Positive pretransplant crossmatches predict early graft loss in liver allograft recipients

We evaluated the influence of donor-recipient HLA compatibility and recipient pretransplant antidonor sensitization on liver allograft recipient survival. The overall graft survival results for 67 cyclosporine-prednisone treated liver allograft recipients at 3, 6, and 12 months posttransplant were 86%, 83%, and 83%, respectively. No significant differences were observed when comparing the one-year survivals of 81% vs. 85% for men and women or 80% vs. 85% for adult and pediatric patients. Similarly, no differences were observed when comparing one-year graft survivals for well vs. poorly matched recipients of 77% vs. 83% for recipients with ≤2 HLA A. B vs. >2 HLA A, B mismatches (MMs) and 82% vs. 82% for recipients with 0-1 HLA-DR MMs vs. 2 HLA-DR MMs, respectively. Pretransplant transfusion history and race also did not influence survival. Standard NIH (long-incubation) and anti-human globulin (AHG) crossmatches were performed. The 12% of recipients (8/67) displaying a positive NIH crossmatch experienced significantly poorer 3-, 6- , and 12-month survivals of 62% vs. 89%, 62% vs. 86%, and 62% vs. 86% (all P<0.05), respectively, than the 59 NIH-crossmatch negative recipients. Similarly, the 16% (11/67) of recipients displaying a positive AHG crossmatch had significantly poorer 3-, 6-, and 12-month survivals of 63% vs. 91%, 54% vs. 89%, and 54% vs. 89% (all P<0.05) respectively, than the 56 AHG crossmatch-negative recipients. NIH and AHG crossmatch-positive sera were treated with dithioerythritol (DTE) to establish whether reactivity was due to IgM or IgG immunoglobulin. One-year graft survivals of 65% vs. 30% (P<0.05) were observed when the crossmatch-positive sera reactivities were due to IgM vs. IgG immunoglobulin. While graft survivals were improved when positive crossmatch serum reactivity was due to IgM, these survivals were still significantly poorer than when the crossmatches were completely negative (86% vs. 60%). P<0.05 for NIH-negative vs. NIH-positive, but DTE negative, and 88% vs. 77%, P<0.05 for AHG-negative vs. AHG-positive, but DTE- negative). Therefore, an NIH- or AHG-positive crossmatch, due either to IgM or IgG reactivity, results in poor early (3- and 6-months) liver allograft survival. Crossmatch-positive recipients experienced significantly (P<0.05) more rejections and more steroid-resistant rejections (P<0.05) than crossmatch-negative recipients. Of great interest was the fact that 55% (6/11) of recipients displaying a positive pretransplant crossmatch experienced a moderate initial rejection episode compared with only 9% (5/56) for crossmatch-negative recipients (P<0.05). These results suggest, therefore, that a positive crossmatch adversely affects the early (3- and 6- month) survival of primary liver allografts. Since a crossmatch often cannot be performed prior to the transplant operation, the clinician's knowledge of the crossmatch results could be of importance in the choice of immunosuppressive therapy for crossmatch-positive recipients during the early posttransplant period.