Liver disease risk attributable to HCV, HIV, and HCV-HIV coinfection: an interaction analysis

OBJECTIVE: To quantify whether living with HIV modifies the effect of hepatitis C (HCV) infection on risk of cirrhosis, hepatic decompensation (decompensation), and hepatocellular carcinoma (HCC) in a real-world healthcare context. DESIGN: A cohort of 1,484,587 individuals from Ontario, Canada that tested negative for HCV antibodies (HCV Ab-) were followed from 1999 to 2018 for diagnoses of HCV, HIV, cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma, using administrative health data. METHODS: Time-dependent Cox regression was used to quantify the risk of each liver disease outcome in individuals who were positive for HCV and HIV (HCV+/HIV+), only HCV+ (HCV+/HIV-), only HIV+ (HCV-/HIV+), and doubly negative (HCV-/HIV-). The relative excess risk due to interaction (RERI) was calculated to quantify the magnitude and significance of interaction effects. RESULTS: HCV+/HIV+ had the highest risk of cirrhosis (Hazard Ratio (HR) = 3.8; 95% Confidence Interval (CI): 2.9, 4.9), decompensation (HR = 2.8; 95% CI: 1.9, 4.1), and HCC (HR = 4.1; 95% CI: 2.7, 6.2) compared to HCV-/HIV-. A significant positive interaction effect was observed for risk of decompensation (RERI = 1.2; 95% CI: 0.1, 2.3) and HCC (RERI = 2.3; 95% CI: 0.6, 4.0), but not for risk of cirrhosis (RERI = 0.9; 95% CI: -0.1, 2.0). CONCLUSIONS: This large population-based cohort study is the first to estimate the interaction effect of HCV and HIV on liver disease risk, providing new evidence of a synergistic additive interaction effect between HCV and HIV infection on risk of decompensation and HCC.