Risk factors for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third cancer-related cause of death worldwide and the first in people with liver cirrhosis. The incidence varies between countries and is estimated at 5-15 new cases per 100,000 population per year in the Mediterranean countries. Genetic predisposition plays a key role. Overexpression of epidermal growth factor (EGFR) is related with HCC in animal models. Certain metabolic diseases increase the risk for HCC. Chronic hepatitis B virus (HBV) infection may lead to HCC with or without cirrhosis, and HBV vaccination or therapy with interferon or nucleot(c) ides may reduce the risk for HCC. Hepatitis C virus (HCV) infection carries a 27-fold increase in risk for HCC. Patients with HBV coinfection or other chronic liver diseases are at higher risk. Cirrhosis is in itself an independent risk factor, and 4 in 5 patients with HCC have pre-existing cirrhosis. Alcohol abuse is a co-factor for liver carcinogenesis, operating by direct and indirect mechanisms; consumption of >80 g alcohol per day for more than 10 years increases the HCC risk 5-fold. The impact of cigarette consumption is still ambiguous. Obesity, diabetes mellitus and non-alcoholic steatohepatitis may lead to cirrhosis and HCC. Certain toxins increase the risk for HCC:.flatoxins, microcystins and red betel chewing related toxins are the best known. There is evidence that B-6 and choline depletion and high plasma levels of ethionin participate in HCC development, and certain organic or inorganic substances have been related with HCC. Anabolic steroids are known to contribute to liver carcinogenesis. Radiation may also contribute to the HCC molecular mechanism, although the role of non-ionizing radiation remains to be clarified. Patients who have received liver transplantation are at higher risk for HCC. Finally, there is evidence that caffeine may protect against HCC development. Recent research has focused on the role of heat-shock proteins and HBx protein in molecular pathogenesis and risk of HCC and in the impact of vaccination programs and antivirus therapy on the reduction of HCC frequency.