Risk factors for development of hepatocellular carcinoma in patients with chronic hepatitis C without sustained response to combination therapy

Abstract

Background/Purpose: Although antiviral therapy reduces development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC), HCC often develops in patients with non-sustained virologic response (non-SVR). We aimed to evaluate risk factors for HCC in HCV patients with non-SVR. Methods: From March 2002 to December 2013, 800 patients with CHC who had received combined pegylated interferon (peg-IFN)/ribavirin (RBV) therapy without achieving SVR were enrolled. Main outcome measure was HCC development. Variables were cirrhosis, platelet count, α-fetoprotein (AFP) levels, aspartate aminotransferase (AST) to platelet ratio index (APRI), and IL28B polymorphism (CT + TT). Results: One-hundred of 800 non-SVR patients developed HCC within a median 53.5-months follow-up. Cumulative incidence of HCC for all patients was 1.4%, 5.6% and 12.3%, respectively, at 1st, 3rd and 5th years of follow-up. In univariate analysis, patients who developed HCC tended to have LC (p< 0.001), lower platelet counts (<150 × 109/l, p < 0.001), higher AFP levels (≥20 ng/ml, p < 0.001), higher Fib-4 levels (p < 0.001), higher APRI levels (p < 0.001), IL 28B polymorphism (CT + TT) (p < 0.001) and higher incidence of diabetes mellitus (DM) (p = 0.019). Multivariate analysis in overall patients revealed that cirrhosis (HR: 2.94, 95% CI: 1.81–4.77, p < 0.001), IL28B rs12979860 (CT + TT) polymorphisms (HR: 3.22, 95% CI: 2.17–4.78, p < 0.001), and high APRI levels (≥2.57) (HR: 2.32, 95% CI: 1.47–3.67, p < 0.001) were independent risk factors for HCC. Conclusion: Liver cirrhosis, high APRI levels, and IL28B rs12979860 at baseline are independent risk factors for HCC development in patients without SVR after peg-IFN combination therapy. Keywords: APRI, Fib-4, Hepatocellular carcinoma, IL28B, Hepatitis C virus, Non-sustained virologic response