The adverse impact on liver transplantation of using positive cytotoxic crossmatch donors

Abstract

Because of the liver graft's ability to resist cytotoxic antibody-mediated rejection, it has become dogma that the conventional transplant crossmatch used to avoid hyperacute rejection of other organs is irrelevant to the liver. We examined this hypothesis in a consecutive series of adult primary liver recipients treated with FK506 and low-dose steroids. Twenty-five of 231 (10.8%) patients received a liver from a cytotoxic-positive crossmatch donor (more than 50% of donor T lymphocytes were killed by dithiothreitol-pretreated recipient serum). The outcome was compared with that of 50 negative crossmatch patients who had their transplantations just before and after the crossmatch positive cases. The one-year graft and patient survivals were 56% and 68%, for positive and 82% and 86% for negative crossmatch patients (P = 0.004, P = 0.03, respectively). The difference between patient and first graft survival was accounted for by retransplantation, which was 4 times more frequent in the positive-crossmatch cases. Histologically, failed allografts obtained at the time of retransplantation revealed a spectrum of pathologic findings related to vascular injury. This study showed a higher difficulty of intraoperative blood product management, a degraded prognosis, and a poorer average quality of ultimate graft function when liver transplantation was performed against positive cytotoxic crossmatches. In such patients for whom crossmatch-negative donors may never be found because of the broad extent and intensity of sensitization, special therapeutic strategies perioperatively must be evolved if results are to improve.

Figure 1

The actuarial graft survival rates in 25 adults positive-crossmatch patients and 50 negative-crossmatch patients.

Figure 2

The actuarial patient survival rates in 25 adult positive-crossmatch and 50 negative-crossmatch patients.

Figure 3

Actuarial graft survival rates for 18 patients whose PRA were ≥40% and 7 patients whose PRA were <40%, with DTT treatment sera in positive-crossmatch patients.

Figure 4

Blood usage in positive- and negative-crossmatch patients. (PRBC) packed red blood cells; (FFP) fresh frozen plasma; (CRYO) cryoprecipitated plasma; (POST OP PLATELETS) postoperative usage of platelets. Mean ± SE is shown.

Figure 5

Serum total bilirubin levels after liver transplantation in positive- (n=17) and negative- (n=47) crossmatch patients who were followed for more than one month (mean ± SE). There was a significant elevation in total bilirubin levels in crossmatch-positive patients.

Figure 6

Serum alkaline-phosphatase levels after liver transplantation in positive- (n=17) and negative-crossmatch patients (n=47) who were followed for more than one month. Mean ± SE is shown.

Figure 7

The platelet count before and after liver transplantation in positive- (n=17) and negative-crossmatch patients (n=47) who were followed for more than one month. Mean ± SE is shown. The platelet counts in positive-crossmatch patients were significantly lower than those of crossmatch-negative patients.

Figure 8

Total bilirubin levels before and after OKT3 treatment in crossmatch-positive patients. The OKT3 was administered at the time of biopsy-proved rejection (n=7).