Hepatitis Viruses and Human Hepatocellular Carcinoma

Two hepatotropic viruses, hepatitis B and C viruses, are known to cause hepatocellular carcinoma in humans. Hepatocarcinogenesis is a complex, stepwise process that evolves over several to many years and precisely how hepatitis viruses contribute to malignant transformation of hepatocytes is uncertain. Hepatitis B vrus is integrated into cellular DNA in the great majority of hepatitis B virus-related hepatocellular carcinomas, whereas replicative intermediates of hepatitis C virus do not insert into chromosomal DNA, making it likely that different pathogenetic mechanisms operate with the two viruses. Indeed, evidence is mounting that both direct and indirect carcinogenic mechanisms, and often the two together, are involved in virus-induced hepatocellular carcinoma. In addition, evidence is now available that hepatitis B and C viruses interact synergistically in the pathogenesis of hepatocellular carcinoma. Animal models, — other members of the Hepadnaviridae family that cause tumors in their respecitve animal hosts, and transgenic mice into which the sequences of hepatitis B virus DNA have been inserted — are proving useful in elucidating putative mechanisms of hepatitis B virus-related hepatocarcinogenesis. Whatever the genesis of hepatitis virus-induced hepatocellular carcinoma, it is clear that hepatitis viruses do not act alone but in conjunction with other environmental carcinogens and a number of host factors.