Hepatitis C virus infection as a major risk factor for hepatocellular carcinoma.
Evidence of a tumorigenic potential of the hepatitis C virus (HCV) has so far come mainly from epidemiological data. Longitudinal studies have shown that 16 of 62 anti-HCV antibody (ab)-positive Japanese patients developed hepatocellular carcinoma (HCC) within 5 yr. HCC-related deaths were significantly (p = 0.01) higher in Swedish anti-HCV ab-positive patients than in anti-HCV ab-negative controls (18 vs. 4%). The relative frequency of anti-HCV ab in HCC patients has been reported to be as high as 72% in Spain, 49-62% in Italy and 58% in France. It ranges between 9 and 36% in the USA and is about 26% in Germany. In HBV-endemic areas like South East Asia and Equatorial Africa, HCV-related HCCs play a minor role. The relative risk of developing HCC was elevated (up to 69.1-fold) for anti-HCV ab-positive patients as compared to anti-HCV ab-negative controls in almost all geographic areas studied to date. There is some evidence for an increased risk of developing HCC when hepatitis B virus (HBV) coinfection is present. Cirrhosis is likely to represent an additional risk factor for the development of HCC in anti-HCV ab-positive patients. Blood transfusions are the source of infection in barely one third of anti-HCV ab-positive HCC patients. There seems to be no significant difference in age or gender between anti-HCV ab-positive and ab-negative HCC patients. The additional impact of alcohol consumption and of the HCV genotype is presently under investigation. On the molecular level, HCV replication intermediates have been detected in HCC tissue and point mutations within the p53 gene have been demonstrated. However, the pathomechanism leading to HCV-mediated cell transformation remains unsolved.
Caselmann
W H
WH
Department of Medicine II, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Alt
M
M
D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000209:etiology*