Primary Liver Cancer and Hepatitis B and C Viruses

Summary

There is now evidence for the involvement of hepatitis B virus (HBV) in both HBsAg-positive and HBsAg-negative primary liver cancers (PLC).

A major difference between HBsAg-positive and HBsAg-negative HBV DNA-positive PLCs is related to the number of viral DNA sequences per cell and the rate of HBV DNA replication. In HBsAg-positive chronic carriers HBV multiplication is sustained for enough time to induce liver cell necrosis and regeneration. In these subjects HBV may therefore act at two complementary steps of liver cell transformation: it might exert a direct role by a combination of transactivation and integration; in addition, it can induce promotion and clonal expansion of the initiated cells by inducing the cirrhosis. In contrast, in HBsAg-negative HBV DNA-positive patients, the number of HBV DNA copies per cell is low and viral DNA replication is barely detectable. In most of these cases, therefore, it is unlikely that HBV is solely involved in liver cell necrosis, chronic active hepatitis, and cirrhosis. Instead, other factors such as HCV, strongly associated to HBsAg-negative PLC, alcohol, or other still unrecognized agents might be responsible for cirrhosis and thus promotion of the neoplastic transformation. On the other hand, we have presented evidence for the persistence of integrated viral DNA which might exert a direct effect via integration and/or transactivation. HBV might, therefore, be able to initiate liver cell transformation in a limited number of clonally expanded cells: the subsequent development of PLC would be dependent on the effect of cofactors able to promote liver cell regeneration via development of cirrhosis.

Extensive epidemiological studies have shown a clear association between chronic hepatitis B virus (HBV) infection and primary liver cancer (PLC)