0.939; P = 0.029), and neutrophil count (OR, 1.000; P = 0.021). For prediction of mortality at predefined time points (28-day and 90-day) in patients with ACLF, areas under the receiver-operating characteristic were significantly greater for the CLIF-C ACLFs than for Child-Pugh, MELD, and MELD-sodium scores.Infection and systemic inflammatory response syndrome play an important role in the development of alcohol-related ACLF in Asian patients with active alcoholism. The CLIF-C ACLFs may be more useful for predicting mortality in ACLF cases than liver-specific scoring systems.

    View details for DOI 10.1111/jgh.13084

    View details for Web of Science ID 000369398400023

    View details for PubMedID 26260091

  • Associations between White Blood Cell Count and the Development of Incidental Nonalcoholic Fatty Liver Disease GASTROENTEROLOGY RESEARCH AND PRACTICE Chung, G. E., Yim, J. Y., Kim, D., Kwak, M., Yang, J. I., Chung, S. J., Yang, S. Y., Kim, J. S. 2016

    Abstract

    Aims. Chronic low-grade inflammation is thought to be associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the association between serum white blood cell (WBC) counts and the development of incidental NAFLD. Methods. In this retrospective longitudinal cohort study, we recruited participants who underwent abdominal ultrasonography and blood samplings during medical checkups in both 2005 and 2010. A total of 2,216 subjects were included in our analyses. Results. The prevalence of NAFLD in 2010 increased steadily in conjunction with increasing WBC counts in 2005 after adjustment for body mass index (BMI) [odds ratio (OR) 2.44, 95% confidence interval (CI) = 1.49-4.00 for women and OR 2.42, 95% CI = 1.61-3.63 for men, lowest quartile versus highest quartile]. Multivariate regression analysis after adjusting for age, BMI, hypertension, smoking, triglycerides, HDL cholesterol, and glucose levels revealed that NAFLD was significantly associated with the highest WBC quartile compared to the lowest quartile [OR 1.85, 95% CI, 1.10-3.10 for women and OR 1.68, 95% CI, 1.08-2.61 for men]. Conclusions. We demonstrated that the risk of developing NAFLD was significantly associated with WBC counts independently of metabolic factors. This finding provides novel evidence indicating that serum WBC counts may be potential surrogate markers of NAFLD.

    View details for DOI 10.1155/2016/7653689

    View details for Web of Science ID 000390793200001

    View details for PubMedID 28070183

    View details for PubMedCentralID PMC5187485

  • The preventive effect of sustained physical activity on incident nonalcoholic fatty liver disease. Liver international : official journal of the International Association for the Study of the Liver Kwak, M. S., Kim, D. n., Chung, G. E., Kim, W. n., Kim, J. S. 2016

    Abstract

    Physical activity (PA) is inversely associated with nonalcoholic fatty liver disease (NAFLD) prevalence. However, few studies evaluated the effect of PA on NAFLD incidence in regard to visceral adipose tissue (VAT) and insulin resistance (IR). We investigated whether PA at baseline and change in PA during follow-up have any effect on incident NAFLD.We enrolled subjects who underwent health screenings between 2007 and 2008 and participated in voluntary follow-up between 2011 and 2013 (median 4.42 years). Incident NAFLD was defined as NAFLD absence at baseline and presence at follow-up by ultrasonography. PA was measured using a detailed questionnaire-based metabolic equivalent at baseline and follow-up; the difference during follow-up was calculated.Of the 1373 subjects enrolled, 288 (21.0%) developed NAFLD. Both total and leisure-time PA at baseline were inversely associated with incident NAFLD (P for trend=.005 and .003 respectively). Decreased PA at follow-up was associated with increased incident NAFLD risk after adjusting for age, gender, body mass index, smoking, hypertension, diabetes and diet [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.04-2.02, 4th (most decreased PA) vs 1st quartile (increased PA), P=.028]. This relationship was attenuated but remained statistically significant after adjustment for VAT(HR 1.48, 95% CI 1.06-2.06, 4th vs 1st quartile) and IR(HR 1.59, 95% CI 1.11-2.27, 4th vs 1st quartile).This study shows an independent protective effect of PA at baseline on incident NAFLD after 4-year follow-up. Furthermore, sustained or increased PA had a preventive effect on incident NAFLD independent of VAT and IR.

    View details for PubMedID 27917585

  • Visceral Obesity Predicts Significant Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Medicine Yu, S. J., Kim, W., Kim, D., Yoon, J., Lee, K., Kim, J. H., Cho, E. J., Lee, J., Kim, H. Y., Kim, Y. J., Kim, C. Y. 2015; 94 (48)

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is associated with visceral obesity. However, the association between visceral adipose tissue (VAT) area and fibrosis in NAFLD patients has not been completely established. This study was aimed to determine the relationship between the computed tomography-measured VAT area and significant fibrosis in NAFLD patients. A total of 324 NAFLD patients and 132 controls were evaluated by liver biopsy. NAFLD was diagnosed based on histological examinations and alcohol consumption <20 g/day. The NAFLD patients showed a higher age and gender-adjusted VAT area than the control group (86.1 ± 2.3 vs 56.7 ± 3.7, P < 0.001). The VAT area increased across the control, NAFLD without significant fibrosis, and NAFLD with significant fibrosis groups (54.9 ± 3.5, 80.6 ± 2.4, and 123.4 ± 6.4, P < 0.001). This association persisted after adjusting for multiple confounders (P for trend = 0.028). A multivariate regression analysis demonstrated the VAT area was independently associated with NAFLD with significant fibrosis (F2-F4) (odds ratio [OR] 1.21 95% confidence interval [CI] 1.07-1.37 per 10 cm(2) increase of VAT area; OR 2.62 [per 1 - standard deviation (SD)] 95% CI 1.41-4.86). Moreover, a multivariate logistic regression analysis revealed the VAT area was independently associated with nonalcoholic steatohepatitis (NASH) in NAFLD (OR 1.17 95% CI 1.05-1.32 per 10 cm increase of VAT area; OR 2.21 [per 1 - SD] 95% CI 1.25-3.89). Increased VAT area is independently associated with NASH or significant fibrosis and VAT might be a central target for lifestyle modifications in NAFLD patients.

    View details for DOI 10.1097/MD.0000000000002159

    View details for PubMedID 26632897

    View details for PubMedCentralID PMC4674200

  • Current and Future Burden of Chronic Nonmalignant Liver Disease. Clinical gastroenterology and hepatology Udompap, P., Kim, D., Kim, W. R. 2015; 13 (12): 2031-2041

    Abstract

    Disease burden is an important indicator of the state of health of a population. It can be measured as the frequency (eg, incidence and prevalence) of a condition or its effects including fatal and non-fatal health loss from disease (eg, disability-adjusted life years) as well as the financial costs (eg, direct healthcare costs and indirect healthcare expenditures related to lost income because of premature death). Accurate disease burden information is essential for policy-making such as prioritization of health interventions and allocation of resources. Chronic liver disease (CLD) causes substantial health and economic burden in the United States, where nearly 2 million deaths annually are attributable to CLD. In the recent past, overall mortality rate of CLD has been increasing. Viral hepatitis and alcoholic liver disease are thought to be the most common etiologies of chronic liver diseases. More recently, the prevalence of nonalcoholic fatty liver disease is rapidly increasing, and nonalcoholic steatohepatitis has become a leading indication for liver transplantation. In this article, we assemble available data on the burden of CLD in the United States, focusing on nonmalignant complications, whereas the impact on mortality and healthcare expenses of hepatocellular carcinoma, an important consequence of CLD, is discussed elsewhere.

    View details for DOI 10.1016/j.cgh.2015.08.015

    View details for PubMedID 26291665

  • Reduced Survival in Elderly Liver Transplant Recipients: How Old is Too Old? Heo, N., Mannalithara, A., Udompap, P., Kim, D., Concepcion, W., Esquivel, C. O., Kim, W. WILEY. 2015: 807A
  • Increasing Prevalence of Cirrhosis among US Adults with Chronic Hepatitis C Virus Infection: Results from NHANES 1988-1994 and 1999-2012 Udompap, P., Mannalithara, A., Heo, N., Kim, D., Kim, W. WILEY-BLACKWELL. 2015: 253A
  • Short Sleep Duration is associated with Nonalcoholic Fatty Liver Disease in US Adults Kim, D., Kim, H., Allen, A. M., Ahmed, A., Heo, N., Udompap, P., Mannalithara, A., Kim, W. WILEY-BLACKWELL. 2015: 1258A
  • The Relationship Between Colonoscopy Procedure Order and Adenoma Detection Rates A Prospective Study JOURNAL OF CLINICAL GASTROENTEROLOGY Kang, H. Y., Kim, D., Kim, H. J., Kang, S. J., Chung, G. E., Song, J. H., Yang, S. Y., Kim, Y. S., Park, M. J., Yim, J. y., Lim, S. h., Kim, J. S. 2015; 49 (8): 683-689

    Abstract

    The aim of this study was to prospectively assess the effects of the order of colonoscopic procedures and other possible factors on the adenoma detection rate (ADR).There have been conflicting studies regarding the timing or order of a colonoscopy and its ability to detect adenomas.Between March 2011 and July 2011, consecutive colonoscopies were prospectively performed by 7 board-certified staff endoscopists at the Seoul National University Hospital Healthcare System Gangnam Center. The primary outcome was the overall ADR according to the procedure order of the colonoscopies, and the secondary outcome was the identification of other possible factors influencing the ADR.A total of 1908 colonoscopies were analyzed. The detection rate was 56.5% for all polyps and 37.3% for adenomas. The ADR increased as the performance order of the colonoscopy increased and was highest for the third procedure (43.4%). However, the ADR of the remaining procedures, including later procedures, was similar throughout the workday. In the multivariable analysis, the ADR was significantly associated with older age, male sex, high body mass index, personal history of colorectal polyps, long withdrawal time, and an experienced endoscopist. However, the colonoscopy procedure order was not significantly associated with the ADR.The ADR was stable according to the procedure order for the later procedures of the workday in a setting of moderate daily procedure volumes. The withdrawal time and experience level of the endoscopist were more important than the procedure order in detecting adenomas by colonoscopy.

    View details for DOI 10.1097/MCG.0000000000000258

    View details for Web of Science ID 000360336500008

    View details for PubMedID 25319736

  • Comparison of Narrow Band Imaging and Fujinon Intelligent Color Enhancement in Predicting Small Colorectal Polyp Histology DIGESTIVE DISEASES AND SCIENCES Kang, H. Y., Kim, Y. S., Kang, S. J., Chung, G. E., Song, J. H., Yang, S. Y., Lim, S. h., Kim, D., Kim, J. S. 2015; 60 (9): 2777-2784

    Abstract

    There are limited data on the performance of narrow band imaging (NBI) and Fujinon intelligent color enhancement (FICE) for differentiating polyp histologies.The aim of this study was to compare the diagnostic performances of NBI and FICE in differentiating neoplastic from non-neoplastic colorectal polyps <10 mm during screening colonoscopy.A total of 955 average-risk adults undergoing screening colonoscopies were randomly allocated to NBI or FICE groups. Four board-certified staff endoscopists without prior experience using NBI or FICE participated. The main outcomes of this study were overall accuracy, sensitivity, and specificity of FICE and NBI in identifying neoplastic polyps.There was no significant difference in the number of subjects with adenoma between the NBI (143/475, 30.1 %) and FICE groups (139/480, 29.0 %) (after excluding adenoma ≥1 cm) (P > 0.05). The overall accuracy of NBI was 81.0 %, compared with 81.4 % for FICE (P = 0.867). The overall sensitivity and specificity of NBI and FICE were 84.6 and 78.0 % (P = 0.054); 75.1 and 86.5 % (P = 0.009), respectively. For polyps measuring ≤5 mm, the accuracy was 79.4 % for NBI and 80.1 % for FICE (P = 0.835; sensitivity 81.9 vs. 74.5 %, P = 0.064; specificity 75.7 vs. 88.4 %, P = 0.006).The overall accuracy of NBI and FICE was similar for differentiating small polyp histologies during screening colonoscopy. However, better results should be achieved before using NBI or FICE as real-time optical biopsy of colorectal polyps in screening colonoscopy.

    View details for DOI 10.1007/s10620-015-3661-5

    View details for Web of Science ID 000359997700087

    View details for PubMedID 25868634

  • The Role of Spleen Stiffness in Determining the Severity and Bleeding Risk of Esophageal Varices in Cirrhotic Patients MEDICINE Kim, H. Y., Jin, E. H., Kim, W., Lee, J. Y., Woo, H., Oh, S., Seo, J., Oh, H. S., Chung, K. H., Jung, Y. J., Kim, D., Kim, B. G., Lee, K. L. 2015; 94 (24)

    Abstract

    Esophageal varix and its hemorrhage are serious complications of liver cirrhosis. Recent studies have focused on noninvasive prediction of esophageal varices. We attempted to evaluate the association of liver and spleen stiffness (LS and SS) as measured by acoustic radiation force impulse imaging, with the presence and severity of esophageal varices and variceal hemorrhage in cirrhotic patients. We measured LS and SS, along with endoscopic examination of esophageal varices for a total of 125 cirrhotic patients at a single referral hospital in this prospective observational study. The diagnostic utility of noninvasive methods for identifying varices and their bleeding risk was compared, including LS, SS, spleen length, Child-Pugh score, and various serum fibrosis indices. Esophageal varices were present in 77 patients (61.6%). SS was significantly higher in patients with varices than in those without varices (3.58 ± 0.47 vs 3.02 ± 0.49; P < 0.001). A tendency toward increasing SS levels was observed with increasing severity of varices (no varix, 3.02 ± 0.49; F1, 3.39 ± 0.51; F2, 3.60 ± 0.42; F3, 3.85 ± 0.37; P < 0.001). SS was significantly higher in patients who experienced variceal hemorrhage than in those who did not (3.80 ± 0.36 vs 3.20 ± 0.51; P = 0.002). An optimal cut-off value of SS for high-risk varices (≥ F2) or variceal hemorrhage was 3.40 m/s. SS was significantly correlated with the presence, severity, and bleeding risk of esophageal varices. Prompt endoscopic evaluation of variceal status and prophylactic measures based on the SS may be warranted for cirrhotic patients.

