Study on the mechanism of hepatocarcinogenesis in hepatitis C viral infection

点击翻译按钮获取中文摘要

Despite numerous lines of epidemiological evidence connecting hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC), it remains controversial whether HCV itself plays a direct role or an indirect role in the pathogenesis of HCC. Through the use of transgenic mice, it has become evident that the core protein of HCV has an oncogenic potential. HCV is directly involved in hepatocarcinogenesis, albeit other factors such as inflammation and environmental factors may also play a role. The direct involvement of HCV in hepatocarcinogenesis would be achieved via two pathways. In one pathway, the core protein acts on the function of mitochondria, leading to the overproduction of oxidative stress, which yields genetic aberrations in cell-growth-related genes. The other pathway involves the modulations of cellular gene expressions and intracellular signal transductions, such as mitogen-activated protein kinases (MAPKs) pathway, which results in the activation of transcription factors and cell cycle machineries. The combination of these alterations would provoke the development of HCC in HCV infection. This would be a mechanism for HCC development in HCV infection that is distinct from those for other cancers. The presence of the HCV core protein, to which an oncogenic potential is ascribed, may allow some of the multiple steps to be bypassed in hepatocarcinogenesis. Therefore, unlike in other cancers, HCV infection can elicit HCC in the absence of a complete set of genetic aberrations. Such a scenario, "non-Vogelstein-type" carcinogenesis, would explain the unusually high incidence and multicentric nature of HCC development in HCV infection.