CYTOMEGALOVIRUS INFECTION OF THE LIVER TRANSPLANT; VIROLOGICAL, HISTOLOGICAL AND IMMUNOLOGICAL FINDINGS

Abstract

P802 Aims: The most common organ specific complication of cytomegalovirus (CMV) infection after liver transplantation is hepatitis. The purpose of the study was to describe retrospectively the detailed virological, histological and immunological observations associated with CMV infection of the liver transplant. Methods: The study included 253 liver transplantations performed on 229 adult recipients during 1991-2000. CMV infection was diagnosed by the frequent monitoring of CMVpp65 antigenemia. CMV antigens were demonstrated by immunohistochemistry and CMV-DNA by hybridization in situ from liver biopsy frozen sections. The histological findings were analyzed according to the Banff criteria. The expression of adhesion molecules (ICAM-1, VCAM-1, ELAM-1), their ligands (LFA-1, VLA-4, sLeX) and lymphoid activation markers (MHC Class II, IL-2-R) were demonstrated by immunohistochemistry. Results: CMV hepatitis was diagnosed in 26 patients (11%). The incidence of CMV hepatitis was higher among seronegative (26%) than in seropositive recipients (9%), but most cases 18/26 (70%) occurred during reactivation. Viral loads were usually high in primary infections (893±1069, range 50-3000, pp65+cells), but varied widely in reactivations (388±740, range 3-3000). CMV antigens were demonstrated in the liver biopsy specimens of all 26 patients and confirmed by a positive finding in CMV-DNA hybridization in situ. CMV antigens were mainly located in the inflammatory cells of the portal infiltrate, but also a few infected hepatocytes were seen. No CMV positive endothelial or bile duct epithelial cells were recorded. The histological Banff-score was slightly increased (2.3±0.9, range 0.5-4.0). Microabcesses, lymphocytic infiltration, ballooning of hepatocytes, slight cholangitis and Kupffer cell reaction were common, but viral inclusions rare. CMV significantly (p<0.05) increased ICAM-1 and VCAM-1 expression and the number of LFA-1, VLA-4 and Class II positive lymphocytes in the graft. CMV hepatitis had no influence on the long-term outcome, but biliary complications were common. Conclusions: CMV hepatitis was not necessarily associated with high viral loads or primary infections. Microabscesses and other histological alterations were common but viral inclusions rare. Increased adhesion molecule expression was associated with lymphocyte infiltration.