Mediation effect of hepatitis B and C on mortality.

Abstract

Hepatitis B (HBV) and C (HCV) viruses cause many liver diseases. To move beyond statistical interaction, we aimed to assess the coordinated effect of the two viruses on mortality using mediation analyses. A prospective cohort study of 3837 residents in Taiwan examined participants seropositive for hepatitis B, of which 181 subjects (4.7%) were co-infected by HCV and 589 died during follow-up. Mediation analyses for cause-specific mortality were performed using Cox proportional hazards model. Follow-up HBV viral load was inversely correlated with baseline HCV viral load (r(2)=-0.074; P<0.001). For HCV serum viral load increasing from 800 to 404,000IU/mL (minimum to median) at baseline, the effect of HCV mediated through HBV viral load decreased the all-cause mortality with a hazard ratio (HR) of 0.89 (95% confidence interval (CI) 0.85, 0.94; P<0.001), and the effect independent of HBV viral load had an opposite HR of 1.25 (95% CI 0.98, 1.60; P=0.08). The protective mediation effects of HCV viral load through HBV DNA level were observed in mortality from causes specific to liver-related diseases and liver cancer, but not in that from non-liver-related diseases. Our findings suggest a suppressive effect of HCV on mortality mediated through decreasing HBV viral load.