Prospective study on the risk of hepatocellular carcinoma among hepatitis C virus-positive blood donors focusing on demographic factors, alanine aminotransferase level at donation and interaction with hepatitis B virus

Int J Cancer. 2004 Dec 20;112(6):1075-80. doi: 10.1002/ijc.20507.


The risk for hepatocellular carcinoma (HCC) among asymptomatic hepatitis C virus (HCV) carriers is not well understood. A community-based prospective study was conducted for over 8 years by record linkage to the Osaka Cancer Registry. The subjects were 1,927 individuals who were positive for anti-HCV through screening for second-generation HCV antibody (passive hemagglutination assay: >or= 2(12)) in voluntary blood donation. The risk factors for HCC and interaction between HCV and hepatitis B virus (HBV) infection were evaluated by including additional blood donors: 2,519 individuals positive for hepatitis B virus surface antigen (HBsAg) alone, 25 positive for both anti-HCV and HBsAg, 150,379 negative for both anti-HCV and HBsAg. The incidence of HCC (/10(5) person-years) among the HCV-positive individuals increased with age in both genders, ranging from 68 to 1,306 among those aged 45-74 years. In the HCV-positive individuals, the cumulative risk of developing HCC between the ages of 40 and 74 year was 21.6% among males and 8.7% among females. A stepwise increase in risk was noted as the serum alanine aminotransferase level increased or serum cholesterol level at baseline decreased in multivariate Cox proportional hazard analysis. The 9-year cumulative incidence of HCC among individuals positive for HCV alone, those positive for HBsAg alone and those positive for both was 3.0%, 2.0% and 12.0%, respectively. The age-and-sex-adjusted rate ratio was 126, 102 and 572, respectively, when those negative for both were used as a reference. The results demonstrate an increased risk for HCC among asymptomatic HCV-positive individuals in Japan. Coinfection with HBV and HCV carried a superadditive risk for HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood*
  • Blood Donors* / statistics & numerical data
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / virology*
  • Female
  • Follow-Up Studies
  • Hepatitis B / complications*
  • Hepatitis B / enzymology
  • Hepatitis B / epidemiology
  • Hepatitis C / complications*
  • Hepatitis C / enzymology
  • Hepatitis C / epidemiology
  • Humans
  • Incidence
  • Japan / epidemiology
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors


  • Alanine Transaminase