THE EFFECT OF HLA MISMATCHES, SHARED CREGS, AND SHARED HLA-DR ON THE OUTCOME AFTER PEDIATRIC LIVER TRANSPLANTATION

Abstract

O96* Aims: Prospective HLA matching is not routinely performed before liver transplantation. However, on the basis of experimental studies, reconsideration of these procedures may be justified, especially in pediatric recipients. The aim of this study was to analyse the effect of the number of HLA mismatches, the number of shared common cross-reactive antigen groups (CREGs), and the number of shared HLA-DR antigens on the outcome after liver transplantation in an exclusively pediatric population. Methods: Inclusion criteria were primary transplants with an ABO-identical or compatible graft with an immunosuppressive regimen consisting of cyclosporine or tacrolimus. All transplants should have had a possible follow-up of at least one year. In this way, 136 consecutive transplants could be analysed. Outcome parameters were graft survival, acute rejection within three months, and portal fibrosis at one year after transplantation. A subgroup analysis was made considering full-size (FS) and technical-variant (TV) liver grafts. The influence of HLA mismatches, shared CREGs, and shared HLA-DR antigens on the outcome was assessed by using adjusted multivariate analysis. Confounding factors related to recipients, donors, transplant procedures (including immunosuppression), and postoperative complications were identified. Results: HLA mismatching, shared CREGs, and shared HLA-DR did not influence overall graft survival, nor survival of FS liver grafts. Survival of TV grafts was better in case of two mismatches at the HLA-DR locus compared to zero or one mismatch at this locus (P=0.01) and better in case of none shared HLA-DR antigens compared to one shared HLA-DR antigen (P=0.004). Of 86 one-year posttransplant biopsies, 33 (38%) showed normal histology and 29 (34%) showed portal fibrosis. The remaining 24 (28%) biopsies were excluded because of other histopathologic abnormalities. The incidence of portal fibrosis in grafts with zero or one mismatch at the HLA-DR locus was 59% compared to 36% with two mismatches at this locus (P=0.08). The incidence of portal fibrosis after FS transplantation was 34% and after TV transplantation 60% (P=0.04). Analyzing the effect of HLA-DR mismatches on the incidence of portal fibrosis considering graft type, revealed 9 of 9 (100%) TV grafts with 0-1 mismatches at the HLA-DR locus showing portal fibrosis compared to 9 of 21 (43%) grafts with 2 mismatches (p=0.004). After adjusted multivariate regression analysis, matching for HLA-DR (β=0.19, 95%CI 0.05–0.75, P=0.02) as well as TV liver grafts (β=6.26, 95%CI 1.49–23.20, P=0.01) proved to be independent risk factors for portal fibrosis. HLA did not influence the incidence of acute rejection. Conclusions: HLA-DR mismatching had a positive effect on survival of technical-variant liver grafts and was associated with a lower incidence of portal fibrosis in such grafts. Shared HLA-DR antigens had a negative influence on survival of technical-variant grafts.