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Preformed donor-specific T-lymphocytotoxic antibody (DSTAb) has an adverse effect on patients with orthotopic liver transplantation (OLTx), yet some liver allografts were tolerated with cytotoxic antibody-mediated rejection.1–3 To study such an antibody effect further, we monitored posttransplant DSTAb for patients who received OLTx across a positive T-lymphocyte crossmatch.
This study consisted of 40 patients who received primary liver transplantation across a positive T-lymphocyte crossmatch at the University of Pittsburgh Medical Center, between November 1989 and December 1991. Initial immunosuppression comprised cyclosporine A (4 cases) or FK 506 (36 cases), in combination with a low-dose (17 cases) or high-dose steroid (23 cases). The protocol for Combined steroid therapy was the following: low dose, 20 mg/d of methylprednisolone given on the day of transplantation and continued during the first 2 weeks posttransplant, then decreased to 10 mg/d. In high-dose steroid therapy, methylprednisolone was started at 200 mg/d in the operating room, and decreased daily by 40 mg until reaching 20 mg/d. All patients were monitored for their DSTAb level in serum samples collected every week for 2 months following OLTx. The lymphocyte cytotoxicity test was performed with dithiothreitol (DTT)-treated sera according to the National Institutes of Health standard procedure, and the reactivity of DSTAb was decided by the end point of cytotoxic titer using 2-fold diluted serum up to 1:32. Actuarial graft survival was computed by the life-table method, and patient death, as well as graft removal, was considered graft failure, regardless of the reason.
According to posttransplant DSTAb titer, 40 patients were divided into two groups: group 1 consisted of 25 patients who became negative in the first 2 months posttransplant, and group 2 comprised 15 patients who had an increased or stable titer over a 2-month period following OLTx. Figure 1 illustrates the graft outcomes of these two groups. The survival rate of group 2 dropped markedly during the first 3 weeks posttransplant, with graft survival rates of 53.3%, 40.0%, and 33.3% at 1, 2, and 3 months, respectively. On the other hand, the graft survival rates of Group 1 were 96.0%, 88.0%, and 88.0% at 1, 2, and 3 months, respectively, which were higher than those of Group 2.
Although a detrimental effect was observed for patients who received orthotopic liver transplantation across a positive crossmatch, our earlier study revealed that this effect was minimal compared to that observed in kidney transplant recipients.1–3 As a result, the liver has been considered invulnerable from an antibody-mediated injury. However, this study clearly indicated that if a patient possessed a persistent DSTAb during the early posttransplant period, the transplant outcome was significantly low. In fact, a 3-month survival rate as low as 33% was observed in such recipients. These data suggest that the transplanted liver could also be a target of the antibody injury, and the presence of posttransplant donor-specific antibody seems to be more substantial than the pretransplant antibody. If this were the case, efforts should be made to reduce the posttransplant antibody titer for patients with a positive crossmatch. Although an extended study is required, our preliminary data reveal that a high dose of steroid administration is effective in reducing posttransplant DSTAb in patients with pretransplant antibody,4 which would relieve the transplanted liver from an antibody-mediated injury.