A population-based cohort study for the risk factors of HCC among hepatitis B virus mono-infected subjects in Japan.

Background: There have only been a few prospective studies investigating risk factors associated with the development of hepatocellular carcinoma (HCC) among chronic hepatitis B patients all over the world, and no study has been conducted in Japanese population.

Methods: A population-based cohort consisting of 19393 subjects (middle aged or older) with over 13 years' follow-up was investigated in Japan.

Results: Of 19393 subjects, 479 had hepatitis B virus (HBV) mono-infection (2.5%). During the 245923 person-years' follow-up (average follow-up period 12.7 years), 13 cases of newly diagnosed HCC were documented in the HBV mono-infected group. Several factors at baseline (male, smoking, alanine aminotransferase, the positivity of HBe antigen and HB core-related antigen, the proportion of HBV DNA ≥ 5 log copies/mL, T1753V mutation, and A1762T/G1764A double mutation) were significantly associated with HCC among HBV mono-infected subjects. Multivariate-adjusted Cox hazard model showed that A1762T/G1764A (hazard ratio 7.05 [95% confidence interval (CI) 1.03-48.12, P = 0.046]) was the only independent risk factor for the development of HCC. Kaplan-Meier method also showed that the probability of HCC occurrence-free was significantly lower in HBV mono-infected subjects with A1762T/G1764A double mutation than those without these mutations.

Conclusion: HBV mono-infected subjects with A1762T/G1764A double mutation could be at high risk of HCC development during the natural course of HBV infection.