Interaction between hepatitis B and C viruses in hepatocellular carcinogenesis

Although hepatitis B (HBV) and C viruses (HCV) are, individually, major causes of hepatocellular carcinoma, the interaction, if any, between the carcinogenic effects of the two viruses is uncertain. Equal numbers of published studies have reported no risk interaction or a synergistic risk interaction. These conflicting results are explained by the rarity of concurrent infection with HBV and HCV in individuals without clinically evident liver disease, which severely limits the ability to accurately estimate the hepatocarcinogenic risk of dual infection compared with that of either infection alone. In an attempt to circumvent this difficulty, two meta-analyses have been performed, one based on studies published from a number of countries and the other on studies confined to Chinese patients. Both analyses concluded that a synergistic carcinogenic interaction existed between the two viruses and that the increased risk was super-additive but not multiplicative. If confirmed, this risk interaction will occur against a background of negative confounding effects on viral replication between HBV and HCV, which may be reciprocal. The mechanisms responsible for the carcinogenic interaction between the viruses are unknown. One possibility is that the increased incidence of cirrhosis with concurrent HBV and HCV infections acts as an even more potent tumour promoter than occurs with either virus alone. Synergism between the direct hepatocarcinogenic effects of the two viruses is another possible mechanism, but proof will have to await a fuller understanding of the pathogenetic mechanisms involved with the individual viruses.