Effects of interferon treatment on development and progression of hepatocellular carcinoma in patients with chronic virus infection: a meta-analysis of randomized controlled trials

Available literature on the effects of interferon (IFN) treatment on development and progression of hepatocellular carcinoma (HCC) in patients with chronic virus infection reports controversial results. The primary objective of this meta-analysis was to evaluate the effect of IFN on HCC risk in patients with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection; IFN's efficacy on local tumor progression and survival of advanced HCC patients was also assessed. All randomized controlled trials (RCTs) comparing IFN with no antiviral treatment were selected. Finally, we identified 11 RCTs including 1,772 patients, who met our inclusion criteria to perform this meta-analysis. Our analysis results showed that IFN significantly decreased the overall HCC incidence in HCV-infected patients [relative risk (RR) = 0.39; 95% confidence interval (CI) = 0.26-0.59; p = 0.000], subgroup analysis indicated that IFN decreased HCC incidence in HCV-related cirrhotic patients evidently (RR = 0.44; 95% CI = 0.28-0.68; p = 0.000); but HCC incidence in nonresponders to initial antiviral therapy did not reduce by maintenance IFN therapy (RR = 0.96; 95% CI = 0.59-1.56; p = 0.864). Analysis results also demonstrated that IFN did not significantly affect the overall rate of HCC in HBV-infected patients although there was a trend favoring IFN therapy (RR = 0.23; 95% CI = 0.05-1.04; p = 0.056). Besides, IFN did not improve one-year overall survival of advanced HCC patients significantly (RR = 1.61; 95% CI = 0.96-2.69; p = 0.072); however, a quantitative analysis on local tumor progression could not be performed owing to lack of unified definitions among trials included in our study. By this meta-analysis, we conclude that IFN therapy is effective in reducing overall HCC risk in chronic HCV-infected patients; using it in this subpopulation seems promising, but its administration in other subpopulations still requires further exploration.