Background & aims: Body mass index (BMI) and alcohol use are risk factors for hepatocellular carcinoma (HCC). We performed a prospective study to determine if these factors have synergistic effects on HCC risk.

Methods: Over 14 years, we followed up 2260 Taiwanese men from the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) Study Cohort who tested positive for the hepatitis B surface antigen (mean age, 46 ± 10 y; mean BMI, 24 ± 3 kg/m(2)); 20% reported alcohol use. Incident HCC cases were identified via linkage to the national cancer registry. Multivariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox-proportional hazards models.

Results: In univariate analysis, the interaction between BMI and alcohol predicted incident HCC (P = .029). Alcohol use and extreme obesity (BMI ≥30 kg/m(2)) had synergistic effects on the risk of incident HCC in analyses adjusted for age (HR, 3.41; 95% CI, 1.25-9.27; P < .025) and multivariables (HR, 3.40; 95% CI, 1.24-9.34; P < .025). The relative risk estimate for the interaction and the attributable proportion from the interaction and synergy index were 1.59, 0.52, and 4.40, respectively; these indicate a multiplicative interaction between alcohol use and extreme obesity. In an analysis stratified into 4 World Health Organization categories of BMI and alcohol use, the risk of incident HCC increased in overweight (HR, 2.4; 95% CI, 1.3-4.4), obese (HR, 2.0; 95% CI, 1.1-3.7), and extremely obese (HR, 2.9; 95% CI, 1.0-8.0) users of alcohol (P for trend = .046).

Conclusions: Obesity and alcohol have synergistic effects to increase the risk of incident HCC in hepatitis B surface antigen-positive men. Lifestyle interventions might reduce the incidence of HCC.