Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC): molecular mechanisms and novel paradigms.
Chronic hepatitis B (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Most HCCs complicate the evolution of an active or inactive cirrhosis. However, some tumors occur on livers with minimal histological changes; the prevalence of such cases varies from one geographical region to the other, being much higher in the Southern half of Africa (around 40% of HCCs) than in Asia, America and Europe, where at least 90% of HCCs are associated in the cirrhosis. This heterogeneity is probably a reflection of different environmental and genetic factors. This review will summarise the current knowledge on the mechanisms involved in HBV-related liver carcinogenesis. It will show in particular how viruses can be viewed as tools to discover and dissect new cellular pathways involved in cancer development and emphasize the potential synergistic effects between HBV and hepatitis C virus (HCV), as well as between viral infections and other environmental factors, such as alcohol.
Brechot
C
C
Inserm U785, Liver Hepatology centre, Paul Brousse Hospital, university Paris-XI, 12, avenue Paul-Vaillant-Couturier, 94804 Villejuif cedex 15, France. christian.brechot@institut-merieux.com
Kremsdorf
D
D
Soussan
P
P
Pineau
P
P
Dejean
A
A
Paterlini-Brechot
P
P
Tiollais
P
P
D000437:Alcoholism; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics* / Q000821:virology*; D004279:DNA, Viral / Q000097:blood; D016174:Hepacivirus; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000821:virology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology*; D051379:Mice; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D054334:Viral Regulatory and Accessory Proteins
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein