Faculty Bibliography

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.

Treatment of chronic hepatitis C virus (HCV) infection has been revolutionized with the development of direct-acting antiviral agents (DAAs). Eight to twelve weeks of all-oral, once-daily treatments is now the standard of care and viral eradication can be achieved in >95% across different patient populations. Despite these advances, several unresolved issues remain, including treatment of HCV genotype 3, chronic kidney disease, and in patients in whom DAA therapy has failed. Glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) are the most recently approved DAA regimens. Given the overwhelming success of modern DAA-based therapies, GLE/PIB and SOF/VEL/VOX are also likely to represent the last DAAs to be approved. Both are pangenotypic, once-daily, all-oral DAA combinations that have the potential to close the gaps in the current DAA treatment portfolio. Here, we review the challenges associated with current DAAs and how these two regimens may be implemented in existing treatment algorithms.

Background: NAFLD and AFLD are overlapping liver diseases in which both metabolic syndrome (MS) and alcohol consumption contribute to progressive liver disease. Aim: To assess the impact of alcohol consumption and MS on mortality of individuals with NAFLD and AFLD. Methods: National Health and Nutrition and Examination Survey III (1988-1994)-National Death Index linked files were used to select participants with at least mild hepatic steatosis on an ultrasound. All other causes of liver disease (HBV, HCV, iron overload) were excluded. Alcohol consumption was selfreported as mean number of drinks per day for 1 year prior to data collection. Using alcohol consumption data, study cohort was divided into 5 groups: no alcohol use, minimal (<=3 and <=1.5 drinks/week for men and women), moderate (>minimal but <=2 and <=1 drinks/day for men and women), substantial (>moderate but <=3 and <=1.5 drinks/day for men and women), and excessive (>3 and 1.5 drinks/day for men and women). Association of alcohol consumption with mortality was quantified using Cox proportional hazard model while accounting for the survey design. Results: The study cohort included 4,309 individuals with hepatic steatosis: mean age 46.0 years, 51% male, 76% white, 46% with MS (ATPIII Criteria). Of the study cohort, 55.8% reported no, 18.4%-minimal, 16.7%-moderate, 3.7%-substantial, and 5.4%-excessive alcohol use. After mean follow-up of 20 years, 23% of participants died. Individuals with steatosis who reported excessive alcohol consumption were more commonly male and smokers (both p<0.05). Despite similar age (p=0.69), they had significantly higher mortality rate in comparison to those with steatosis and non-excessive alcohol use (33.0% vs. 22.5%, p=0.001), especially after 5 years of follow-up. In multivariate analysis, presence of MS [adjusted hazard ratio (aHR)=1.38 (1.09-1.76)], older age [aHR=1.094 (1.080-1.108)], smoking [aHR=2.101 (1.628-2.710)] and male gender [aHR=1.315 (1.125-1.538)] were independently associated with an increased risk of mortality in individuals with hepatic steatosis. In addition, excessive alcohol consumption was independently associated with mortality after adjustment for confounders: aHR=1.61 (1.12-2.33), p=0.01; lower average amounts of alcohol consumption were not associated with mortality (all p>0.20). In a subgroup analysis, association of excessive alcohol use with mortality was significant in individuals with MS [aHR=2.45 (1.37-4.39)] but not without MS (p=0.86). Conclusion: Excessive alcohol consumption is associated with increased mortality in the presence of MS, suggesting an important overlap between NAFLD and AFLD