A Population-Based Cohort Study for the Risk Factors of HCC Among Hepatitis B Virus Mono-Infected Subjects in Japan

J Gastroenterol. 2011 Jan;46(1):117-24. doi: 10.1007/s00535-010-0307-4. Epub 2010 Sep 7.


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.

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / virology*
  • Female
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / virology
  • Humans
  • Japan
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Mutation
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors