Hepatitis B virus and hepatocellular carcinoma: molecular biology and mechanistic considerations.
The question of whether HBV causes HCC has to date best been answered by epidemiologic studies, in particular prospective analysis such as the ongoing study in Taiwan. The mechanism whereby HBV may cause HCC by genetic or epigenetic means, acting alone or in concert with other agents, is still moot . To date, studies of HBV gene expression have not shown the presence of a transforming gene or an oncogene associated with this virus. The finding of integrated HBV DNA in most HCC of carriers is highly suggestive of a causal role of the virus in the pathogenesis of neoplasia. In order to be more certain, it will be necessary to show that expression of integrated HBV genes or of cellular genes, as a result of HBV infection, causes neoplastic transformation of cells. Failure to date to demonstrate that HBV DNA induces neoplastic transformation of eukaryotic cells in culture may be simply due to an inadequate experimental model. The majority of these experiments have used fibroblasts or monkey kidney cells as the recipient cell, whereas cultured human hepatocytes might be more suitable. Whatever role HBV eventually is shown to have in the pathogenesis of HCC, molecular biologic techniques will have in great measure contributed to that knowledge. The use of these powerful new methods will permit studies of the replication of HBV and possible elucidation of how this virus affects the hepatocyte during persistent infection and will in time lead to a better understanding of cell and molecular events leading to development of hepatic malignancy.