Faculty Bibliography

BACKGROUND:Fibroscan-derived liver stiffness decreases after anti-viral treatment for hepatitis C virus (HCV) infection, which may affect the associations and interpretation of liver stiffness. AIMS:To assess whether liver stiffness pre- or post-anti-viral therapy is associated with the development of decompensated cirrhosis, hepatocellular carcinoma (HCC) or death. METHODS:In this retrospective cohort study, we identified US veterans who initiated HCV treatment and had at least one liver stiffness before (n = 492) or after (n = 877) HCV therapy. We used Cox proportional hazards regression (adjusting for age, race/ethnicity, history of cirrhosis, body mass index, diabetes, FIB-4 score, Charlson comorbidity index, alcohol use disorder, Model for end-stage liver disease score and sustained virological response status) to determine the associations between pre- or post-treatment liver stiffness values and the development of decompensated cirrhosis, HCC, death or liver transplant. RESULTS:In the post-treatment liver stiffness cohort, during a mean follow-up of 27.3 months, 21 (2.4%) developed decompensated cirrhosis, 26 (3.0%) developed HCC and 57 (6.5%) died or underwent liver transplant. Compared to patients with post-treatment liver stiffness ≤12.5 kPa, those with post-treatment liver stiffness >20 kPa, had higher rates of developing decompensated cirrhosis (adjusted HR 3.85, 95% CI 1.29-11.50) and the composite outcome of death, liver transplant, decompensated cirrhosis or HCC (adjusted HR 1.95, 95% CI: 1.07-3.56). There were no significant associations between pre-treatment liver stiffness and any outcomes on multivariable analysis. CONCLUSIONS:Post-treatment liver stiffness >20 kPa, but not pre-treatment liver stiffness, was independently associated with the development of decompensated cirrhosis and the composite outcome in multivariable analyses. Measuring liver stiffness should be considered after anti-viral treatment because it predicts adverse outcomes even beyond routinely available clinical predictors.

Outcomes related to alcohol use after hepatitis C virus (HCV) treatment are unknown in the direct-acting antiviral (DAA) era. We assessed levels of alcohol use before and after HCV treatment and their association with long-term outcomes in a cohort of U.S. veterans. In this retrospective cohort analysis, 29,037 patients who initiated DAA regimens between 2013 and 2015 were followed for a mean of 3.04 years. We categorized alcohol use into three categories (nondrinking, low-level drinking, and unhealthy drinking) using Alcohol Use Disorders Identification Test-Consumption questionnaires administered within 1 year before (baseline) and after treatment. Multivariable Cox proportional hazards regression was used to determine the associations between alcohol use and mortality or liver-related outcomes. Before DAA treatment, 68% of veterans reported nondrinking, 22.9% reported low-level drinking, and 9.1% reported unhealthy drinking. Compared to patients with baseline non-drinking, those with unhealthy drinking had a higher risk of mortality (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI]: 1.34-1.75) and decompensated cirrhosis (adjusted HR 1.30, 95% CI: 1.06-1.59) and lower likelihood of liver transplantation (adjusted HR 0.24, 95% CI: 0.06-0.92). These associations were greater in patients without sustained virologic response than in those with sustained virologic response. When alcohol use before and after treatment was modeled as a time-varying covariate, similar associations were observed. Survival analysis also found that unhealthy drinking was significantly associated with a lower probability of survival compared with nondrinking. Low-level alcohol use was not associated with increased risk of adverse outcomes. Conclusion: In this large cohort of U.S. veterans with HCV who received DAAs, unhealthy drinking was common and associated with a higher risk of posttreatment mortality. Interventions to achieve alcohol cessation before and during antiviral treatment should be encouraged.