New epidemiological data on liver oncogenesis.

The purpose of this review is to address and discuss the following: a) the malignant transformation of hepatocytes may occur, irrespective of the etiologic agent, in the context of increased cellular turnover induced by chronic hepatic damage and regeneration, with genetic mutations being a frequent event prior to the development of this tumor; b) although it is clear that hepatitis B virus-induced chronic liver injury, regeneration and cirrhosis is a major risk factor for hepatocellular carcinoma development, there are also several reports of the direct carcinogenic effects of hepatitis B virus. For instance, integration of hepatitis B virus DNA can directly induce chromosomal rearrangements and viral gene product transactivating properties may influence cellular genes important in the control of the growth process; c) hepatitis C virus and other risk agents, including alcohol, environmental factors and metabolic diseases may operate, mainly through chronic liver damage that progress to liver cirrhosis, a major predisposing factor for the development of hepatocellular carcinoma, regardless of etiology; d) at the molecular level, the interaction between oncogenes, tumor suppressor genes (with or without aflatoxins and hepatitis B virus) and several growth factors may play an additional role in hepatocellular carcinoma development.