Metabolic factors and subsequent risk of hepatocellular carcinoma by hepatitis virus infection status: a large-scale population-based cohort study of Japanese men and women (JPHC Study Cohort II)

Objective The association between metabolic factors and hepatocellular carcinoma (HCC) has not been well clarified. We prospectively examined whether metabolic factors predicts the subsequent risk of HCC in the Japan Public Health Center-based Prospective Study Cohort II, in consideration of hepatitis virus infection status. Methods A total of 17,590 subjects aged 40-69 participating in a questionnaire and health checkup survey during 1993-1994 were followed for incidence of HCC through 2006. A total of 102 cases of HCC were newly documented. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for metabolic factors controlling for potential confounding factors. Results The presence of metabolic factors in the aggregate was associated with a significantly increased risk of HCC, especially with hepatitis virus infection. HCC was positively associated particularly with high glucose (HR = 1.75, CI = 1.11-2.74) and overweight (HR = 2.22, CI = 1.42-3.48). Results were similar when analyses were limited to subjects with HCV infection. Conclusions Although metabolic factors in the aggregate may be associated with an increased risk of HCC, the main contributors to this association under HCV infection appear to be overweight and high glucose. Improvement of these factors may be a crucial target in preventing progression to HCC in those with HCV infection.