    View details for DOI 10.1097/MD.0000000000001031

    View details for Web of Science ID 000360808800001

    View details for PubMedID 26091449

    View details for PubMedCentralID PMC4616530

  • Cholecystectomy is independently associated with nonalcoholic fatty liver disease in an Asian population WORLD JOURNAL OF GASTROENTEROLOGY Kwak, M., Kim, D., Chung, G. E., Kim, W., Kim, Y. J., Yoon, J. 2015; 21 (20): 6287-6295

    Abstract

    To investigate the relationship between gallstone disease and nonalcoholic fatty liver disease (NAFLD) in a large Asian population.A cross-sectional study including 17612 subjects recruited from general health check-ups at the Seoul National University Hospital, Healthcare System Gangnam Center between January 2010 and December 2010 was conducted. NAFLD and gallstone disease were diagnosed based on typical ultrasonographic findings. Subjects who were positive for hepatitis B or C, or who had a history of heavy alcohol consumption (> 30 g/d for men and > 20 g/d for women) or another type of hepatitis were excluded. Gallstone disease was defined as either the presence of gallstones or previous cholecystectomy, and these two entities (gallstones and cholecystectomy) were analyzed separately. Clinical parameters including body mass index, waist circumference, hypertension, diabetes, smoking status, and regular physical activity were reviewed. Laboratory parameters, including serum levels of gamma-glutamyl transpeptidase, alanine aminotransferase, aspartate aminotransferase, fasting glucose, fasting insulin, total cholesterol, triglycerides, and high-density lipoprotein, were also reviewed.The mean age of the subjects was 48.5 ± 11.3 years, and 49.3% were male. Approximately 30.3% and 6.1% of the subjects had NAFLD and gallstone disease, respectively. The prevalence of gallstone disease (8.3% vs 5.1%, P < 0.001), including both the presence of gallstones (5.5% vs 3.4%, P < 0.001) and a history of cholecystectomy (2.8% vs 1.7%, P < 0.001), was significantly increased in the NAFLD group. In the same manner, the prevalence of NAFLD increased with the presence of gallstone disease (41.3% vs 29.6%, P < 0.001). Multivariate regression analysis showed that cholecystectomy was associated with NAFLD (OR = 1.35, 95%CI: 1.03-1.77, P = 0.028). However, gallstones were not associated with NAFLD (OR = 1.15, 95%CI: 0.95-1.39, P = 0.153). The independent association between cholecystectomy and NAFLD was still significant after additional adjustment for insulin resistance (OR = 1.45, 95%CI: 1.01-2.08, P = 0.045).This study shows that cholecystectomy, but not gallstones, is independently associated with NAFLD after adjustment for metabolic risk factors. These data suggest that cholecystectomy may be an independent risk factor for NAFLD.

    View details for DOI 10.3748/wjg.v21.i20.6287

    View details for Web of Science ID 000355116300019

    View details for PubMedID 26034364

    View details for PubMedCentralID PMC4445106

  • Hepatic fat, not visceral fat, is associated with gallbladder polyps: A study of 2643 healthy subjects JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Lim, S. h., Kim, D., Kang, J. H., Song, J. H., Yang, S. Y., Yim, J. Y., Chung, S. J., Kim, J. S., Cho, S. 2015; 30 (4): 767-774

    Abstract

    Gallbladder polyps (GBPs) appear to be strongly associated with obesity and metabolic disease. To date, the relationship between GBPs and fatty liver has not been adequately evaluated. The aim of the present study was to investigate whether GBPs are associated with fatty liver, which is an ectopic regional fat deposit, independent of visceral adipose tissue (VAT).A cross-sectional study using 2643 health checkup subjects (961 patients with GBP and 1682 age- and sex-matched healthy controls) was conducted. The subjects underwent various laboratory tests, abdominal fat computed tomography (CT), and hepatic ultrasonography.The mean age of the subjects was 51.4 ± 8.3 years, and 74.1% were male. GBPs were significantly associated with fatty liver. Multivariate regression analysis revealed that GBPs were significantly associated with the presence of fatty liver (odds ratio [OR] 1.23, 95% confidence interval [CI]: 1.02-1.48), and adjusting for the homeostatic metabolic assessment index had little effect on this association (OR 1.23, 95% CI: 1.02-1.48). Additionally, GBPs remained significantly associated with the presence of fatty liver after adjustments for CT-measured VAT and subcutaneous adipose tissue (OR 1.24, 95% CI: 1.03-1.50). The degree of fatty liver showed an independent (OR 1.37 95% CI: 1.03-1.80) and dose-dependent relationship (moderate-severe fatty liver: OR 1.55 95% CI: 1.07-2.23, P for trend = 0.014) with large GBPs (≥ 5 mm).Fatty liver, an ectopic regional fat deposit, was found to be closely associated with GBPs independent of known metabolic risk factors, insulin resistance, and CT-measured VAT, confirming a relevant clinical relationship between the two diseases.

    View details for DOI 10.1111/jgh.12841

    View details for Web of Science ID 000351403200026

    View details for PubMedID 25376159

  • Nonalcoholic fatty liver disease is associated with coronary artery calcium score in diabetes patients with higher HbA1c DIABETOLOGY & METABOLIC SYNDROME Kwak, M., Yim, J. Y., Kim, D., Park, M. J., Lim, S. h., Yang, J. I., Chung, G. E., Kim, Y. S., Yang, S. Y., Kim, M. N., Lee, C., Yoon, J., Lee, H. 2015; 7

    Abstract

    In patients with diabetes, studies investigating the association between nonalcoholic fatty liver disease (NAFLD) and coronary artery calcium score (CACS) have shown conflicting results. The aim of this study was to evaluate the association between NAFLD and CACS in diabetic patients.This is the cohort study performed in Seoul National University Hospital Gangnam Healthcare Center. NAFLD was defined as cases with the typical ultrasonographic findings without excessive alcohol consumption, medications causing hepatic steatosis or other chronic liver diseases. CACS was evaluated using the Agatston method. Diabetes was defined as cases with fasting serum glucose ≥ 126 mg/dl, glycated hemoglobin (HbA1c) ≥ 6.5%, or those taking anti-diabetic medications. Multivariate linear regression analyses were performed with use of the interaction term of NAFLD × glycemic level and other confounders of CACS such as age, sex, hypertension, body mass index, waist circumference, HDL cholesterol and triglyceride.A total of 213 participants with diabetes were included in the study. As 77 subjects (36.2%) had CACS 0, causing left sided skewness, CACS was analyzed after log transformation to Ln (CACS + 1). A statistically significant interaction was observed between NAFLD and HbA1c ≥ 7% (P for interaction = 0.014). While NAFLD was not associated with CACS in the group with HbA1c < 7% (P = 0.229), it was significantly associated in the group with HbA1c ≥ 7% (P = 0.010) after adjusting for covariates in multivariate analyses.This study demonstrated an effect modification of glycemic level on the association between NAFLD and CACS. NAFLD was independently associated with CACS only in diabetes patients with higher HbA1c, after adjustment for confounders.

    View details for DOI 10.1186/s13098-015-0025-4

    View details for Web of Science ID 000352068800001

    View details for PubMedID 25844093

    View details for PubMedCentralID PMC4384364

  • Role of physical activity in nonalcoholic fatty liver disease in terms of visceral obesity and insulin resistance LIVER INTERNATIONAL Kwak, M., Kim, D., Chung, G. E., Kim, W., Kim, Y. J., Yoon, J. 2015; 35 (3): 944-952

    Abstract

    Limited evidence supports a role for physical activity (PA) in nonalcoholic fatty liver disease (NAFLD) independent of visceral obesity or/and insulin resistance. We investigated the association between PA and NAFLD while considering visceral adipose tissue (VAT) and insulin resistance in a large general population.Nonalcoholic fatty liver disease was diagnosed based on typical ultrasonographic findings. A detailed PA questionnaire included type, frequency, duration and length of time that the subject engaged in PA. PA was determined by a metabolic equivalent. VAT was evaluated by computed tomography taken at the umbilicus level.A total of 3718 subjects were enrolled in the analysis. After adjusting for age, gender, body mass index, smoking, hypertension, diabetes, soft drink and coffee consumption, the total PA was inversely associated with NAFLD [4th quartile (highest activities), odds ratio (OR) 0.68, 95% confidence interval (CI) 0.54-0.85; 3rd quartile, OR 0.74, 95% CI 0.59-0.93 vs. 1st quartile (lowest activities), P for trend <0.001]. After further adjusting for VAT or insulin resistance or both (P for trend = 0.027, 0.001 and 0.040 respectively), this relationship was slightly attenuated but remained statistically significant. The leisure-time PA and weighted PA also had inverse associations with NAFLD independent of the VAT or insulin resistance or both.This study showed an inverse association between various types of PA and the prevalence of NAFLD in a dose-dependent manner that was independent of visceral obesity and insulin resistance. This finding suggests a beneficial association between PA and NAFLD.

    View details for DOI 10.1111/liv.12552

    View details for Web of Science ID 000349781900028

    View details for PubMedID 24684289

  • Visceral Adipose Tissue Area as an Independent Risk Factor for Elevated Liver Enzyme in Nonalcoholic Fatty Liver Disease MEDICINE Chung, G. E., Kim, D., Kwark, M. S., Kim, W., Yim, J. y., Kim, Y. J., Yoon, J. 2015; 94 (9)

    Abstract

    Chronic elevations in alanine aminotransferase (ALT) levels are associated with body composition. The aim of this study was to evaluate the relationship between elevated liver enzyme levels and the visceral tissue area in subjects with and without nonalcoholic fatty liver disease (NAFLD).An observational cohort study was conducted with subjects undergoing general health examinations. To evaluate the visceral and subcutaneous abdominal adipose tissue area, a computed tomography scan was performed. NAFLD was diagnosed if a person demonstrated fatty liver on ultrasonography without a history of significant alcohol consumption or chronic liver disease. Abnormal liver enzyme levels were based on ALT elevations according to the updated Asian definition.Of the 5100 subjects, 3712 (72.8%) met the inclusion criteria, and NAFLD was found in 1185 subjects. Elevated ALT values were positively correlated with body mass index, waist circumference, and subcutaneous and visceral adipose tissue area. These relationships were attenuated, although they remained significant in a dose-dependent manner, after adjusting for multiple liver injury risk factors. In addition, when body mass index and subcutaneous and visceral tissue areas were finally considered in combination, only visceral adipose tissue remained independently associated with elevated ALT levels in the ultrasonographically diagnosed NAFLD group (P for trend <0.001 for men and women).Elevated ALT levels were independently and dose-dependently associated with visceral fat accumulation in the healthy general population, especially in ultrasonographically diagnosed NAFLD patients. These results reemphasize the importance of visceral fat in the pathogenesis of NAFLD.

    View details for DOI 10.1097/MD.0000000000000573

    View details for Web of Science ID 000350756800007

    View details for PubMedID 25738475

    View details for PubMedCentralID PMC4553965

  • Nonalcoholic Fatty Liver Disease as a Risk Factor of Arterial Stiffness Measured by the Cardioankle Vascular Index MEDICINE Chung, G. E., Choi, S., Kim, D., Kwak, M., Park, H. E., Kim, M., Yim, J. y. 2015; 94 (12)

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is associated with risk factors for cardiovascular disease. The cardioankle vascular index (CAVI), a new measure of arterial stiffness, was recently developed and is independent of blood pressure. We investigated whether NAFLD is associated with arterial stiffness as measured using the CAVI in an apparently healthy population.A total of 2954 subjects without any known liver diseases were enrolled. NAFLD was diagnosed via typical ultrasonography. The clinical characteristics examined included age, sex, body mass index (BMI), waist circumference (WC), and the levels of aspartate aminotransferase, alanine aminotransferase, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol triglycerides, and glucose. Arterial stiffness was defined using an age- and sex-specific threshold of the upper quartile of the CAVI.NAFLD was found in 1249 (42.3%) of the analyzed subjects. Using an age-, sex-, and BMI-adjusted model, NAFLD was associated with a 42% increase in the risk for arterial stiffness (highest quartile of the CAVI). The risk for arterial stiffness increased according to the severity of NAFLD (adjusted odds ratio [95% confidence interval], 1.27 [1.02 - 1.57] vs 1.78 [1.37 - 2.31], mild vs moderate-to-severe, respectively). When adjusted for other risk factors, including BMI, WC, smoking status, diabetes, and hypertension, these relationships remained statistically significant.Patients with NAFLD are at a high risk for arterial stiffness regardless of classical risk factors. The presence of cardiometabolic risk factors may attenuate the prediction of arterial stiffness by means of NAFLD presence. Thus, physicians should carefully assess subjects with NAFLD for atherosclerosis and associated comorbidities.

    View details for DOI 10.1097/MD.0000000000000654

    View details for Web of Science ID 000351875600009

    View details for PubMedID 25816034

    View details for PubMedCentralID PMC4554011

  • The Influence of Metabolic Factors for Nonalcoholic Fatty Liver Disease in Women BIOMED RESEARCH INTERNATIONAL Chung, G. E., Yim, J. Y., Kim, D., Lim, S. h., Yang, J. I., Kim, Y. S., Yang, S. Y., Kwak, M., Kim, J. S., Cho, S. 2015

    Abstract

    Women after menopause have increased insulin resistance and visceral fat, which may increase the prevalence of nonalcoholic fatty liver disease (NAFLD). However, the pathogenesis of NAFLD in women has not been clearly defined. In this study, we aimed to determine the risk factors for NAFLD in women.A retrospective cohort study was conducted. Women who underwent abdominal ultrasonography and blood sampling for routine health check-ups were recruited.Among 1,423 subjects, 695 women (48.9%) were in a menopausal state. The prevalence of NAFLD was higher in postmenopausal women than in premenopausal women (27.2% versus 14.4%, P < 0.001). In premenopausal women, low HDL-cholesterol, central obesity, and homeostasis model assessment-estimated insulin resistance showed a significant association with the increased risk of NAFLD in multivariate analysis. In postmenopausal women, the presence of diabetes, triglyceridemia, and central obesity showed a significant association with the risk of NAFLD. The presence of menopause and hormone replacement therapy in postmenopausal women were not risk factors for NAFLD.Our findings showed different metabolic factors for NAFLD in pre- and postmenopausal women. However, the key issues are the same: central obesity and insulin resistance. These results reemphasize the importance of metabolic factors irrespective of menopausal status in the pathogenesis of NAFLD in women.

