Mechanisms of HCV reinfection and allograft damage after liver transplantation  Geoffrey W McCaughan, Amany Zekry  Journal of Hepatology  Volume 40, Issue 3, Pages 368-374 (March 2004) DOI: 10.1016/j.jhep.2004.01.014

Fig. 1 A proposed model for the pathogenesis of allograft injury in cholestatic hepatitis C. High levels of immunosuppression in cholestatic hepatitis result in a reduced immune response (absent CD4 responses and stable quasispecies). In addition, an intrahepatic non-specific TH2 cytokine response occurs (increased IL-10 and IL-4). Taken together, these events allow HCV to proliferate rapidly with consequent extremely high viral burdens. The absence of a specific and effective immune response in the presence of high viral burden results in HCV mediating cytopathic allograft damage. Journal of Hepatology 2004 40, 368-374DOI: (10.1016/j.jhep.2004.01.014)

Fig. 2 A proposed model for the pathogenesis of allograft injury in recurrent chronic HCV post-transplant. Increased hepatitis C viral load in the post-transplant setting appears to overcome the inhibitory effect of immunosuppression on the immune system. This results in induction of the immune system to act at a higher level than in the pre-transplant setting. As a consequence the following events occur at the molecular level: (1) an enhanced inflammatory response characterised by upregulation of IFN-γ inducible genes; (2) induction of antiviral IFN-α inducible genes which are not associated with reduced viral replication; (3) a hepatitis C virus driven enhanced proliferation, apoptosis and fibrosis response in the allograft. Acute rejection on the other hand is characterised by increased inflammation and induction of stress response related genes. Journal of Hepatology 2004 40, 368-374DOI: (10.1016/j.jhep.2004.01.014)