HEPATITIS VIRUSES AND HUMAN HEPATOCELLULAR-CARCINOMA

Two hepatotropic viruses, hepatitis B and C viruses, are known to caus e hepatocellular carcinoma in humans. Hepatocarcinogenesis is a comple x, stepwise process that evolves over several to many years and precis ely how hepatitis viruses contribute to malignant transformation of he patocytes is uncertain. Hepatitis B vrus is integrated into cellular D NA in the great majority of hepatitis B virus-related hepatocellular c arcinomas, whereas replicative intermediates of hepatitis C virus do n ot insert into chromosomal DNA, making it likely that different pathog enetic mechanisms operate with the two viruses. Indeed, evidence is mo unting that both direct and indirect carcinogenic mechanisms, and ofte n the two together, are involved in virus-induced hepatocellular carci noma. In addition, evidence is now available that hepatitis B and C vi ruses interact synergistically in the pathogenesis of hepatocellular c arcinoma. Animal models, - other members of the Hepadnaviridae family that cause tumors in their respecitve animal hosts, and transgenic mic e 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 hepatiti s virus-induced hepatocellular carcinoma, it is clear that hepatitis v iruses do not act alone but in conjunction with other environmental ca rcinogens and a number of host factors.