Pathophysiology of hepatitis C virus infection and related liver disease.
Hepatitis C virus (HCV) infects over 170 million people worldwide. Chronic infection occurs in 50-80% of cases and eventually leads to cirrhosis and hepatocellular carcinoma. The HCV lifecycle is only partly understood owing to the lack of a productive cell culture system. Several molecules have been implicated in the receptor complex at the surface of target cells, but the mode of HCV entry remains unknown. Persistent infection appears to be due to weak CD4+and CD8+ T-cell responses during acute infection, which fail to control viral replication. When chronic infection is established, HCV does not appear to be cytopathic. Liver lesions appear to result from locally driven immune responses, which are mainly non-specific. Local inflammation triggers fibrogenesis, in which hepatic stellate cells play a major role. Cirrhosis is facilitated by external factors, such as chronic alcohol consumption and viral co-infections. Patients with cirrhosis are at high risk of developing hepatocellular carcinoma. The role of HCV proteins in hepatocarcinogenesis is unknown. Further progress in our understanding of HCV infection and pathogenesis awaits the advent of new model systems and technologies.
Pawlotsky
Jean-Michel
JM
Department of Virology (EA 3489), Hôpital Henri Mondor, Université Paris XII, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. jean-michel.pawlotsky@hmn.ap-hop-paris.fr
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D016174:Hepacivirus / Q000254:growth & development / Q000472:pathogenicity*; D006526:Hepatitis C / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D018417:Th1 Cells / Q000276:immunology; D014779:Virus Replication