Background: Entecavir (ETV) is one of the first-line nucleoside analogs for treating patients with chronic hepatitis B virus (HBV) infection. However, the hepatocellular carcinoma (HCC) risk for ETV-treated patients remains unclear.
Methods: A total of 496 Japanese patients with chronic HBV infection undergoing ETV treatment were enrolled in this study. The baseline characteristics were as follows: age 52.6 ± 12.0 years, males 58%, positive for hepatitis B e antigen 45 %, cirrhosis 19%, and median HBV DNA level 6.9 log copies (LC) per milliliter. The mean treatment duration was 49.9 ± 17.5 months.
Results: The proportions of HBV DNA negativity (below 2.6 LC/mL) were 68% at 24 weeks and 86% at 1 year, and the rates of alanine aminotransferase (ALT) level normalization were 62 and 72%, respectively. The mean serum alpha-fetoprotein (AFP) levels decreased significantly at 24 weeks after ETV treatment initiation (from 29.0 ± 137.1 to 5.7 ± 27.9 ng/mL, p < 0.001). The cumulative incidence of HCC at 3, 5, and 7 years was 6.0, 9.6, and 17.2%, respectively, among all enrolled patients. In a multivariate analysis, advanced age [55 years or older, hazard ratio (HR) 2.84; p = 0.018], cirrhosis (HR 5.59, p < 0.001), and a higher AFP level (10 ng/mL or greater) at 24 weeks (HR 2.38, p = 0.034) were independent risk factors for HCC incidence. HCC incidence was not affected by HBV DNA negativity or by ALT level normalization at 24 weeks.
Conclusions: The AFP level at 24 weeks after ETV treatment initiation can be the on-treatment predictive factor for HCC incidence among patients with chronic HBV infection.