Effect of IFN therapy and amino acid substitutions in the hepatitis C virus (HCV) core region on hepatocarcinogenesis in HCV-related cirrhotic patients.

Abstract

4009 Background: Although some reports have shown that interferon (IFN) can reduce the hepatocarcinogenesis in HCV-related noncirrhotic and cirrhotic patients through reduction or complete remission of inflammatory activity, the effect of IFN therapy without anti-inflammation has not been clear. In patients with HCV genotype 1b(HCV-1b), amino acid (aa) substitutions in hepatitis C virus core region (HCVCR) are negative predictors of virologic response to pegylated interferon plus ribavirin and they may be one of the important predictors of hepatocarcinogenesis. Then, the purpose of this study is to evaluate the effect of IFN therapy and aa substitutions in HCVCR on the carcinogenesis in HCV-related cirrhotic patients. Methods: The hepatocellular carcinogenesis rate was analyzed statistically in 1,015 patients with cirrhosis C: 268 with IFN therapy and 747 without IFN therapy. HCV genotyping was performed in 818 patients. As for HCV-1b, aa substitution was measured using the PCR Method with mutation-specific primer as an alternative to the direct sequencing method. Results: Hepatocarcinogenesis rates in sustained virological responder (SVR), biochemical responder (BR), non responder (NR) and untreated groups were 29%, 38%, 54% and 57% at the end of the tenth year. The carcinogenesis rate in SVR/BR is lower than that in untreated group. As for male patients with Child-Pugh A, the carcinogenesis rate in NR group is lower than that in untreated group (p = 0.058). The carcinogenesis rate in NR patients who received IFN therapy for 3 years or longer was lower than that in NR patients who received shorter IFN therapy (p = 0.030). Multivariate analysis showed that the risk of carcinogenesis was decreased to 0.52 (p = 0.003) and 0.53 (p = 0.012) in SVR/BR and in NR with 3 years or longer IFN therapy, respectively. In patients with HCV-1b, the hazard ratio of non-double wild aa in core region was 2.01 (p < 0.0001). Conclusions: IFN therapy should be continued in HCV-related cirrhotic patients as long as possible, because IFN therapy of 3 years or longer can suppress the hepatocarcinogenesis even when either HCV RNA clearance or ALT normalization cannot be observed. No significant financial relationships to disclose.