Role of Hepatitis C Virus in Hepatocarcinogenesis: Oxidative Stress in the Absence of inflammation

摘要

Summary. Overwhelming lines of epidemiological evidence have indicated that chronic infection with hepatitis C virus (HCV) poses a major risk toward development of hepatocellular carcinoma (HCC). In the pathogenesis of HCC associated with HCV, it remains controversial whether the virus plays a direct role or merely an indirect role. Through the use of a transgenic mouse model established by us, it has become evident that the core protein of HCV has an oncogenic potential. The findings in our studies indicate that HCV is directly involved in hepatocarcinogenesis, although other factors such as continued cell death and regeneration associated with chronic hepatitis may play a role as well. Combined, our results suggest that there is a mechanism for the development of HCC in persistent HCV infection that is distinct from those for other cancers. As with the pathogenesis of other malignancies, for example, colorectal cancer, the accumulation of a set of genetic aberrations may also be necessary for the multistage development of HCC. However, the HCV core protein, to which an oncogenic potential is ascribed, may allow some of the multiple stages of hepatocarcinogenesis to be skipped. Unlike in the case of those other cancers, therefore, infection with HCV may be capable of inducing HCC in the absence of a complete set of genetic aberrations. Such a scenario would explain the unusually high incidence and multicentric nature of HCC developing in patients with chronic hepatitis C.