Immunohistochemical evidence of immunopathogenetic mechanisms in chronic hepatitis C recurrence after liver transplantation.
Viremia and genotype are implicated in a rapid course of posttransplant hepatitis C virus (HCV) infection recurrence, but the role played by host immune reactions has not yet been evaluated. We correlated the degree of liver injury with the intrahepatic expression of molecules involved 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 assessed by immunohistochemistry, using a wide panel of monoclonal antibodies. Correlations between histological-immunohistochemical semiquantitative 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 vascular 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 with the degree of liver damage. The severe forms of post-transplant HCV infection recurrence are associated with a marked and aberrant intrahepatic expression of molecules involved in antigen recognition, and intercellular and vascular adhesion, decisive in regulating the recruitment and activation of cytotoxic T lymphocytes.
Asanza
C G
CG
Liver Section, Hospital Gregorio Marañón, Universidad Complutense de Madrid, Spain.
García-Monzón
C
C
Clemente
G
G
Salcedo
M
M
García-Buey
L
L
García-Iglesias
C
C
Bañares
R
R
Alvarez
E
E
Moreno-Otero
R
R
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D001707:Biopsy, Needle; D015815:Cell Adhesion Molecules / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006526:Hepatitis C / Q000473:pathology* / Q000601:surgery*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D014766:Viremia / Q000473:pathology; D001613:beta 2-Microglobulin / Q000032:analysis
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D001613:beta 2-Microglobulin