    View details for DOI 10.1155/2015/131528

    View details for Web of Science ID 000353797700001

    View details for PubMedID 25973422

    View details for PubMedCentralID PMC4417996

  • The relationship between colonoscopy procedure order and adenoma detection rates: a prospective study Kang, H., Kim, D., Kim, H. WILEY-BLACKWELL. 2014: 82
  • Spontaneous Evolution in Bilirubin Levels Predicts Liver-Related Mortality in Patients with Alcoholic Hepatitis PLOS ONE Lee, M., Kim, W., Choi, Y., Kim, S., Kim, D., Yu, S. J., Lee, J., Kim, H. Y., Jung, Y. J., Kim, B. G., Kim, Y. J., Yoon, J., Lee, K. L., Lee, H. 2014; 9 (7)

    Abstract

    The accurate prognostic stratification of alcoholic hepatitis (AH) is essential for individualized therapeutic decisions. The aim of this study was to develop a new prognostic model to predict liver-related mortality in Asian AH patients. We conducted a hospital-based, retrospective cohort study using 308 patients with AH between 1999 and 2011 (a derivation cohort) and 106 patients with AH between 2005 and 2012 (a validation cohort). The Cox proportional hazards model was constructed to select significant predictors of liver-related death from the derivation cohort. A new prognostic model was internally validated using a bootstrap sampling method. The discriminative performance of this new model was compared with those of other prognostic models using a concordance index in the validation cohort. Bilirubin, prothrombin time, creatinine, potassium at admission, and a spontaneous change in bilirubin levels from day 0 to day 7 (SCBL) were incorporated into a model for AH to grade the severity in an Asian patient cohort (MAGIC). For risk stratification, four risk groups were identified with cutoff scores of 29, 37, and 46 based on the different survival probabilities (P<0.001). In addition, MAGIC showed better discriminative performance for liver-related mortality than any other scoring system in the validation cohort. MAGIC can accurately predict liver-related mortality in Asian patients hospitalized for AH. Therefore, SCBL may help us decide whether patients with AH urgently require corticosteroid treatment.

    View details for DOI 10.1371/journal.pone.0100870

    View details for Web of Science ID 000339378400013

    View details for PubMedID 25013906

    View details for PubMedCentralID PMC4094461

  • Visceral adipose tissue area is associated with coronary stenosis and noncalcified plaques INTERNATIONAL JOURNAL OF OBESITY Kang, S. J., Kim, D., Park, H. E., Choi, S. H., Choi, S., Lee, W., Kim, J. S., Cho, S. 2014; 38 (2): 272-278

    Abstract

    Few studies have investigated the relationships between visceral adipose tissue (VAT) and coronary stenosis and noncalcified plaques at the subclinical stage. The aim of this study was to investigate relationship between VAT and coronary lesions assessed by coronary computed tomography (CT) in an apparently healthy population.Retrospective cross-sectional study.One thousand six hundred and fifty-eight subjects free of cardiovascular disease underwent coronary CT and abdominal fat CT as part of a routine medical examination.VAT area was measured at the level of the umbilicus using CT. Coronary stenoses and plaques were evaluated using coronary CT.The mean age of the study population was 55.9±8.0 years, and 1198 (72.3%) subjects were men. There were 201 subjects (12.1%) with coronary stenosis <50% and 144 (8.7%) had significant stenosis. Noncalcified plaques were observed in 108 (6.5%) subjects. Coronary stenosis <50% and noncalcified plaques increased steadily as the VAT area increased (P<0.001). The 4th quartile of VAT area was significantly associated with prevalence of coronary stenosis <50% and the presence of noncalcified plaques when compared with the first through third VAT quartiles in the cardiovascular risk factor-adjusted model (odds ratio (OR): 1.58, 95% confidence interval (CI): 1.09-2.30 and OR: 1.66; 95% CI: 1.02-2.68, respectively).Excess VAT area was associated with coronary stenosis <50% and noncalcified plaques, independent of traditional cardiovascular risk factors, in an asymptomatic population without a history of coronary artery disease.

    View details for DOI 10.1038/ijo.2013.105

    View details for Web of Science ID 000331404300016

    View details for PubMedID 23748189

  • Nonalcoholic Fatty Liver Disease Is Associated With Arterial Stiffness Measured by Cardio-Ankle Vascular Index Kim, D., Chung, G., Choi, S., Kwak, M., Kim, W., Kim, Y., Yoon, J. WILEY-BLACKWELL. 2014: 619A
  • Body Fat Distribution and the Risk of Incident and Remittent Nonalcoholic Fatty Liver Disease: Prospective Cohort Study Kim, D., Chung, G., Kwak, M., Kim, W., Kim, Y., Yoon, J. WILEY-BLACKWELL. 2014: 599A
  • Nonalcoholic Fatty Liver Disease Is Associated with Left Ventricular Diastolic Dysfunction Lee, J., Kim, D., Chung, G., Kwak, M., Kim, Y., Yoon, J., Lee, H. WILEY-BLACKWELL. 2014: 616A
  • Association of visceral obesity and early colorectal neoplasia WORLD JOURNAL OF GASTROENTEROLOGY Choe, E. K., Kim, D., Kim, H. J., Park, K. J. 2013; 19 (45): 8349-8356

    Abstract

    To examine whether visceral adipose tissue (VAT) serves as a risk factor for colorectal adenoma-early colorectal cancer (CRC) sequence.A retrospective case-control study was conducted with 153 patients with stage I CRC, age/sex-matched 554 patients with colorectal adenoma and 557 normal controls. All subjects underwent various laboratory tests, abdominal fat computed tomography (CT), and colonoscopy. VAT was defined as an intra-abdominal adipose tissue area measured by CT scan. Adipose tissue area was measured at the level of the umbilicus from CT scan. We used the lowest quartile of VAT and subcutaneous adipose tissue area as a reference group.The body mass index (BMI), total cholesterol, fasting glucose and VAT areas were significantly different among normal, adenoma and CRC groups. The VAT area was 120.6 ± 49.0 cm(2) in normal controls, 130.6 ± 58.4 cm(2) in adenoma group and 117.6 ± 51.6 cm(2) in CRC group (P = 0.002). In univariate analysis, increased BMI was a risk factor for CRC compared to control (P = 0.025). However, VAT area was not a risk factor for CRC compared to control. In multivariate analysis that adjusted for smoking, alcohol consumption and subcutaneous adipose tissue area, VAT area was inversely related to CRC, compared to the adenoma (OR = 0.53, 95%CI: 0.31-0.92, highest quartile vs lowest quartile).Our study shows that visceral obesity is not a risk factor for early CRC. Visceral obesity might influence the normal-adenoma sequence but not the adenoma-early carcinoma sequence.

    View details for DOI 10.3748/wjg.v19.i45.8349

    View details for Web of Science ID 000328082500023

    View details for PubMedID 24363527

    View details for PubMedCentralID PMC3857459

  • KASL clinical practice guidelines: management of nonalcoholic fatty liver disease. Clinical and molecular hepatology 2013; 19 (4): 325-348

    View details for DOI 10.3350/cmh.2013.19.4.325

    View details for PubMedID 24459637

    View details for PubMedCentralID PMC3894432

  • STAT6 Expression and IL-13 Production in Association with Goblet Cell Hyperplasia and Worm Expulsion of Gymnophalloides seoi from C57BL/6 Mice KOREAN JOURNAL OF PARASITOLOGY Lee, J., Kim, D., Pyo, K., Kim, M., Kim, H., Chai, J., Shin, E. 2013; 51 (5): 589-594

    Abstract

    In intestinal helminth infections, Th2 immune respones are generally associated with mucin secretion for worm expulsion from the host intestine. In particular, IL-4 and IL-13 are the important cytokines related with intestinal mucus production via STAT6 signalling in nematode infections. However, this perspective has never been studied in Gymnophalloides seoi infection. The present study aimed to observe the STAT6 signalling and cytokine responses in C57BL/6 mice, a mouse strain resistant to infection with this trematode. The results showed that worm expulsion occurred actively during days 1-2 post-infection (PI), when goblet cells began to proliferate in the small intestine. The STAT6 gene expression in the mouse spleen became remarkable from day 2 PI. Moreover, G. seoi infection induced a significant increase of IL-13 from day 4 PI in the spleen of infected mice. Our results suggested that goblet cell hyperplasia and worm expulsion in G. seoi-infected mice should be induced by STAT6 signalling, in which IL-13 may be involved as a dominant triggering cytokine.

    View details for DOI 10.3347/kjp.2013.51.5.589

    View details for Web of Science ID 000326997900016

    View details for PubMedID 24327788

    View details for PubMedCentralID PMC3857510

  • Association between Gallstone Disease and Fatty Liver in a Large Apparently Healthy Population Kim, D., Kwak, M., Chung, G., Kim, W., Kim, Y., Yoon, J. WILEY-BLACKWELL. 2013: 505A
  • Association between Helicobacter pylori and Nonalcoholic Fatty Liver Disease in the General Population Kim, D., Kang, S., Kim, H., Kim, W., Kim, Y., Yoon, J. WILEY-BLACKWELL. 2013: 519A
  • Serum Vitamin D is Inversely Associated with Nonalcoholic Fatty Liver Disease and Advanced Fibrosis in the General Population Kim, D., Kim, W., Kim, H. WILEY-BLACKWELL. 2013: 514A
  • Association Between Insulin Resistance and Hepatic Fibrosis in Patients with Combined Chronic Hepatitis B and Steatosis Kim, H., Joo, S., Jung, J., Jung, Y., Kim, D., Kim, W. WILEY-BLACKWELL. 2013: 612A
  • Diabetes is not associated with increased risk of hepatocellular carcinoma in patients with hepatitis C and advanced fibrosis or cirrhosis Yang, J., Kim, D., Roberts, L. R., Kim, W. WILEY-BLACKWELL. 2013: 1218A–1219A
  • Elevated serum bilirubin levels are inversely associated with coronary artery atherosclerosis ATHEROSCLEROSIS Kang, S. J., Kim, D., Park, H. E., Chung, G. E., Choi, S. H., Choi, S., Lee, W., Kim, J. S., Cho, S. 2013; 230 (2): 242-248

    Abstract

    Inverse correlations of high serum bilirubin with metabolic and cardiovascular disease have been suggested. However, anti-atherogenic effects of bilirubin have not been well-established in terms of the presence of plaques and stenosis identified in coronary computed tomography (CT).A cross-sectional study was conducted on 2862 men who were free of cardiovascular disease and underwent coronary CT as part of a routine medical screening examination. Coronary stenotic lesions were considered to be incidences of coronary atherosclerosis, and stenosis was classified as stenosis <50% or ≥50%, according to degree of stenosis.The prevalences of coronary atherosclerosis and stenosis ≥50% in subjects with elevated bilirubin levels (>1.2 mg/dL) were lower than those in subjects with normal bilirubin levels (≤1.2 mg/dL) (19.9% vs. 27.9%, p < 0.001, 8.5% vs. 10.3%, p = 0.044). Bilirubin was inversely associated with total plaques (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.48-0.73 in the 4th quartile vs. 1st quartile) and calcified plaques (OR 0.60, 95% CI 0.49-0.75) in univariate analysis. After adjusting for traditional risk factors, it was found that coronary atherosclerosis (OR 0.73, 95% CI 0.56-0.94 in the 4th quartile vs. 1st quartile) and calcified plaque (OR 0.66, 95% CI 0.53-0.84) were inversely associated with the bilirubin grade in a dose-dependent manner.The serum bilirubin level was inversely associated with coronary atherosclerosis and calcified plaques in a dose-dependent manner. These results suggested that serum bilirubin could be used as a protective biomarker of coronary artery disease.

    View details for DOI 10.1016/j.atherosclerosis.2013.06.021

    View details for Web of Science ID 000324747800012

    View details for PubMedID 24075751

  • Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: Noninvasive Assessment with MR Elastography RADIOLOGY Kim, D., Kim, W. R., Talwalkar, J. A., Kim, H. J., Ehman, R. L. 2013; 268 (2): 411-419

    Abstract

    To evaluate the diagnostic accuracy of magnetic resonance (MR) elastography as a method to help diagnose clinically substantial fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and, by using MR elastography as a reference standard, to compare various laboratory marker panels in the identification of patients with NAFLD and advanced fibrosis.This retrospective study was institutional review board approved and HIPAA complaint. Informed consent was waived. This study was conducted in patients with NAFLD, who were identified by imaging characteristics consistent with steatosis in a prospective database that tracks all MR elastographic examinations. Six laboratory-based models of fibrosis were compared with MR elastographic results as well as fibrosis stage from liver biopsy results. The area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value of each data set were compared.Among 325 patients with NAFLD with MR elastographic data, there were 142 patients who underwent liver biopsy within 1 year of MR elastography. When comparing MR elastography results with liver biopsy results, the best cutoff for advanced fibrosis (stage F3-F4, 46 [32.4%] of 142) was 4.15 kPa (AUROC = 0.954, sensitivity = 0.85, specificity = 0.929). This cutoff value identified 104 patients with advanced fibrosis (32.0% of 325 patients). The FIB-4 score (AUROC = 0.827) and NAFLD fibrosis score (AUROC = 0.821) had the best diagnostic accuracy for advanced fibrosis, with high negative predictive values (NAFLD fibrosis score = 0.90 and FIB-4 score = 0.899).MR elastography is a useful diagnostic tool for detecting advanced fibrosis in NAFLD. Of the laboratory-based methods, the NAFLD fibrosis and FIB-4 scores can most reliably detect advanced fibrosis.

