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

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Abstract
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: ≥ 212) 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 (/105 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.