title: A population-based cohort study for the risk factors of HCC among hepatitis B virus mono-infected subjects in Japan.
abstract: 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.
  
  
  CONCLUSIONS
  HBV mono-infected subjects with A1762T/G1764A double mutation could be at high risk of HCC development during the natural course of HBV infection.
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kusakabe
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Manami
authors.initials: M
authors.lastname: Inoue
authors.forename: Fuat
authors.initials: F
authors.lastname: Kurbanov
authors.forename: Kanako
authors.initials: K
authors.lastname: Tatematsu
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Nojiri
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsugane
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000175:diagnosis / Q000821:virology; D006801:Humans; D007564:Japan; D008113:Liver Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
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