Pathogenesis of hepatitis C virus recurrence in the liver allograft

Abstract

Key Points 1. Hepatitis C virus (HCV) infection in the allograft occurs in the setting of greater viral burden than in non-transplantation patients. 2. Infection of the allograft occurs early (within days and possibly during the intraoperative reperfusion phase). 3. Viral burden plateaus at 1 month posttransplantation and (in the absence of cholestatic HCV) peaks at the time of acute hepatitis (1 to 4 months). 4. Acute hepatitis is associated with immune cell infiltration and hepatocyte apoptosis. 5. Cholestatic HCV seems to be a disease of direct HCV cytopathic injury in the setting of extreme virus levels, an intrahepatic T helper subtype 2 cell (TH2)-like response, and lack of a specific HCV-directed response. 6. Chronic hepatitic HCV seems to behave at the molecular and/or cellular level in a similar fashion to the non-transplantation setting, with activation of TH1 inflammatory, profibrotic, and proapoptotic pathways. This process operates at a greater viral burden than pretransplantation and leads to more progressive disease. 7. More studies are required to examine and distinguish allograft rejection in the setting of HCV infection from HCV infection alone.