Mechanisms of HBV-related hepatocarcinogenesis.
The hepatitis B virus (HBV) is a small enveloped DNA virus, which primarily infects hepatocytes and causes acute and persistent liver disease. Epidemiological studies have provided overwhelming evidence for a causal role of chronic HBV infection in the development of hepatocellular carcinoma, but the molecular mechanisms underlying virally-induced tumourigenesis remain largely debated. In the absence of a dominant oncogene encoded by the HBV genome, indirect roles have been proposed, including insertional activation of cellular cancer-related genes by HBV DNA integration, induction of genetic instability by viral integration or by the regulatory protein HBx, and long-term effects of viral proteins in enhancing immune-mediated liver disease. Recent genetic studies indicate that HBV-related tumours display a distinctive profile with a high rate of chromosomal alterations and low frequency of beta-catenin mutations. This review will discuss the evidence implicating chronic HBV infection as a causal risk factor of primary liver cancer. It will also discuss the molecular mechanisms that are critical for the tumourigenic process due to long lasting infection with HBV.
Neuveut
Christine
C
Oncogenesis and Molecular Virology Unit, Institut Pasteur, Inserm U579, 28 rue du Dr Roux, Paris cedex 15, France.
Wei
Yu
Y
Buendia
Marie Annick
MA
D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000503:physiopathology / Q000821:virology; D016147:Genes, Tumor Suppressor / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000503:physiopathology / Q000821:virology; D009857:Oncogenes / Q000502:physiology