The oncogenic role of hepatitis B virus.

The hepatitis B virus (HBV) is a small enveloped DNA virus that causes acute and chronic hepatitis. HBV infection is a world health problem, with 350 million chronically infected people at increased risk of developing liver disease and hepatocellular carcinoma (HCC). HBV has been classified among human tumor viruses by virtue of a robust epidemiologic association between chronic HBV carriage and HCC occurrence. In the absence of cytopathic effect in infected hepatocytes, the oncogenic role of HBV might involve a combination of direct and indirect effects of the virus during the multistep process of liver carcinogenesis. Liver inflammation and hepatocyte proliferation driven by host immune responses are recognized driving forces of liver cell transformation. Genetic and epigenetic alterations can also result from viral DNA integration into host chromosomes and from prolonged expression of viral gene products. Notably, the transcriptional regulatory protein HBx encoded by the X gene is endowed with tumor promoter activity. HBx has pleiotropic activities and plays a major role in HBV pathogenesis and in liver carcinogenesis. Because hepatic tumors carry a dismal prognosis, there is urgent need to develop early diagnostic markers of HCC and effective therapies against chronic hepatitis B. Deciphering the oncogenic mechanisms that underlie HBV-related tumorigenesis might help developing adapted therapeutic strategies.