Obesity and alcohol synergize to increase the risk of incident hepatocellular carcinoma in men.
OBJECTIVE
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.
Loomba
Rohit
R
Division of Gastroenterology, University of California at San Diego, La Jolla, California 92093, USA. roloomba@ucsd.edu
Yang
Hwai-I
HI
Su
Jun
J
Brenner
David
D
Iloeje
Uchenna
U
Chen
Chien-Jen
CJ
D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects*; D015992:Body Mass Index; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D006509:Hepatitis B / Q000150:complications*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D011446:Prospective Studies; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
D006514:Hepatitis B Surface Antigens