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 etio logic agent, in the context of increased cellular turnover induced by chron ic 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 vir us. For instance, integration of hepatitis B virus DNR can directly induce chromosomal rearrangements and viral gene product transactivating propertie s may influence cellular genes important in the control of the growth proce ss; c) hepatitis C virus and other risk agents, including alcohol, environm ental factors and metabolic diseases may operate, mainly through chronic li ver damage that progress to liver cirrhosis, a major predisposing factor fo r the development of hepatocellular carcinoma, regardless of etiology; d) a t 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 developmen t.