New Insights into Hepatitis C and Hepatocellular Carcinoma

Hepatitis C virus infection is a principal etiological agent of liver cancer in the world. Professor T. Jake Liang, from the Liver Diseases Branch, NIDDK, NIH, USA, presented a report on hepatitis C and hepatocellular carcinoma. He said that the mechanisms of HCV-related oncogenesis remained largely elusive, mostly because of the lack of convenient and suitable tissue culture and animal models and the long duration from infection to cancer development. The pathogenesis of HCV-associated HCC can be viewed in two ways: viral factors and host related events. Several HCV proteins including core, NS3 and NS5A have been associated with diverse pleiotropic functions including transcriptional activation, signal transduction, in vitro transformation that could be linked to cancer development. Core and NS5A have also been shown to induce the production of reactive oxygen species (ROS) in tissue culture and transgenic animal model. The production of ROS can predispose hepatocytes to DNA damage, which could lead to cumulative mutational events resulting in malignant transformation.

Professor Liang pointed out that other than virus-specific mechanisms that might contribute to carcinogenesis, the chronic “injury and regeneration” model was closely linked to HCC development. Chronic inflammatory changes render a highly carcinogenic environment for the hepatocytes. The production of inflammatory cytokines with generation of reactive oxygen species can induce chromosomal mutations. In addition, the liver is the major organ of detoxifying xenobiotics and toxic by-products. The condition of chronic hepatitis can result in aberrant processing and accumulation of these compounds that are often potent DNA mutagens. As a large number of infected hepatocytes die from host immune response, new hepatocytes are generated and the liver becomes an actively dividing organ. The proliferating hepatocytes, in a mutagenic environment, accumulate mutations and eventually become transformed.

Finally, he concluded that as we understood more about the biology and pathogenesis of the HCV-associated HCC, we would garner valuable information to develop better diagnostic, preventive and therapeutic means.