The putative risk factors for hepatocellular carcinoma (HCC) are several, even in countries endemic for hepatitis B virus (HBV) infection. Cirrhosis characterizes more than 90% of HCC cases. The phases of inflammation, necrosis and regeneration, present for long periods in cirrhosis, might be most relevant in hepatocarcinogenesis. It is not clear what role is played by sex hormones while alcohol probably has a promoter role. Aflatoxins are known carcinogenins in the experimental animal: however it is difficult to evaluate the impact in human carcinogenesis due to the lack of reliable methods of measuring aflatoxin exposure in population studies. In conclusion, the aetiology of HCC is multifactorial and the main risk factor resides in the presence of underlying chronic liver disease.
PIP: Experimental and epidemiological studies of risk factors for hepatocellular carcinoma (HCC): cirrhosis, male sex, oral contraceptives, alcohol, smoking, and aflatoxins, are evaluated, with meta-analysis for oral contraceptives, alcohol, and smoking. It is likely that an initiating event and one or more promoting events interact, probably with prolonged inflammation, necrosis and regeneration, to cause cancer in several types of cirrhosis. Over 90% of HCC patients have cirrhosis, usually from hepatitis B virus. The viral post-necrotic liver is often chronically dysplastic, but other types of cirrhosis are associated with HCC if they endure long enough. The proportion of men with HCC increases as hepatitis progressors to cirrhosis and then to HCC. Meta-analyses of 3 oral contraceptive studies resulted in a risk of 2.8 for 8 years of use, but 9.9 for 8 years. Population studies do not show any concentration of HCC in countries with high pill use, so the rarity of this cancer may have biased the results. Large epidemiologic studies are needed to refine risk estimates for oral contraceptives and HCC. Alcohol abuse of 80 g/day gives a risk of about 1.65 in pooled studies, compared to a risk of 1.1 for 80 g/day. Smoking gives a risk of 1.9, but there is no evidence for a secular trend by country in proportion to dose, as is evident for lung cancer. There is good experimental evidence that aflatoxin acts as an initiator for liver cancer, but there is not practical way to judge exposure for clinical studies.