IMMUNOHISTOCHEMICAL EVIDENCE OF IMMUNOPATHOGENETIC MECHANISMS IN CHRONIC HEPATITIS-C RECURRENCE AFTER LIVER-TRANSPLANTATION

Viremia and genotype are implicated in a rapid course of posttransplan t hepatitis C virus (HCV) infection recurrence, but the role played by host immune reactions has not yet been evaluated. We correlated the d egree of liver injury with the intrahepatic expression of molecules in volved in immune response, The study included 32 biopsies of 30 liver transplant recipients, Recurrence of viremia was detected by Amplicor assay, Genotype was tested by Inno-Lipa. Cryostat sections were assess ed by immunohistochemistry, using a wide panel of monoclonal antibodie s. Correlations between histological-immunohistochemical semiquantitat ive evaluation and levels of viremia were performed. In severe hepatic inflammation, high numbers of activated cytotoxic T cells were found, along with marked hepatocellular expression of beta 2-microglobulin ( beta 2-MG) and intercellular adhesion molecules. Likewise, a strong va scular adhesion molecule expression was observed mainly in those areas that were more inflamed, A striking endoglin reactivity was detected in enlarged portal tracts, and the presence of neoformed microvessels was also noteworthy, By contrast, in mild hepatic inflammation only a few activated T cells were detected, together with a weaker reactivity for all molecules studied. The level of viremia did not correlate wit h the degree of liver damage. The severe forms of post-transplant HCV infection recurrence are associated with a marked and aberrant intrahe patic expression of molecules involved in antigen recognition, and int ercellular and vascular adhesion, decisive in regulating the recruitme nt and activation of cytotoxic T lymphocytes.