| [ Summary ] |
Hepatitis C virus (HCV) is the major cause of chronic hepatitis worldwide, leading to the development of hepatocellular carcinoma (HCC). However, the mechanism of hepatocarcinogenesis in chronic HCV infection is still unclear. The ability of the core protein of HCV to modulate gene transcription, cell proliferation and cell death has been suggested as being involved in the pathogenesis of HCC. Here in we report on the development of HCC in two independent lines of HCV core gene transgenic mice, which develop hepatic steatosis early in life as a histological feature characterlstic of chronic hepatitis C. After the age of 16 months, mice of both lines succumbed to hepatic tumors which first appeared as adenoma containing fat droplets in the cytoplasm. Then HCC, a more poorly differentiated neoplasia, developed from within adenoma, presenting a "nodule in nodule" feature without cytoplasmic fat droplets. This feature closely resembled the histopathological characteristics previously observed in the early stage of HCC in patients with chronic hepatitis C. These results suggest that the HCV core protein has a major role in the development of HCC, and that these transgenic mice would provide good animal models for defining molecular events in hepatocarcinogenesis associated with HCV infection. |