BOSTON-Alcohol, obesity, and tobacco are all independent risk factors for hepatocellular carcinoma (HCC), according to a case-control study presented at the 54th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD abstract 253). Jorge A. Marrero, MD, of the University of Michigan Health System, Ann Arbor, found lifetime smokers were most vulnerable, and suggested lifetime exposure to more than one risk factor would significantly raise a person's risk of liver cancer. "Tobacco, alcohol(Drug information on alcohol), and obesity interact synergistically to increase the risk of hepatocellular carcinoma," he said. The study matched 65 consecutive HCC patients with two control groups: 65 patients with cirrhosis but no signs of HCC, and 65 healthy persons with normal liver tests and no history of liver disease. Each group had an aver age age in the mid-50s and more men than women. The investigators used validated questionnaires to gather information on lifetime tobacco and alcohol use, which were measured in pack-years and kilogram-years, respectively. Body mass index (BMI) was recorded when the patients were interviewed. Lifetime exposure to alcohol and tobacco was significantly higher in HCC patients and in cirrhotic patients: 73% of the cancer group and 83% of the cirrhotic patients, but only 5% of the healthy controls, were former drinkers; 12% of the cancer patients and 6% percent of the controls, but none of the cirrhotic patients, were current drinkers. Only 2% of those with healthy livers reported being current smokers; the same percentage identified themselves as former smokers. Among HCC patients, however, 63% said they used to smoke and 18% were current smokers. In the cirrhotic group, 37% were former smokers and 29% continued to smoke. Significant Predictors for HCC Dr. Marrero and his colleagues calculated that alcohol intake greater than 6 kilogram-years of ethanol (defined as 20 g/d for 15 years) and tobacco use greater than 15 pack-years were significant predictors of HCC. The average total alcohol consumption was 34 kilogram-years for the cancer patients, 24 for the cirrhosis patients, and 5 for the healthy controls. Cancer patients had double the lifetime tobacco exposure of cirrhotic patients- 31 pack-years vs 15. In contrast, the healthy group's exposure was 2 pack- years on average. The HCC patients also smoked longer than the cirrhotic patients (22 years vs 17) and drank longer (29 years vs 22). Both groups had much longer exposures than the healthy people. HCC risk increased 2.6-fold with moderate exposure to tobacco, but shot up 8.2-fold with heavy exposure, Dr. Marrero said. Similarly, the risk increased almost 3-fold with moderate alcohol consumption, but almost 4.5-fold with heavy consumption. Average BMI was 32 for the HCC patients and 28 for the cirrhosis patients. Among heavy smokers, Dr. Marrero said, HCC risk increased almost 5-fold in people with a BMI greater than 30. Yet obesity increased risk only 1.5-fold in people who did not smoke. While smoking and drinking tripled risk for lean patients, no significant interaction was found between alcohol by itself and BMI. Dr. Marrero called for prospective studies toward developing a method to stratify cirrhotic patients into highand low-risk groups for HCC.