    View details for DOI 10.1148/radiol.13121193

    View details for Web of Science ID 000322116000015

    View details for PubMedID 23564711

    View details for PubMedCentralID PMC3721049

  • Noninvasive fibrosis indices predict intrahepatic distant recurrence of hepatitis B-related hepatocellular carcinoma following radiofrequency ablation LIVER INTERNATIONAL Seo, J. Y., Kim, W., Kwon, J. H., Jin, E. H., Yu, S. J., Kim, H. Y., Jung, Y. J., Kim, D., Kim, Y. J., Yoon, J., Lee, H. 2013; 33 (6): 884-893

    Abstract

    Intrahepatic recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) occurs as a result of direct dissemination or de novo oncogenesis. Hepatocellular carcinogenesis is related to the progression of cirrhosis, and noninvasive fibrosis scoring systems reflect the severity of hepatic fibrosis. Hence, the aim of this study was to elucidate the correlation between noninvasive fibrosis indices and intrahepatic distant recurrence (IDR) of HCC after RFA.Patients with hepatitis B virus (HBV)-related, solitary HCC undergoing RFA were prospectively enrolled. Noninvasive serum fibrosis indices were calculated at the time of RFA. IDR was defined as recurrent HCC beyond >2 cm from the ablation margin of RFA. Predictors of IDR and overall survival were analysed by a Cox regression model.Two hundred forty-six patients received RFA as initial treatment, and the median follow-up duration was 19.7 months (IQR, 11.9-29.8). Among these cases, 133 (45.9%) showed IDR after RFA. In multivariable analysis, serum alpha-fetoprotein (AFP) (HR, 1.000; 95% CI, 1.000-1.001; P = 0.001) and age-platelet index (API) (1.19; 1.01-1.39; P = 0.033) were independent predictors of IDR. In particular, patients with API ≤7 showed a significantly higher recurrence-free survival rate than patients with API >7 (P = 0.004). With regard to overall survival, male sex (4.69; 1.52-14.52; P = 0.007), serum bilirubin (2.78; 1.31-5.90; P = 0.008) and AFP (1.000; 1.000-1.001; P = 0.006) were significantly correlated with shortened survival.High levels of AFP and API predict IDR of HBV-related HCC after RFA. Therefore, noninvasive fibrosis indices could play an important role in predicting IDR of HCC following percutaneous ablation.

    View details for DOI 10.1111/liv.12132

    View details for Web of Science ID 000320139000010

    View details for PubMedID 23461618

  • Noninvasive markers: a double-edged sword that stratifies nonalcoholic steatohepatitis CLINICAL AND MOLECULAR HEPATOLOGY Chung, G., Kim, D. 2013; 19 (2): 116–19

    View details for DOI 10.3350/cmh.2013.19.2.116

    View details for Web of Science ID 000409415800003

    View details for PubMedID 23837135

    View details for PubMedCentralID PMC3701843

  • Prediction of Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: An Enhanced Model of BARD Score GUT AND LIVER Lee, T., Han, S., Yang, J., Kim, D., Ahmed, M. 2013; 7 (3): 323–28

    Abstract

    The BARD score is a model to detect advanced liver fibrosis in nonalcoholic fatty liver disease (NAFLD) patients. The aims of this study were to identify additional factors and then to build an enhanced version of the BARD score.One hundred seven patients with biopsy-proven NAFLD were enrolled retrospectively. Logistic regressions were performed to identify independent risk factors for advanced liver fibrosis (stage 3 or 4). An enhanced model of the BARD score (BARDI score) was built and evaluated with a receiver operating characteristic (ROC) curve.In multivariate analysis, age (odds ratio [OR], 0.89; p=0.04), aspartate aminotransferase/alanine aminotransferase ratio (OR, 1.73; p<0.01), and international normalized ratio (INR) (OR, 8.85; p<0.01) were independently significant factors. The BARDI score was created by adding the INR to the BARD. The area under the ROC curve of the BARDI score was significantly larger than that of the BARD score (0.881 vs 0.808, p<0.01). A BARDI score of 3 or more showed a positive predictive value (PPV) of 51.0% and a negative predictive value (NPV) of 96.0%.The BARDI score had an improved PPV over the BARD score and maintained an excellent NPV. Further study is warranted for its external validation and comparison with other models.

    View details for DOI 10.5009/gnl.2013.7.3.323

    View details for Web of Science ID 000319100000010

    View details for PubMedID 23710314

    View details for PubMedCentralID PMC3661965

  • Serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease. Clinical and molecular hepatology Kwak, M., Kim, D., Chung, G. E., Kang, S. J., Park, M. J., Kim, Y. J., Yoon, J., Lee, H. 2012; 18 (4): 383-390

    Abstract

    Serum bilirubin exerts antioxidant and cytoprotective effects. In addition, elevated serum bilirubin levels are associated with a decreased risk of metabolic and cardiovascular diseases. However, few studies have evaluated whether serum bilirubin is associated with non-alcoholic fatty liver disease (NAFLD), which is closely associated with other metabolic diseases. The aim of this study was thus to elucidate the association between serum total bilirubin levels and NAFLD.A cross-sectional study of 17,348 subjects undergoing a routine health check-up was conducted. Subjects positive for hepatitis B or hepatitis C virus, or with other hepatitis history were excluded. NAFLD was diagnosed on the basis of typical ultrasonographic findings and an alcohol consumption of less than 20 g/day.The mean age of the subjects was 49 years and 9,076 (52.3%) were men. The prevalence of NAFLD decreased steadily as the serum bilirubin level increased in both men and women (P<0.001 for both). Multivariate regression analysis adjusted for other metabolic risk factors showed that serum bilirubin level was inversely associated with the prevalence of NAFLD [odds ratio (OR)=0.88, 95% confidence interval (CI)=0.80-0.97]. Furthermore, there was an inverse, dose-dependent association between NAFLD and serum total bilirubin levels (OR=0.83, 95% CI=0.75-0.93 in the third quartile; OR=0.80, 95% CI=0.71-0.90 in the fourth quartile vs. lowest quartile, P for trend <0.001).Serum bilirubin levels were found to be inversely associated with the prevalence of NAFLD independent of known metabolic risk factors. Serum bilirubin might be a protective marker for NAFLD.

    View details for DOI 10.3350/cmh.2012.18.4.383

    View details for PubMedID 23323254

    View details for PubMedCentralID PMC3540375

  • Clinical Prediction of Failure of Lamivudine Prophylaxis for Hepatitis B Virus-Infected Patients Undergoing Cytotoxic Chemotherapy for Malignancy ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Kim, I. K., Kim, B. G., Kim, W., Kim, D., Kim, Y. J., Yoon, J., Lee, H. S. 2012; 56 (11): 5511-5519

    Abstract

    Although lamivudine (LAM) prophylaxis is recommended for patients infected with hepatitis B virus (HBV) undergoing chemotherapy for malignant disease, HBV reactivation sometimes occurs during or after LAM administration. The aim of this study was to determine predictors of LAM prophylactic failure in patients with malignancies. Patients with malignancies were routinely screened for serum hepatitis B surface antigen (HBsAg) from June 2002 to August 2008. All consecutive, HBsAg-positive patients received LAM prophylaxis during and after completion of chemotherapy. We assessed risk factors for virologic breakthrough and withdrawal hepatitis. Death without HBV reactivation was regarded as a competing risk event, which was adjusted by Fine and Gray's model. A total of 110 patients were included in this study. They received LAM prophylaxis for a median of 9.2 months. Virologic breakthrough occurred in 15 patients at a median of 10.9 months from the initiation of LAM prophylaxis. Withdrawal hepatitis occurred in 15 patients at a median of 2.4 months after cessation of LAM prophylaxis. Multivariable analysis showed that high baseline HBV DNA titer (≥2,000 IU/ml) (hazard ratio [HR], 9.94; P = 0.0063) and the use of rituximab (HR, 3.19; P = 0.027) were significant predictors of virologic breakthrough and that high baseline HBV DNA titer (HR, 5.90; P = 0.007), liver cirrhosis (HR, 10.4; P = 0.002), and distant metastasis (HR, 5.14; P = 0.008) were independent risk factors for withdrawal hepatitis. Patients with high viremia, liver cirrhosis, rituximab treatment, and distant metastasis are at high risk of prophylactic failure and need antiviral agents with a greater barrier to resistance.

    View details for DOI 10.1128/AAC.00821-12

    View details for Web of Science ID 000310055800010

    View details for PubMedID 22890764

    View details for PubMedCentralID PMC3486524

  • Physical Activity in Nonalcoholic Fatty Liver Disease in terms of Visceral Obesity Kim, D., Kwak, M., Chung, G., Kim, W., Kim, Y., Yoon, J. WILEY-BLACKWELL. 2012: 902A
  • Spleen stiffness measurement determines the severity of esophageal varix in patients with liver cirrhosis Jin, E., Lee, J., Lee, M., Kim, H., Jung, Y., Kim, D., Kim, B., Lee, K., Kim, W. WILEY-BLACKWELL. 2012: 757A
  • Noninvasive fibrosis scoring systems predict intrahepatic distant recurrence of hepatitis B-related hepatocellular carcinoma following radiofrequency ablation therapy Seo, J., Kim, W., Kwon, J., Jin, E., Yu, S., Kim, H., Jung, Y., Kim, D., Kim, Y., Yoon, J., Lee, H. WILEY-BLACKWELL. 2012: 810A
  • Non-overweight fatty liver disease (NOFLD): A Distinct Entity? Kim, D., Kim, W. WILEY-BLACKWELL. 2012: 886A–887A
  • [Dietary risk factors in relation to colorectal adenoma]. The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi Yang, S. Y., Kim, Y. S., Song, J. H., Chung, S. J., Lee, I. H., Hong, K. J., Lee, E. J., Kim, D. H., Yim, J. y., Park, M. J., Lim, S. h., Kim, J. S. 2012; 60 (2): 102-108

    Abstract

    The role of dietary risk factors in colorectal carcinogenesis remains unclear. We investigated the association between dietary intakes and colorectal adenomas who visited a health promotion center for a routine health check-up colonoscopy.We conducted a retrospective case-control study using data from individuals who had colonoscopy at Seoul National University Hospital Healthcare System Gangnam Center from October 2003 to December 2007. The subjects were 242 patients (162 males and 80 females) with histopathologically confirmed colorectal adenoma, and 464 (272 males and 192 females) controls. Dietary data were obtained via 24 hour dietary recall, assisted by a registered dietitian. The student's t-test and the chi-square test were performed for the statistical comparison of means and proportions among groups. Multivariate analyses using logistic regression were performed to assess the relation between dietary intake and colorectal adenoma.The total average energy intake of the patients (male: 2,407.5±429.2 kcal, female: 1,901.3±316.9 kcal) was higher than the controls (male: 2,249.6±430.4 kcal, female: 1,752.4±275.0 kcal; p=0.001). High energy intake (male: OR=4.13, 95% CI=1.70-10.05, p=0.002; female: OR=4.00, 95% CI=1.51-10.61, p=0.005) and animal protein intake (male: OR=3.97, 95% CI=1.66-9.49, p=0.002; female: OR=5.76, 95% CI=1.99-16.169, p=0.001) were found to be associated with the risk of colorectal adenoma after adjusting for confounders such as age, BMI, waist circumference, metabolic syndrome and smoking.In summary, high energy intake and animal protein were associated with colorectal adenoma.

    View details for PubMedID 22926121

  • A low level of serum total testosterone is independently associated with nonalcoholic fatty liver disease BMC GASTROENTEROLOGY Kim, S., Kwon, H., Park, J., Cho, B., Kim, D., Oh, S., Lee, C. M., Choi, H. 2012; 12

    Abstract

    The association between low serum testosterone levels, visceral adipose tissue (VAT), and metabolic syndrome is now well known. However, the relationship between hepatic steatosis and serum testosterone levels has not been extensively studied. Our aim was to investigate the association of serum total testosterone levels with nonalcoholic fatty liver disease (NAFLD), adjusting for the influence of VAT and insulin resistance.This study is a retrospective observational cross-sectional one of healthy Korean men and was conducted at the Seoul National University Hospital Healthcare System Gangnam Center. We used data obtained from 495 men who were at least 20 years of age and who had undergone blood testing, abdominal computed tomography, and ultrasonography. Multiple logistic regression analysis was used to explore the association of serum total testosterone levels with NAFLD.Men in the low serum testosterone quintile were at a higher risk for NAFLD than men in the highest serum testosterone quintile. After adjusting for age, smoking, diabetes, exercise, BMI, triglycerides, and high-density-lipoprotein cholesterol, subjects with serum testosterone levels in the lowest quintile had an odds ratio (OR) (95% confidence interval (CI)) of 5.12 (2.43-10.77) for NAFLD (p value, 0.0004). The inverse association between serum testosterone and NAFLD was attenuated by further adjustment for variables including VAT; however, it remained statistically significant (OR (95% CI): 4.52 (2.09-9.80) in the lowest quintile; p value=0.004).A low serum total testosterone level was independently associated with NAFLD. This report is the first one suggesting the association remains unchanged even after controlling for VAT and insulin resistance.

    View details for DOI 10.1186/1471-230X-12-69

    View details for Web of Science ID 000306853300001

    View details for PubMedID 22691278

    View details for PubMedCentralID PMC3406998

  • SERUM VITAMIN D IS INVERSELY ASSOCIATED WITH NONALCOHOLIC FATTY LIVER DISEASE IN GENERAL POPULATION Kim, D., Chung, G. E., Lim, S. H., Yim, J. Y., Park, M. J., Kim, W., Kim, Y. J., Yoon, J., Lee, H. ELSEVIER SCIENCE BV. 2012: S511
  • Comparison of Sterilization of Reusable Endoscopic Biopsy Forceps by Autoclaving and Ethylene Oxide Gas DIGESTIVE DISEASES AND SCIENCES Yoon, J. H., Yoon, B. C., Lee, H. L., Lee, J. K., Kim, Y., Lee, D. H., Choi, I. J., Lee, D. H., Kim, D. H. 2012; 57 (2): 405-412

    Abstract

    Every country has standardized reprocessing guidelines for reducing the risk of microorganism transmission via reusable biopsy forceps. Sterilization is performed either by autoclaving or with the use of ethylene oxide (EO) gas. However, there are no clear standard global recommendations. The aim of this study was to determine whether EO gas or autoclaving is a safer and more effective method for the sterilization of reusable forceps.This was a prospective study conducted at multiple tertiary referral centers. Seventy reusable biopsy forceps that had been reused at least 20 times each were collected from six endoscopy centers. In all, 61 forceps from five centers were sterilized using EO gas, and the nine forceps from the remaining center were placed in an autoclave. We performed real-time polymerase chain reaction (RT-PCR) for Mycobacterium tuberculosis and hepatitis B virus and performed bacterial cultures on the reusable forceps, which were cut into 2- to 3-cm sections. The forceps were also scanned with an electron microscope (EM) to detect surface damage and contamination.Escherichia coli bacteria were cultured from 2 of the 61 (3.3%) reusable biopsy forceps sterilized with EO gas. On EM scanning, abundant debris and tissue materials remained on the cup surfaces of the reused biopsy forceps and on their inner wires. No microorganisms were found on the autoclaved forceps.Sterilization with EO gas may be inadequate because the complicated structure of the forceps may interfere with sterilization. Therefore, for optimum safety, reusable biopsy forceps should be sterilized by autoclaving.

