Hepatitis C virus and hepatocellular carcinoma.

In the short time that the hepatitis C virus has been known to be the major cause of parenterally acquired non-A, non-B hepatitis, it has become increasingly apparent that chronic infection with this virus is closely associated with the occurrence of hepatocellular carcinoma. Evidence for the link is provided mainly by case/control studies and case series but also by longitudinal studies. The proportion of patients with hepatocellular carcinoma who have circulating antibody to hepatitis C virus shows a pronounced geographical variation. In Japan, Spain, and Italy antibody is present in 47-83% of the patients, with relative risks of 52 (95% confidence interval 24-114) in Japanese and 69 (15-308) in Italian carriers of the virus. In regions where hepatitis B virus infection is endemic and is the major risk factor for hepatocellular carcinoma, antibody to hepatitis C virus is present in the serum of a smaller proportion (6-39%) of patients, with relative risks of 7 (1.6-39) in Taiwan and 6 (0.5-69) in Senegal. Comparatively low prevalences (13-35%) have also been recorded in the remaining geographical regions for which information is available, with relative risks of 10.4 (4-26) in Greece and 10.5 (3.5-31) in North America. There is some evidence for an interaction between hepatitis C and B viruses in hepatocellular carcinogenesis, but this remains to be proved. In most populations hepatocellular carcinoma develops at an older age in patients with hepatitis C virus-induced tumours than in those with hepatitis B virus-induced tumours. The pathogenesis of hepatitis C virus-related hepatocellular carcinoma is unknown. Because it always arises in association with cirrhosis or chronic hepatitis and because there is no evidence that the virus is directly carcinogenic, it appears that hepatitis C virus induces malignant transformation indirectly by causing chronic necroinflammatory hepatic disease which in turn is responsible for tumour formation.