Animal models for hepatitis C and related liver disease
Article first published online: 17 JAN 2010
© 2010 The Japan Society of Hepatology
Volume 40, Issue 1, pages 69–82, January 2010
How to Cite
Koike, K., Moriya, K. and Matsuura, Y. (2010), Animal models for hepatitis C and related liver disease. Hepatology Research, 40: 69–82. doi: 10.1111/j.1872-034X.2009.00593.x
- Issue published online: 17 JAN 2010
- Article first published online: 17 JAN 2010
- Received 19 June 2009; revision 31 July 2009; accepted 31 July 2009.
- core protein;
- hepatitis C;
- hepatocellular carcinoma;
- insulin resistance;
- transgenic mouse
Persistent infection with hepatitis C virus (HCV) is a major risk toward development of hepatocellular carcinoma (HCC). The elucidation of pathogenesis of HCV-associated liver disease is hampered by the absence of appropriate animal models: there has been no animal model for HCV infection/pathogenesis except for the chimpanzee. In contrast, a number of transgenic mouse lines carrying the cDNA of the HCV genome have been established and evaluated in the study of HCV pathogenesis. The studies using transgenic mouse models, in which the HCV proteins such as the core protein are expressed, indicate the direct pathogenicity of HCV, including oncogenic activities. HCV transgenic mouse models also show a close relationship between HCV and some hepatic and extrahepatic manifestations such as hepatic steatosis, insulin resistance or Sjögren's syndrome. A crucial role of hepatic steatosis and insulin resistance in the pathogenesis of liver disease in HCV infection has been demonstrated, implying hepatitis C to be a metabolic disease. Besides the data connecting liver fibrosis progression and the disturbance in lipid and glucose metabolisms in hepatitis C patients, a series of evidence was found showing the association between these two conditions and HCV infection, chiefly using transgenic mouse carrying the HCV genome. Furthermore, the persistent activation of peroxisome proliferator-activated receptor (PPAR)-α has recently been found, yielding dramatic changes in the lipid metabolism and oxidative stress overproduction in cooperation with the mitochondrial dysfunction. These results would provide a clue for further understanding of the role of lipid metabolism in pathogenesis of hepatitis C including liver injury and hepatocarcinogenesis.