    View details for DOI 10.1007/s10620-011-1884-7

    View details for Web of Science ID 000299487500020

    View details for PubMedID 21904859

  • Negative hepatitis B envelope antigen predicts intrahepatic recurrence in hepatitis B virus-related hepatocellular carcinoma after ablation therapy JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Chung, G. E., Kim, W., Lee, J., Kim, Y. J., Yoon, J., Lee, J. M., Lee, J. Y., Kim, S. H., Kim, D., Lee, H. 2011; 26 (11): 1638-1645

    Abstract

    Patients with persistently active hepatitis B virus (HBV) replication are at high risk for progression to liver cirrhosis and hepatocellular carcinoma (HCC). The influence of the viral load of HBV on intrahepatic recurrence after local ablation therapy in patients with HBV-related HCC has not been elucidated. We aimed to evaluate predictors of intrahepatic recurrence and clarify the correlation between viral load and intrahepatic recurrence after percutaneous ablation.Patients with HBV-related, solitary HCC undergoing radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI), between October 2004 and December 2008 were prospectively enrolled. Statistical analyses were performed using the Kaplan-Meier method and Cox regression model to identify risk factors for intrahepatic recurrence.A total of 145 patients (male, 81.4%; mean age, 55.3 years) were included. Ninety patients (62.1%) had serum HBV DNA ≥2000 IU/mL. The median follow-up duration was 28.9 months (range, 12.0-57.0) and 63 patients (43.4%) experienced intrahepatic tumor recurrence. Multivariate analysis indicated that seropositivity for hepatitis B envelope antigen (HBeAg) was an independent negative predictor of intrahepatic recurrence (hazard ratio, 0.473; P=0.026) and late (≥1 year) recurrence (HR, 0.288; P=0.012). The serum alpha fetoprotein (AFP) level also significantly predicted late recurrence (HR, 1.001; P=0.005). However, neither the ablation method nor serum HBV DNA titers were correlated with intrahepatic recurrence.These findings show that HBeAg-negativity and serum AFP levels were associated with late intrahepatic recurrence of HCC, implicating HBeAg-negativity as a risk factor for de novo recurrence after percutaneous ablation in HBV-related HCC.

    View details for DOI 10.1111/j.1440-1746.2011.06777.x

    View details for Web of Science ID 000296858100012

    View details for PubMedID 22011297

  • ASSOCIATION BETWEEN CLINICAL OR SUBCLINICAL HYPOTHYROIDISM AND NON-ALCOHOLIC FATTY LIVER DISEASE Chung, G., Kim, D., Yim, J., Park, M., Kim, W., Kim, Y., Yoon, J., Lee, H. WILEY-BLACKWELL. 2011: 1128A
  • ACCURACY OF NON-INVASIVE FIBROSIS MARKERS IN THE DIAGNOSIS OF ADVANCED FIBROSIS IN NONALCOHOLIC FATTY LIVER DISEASE Kim, D., Kim, W., Talwalkar, J. A., Ehman, R. WILEY-BLACKWELL. 2011: 1118A–1119A
  • THE IMPACT OF OBESITY AND SERUM ALANINE AMINOTRANSFERASE (ALT) ACTIVITIES ON LONG TERM SURVIVAL: A POPULATION-BASED STUDY Kim, D., Kim, W., Fan, C., Larson, J. J., Benson, J. T., Therneau, T. M. WILEY-BLACKWELL. 2011: 1130A
  • Association between Helicobacter pylori Seropositivity and the Coronary Artery Calcium Score in a Screening Population GUT AND LIVER Park, M. J., Choi, S. H., Kim, D., Kang, S. J., Chung, S. J., Choi, S. Y., Yoon, D. H., Lim, S. h., Kim, Y. S., Yim, J. y., Kim, J. S., Jung, H. C. 2011; 5 (3): 321-327

    Abstract

    Helicobacter pylori causes numerous extragastric manifestations, including coronary heart disease. The coronary artery calcification (CAC) score, measured using computed tomography (CT) has been used as a screening test for coronary atherosclerosis. This study investigated the association between H. pylori seropositivity and CAC scores in a screening population.Patients who underwent a health checkup between October 2003 and July 2007 and who did not have a history of ischemic heart disease were enrolled in the study. Subjects were screened with a multidetector CT scan to determine the CAC score and for anti-H. pylori antibody immunoglobulin G; traditional risks for coronary heart disease were evaluated using a structured questionnaire, anthropometric measurements, and laboratory tests.Of the 2,029 subjects enrolled (1,295 males), 1,214 (59.8%) subjects were H. pylori positive and 815 were H. pylori negative. There were no significant differences in the baseline characteristics of the seropositive and seronegative patients. When the CAC presence or absence scores were considered, multivariate analysis revealed that H. pylori seropositivity was statistically associated with the presence of CAC and that this association was stronger in the mild CAC score category.H. pylori seropositive patients are at a higher risk for coronary atherosclerosis regardless of traditional cardiovascular risk factors. This association is particularly applicable for early coronary atherosclerosis.

    View details for DOI 10.5009/gnl.2011.5.3.321

    View details for Web of Science ID 000294104800010

    View details for PubMedID 21927661

    View details for PubMedCentralID PMC3166673

  • Reply to the Letter to the Editor: Hepatitis A in Developed Country, the Result Should Interpret Carefully GUT AND LIVER Chung, G., Yim, J., Kim, D., Lim, S., Park, M., Kim, Y., Yang, S., Yang, J., Cho, S. 2011; 5 (3): 395–96
  • Add-On Adefovir Is Superior to a Switch to Entecavir as Rescue Therapy for Lamivudine-Resistant Chronic Hepatitis B (vol 56, pg 2130, 2011) DIGESTIVE DISEASES AND SCIENCES Chung, G., Kim, W., Lee, K., Hwang, S., Lee, J., Kim, H., Jung, Y., Kim, D., Jeong, J., Kim, B., Kim, Y., Yoon, J., Lee, H. 2011; 56 (8): 2509
  • Add-On Adefovir Is Superior to a Switch to Entecavir as Rescue Therapy for Lamivudine-Resistant Chronic Hepatitis B DIGESTIVE DISEASES AND SCIENCES Chung, G. E., Kim, W., Lee, K. L., Hwang, S. Y., Lee, J., Kim, H. Y., Jung, Y. J., Kim, D., Jeong, J. B., Kim, B. G., Kim, Y. J., Yoon, J., Lee, H. 2011; 56 (7): 2130-2136

    Abstract

    Lamivudine (LAM) has been extensively used to treat hepatitis B, but high incidence of drug resistance has required rescue studies. We validated the optimum treatment strategy for LAM-resistant patients by means of a comparative study of add-on adefovir (ADV) and a switch to entecavir (ETV).We assessed the virologic response in consecutive LAM-resistant patients who received add-on ADV or a switch to ETV.The mean reduction of serum hepatitis B virus (HBV) DNA levels was significantly less in the ETV group than in the add-on ADV group (-3.45 vs. -4.17; P = 0.047 at week 24 and -3.81 vs. -4.68 log(10) IU/mL; P = 0.044 at week 48). Achievement of undetectable HBV DNA was significantly lower in the ETV group than in the add-on ADV group (P = 0.043). Multivariate analysis showed that add-on ADV, baseline HBV DNA levels, and initial virologic response were significant predictors of HBV DNA negativity (adjusted OR, 2.582; P = 0.008, 0.304; P = 0.001, and 5.928; P = 0.001). Virologic breakthrough was observed for 12 patients, in the ETV group only.Add-on ADV was more effective and durable than ETV as rescue therapy. Therefore, add-on ADV might be the preferred strategy for LAM-resistant patients who need long-term antiviral treatment.

    View details for DOI 10.1007/s10620-010-1561-2

    View details for Web of Science ID 000291481800032

    View details for PubMedID 21253834

  • Helicobacter pylori Serology Inversely Correlated With the Risk and Severity of Reflux Esophagitis in Helicobacter pylori Endemic Area: A Matched Case-Control Study of 5,616 Health Check-Up Koreans. Journal of neurogastroenterology and motility Chung, S. J., Lim, S. h., Choi, J., Kim, D., Kim, Y. S., Park, M. J., Yim, J. y., Kim, J. S., Cho, S., Jung, H. C., Song, I. S. 2011; 17 (3): 267-273

    Abstract

    The role of Helicobacter pylori in gastroesophageal reflux disease remains still controversial and the effect of the organism on severity of reflux esophagitis have been rarely issued. The aim of this study was to investigate the relationship between H. pylori infection and reflux esophagitis, and especially the severity of reflux esophagitis.We performed a cross-sectional case-control study of 5,616 subjects undergoing both upper endoscopy and H. pylori serology during health Check-up (2,808 cases vs age- and sex-matched controls). Smoking, alcohol, body mass index and waist circum - ference were added to a multiple regression model.Prevalence of H. pylori infection was lower in cases with reflux esophagitis than in controls (38.4% vs 58.2%, P < 0.001) and negative associations with H. pylori infection continued across the grade of esophagitis (46.7% in Los Angeles classification M [LA-M], 34.3% in LA-A or LA-B and 22.4% in LA-C or LA-D, P < 0.001). Positive serology for H. pylori independently reduced the risk of reflux esophagitis (adjusted OR, 0.44; 95% CI, 0.39-0.49). Notably, the negative associations continued across the grade of esophagitis with adjusted ORs of 0.63 in LA-M, 0.36 in LA-A or LA-B and 0.20 in LA-C or LA-D (P < 0.001).In a age-sex matched Korean, H. pylori seropositivity was independently and inversely associated with the risk and severity of reflux esophagitis, suggesting the organism may have a protective role against gastroesophageal reflux disease.

    View details for DOI 10.5056/jnm.2011.17.3.267

    View details for PubMedID 21860818

    View details for PubMedCentralID PMC3155062

  • Prospective evaluation of a new stool antigen test for the detection of Helicobacter pylori, in comparison with histology, rapid urease test, 13C-urea breath test, and serology JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Choi, J., Kim, C. H., Kim, D., Chung, S. J., Song, J. H., Kang, J. M., Yang, J. I., Park, M. J., Kim, Y. S., Yim, J. y., Lim, S. h., Kim, J. S., Jung, H. C., Song, I. S. 2011; 26 (6): 1053-1059

    Abstract

    This study aimed to evaluate the efficacy of a new polyclonal enzyme immunoassay for the detection of Helicobacter pylori (H. pylori) antigen in stool by determination of the optimal cut-off value in the screening population.A consecutive 515 patients undergoing a routine health check-up were prospectively enrolled. H. pylori infection was defined if at least two of four tests (histology, rapid urease test, (13)C-urea breath test, and serology) were positive. A stool antigen test (EZ-STEP H. pylori) was performed for the detection of H. pylori. The optimal cut-off value was determined by the receiver-operator characteristic curve. The diagnostic performance of each test was evaluated with regard to the histological diagnosis of atrophic gastritis (AG)/intestinal metaplasia (IM), degree of AG/IM, and old age.Sensitivity, specificity, positive and negative predictive values, and accuracy of the stool antigen test were 93.1%, 94.6%, 95.1%, 92.3%, and 93.8%, respectively. The sensitivity of histology, rapid urease test, and the (13)C-urea breath test ranged from 89.1% to 97.6%, and their specificity was > 98%, while serology had high sensitivity, but low specificity. The accuracy of the stool antigen test was comparable to that of other methods (93.6-95.9%), whereas it was higher than that of serology. The stool antigen test still showed good diagnostic performance in the setting of progression of AG/IM and in patients over 40 years.The performance of a new stool antigen test was comparable to that of other methods in the diagnosis of H. pylori infection for the screening population, even with the presence of AG/IM.

    View details for DOI 10.1111/j.1440-1746.2011.06705.x

    View details for Web of Science ID 000290581100021

    View details for PubMedID 21362044

  • Non-Alcoholic Fatty Liver Disease as a Harbinger of Subclinical Coronary Artery Disease Kim, D., Kim, W., Park, M., Kim, Y., Yoon, J., Lee, H. W B SAUNDERS CO-ELSEVIER INC. 2011: S985-S986
  • Association Visceral Obesity and Colonrectal Neoplasia: Aspect of Adenoma-Carcinoma Sequence Kim, D., Choe, E., Park, K., Im, J., Park, M., Kim, J., Jung, H., Song, I. W B SAUNDERS CO-ELSEVIER INC. 2011: S380
  • Visceral Obesity is a Risk Factor for Colorectal Adenoma 's Occurrence in Surveillance Colonoscopy, Preliminary Data of a Prospective Cohort Study Im, J., Kim, D., Chung, S., Park, M., Kim, S., Kim, J., Jung, H., Song, I. W B SAUNDERS CO-ELSEVIER INC. 2011: S389
  • Seroprevalence of Hepatitis A and Associated Socioeconomic Factors in Young Healthy Korean Adults GUT AND LIVER Chung, G. E., Yim, J. Y., Kim, D., Lim, S. H., Park, M. J., Kim, Y. S., Yang, S. Y., Yang, J. I., Cho, S. 2011; 5 (1): 88-92

    Abstract

    An epidemiologic shift of hepatitis A virus (HAV) seroprevalence is expected due to an improvement in socioeconomic status in young adults in Korea. We investigated the age-specific seroprevalence and socioeconomic factors associated with HAV seropositivity in young, healthy Korean adults.Between March 2009 and February 2010, a total of 5,051 persons from 20 to 49 years of age presenting for a health check-up were included and responded to a questionaire. The seroprevalence of HAV was investigated by measuring immunoglobulin G (IgG) anti-HAV. A total of 984 pairs of cases and age- and sex-matched controls were analyzed for associated socioeconomic factors.The prevalence of seropositive HAV was 6.2% in the 20 to 29 age range, 33.1% in the 30 to 39 range and 82.4% in the 40 to 49 range (p<0.001). There were no significant differences in any group according to gender. A multivariate analysis for paired cases indicated that HAV seropositivity was significantly higher in the low monthly income (below five million won, approximately 4,300 dollars) group and the Helicobacter pylori (H. pylori)-positive group (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.27-2.14; p<0.001; OR, 1.45; 95% CI, 1.19-1.76; p<0.001, respectively).HAV seropositivity in young adults presenting for a health checkup appears to be decreasing, and the prevalence was significantly higher in the low monthly income group and the H. pylori-positive group.

