Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C: systematic review and meta-analysis of randomised controlled trials

OBJECTIVES: To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C. DESIGN: Systematic review and meta-analyses of randomised controlled trials. Prospective cohort studies were included in sensitivity analyses. DATA SOURCES: Eligible trials were identified through electronic and manual searches. STUDY SELECTION: Eight randomised controlled trials comparing antiviral therapy (interferon or pegylated interferon alone or with ribavirin) versus placebo or no intervention were included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers assessed the methodological quality of studies and extracted data. Random effects meta-analyses were performed. Subgroup, sensitivity, regression and sequential analyses were performed to evaluate sources of intertrial heterogeneity, the risk of bias and the robustness of the results after adjusting for multiple testing. RESULTS: Random effects meta-analysis showed that antiviral therapy reduced the risk of HCC (81/1156 vs 129/1174; risk ratio 0.53, 95% CI 0.34 to 0.81). In subgroup analyses, antiviral therapy was more beneficial (test for subgroup differences p=0.03) in virological responders (0.15, 0.05 to 0.45) than in non-responders (0.57; 0.37 to 0.85). No evidence of bias was seen in regression analyses. Sequential analysis confirmed the overall result. The sensitivity analyses showed that the cohort studies found that antiviral therapy reduced the risk of HCC. There was clear statistical evidence of bias in the cohort studies (p=0.02). CONCLUSIONS: Antiviral therapy may reduce the risk of HCC in hepatitis C-related fibrosis and cirrhosis. The effect may be seen irrespective of the virological response, but is more pronounced among virological responders compared with non-responders.