Role of hepatitis C virus in the development of hepatocellular carcinoma: transgenic approach to viral hepatocarcinogenesis.

Overwhelming lines of epidemiologic evidence have indicated that chronic infection with hepatitis C virus (HCV) poses a major risk towards the development of hepatocellular carcinoma (HCC). It remains controversial whether HCV plays a direct role in the pathogenesis of HCV-associated HCC or whether it merely serves an indirect role. Using the transgenic mouse model established by us, it has become evident that the core protein of HCV confers oncogenic potential. The findings in our studies indicate that HCV is directly involved in hepatocarcinogenesis, albeit other factors, such as continued cell death and regeneration associated with chronic hepatitis, may also play a role. Taken together, our results indicate that there could be a mechanism for the development of HCC in persistent hepatitis virus infection that is distinct from the pathogenesis of other cancers, like colorectal cancer. Thus, although accumulation of a set of genetic aberrations may also be necessary for a multistage development of HCC, HCV core protein, to which an oncogenic potential is ascribed, may allow some stages to be skipped in hepatocarcinogenesis. The possibility that infection with HCV may be capable of inducing HCC in the absence of a complete set of genetic aberrations would help explain the unusually high incidence and multicentric nature of HCC developing in chronic hepatitis C.