    View details for DOI 10.5009/gnl.2011.5.1.88

    View details for Web of Science ID 000288569700014

    View details for PubMedID 21461079

    View details for PubMedCentralID PMC3065100

  • Elevated Peripheral Blood Monocyte Fraction in Nonalcoholic Fatty Liver Disease TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE Kim, H., Chung, G. E., Park, I. Y., Choi, J. M., Hwang, S., Lee, J., Kim, D. 2011; 223 (3): 227-233

    Abstract

    An elevated white blood cell (WBC) count is associated with nonalcoholic fatty liver disease (NAFLD); however, a leukocyte subtype that is involved in the pathogenesis of NAFLD is not known. This study was conducted to investigate the association between NAFLD and WBC subtype fractions (%) among healthy elderly Koreans. A total of 794 subjects who underwent a health check-up were investigated. After excluding excessive alcohol intake and other liver diseases, NAFLD was diagnosed based on sonographic findings: hyperechogenecity of liver tissue, difference of echogenicity between liver and kidney, and visibility of vascular structures. The prevalence of NAFLD among entire cohort was 39.0% (310/794). The presence of NAFLD was significantly associated with higher blood WBC counts (5,485 ± 1073 vs. 5,230 ± 995 per mm(3), p = 0.001) and monocyte fraction (6.08 ± 2.40% vs. 5.12 ± 1.31%, p < 0.001). The multiple logistic regression analysis, after controlling confounders, including age, gender, body mass index, systolic and diastolic blood pressure, fasting blood glucose, alanine aminotransferase, triglyceride, and high-density lipoprotein cholesterol, showed that the prevalence risk of NAFLD was increased significantly according to the monocyte fraction quartiles: odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were 1.00, 2.75 (1.63-4.62), 2.84 (1.67-4.84) and 5.17 (3.03-8.83), respectively. There were no significant associations between NAFLD and the total WBC count quartiles in this model. These results indicate that the elevated peripheral blood monocyte fraction is associated with NAFLD. The monocyte fraction might be a useful marker for NAFLD.

    View details for DOI 10.1620/tjem.223.227

    View details for Web of Science ID 000290129400011

    View details for PubMedID 21403434

  • Distribution of Abdominal Visceral and Subcutaneous Adipose Tissue and Metabolic Syndrome in a Korean Population DIABETES CARE Kim, S., Cho, B., Lee, H., Choi, K., Hwang, S., Kim, D., Kim, K., Kwon, H. 2011; 34 (2): 504–6

    Abstract

    This study aimed to assess the correlation between abdominal subcutaneous adipose tissue (SAT) and metabolic syndrome (MetS) in Korean adults after adjusting for the effects of visceral adipose tissue (VAT).The SAT/VAT ratio (SVR) was calculated using abdominal computed tomography in 2,655 subjects. We used regression analyses to assess whether the SVR predicted MetS.For both sexes, the prevalence of elevated triglycerides, reduced HDL, and elevated fasting glucose significantly decreased with increasing quintiles of SVR (P for trend < 0.05). The prevalence and odds ratios of MetS significantly decreased as the SVR increased (men: odds ratio 0.5 [95% CI 0.3-0.7]; women: 0.2 [0.1-0.5] for comparisons of lowest vs. highest quintile; P for trend < 0.05).After adjustment for VAT, abdominal SAT was inversely correlated with the occurrence of MetS.

    View details for DOI 10.2337/dc10-1364

    View details for Web of Science ID 000287433900048

    View details for PubMedID 21228245

    View details for PubMedCentralID PMC3024376

  • Validation of P2/MS and other noninvasive fibrosis scoring systems in the Korean population with nonalcoholic fatty liver disease. The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi Yu, S. J., Kim, D. H., Lee, J. H., Chung, G. E., Yim, J. y., Park, M. J., Kim, Y. J., Yoon, J. H., Jang, J. J., Lee, H. S. 2011; 57 (1): 19-27

    Abstract

    P2/MS is a noninvasive marker for detecting hepatic fibrosis in patients with viral hepatitis. However, the applicability of P2/MS in patients with nonalcoholic fatty liver disease (NAFLD) has not yet been validated. This study aimed to validate P2/MS and compare it to other noninvasive fibrosis scoring systems in Korean patients with NAFLD.Consecutive patients who underwent liver biopsy between January 2002 and December 2009 at Seoul National University Hospital, Seoul, Korea were enrolled in this study. Fibrosis stage was determined using the METAVIR scoring system.A total of 235 patients were included in the study: advanced fibrosis (METAVIR F3-F4) was present in 7 patients. No patient was over-staged among 162 patients with a P2/MS score above the high cut-off (95), resulting in a high negative predictive value (NPV) of 100% (95% confidence interval, 97.1-100). There was no significant difference between the area under the receiver-operating characteristic curve (AUROC) of the FIB-4 (0.964) and the AUROC of the NAFLD fibrosis score (0.964) or P2/MS (0.940) for detecting advanced fibrosis. If P2/MS was implemented in the Korean patients with NAFLD, 68.9% of liver biopsies might be avoided.P2/MS has a high NPV for excluding advanced fibrosis in Korean patients with NAFLD, and can reduce the burden of liver biopsy in the majority of cases. Since there were few patients with advanced fibrosis, further studies are warranted in a cohort including more patients with advanced fibrosis to validate the low cut-off value.

    View details for PubMedID 21258197

  • Association between colorectal adenoma and coronary atherosclerosis detected by CT coronary angiography in Korean men; a cross-sectional study JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Yang, S. Y., Kim, Y. S., Chung, S. J., Song, J. H., Choi, S. Y., Park, M. J., Yim, J. y., Lim, S. h., Kim, D., Kim, C. H., Kim, J. S., Song, I. S. 2010; 25 (11): 1795-1799

    Abstract

    Colorectal adenoma and coronary artery disease (CAD) appear to share common risk factors, such as male gender, diabetes mellitus, smoking, and obesity. We investigated the relationship between colorectal adenoma and coronary atherosclerosis, as a risk factor for colorectal adenoma.A cross-sectional study was conducted on Korean men who presented for a health check-up. The subjects were 488 men (217 colorectal adenoma and 271 normal colonoscopic findings) who underwent colonoscopy and coronary computed tomography angiography (CTA) on the same day as a screening examination. Advanced colonic lesion was defined as a presence of adenoma with villous component, high-grade dysplasia, and/or with size of ≥1 cm. CTA findings were classified as normal, mild (low-grade atherosclerosis or <50% stenosis), and significant CAD (≥50% stenosis). Abnormal CTA findings included mild and significant CAD.Patients with abnormal CTA findings were more likely to have colorectal adenoma compared with those with normal CTA findings (P < 0.005). Furthermore, presence of advanced adenoma was significantly associated with significant CAD (P < 0.01). On multivariate analyses, abnormal CTA findings (OR = 1.66, 95% CI: 1.14-2.41, P < 0.01) and significant CAD (OR = 1.96, 95% CI: 1.15-3.35, P < 0.05) were found to be independent risk factors for colorectal adenoma after adjusting for age, current smoking, and metabolic syndrome.In this study, in the population who underwent CTA and colonoscopy for health check-up, prevalence of colorectal adenoma was greater in subjects with low-grade coronary atherosclerosis or significant CAD. The presence of advanced adenoma was significantly associated with significant CAD.

    View details for DOI 10.1111/j.1440-1746.2010.06330.x

    View details for Web of Science ID 000283597900015

    View details for PubMedID 21039843

  • General and abdominal obesity and abdominal visceral fat accumulation associated with coronary artery calcification in Korean men ATHEROSCLEROSIS Choi, S., Kim, D., Oh, B., Kim, M., Park, H. E., Lee, C., Cho, S. 2010; 213 (1): 273-278

    Abstract

    It is unclear whether visceral adipose tissue (VAT) is responsible for an increased risk of coronary artery calcification (CAC). We evaluated the associations between body mass index (BMI), waist circumference (WC) and abdominal VAT area with the CAC in healthy Korean men.This is a cross-sectional study of 1336 Korean men free of cardiovascular disease who underwent CAC score (CACS) by multislice computed tomography (CT) and abdominal CT as part of a routine medical examination. VAT area was measured at the level of the umbilicus using CT.Mean BMI, WC, total adipose tissue and VAT area were higher in subjects with moderate-to-severe CAC (CACS>100) compared to subjects with CACS ≤ 100. The subjects in the fourth quartile of VAT had significantly higher CACS and the greater prevalence of CAC presence and moderate-to-severe CAC than those in the first to third quartiles. The highest quartiles of BMI, WC and VAT area were significantly associated with moderate-to-severe CAC in the age- and CVD risk factor-adjusted model (OR [95% CI]=1.56 [1.11-2.19], 1.56 [1.12-2.18] and 1.42 [1.01-1.98] with p<0.05 for all, respectively).The higher levels of general and central measure of obesity and the amount of abdominal visceral fat were related to moderate-to-severe CAC in asymptomatic Korean men with relatively low risk.

    View details for DOI 10.1016/j.atherosclerosis.2010.07.052

    View details for Web of Science ID 000283356400092

    View details for PubMedID 20813366

  • Antituberculosis drug-induced liver injury in chronic hepatitis and cirrhosis JOURNAL OF INFECTION Park, W. B., Kim, W., Lee, K. L., Yim, J., Kim, M., Jung, Y. J., Kim, N. J., Kim, D. H., Kim, Y. J., Yoon, J., Oh, M., Lee, H. S. 2010; 61 (4): 323-329

    Abstract

    To evaluate the incidence, risk factors and outcomes for anti-tuberculosis (TB) drug-induced liver injury (DILI) in patients with chronic liver disease including cirrhosis.A total of 107 patients with chronic liver disease were assessed for anti-TB DILI. Anti-TB DILI was defined as elevation of alkaline phosphatase (ALP), aspartate transaminase, or alanine transaminase, or an increase in Child-Turcotte-Pugh score within 2 months of initiating anti-TB medication. The risk factors for anti-TB DILI were evaluated by multivariate logistic regression analysis.Fifty-eight (54%) patients had cirrhosis. Of 93 patients receiving one or more hepatotoxic anti-TB drugs, 18 (17%) experienced DILI: 11 (24%) among 46 patients with chronic hepatitis and 7 (15%) among 46 patients with compensated liver cirrhosis (P = 0.271). Independent risk factors for DILI were female sex, number of hepatotoxic anti-TB drugs administered and baseline ALP levels but not cirrhosis itself. Of the 18 patients with DILI, 13 (72%) successfully completed anti-TB treatment after switching to less hepatotoxic drug regimens.Hepatotoxic anti-TB drugs may be safely used in the patients with chronic liver disease including compensated cirrhosis if number of hepatotoxic drugs used is adjusted appropriately.

    View details for DOI 10.1016/j.jinf.2010.07.009

    View details for Web of Science ID 000281918100007

    View details for PubMedID 20670648

  • SERUM HBSAG LEVELS DURING PEGINTERFERON ALFA-2A TREATMENT IN HBEAG-POSITIVE CHRONIC HEPATITIS B: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL Kim, B., Kim, W., Song, F., Park, M., Yoon, J., Lee, Y., Park, S., Jung, E., Kim, D., Kim, Y., Lee, H. WILEY-BLACKWELL. 2010: 514A
  • ADD-ON ADEFOVIR IS SUPERIOR TO A SWITCH TO ENTECAVIR AS RESCUE THERAPY FOR LAMIVUDINE-RESISTANT PATIENTS WITH CHRONIC HEPATITIS B Kim, W., Jung, Y., Kim, D. WILEY-BLACKWELL. 2010: 540A
  • NON-ALCOHOLIC FATTY LIVER DISEASE IS ASSOCIATED WITH CORONARY ARTERY CALCIFICATION SCORE INDEPENDENT OF COMPUTED TOMOGRAPHY MEASURED VISCERAL ADIPOSITY Kim, D., Choi, S., Park, E., Yim, J., Kang, J., Kim, W., Kim, Y., Yoon, J., Lee, H. WILEY-BLACKWELL. 2010: 618A–619A
  • ASSOCIATION BETWEEN SUSPECTED NONALCOHOLIC FATTY LIVER DISEASE AND POLYCYSTIC OVARY SYNDROME Kim, D., Kim, J., Yim, J., Choi, Y. WILEY-BLACKWELL. 2010: 655A
  • HEPATITIS B ENVELOPE ANTIGEN SERONEGATIVITY PREDICTS INTRAHEPATIC RECURRENCE IN HEPATITIS B VIRUS-RELATED HEPATOCELLULAR CARCINOMA AFTER LOCAL ABLATION THERAPY: PROSPECTIVE COHORT STUDY Kim, W., Chung, G., Jung, Y., Kim, D., Kim, Y., Yoon, J., Kim, B. WILEY-BLACKWELL. 2010: 1173A
  • Efficacy of computed virtual chromoendoscopy on colorectal cancer screening: a prospective, randomized, back-to-back trial of Fuji Intelligent Color Enhancement versus conventional colonoscopy to compare adenoma miss rates GASTROINTESTINAL ENDOSCOPY Chung, S. J., Kim, D., Song, J. H., Park, M. J., Kim, Y. S., Kim, J. S., Jung, H. C., Song, I. S. 2010; 72 (1): 136-142

    Abstract

    Colonoscopy is the criterion standard for screening of colorectal neoplasms. Nonetheless, a substantial miss rate with conventional, white-light colonoscopy (WL) remains a challenge.To assess whether Fuji Intelligent Color Enhancement (FICE) can detect more adenomas than WL in screening colonoscopy.Prospective, randomized trial of tandem colonoscopy adjusted for withdrawal time and lavage effect.Seoul National University Hospital Healthcare System Gangnam Center, Korea.This study involved 359 average-risk adults undergoing screening colonoscopy.Patients were randomized to the first withdrawal with either FICE (FICE-WL group) or WL (WL-FICE group).The primary end point measure was the difference in adenoma miss rates, and the secondary outcome measure was the adenoma detection rate.We enrolled 359 patients (mean age 50.6 years, male 66.9%) and randomly assigned 181 to the WL-FICE group and 178 to the FICE-WL group. The number of adenomas detected by FICE and WL was 123 and 107, respectively. The adenoma miss rate with FICE showed no significant difference compared with that of WL (6.6% vs 8.3%, P = .59). Characteristics of lesions missed by use of FICE were similar to those missed by use of WL; 93% of overall missed polyps were < or =5 mm, and none were > or =1 cm. All missed adenomas were low grade and nonpedunculated. There was no significant difference between FICE and WL in adenoma detection rate (mean 0.64 vs 0.55 per patient, P = .65) nor percentage of patients with > or =1 adenoma (33.7% vs 30.4%, P = .74).Single-center study.FICE at screening colonoscopy did not improve the adenoma miss rate or detection rate compared with WL.

