Analysis of Repeat Hepatitis C Viremia After Sustained Virologic Response in a Large Cohort of US Veterans.

Abstract

Background: Chronic hepatitis C virus (HCV) infection affects >1% of the US population and a larger percentage of US veterans. Direct-acting antiviral (DAA) medications achieve viral cure, termed sustained virologic response (SVR), but repeat viremia after SVR is recognized. Prior work has been limited by electronic medical record data. We aim to better understand repeat viremia in the DAA era through detailed chart review.

Methods: We identified 1129 individuals from the Veterans Health Administration (VHA) who achieved SVR using DAA therapy but subsequently had detectable HCV viremia. A random subset of 110 was chart-reviewed and assigned to 1 of the following 4 categories using laboratory, diagnosis, and chart review data: definite reinfection (25.5%), probable reinfection (25.5%), false-positive (11.8%), and presumed late relapse (37.3%). We conducted between-group analysis of variance to identify demographic, behavioral, and laboratory features specific to each.

Results: In our medical record cohort (n = 1129), substance use and unstable housing were common, and median time to repeat viremia was 1.9 years. In our chart review cohort (n = 110), younger age (18-34 years) and substance use were more frequent in definite or probable reinfection. Presumed relapse had comparatively more hepatocellular carcinoma (HCC; 20%, P < .05), and more than half occurred prior to 1 year. The unique category of false-positive has not previously been reported.

Conclusions: This study deepens our understanding of HCV reinfection and relapse and highlights features including the HCV and opioid syndemic, contribution of laboratory error, possibility of a viral reservoir in HCC, and clinical engagement implications for those with ongoing risk.