HLA compatibility and liver transplant outcome: Improved patient survival by HLA and cross-matching

In liver transplantation (LTx), numerous studies have failed to demonstrate an adverse effect of HLA-A, B, DR incompatibility or of donor-specific positive cross-match on survival of the recipients. In this study, we examined the effect of antidonor cytotoxic antibody and HLA compatibility in 800 LTx recipients with CsA-based immunosuppression. Thirty-four of 482 (7%) recipients were transplanted across a positive donor-specific T cell cross-match. Four-year patient and graft survival was 71% and 67%, respectively, in negative cross-match recipients and 53% and 50%, respectively, in positive cross-match recipients (P=0.0051 and P=0.023). Neither B cell-positive crossmatch nor the presence of panel reactive antibody (PRA) had an adverse impact on the liver allograft outcome. Interestingly, 21/58 (36.2%) patients with PRA ≥ 10% had a positive T cell cross-match, whereas only 7/382 (1.8%) patients with PRA < 10% did (P<0.0001). This indicates the predictive value of PRA cross-match results. B lymphocyte cross-match results also were strongly correlated with the presence of PRA, as 26/57 (45.6%) of the patients with PRA ≥ 10% had a positive cross-match, whereas only 22/394 (5.6%) with PRA < 10% did (P<0.0001). Analysis of HLA compatibility demonstrated a significant impact on patient’s survival, comparing only 0-2 vs. 6 HLA-A+B+DR mismatches and 0 vs. 1 vs. 2 HLA-DR mismatches. Four-year patient survival rate for 0 to 2 antigen mismatches was 86%, whereas for 6 antigen mismatches it was 62% (P=0.025). Overall actuarial 4-year patient survival rate in HLA-DR-mis-matched groups (0 vs. 1 vs. 2) was 84%, 73%, and 64%, respectively (P=0.033). In no mismatched category was graft survival rate significantly different. Sepsis or rejection was the cause of graft loss in 1/10 (10%), 21/75 (28%), and 34/85 (40%) patients with 0, 1, and 2 HLA-DR mismatches, respectively. The difference between patient and graft survival was accounted for by survival after retransplantation, which was lower in patients with more HLA-DR mismatches in primary transplants. The latter group received intensive immunosuppressive therapy during the first month after primary transplantation, as compared with those with fewer HLA-DR mismatches (P=0.04). The above data suggest that prospective crossmatch should be performed in patients with > 10% PRA if it is logistically feasible. Alternatively, special immunosuppressive therapy strategies may be applied to LTx recipients having HLA incompatibility with donors (either in cross-match or HLA mismatching) in order to improve the survival rates.