    View details for DOI 10.1016/j.gie.2010.01.055

    View details for Web of Science ID 000279687600023

    View details for PubMedID 20493487

  • Hepatic steatosis index: A simple screening tool reflecting nonalcoholic fatty liver disease DIGESTIVE AND LIVER DISEASE Lee, J., Kim, D., Kim, H. J., Lee, C., Yang, J. I., Kim, W., Kim, Y. J., Yoon, J., Cho, S., Sung, M., Lee, H. 2010; 42 (7): 503-508

    Abstract

    To optimize management of nonalcoholic fatty liver disease (NAFLD), a simple screening tool is necessary. In this study, we aimed to devise a simple index of NAFLD.A cross-sectional study with 10,724 health check-up subjects (5362 cases with NAFLD versus age- and sex-matched controls) was conducted. Study subjects were randomly assigned to a derivation cohort or a validation cohort.Multivariate analysis indicated that high serum alanine aminotransferase (ALT) to serum aspartate aminotransferase (AST) ratio, high body mass index (BMI), and diabetes mellitus were independent risk factors of NAFLD (all P<0.001). Using these variables, a formula was derived by a logistic regression model: hepatic steatosis index (HSI)= 8 x(ALT/AST ratio)+BMI (+2, if female; +2, if diabetes mellitus). HSI had an area under receiver-operating curve of 0.812 (95% confidence interval, 0.801-0.824). At values of <30.0 or >36.0, HSI ruled out NAFLD with a sensitivity of 93.1%, or detected NAFLD with a specificity of 92.4%, respectively. Of 2692 subjects with HSI <30.0 or >36.0 in the derivation cohort, 2305 (85.6%) were correctly classified. HSI was validated in the subsequent validation cohort.HSI is a simple, efficient screening tool for NAFLD that may be utilized for selecting individuals for liver ultrasonography and for determining the need for lifestyle modifications.

    View details for DOI 10.1016/j.dld.2009.08.002

    View details for Web of Science ID 000279515500011

    View details for PubMedID 19766548

  • Efficacy of Computed Virtual Chromoendoscopy on Colorectal Cancer Screening: A Prospective Randomized Rack-to-Back Trial of Fuji Intelligent Color Enhancement vs Conventional Colonoscopy to Compare Adenoma Miss Rates Chung, S., Kim, D., Park, M., Song, J., Kim, Y., Kim, J., Jung, H., Song, I. MOSBY-ELSEVIER. 2010: AB247
  • The Prevalence of and Risk Factors for Barrett's Esophagus in a Korean Population A Nationwide Multicenter Prospective Study JOURNAL OF CLINICAL GASTROENTEROLOGY Park, J., Kim, J., Kim, H., Chung, M., Park, S., Baik, G., Nah, B., Nam, S., Seo, K., Ko, B., Jang, J., Kim, B., Kim, J., Choi, Y., Joo, M., Kim, J., Cho, M., Kim, N., Park, S., Jung, H., Chung, I., Korean Coll Helicobacter Upper Gas 2009; 43 (10): 907–14

    Abstract

    The aim of this study was to evaluate the prevalence of Barrett's esophagus (BE) in the general Korean population by evaluating screening esophagogastroduodenoscopy. In addition, the risk factors for BE were identified.An esophagogastroduodenoscopy examination was performed in 25,536 subjects who had upper endoscopy screening from January 2006 to July 2006.Two hundred and fifteen subjects were confirmed to have BE by pathology, thus the prevalence of BE was calculated to be 0.84%. The endoscopic findings were subdivided into 2 groups: BE without reflux esophagitis (RE), which included 167 (77.7%), and BE with RE, which included 48 (22.3%). The analysis of symptoms showed that only 60.1% of the subjects with BE had reflux symptoms. Chest pain [odds ratio (OR): 1.48, 95% confidence interval (CI): 1.04-2.11] and epigastric soreness (OR: 1.42, 95% CI: 1.05-1.93) were found more frequently in the subjects with BE compared with the normal subjects. The multivariate analysis showed that the risk factors for all subjects with BE were a male sex (OR: 1.82, 95% CI: 1.32-2.50), nonsteroidal anti-inflammatory drug use (OR: 2.02, 95% CI: 1.28-3.20), hiatal hernia (OR: 5.66, 95% CI: 3.70-8.66), and an age > or = 60 compared with an age < 40 (OR: 1.81, 95% CI: 1.07-3.09). There was no significant difference associated with RE.The prevalence of BE in Korean patients presenting for a routine health check-up was 0.84%, lower than reported in Western countries. Among the subjects with BE 77.7% did not have endoscopic erosions and there were no reflux symptoms in 39.9%. These results suggest that regular endoscopic screening with a high index of suspicion is necessary for the diagnosis of BE.

    View details for DOI 10.1097/MCG.0b013e318196bd11

    View details for Web of Science ID 000271307200004

    View details for PubMedID 19417682

  • Clinical Spectrum of Reflux Esophagitis Among 25,536 Koreans Who Underwent a Health Check-up A Nationwide Multicenter Prospective, Endoscopy-based Study JOURNAL OF CLINICAL GASTROENTEROLOGY Shim, K., Hong, S. J., Sung, J. K., Park, K. S., Kim, S., Park, H., Kim, Y. S., Lim, S. h., Kim, C. H., Park, M. J., Kim, J. Y., Cho, K. R., Kim, D., Park, S. J., Jee, S., Kim, J. I., Park, J. Y., Song, G. A., Jung, H., Lee, Y. C., Kim, J. G., Kim, J. J., Kim, N., Park, S., Jung, H. C., Chung, I. 2009; 43 (7): 632-638

    Abstract

    Gastroesophageal reflux is a commonly encountered condition, but detailed data on reflux symptoms in Asian countries are lacking.To evaluate the prevalence and to document the clinical spectrum of endoscopic reflux esophagitis (RE).A total 25,536 subjects underwent an upper gastrointestinal endoscopic examination as part of a health check, and completed a gastroesophageal reflux questionnaire. Endoscopic findings classified according to the Los Angeles (LA) classification and the data from gastroesophageal reflux questionnaire were analyzed.On the basis of endoscopic findings, 2019 subjects (7.91%) were found to have RE: 5.87% in LA-A; 1.84% in LA-B; 0.18% in LA-C; and 0.02% in LA-D. Heartburn, acid regurgitation, chest pain, hoarseness, globus sensation, cough, and epigastric soreness were found to be associated with RE (P<0.05). Heartburn, acid regurgitation, and epigastric soreness were more frequent in LA-B than in LA-A (P<0.05). Epigastric soreness was most bothersome in LA-A and LA-B, and acid regurgitation was most bothersome in LA-C and LA-D (P<0.01). Heartburn, hoarseness, and globus sensation were more frequent in men with RE, and acid regurgitation was most common in women.The prevalence of RE was found to be 7.91% in Korea, and the profiles of reflux symptoms were found to depend on grade of RE and sex.

    View details for Web of Science ID 000268350100007

    View details for PubMedID 19169148

  • ELEVATED LIVER ENZYMES AS A MARKER OF METABOLIC SYNDROME AND INSULIN RESISTANCE; A CROSS-SECTIONAL CASE-CONTROL STUDY OF 16,621 HEALTHY SUBJECTS Kim, D., Kim, Y., Kim, W., Kim, B., Yoon, J., Lee, H. JOHN WILEY & SONS INC. 2008: 823A
  • The efficacy of intravenous contrast-enhanced 16-raw multidetector CT colonography for detecting patients with colorectal polyps in an asymptomatic population in Korea JOURNAL OF CLINICAL GASTROENTEROLOGY Kim, Y. S., Kim, N., Kim, S. H., Park, M. J., Lim, S. h., Yim, J. y., Cho, K. R., Kim, S. S., Kim, D. H., Eun, H. W., Cho, K. s., Kim, J. H., Choi, B. I., Jung, H. C., Song, I. S., Shin, C. s., Cho, S., Oh, B. 2008; 42 (7): 791-798

    Abstract

    The purpose of this study is to compare the sensitivity of computed tomography (CT) colonography (CTC) with that of colonoscopy for detecting patients with colorectal polyps in an asymptomatic screening population in Korea, thus to evaluate a possibility, whether CTC could be used as a screening tool for colorectal polyps.A total of 241 asymptomatic adults underwent intravenous contrast-enhanced CTC and colonoscopy successively on the same day. Bowel preparation was performed by 4 L of polyethylene glycol (n=172) or 90 mL of sodium phosphate (n=69). The CTC findings were released to the colonoscopists after the first examination of each segment, a procedure known as segmental unblinded colonoscopy, and were used as the reference standard. The diagnostic performance of CTC for colorectal polyps was calculated.The per-patient sensitivities of CTC were 68.5% (37/54) and 86.7% (13/15) for polyp > or = 6 and > or = 10 mm, inferior to those of colonoscopy, 92.6% (50/54) and 100% (15/15), respectively. The per-polyp sensitivities of CTC were 60.4% (61/101) and 72.7% (16/22) for polyp > or = 6 and > or = 10 mm, respectively. The low sensitivity of CTC was related with flat morphology. CTC detected only 37.5% (9/24) of flat polyps > or = 6 mm. Bowel preparation by sodium phosphate further decreased the positive predictive value and specificity than by polyethylene glycol.Screening by CTC with asymptomatic population was not promising in Korea despite using advanced CT technology (16-row detector). Bowel preparation was one of the key determinants of the specificity of CTC.

    View details for Web of Science ID 000258389800006

    View details for PubMedID 18580500

  • Clinical significance of minimal change lesions of the esophagus in a healthy Korean population: A nationwide multi-center prospective study JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Lee, J., Kim, N., Chung, I., Jo, Y., Seo, G., Kim, S., Im, E., Kim, H., Park, S., Lee, S., Cha, H., Lee, K., Hyun, D., Kim, H., Kim, S., Shin, J., Park, S., Chung, H., Chung, I., Korean Coll Helicobacter Upper 2008; 23 (7): 1153–57

    Abstract

    At least half of the patients with typical reflux symptoms have non-erosive reflux disease (NERD). Minimal change lesions are commonly seen in the screening endoscopic examinations for individuals without clinically significant symptoms. We evaluated the correlation between minimal changes and symptoms in individuals visiting the hospital for routine health check-up by a nationwide survey in 2006.Upper gastrointestinal endoscopic examinations as a health check-up were performed for 25,536 patients. Among them, symptom questionnaires were given in 23,350 patients without mucosal break or Barrett's esophagus. Endoscopic findings of the lower esophagus were divided into normal or minimal changes. Minimal changes in the present study included white turbid discoloration and Z-line blurring.Among a total of 25,536 subjects, reflux esophagitis was found in 2019 subjects (7.91%) and 3043 patients (11.9%) were classified as having minimal changes. History of gastroesophageal reflux disease (GERD) was more commonly found in individuals with minimal changes. Among the reflux-related symptoms, heartburn, acid regurgitation, globus sensation, and epigastric soreness were related to the minimal changes of the esophagus. Especially, individuals with globus sensation or epigastric soreness were more likely to have minimal changes compared to individuals without respective symptoms. Male gender, current smoker, history of H. pylori eradication, frequent stooping at work, hiatal hernia, and atrophic/metaplastic gastritis were found to be risk factors for minimal changes.The minimal changes were closely related with upper gastrointestinal symptoms and had similar risk factors for GERD, suggesting that minimal changes could be considered as early endoscopic findings of GERD.

    View details for DOI 10.1111/j.1440-1746.2008.05299.x

    View details for Web of Science ID 000257756400026

    View details for PubMedID 18205773

  • Extracolonic findings in an asymptomatic screening population undergoing intravenous contrast-enhanced computed tomography colonography JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Kim, Y., Kim, N., Kim, S., Cho, K., Park, M., Choi, S., Lim, S., Yim, J., Cho, K., Kim, C., Kim, D., Kim, S., Kim, J., Choi, B., Jung, H., Song, I., Shin, C., Cho, S., Oh, B. 2008; 23 (7): E49–E57

    Abstract

    The purpose of this study was to evaluate extracolonic findings that could be encountered with computed tomography colonography (CTC) using intravenous (IV) contrast material in an asymptomatic screening population.Intravenous contrast medium-enhanced CTC was performed in 2230 asymptomatic adults (mean age, 57.5 years). Axial images were prospectively examined for extracolonic lesions. These findings were classified into three categories: potentially important findings, likely unimportant findings, and clinically unimportant findings. Potentially important extracolonic findings were defined as those which required immediate further diagnostic studies and treatment. Clinical and radiologic follow up, missed lesions and clinical outcomes were assessed using medical records (mean duration of follow up, 1.6 years).A total of 115 new potentially important findings in 5.2% of subjects (115/2230) were found. Subsequent medical or surgical intervention was performed in 2.0% (45/2230). New extracolonic cancer was detected in 0.5% (12/2230), and the majority of them (83.3%) were not metastasized. Computed tomography colonography missed eight potentially important extracolonic findings in eight subjects (0.4%, 8/2230): 0.8-cm early-stage prostatic cancer, six adrenal mass and one intraductal papillary mucinous tumor. There were no severe life-threatening complications related to contrast medium.Intravenous contrast-enhanced CTC could safely detect asymptomatic early-stage extracolonic malignant diseases without an unreasonable number of additional work-ups, thus reducing their morbidity or mortality.

    View details for DOI 10.1111/j.1440-1746.2007.05060.x

    View details for Web of Science ID 000257756500009

    View details for PubMedID 17645481

  • Visceral adipose tissue area is an independent risk factor for hepatic steatosis JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Park, B. J., Kim, Y. J., Kim, D. H., Kim, W., Jung, Y. J., Yoon, J. H., Kim, C. Y., Cho, Y. M., Kim, S. H., Lee, K. B., Jang, J. J., Lee, H. S. 2008; 23 (6): 900-907

    Abstract

    Recent data indicate that hepatic steatosis is associated with insulin resistance, dyslipidemia and obesity (especially central body fat distribution). There have been few studies on the correlation between biopsy-proven hepatic steatosis and the above factors in a disease-free population. The aim of the present study was to evaluate the relation between hepatic steatosis assessed by biopsy and clinical characteristics including regional fat distribution measured by computed tomography (CT) in living liver donors.Laboratory data, liver/spleen Hounsfield ratio (L/S ratio), regional fat distribution by CT and liver status by biopsy were evaluated retrospectively in a total of 177 living liver donors without a history of alcohol intake.The unpaired t-test showed that age, triglycerides (TG), high density lipoprotein, total cholesterol, alanine aminotransferase, body mass index, L/S ratio, visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) were associated with hepatic steatosis. In the multiple logistic regression analysis, VAT (odds ratio 1.031, 95% CI 1.013-1.048, P < 0.01) and TG (odds ratio 1.012, 95% CI 1.004-1.020, P < 0.01) were independent risk factors of hepatic steatosis. Subgroup analysis also showed that VAT was an independent risk factor in men (odds ratio 1.022, 95% CI 1.003-1.041, P < 0.05) and women (odds ratio 1.086, 95% CI 1.010-1.168, P < 0.05).Our results suggest that visceral abdominal adiposity is correlated with hepatic steatosis in healthy living liver donors.

