| セッション情報 |
International Forum 2(Liver) 1.Pathogenesis and Epidemiology
|
| タイトル |
IF2-1-I (Keynote lecture) Pathogenesis of HCV-associated HCC
|
| 演者 |
Kazuhiko Koike（Department of Infectious DiseasesInternal MedicineGraduate School of MedicineUniversity of TokyoTokyoJapan） |
| 共同演者 |
|
| 抄録 |
In addition to the link with development of hepatocellular carcinoma （HCC）hepatitis C virus （HCV） infec－tion is associated with several hepatic and extrahepatic manifestations． A role of hepatic steatosis in thepathogenesis of chronic hepatitis C has been knownimplying hepatitis C as a metabolic disease． ln addi－tionrecent epidemiological studies have suggested a linkage between insulin resistance and chronic HCVinfection． ln addition to the data indicating the presence of lipid metabolism disturbance and insulin resis－tance in the cohort of chronic hepatitis C patientswe found a series of evidence showing the associationbetween these two conditions and HCV infection in a mouse model that is transgenic for the HCV coregene． These mice develop HCC late in life after the phase of hepatic steatosis and insulin resistance． Thenonappearance of both steatosis and HCC in HCV core gene transgenic mice that are null f6r the protea－some activator （PA28）一yimplies a close relationship between lipid metabolism disturbance and hepato－carcinogenesis． AlsoThe core protein is shown to bind with retinoid X receptor （RXR）一〇r in its DNA－binding domainresulting in the up－regulation of some lipid metabolism enzymes including cellular retinolbinding protein （CRBP） II and acyl－CoA oxidase （AOX）． ln additionthe persistent activation of perox－isome proliferatoractivated receptor （PPAR）一〇r has recently been found in the liver of HCV core genetransgenic micecausing dramatic changes in the lipid metabolism and hepatocyte proliferation includingHCC development． These results would provide a clue for further understanding of the role of lipid me－tabolism in pathogenesis一 of HCV infection including liver inj ury and hepatocarcinogenesis． |
| 索引用語 |
|
