Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma

Alcohol has been shown to be an important risk factor for hepatocellular carcinoma (HCC). The role of tobacco as a risk factor for HCC is controversial. Recently, obesity has been reported to be a risk factor for HCC. We investigated whether these factors increase the risk of HCC in American patients. Consecutive patients with HCC, cirrhosis without HCC and, control patients without liver disease were enrolled and exposure to risk factors was assessed. When HCC cases were compared to cirrhotic controls, the risk of HCC increased 6-fold for alcohol (OR 5.7; 95% CI: 2.4–13.7), 5-fold for tobacco (OR 4.9; 95% CI: 2.2–10.6), and 4-fold with obesity (OR 4.3; 95% CI: 2.1–8.4). Using spline regression, a dose-dependent relationship between alcohol and tobacco exposure with risk of HCC was noted. There was significant interaction between alcohol, tobacco and obesity, with synergistic indices greater than 1. Alcohol, tobacco and obesity are independent risk factors for HCC in our patient population, and they interact synergistically to increase the risk of HCC. Data from this study may allow us to stratify cirrhotics into low- and high-risk groups for the development of HCC surveillance strategies.