Mechanisms Of Liver Injury From Recurrent Hepatitis C

Hepatitis C virus (HCV) re-infection is a universal problem when liver transplantation is performed in patients with HCV-related cirrhosis. The spectrum of diseases resulting from recurrent HCV infection is highly variable and may span acute resolving hepatitis to fibrosing cholestatic hepatitis which can lead to rapid graft failure and death.The balance between viral replication, immunosuppression and the host's antiviral immune response is considered to determine the outcome of infection. High activity of natural killer cells, expansion of CD4+ and CD8+ T cells, and a type 1 cytokine profile are considered correlates of protective immunity and good suppression of viral replication.Immunosuppression enables HCV to reach increased viral loads with infection of many hepatocytes. This will result in enhanced loss of liver cells once immunity recovers. When viral infection persists, constant re-infection with the need for removal of infected hepatocytes will lead to a state of regenerative exhaustion, fibrogenesis, and ultimately cirrhosis. Finally, almost complete suppression of T cell functions results in a pathological state of excessive viral replication, where cytopathic effects of HCV become visible.Direct activation of hepatic stellate cells and cytopathic damage of infected hepatocytes causes FCH, which has a grave prognosis. Pathogenic mechanisms in recurrent HCV may be even more complex, because allograft rejection and specific interactions between immunosuppressive drugs and HCV may be superimposed to the battle between HCV and the host.