    View details for DOI 10.1111/j.1440-1746.2007.05212.x

    View details for Web of Science ID 000256540200015

    View details for PubMedID 17995942

  • Evaluation of the Korean Isolate-1 tachyzoite antigen for serodiagnosis of toxoplasmosis KOREAN JOURNAL OF PARASITOLOGY Shin, E., Kim, D., Lin, M., Lee, J., Kim, H., Ahn, M., Chai, J. 2008; 46 (1): 45-48

    Abstract

    To evaluate the usefulness of the Korean Isolate-1 (KI-1) antigen for serodiagnosis of toxoplasmosis, antigen profiles of KI-1 tachyzoites were analyzed in comparison with RH tachyzoites by SDS-PAGE and immunoblotting. ELISA was performed on latex agglutination (LA)-positive and negative serum samples using KI-1 and RH antigens. Immunoblotting of the KI-1 antigen showed multiple antigen bands with molecular sizes of 22-105 kDa. Among them, 1 and 6 common bands were noted against a KI-1-infected and a RH-infected human serum, respectively, which represented differences in antigenic profiles between KI-1 and RH tachyzoites. However, all 9 LA-positive human sera were found positive by ELISA, and all 12 LA-negative sera were negative by ELISA; the correlation between the ELISA titers and LA titers was high (r = 0.749). Our results suggest that tachyzoites of KI-1 may be useful for serodiagnosis of human toxoplasmosis.

    View details for DOI 10.3347/kjp.2008.46.1.45

    View details for Web of Science ID 000255714000008

    View details for PubMedID 18344678

    View details for PubMedCentralID PMC2526296

  • [A case of mucinous noncystic carcinoma of the pancreas]. The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi Jung, J. Y., Song, M. H., Park, Y. S., Jo, Y. J., Kim, S. H., Jun, D., Kim, D. H., Lee, W. M. 2008; 51 (3): 204–8

    Abstract

    Mucinous (colloid) carcinoma is defined as pools of stromal extracellular mucin containing scanty, floating carcinoma cells. It is a well-defined entity in breast or large bowel. However, mucinous noncystic carcinoma of the pancreas (MNCC) is uncommon, comprising between 1% and 3% of all carcinomas of the pancreas. In the past, MNCC generally had been categorized together with ordinary ductal adenocarcinoma or misdiagnosed as mucinous cystadenocarcinoma or signet-ring cell carcinoma. The new WHO classification lists MNCC as a variant of ductal adenocarcinoma. Herein, we report a 32-year-old woman with incidentally found pancreatic body mass who underwent subtotal pancreatectomy. She was diagnosed as MNCC histologically.

    View details for PubMedID 18451696

  • [Nonalcoholic fatty liver disease as a risk factor of cardiovascular disease: relation of non-alcoholic fatty liver disease to carotid atherosclerosis]. The Korean journal of hepatology Choi, S., Kim, D., Kang, J. H., Park, M. J., Kim, Y. S., Lim, S. h., Kim, C. H., Lee, H. 2008; 14 (1): 77-88

    Abstract

    Non-alcoholic fatty liver disease (NAFLD) is closely associated with abdominal obesity, dyslipidemia, hypertension, and Type 2 diabetes, which are all features of the metabolic syndrome. The aim of the present study was to elucidate whether NAFLD is associated with carotid atherosclerosis.The study population comprised 659 subjects without hepatitis B and C infections and who did not consume alcohol. Fatty infiltrations of liver were detected by abdominal ultrasonography, and intima-media thickness (IMT) and plaque prevalence were estimated by carotid ultrasonography.The mean values of systolic and diastolic pressures, body mass index (BMI), aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, uric acid, total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, fasting glucose, fasting insulin, homeostasis model of assessment (HOMA) index, hemoglobin A1c, and plasminogen activator inhibitor-1 differed significantly between patients with NAFLD (n=314) and normal controls (n=345). The carotid IMT was 0.817+/-0.212 (mean+/-SD) mm in patients with NAFLD and 0.757+/-0.198 mm in normal controls (p<0.001). The prevalence of carotid plaques was higher in patients with NAFLD (26.4%) than in normal controls (15.9%) (p<0.001). This association persisted significantly after adjusting for age, sex, BMI, HOMA index and individual factors of metabolic syndrome by multiple logistic regression analysis.Patients with NAFLD are at a high risk of carotid atherosclerosis regardless of metabolic syndrome and classical cardiovascular risk factors. Therefore, the detection of NAFLD should alert to the existence of an increased cardiovascular risk. Moreover, NAFLD might be an independent risk factor for cardiovascular disease.

    View details for DOI 10.3350/kjhep.2008.14.1.77

    View details for PubMedID 18367860

  • Is Metabolic Syndrome One of the Risk Factors for Gallbladder Polyps Found by Ultrasonography during Health Screening? GUT AND LIVER Lim, S. h., Kim, D. H., Park, M. J., Kim, Y. S., Kim, C. H., Yim, J. Y., Cho, K. R., Kim, S. S., Choi, S. H., Kim, N., Cho, S. H., Oh, B. 2007; 1 (2): 138-144

    Abstract

    We conducted this study to identify the risk factors for finding gallbladder polyps (GBP) in Korean subjects during health screening, and to determine the nature of the association between the presence of metabolic syndrome (MS) and the development of GBP METHODS: A total of 1,523 subjects were enrolled, comprising 264 with GBP (81 women and 183 men) and 1,259 controls (696 women and 563 men with normal GB). Body mass index (BMI), waist circumference (WC), blood pressure (BP), insulin, fasting blood sugar (FBS), lipids, liver enzymes, hepatitis B antigens (HBs Ag), and hepatitis C antibodies (HCV Ab) were measured. MS was considered to be present when three or more of the NCEP-ATPIII (National Cholesterol Education Program-Adult Treatment Panel III) criteria were satisfied. Insulin resistance was calculated by homeostasis model assessment of insulin resistance (HOMA-IR). Independent risk factors were analyzed by logistic regression analysis.Univariate analysis revealed that the risk factors for GBP were age, sex, WC, smoking history, BP, BMI, FBS, serum lipids, HOMA-IR score, and MS. Multivariate logistic regression analysis revealed that the risk factors for GBP were presence of MS (Odds Ratio (OR)=2.35, 95%Confidence Interval (CI)=1.53-3.60), being male (OR=2.34, 95%CI=1.72-3.18), HOMA-IR score>2.5 (OR=1.64, 95%CI=1.19-2.26), and higher WC (OR=1.4, 95%CI=1.05-1.88). MS was present in 20.8% and 5.9% of GBP patients and controls, respectively, and was the highest risk factor for GBP.MS, male, insulin resistance, and abdominal obesity are probably risk factors for GBP, with MS appearing to be strongly associated with GBP in Koreans.

    View details for Web of Science ID 000206470000006

    View details for PubMedID 20485630

    View details for PubMedCentralID PMC2871628

  • Gene expression based recurrence prediction of HBV-related human hepatocellular carcinoma Kim, Y., Woo, H., Jung, Y., Kim, D., Park, B., Yi, N., Suh, K., Lee, K., Yoon, J., Thorgeirsson, S. S., Lee, H. JOHN WILEY & SONS INC. 2007: 789A
  • Features of Gastric Neoplasm Detected during the Screening Examination GUT AND LIVER Park, M. J., Kim, D. H., Lim, S. H., Yim, J. y., Kim, Y. S., Cho, K. R., Kim, C. H., Jung, H. C., Song, I. S., Kim, S. S., Yoon, D. H., Shin, C. s., Cho, S., Oh, B., Lee, D. H. 2007; 1 (1): 33-39

    Abstract

    Gastric cancer is the leading malignancy in Korea and early detection through the health screening seems to be important. The aims of this study were to investigate the features of gastric neoplasms detected during screening, and to figure out the risk factors of these lesions.From October 2003 to September 2005, subjects who visited Seoul National University Hospital Healthcare System Gangnam Center for health check-up were included in the study. The program included a questionnaire and tests including anti-Helicobacter pylori (H. pylori) antibody, esophagogastroduodenoscopy or double contrast upper gastrointestinal study. To figure out the risk factors, an age and gender-matched, four-fold sized control group was selected from the subjects.Of 25, 432 subjects, 122 cases of gastric neoplasms were detected including 61 adenocarcinoma (45 early gastric cancers), 53 adenoma, 7 mucosa-associated lymphoid tissue lymphoma, and one metastatic cancer. There was no significant statistical difference in basal characteristics of the subjects between gastric adenocarcinoma and adenoma. When comparing with the control group those without gastric neoplasms, smoking history, family history of stomach cancer, and H. pylori seropositivity were found to be significant risk factors for gastric neoplasms. Metabolic syndrome was more prevalent in adenoma than in the control (p<0.05).The health screening may be beneficial in early detection of gastric cancer. In addition, metabolic syndrome might be related with gastric adenoma.

    View details for Web of Science ID 000264332600007

    View details for PubMedID 20485656

    View details for PubMedCentralID PMC2871660

  • Efficacy of esomeprazole and rabeprazole for Helicobacter pylori eradication in patients with peptic ulcer Kim, D., Kim, J. J., Kim, Y., Rhee, P. BLACKWELL PUBLISHING. 2006: A404
  • NSC (New Songdo City: newly developed city as free economic zone in South Korea) ubiquitous healthcare project--developing prospective health management model, integrating on-line and off-line healthcare service. AMIA ... Annual Symposium proceedings. AMIA Symposium Yoon, D. H., Park, M. J., Kim, D. H., Park, J. H., Choi, S. H., Choi, S. Y., Jeong, I. K., Sim, W. H., Shin, C. S., Cho, S. H., Oh, B. H. 2006: 1152

    View details for PubMedID 17238771

  • [Expression of hedgehog proteins in periampullary cancer]. The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi Lee, S. Y., Lee, K. T., Jang, K. T., Choi, S. H., Heo, J. S., Kim, D. H., Lee, J. K., Paik, S. W., Rhee, J. C. 2005; 46 (4): 291-296

    Abstract

    Hedgehog protein is an essential molecule for gastrointestinal tract development, and disruption of hedgehog signaling pathway is linked to some gastrointestinal tumorigenesis. Here, we performed hedgehog immunostaining in periampullary cancer to evaluate the differences according to the location type of cancer and the differentiation of adenocarcinoma.We retrieved surgical specimens from 43 periampullary cancer patients (15 ampulla of Vater cancer, 12 distal common bile duct cancer, 13 pancreatic head cancer, and 3 combined ampulla of Vater/bile duct cancer). Immunohistochemical stain was performed in both normal and cancerous tissue portions of each case using Sonic hedgehog (H-160) rabbit polyclonal antibody. Immunohistochemical stain results were grouped into three groups according to the percentage of positive cytoplasmic stain in tumor volume (unstained: <5%, weakly stained: 5-50%, and strongly stained: >50%).All of the normal tissue revealed negative immunohistochemical stain while cancerous tissue revealed positivity in 95.3% (41/43 cases). Strongly stained cases were more frequently seen in ampulla of Vater cancers (13/15) and in combined ampulla of Vater/bile duct cancers (3/3) than in distal common bile duct cancers (4/12) and in pancreatic head cancers (3/13) (p=0.002). In addition, strongly stained cases were more frequently seen in well-differentiated adenocarcinoma than the others (p<0.001).Most of the periampullary cancers show hedgehog protein expression. In addition, hedgehog protein immunostainings shows stronger expression in ampulla of Vater cancers and in well-differentiated adenocarcinoma.

    View details for PubMedID 16247273

  • [A prospective study on the prevalence and clinical significance of autoantibodies in patients with suspected nonalcoholic fatty liver disease]. The Korean journal of hepatology Cho, D. H., Choi, M. S., Kim, D. H., Kim, D. Y., Shim, S. G., Lee, J. H., Koh, K. C., Paik, S. W., Yoo, B. C., Rhee, J. C. 2005; 11 (3): 261-267

    Abstract

    Exclusion of liver disease from other causes such as autoimmune hepatitis is necessary for diagnosis of nonalcoholic fatty liver disease (NAFLD). However, there has been no study on the prevalence and significance of autoantibodies in the patients with clinically suspected NAFLD in Korea, where hepatitis B is endemic and autoimmune hepatitis is relatively uncommon.We prospectively tested for anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and anti-mitochondrial antibody (AMA) in 135 serially enrolled patients with suspected NAFLD. We compared the clinical characteristics and biochemical indices of the ANA-positive or ASMA-positive group with those of the autoantibody-negative group.Sixteen patients (11.8%) had serum autoantibodies; there was ANA in 8 patients (5.9%), ASMA in 7 (5.1%), and AMA in 2 (1.5%). Both ANA and AMA were positive in one patient. The ANA-positive or ASMA-positive group showed an older age (49.5+/-13.0 vs. 42.0+/-10.9 years, respectively, P=0.018) and higher levels of serum globulin (3.1+/-0.4 vs. 2.9+/-0.4 g/dL, respectively, P=0.037), compared with the autoantibody-negative group. Two cases with positive ANA or ASMA fulfilled the diagnostic criteria for probable autoimmune hepatitis and two cases with positive AMA were suspected as primary biliary cirrhosis.These findings suggest that autoantibodies could be found in some patients with suspected NAFLD in Korea, AMA-positivity or ASMA-positivity could be associated with old age and high serum globulin, and some of the autoantibody-positive cases could be diagnosed as autoimmune hepatitis or primary biliary cirrhosis. Further studies are necessary to clarify the clinical significance of autoantibody positivity in those patients.

    View details for PubMedID 16177552