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抗白细胞介素2受体抗体和霉酚酸酯用于治疗成人肝移植中对类固醇耐药的排斥反应。

Anti-interleukin 2 receptor antibodies and mycophenolate mofetil for treatment of steroid-resistant rejection in adult liver transplantation.

作者信息

Orr D W, Portmann B C, Knisely A S, Stoll S, Rela M, Muiesan P, Bowles M J, Heaton N D, O'Grady J G, Heneghan M A

机构信息

King's College Hospital, Institute of Liver Studies, London, England.

出版信息

Transplant Proc. 2005 Dec;37(10):4373-9. doi: 10.1016/j.transproceed.2005.10.022.

Abstract

BACKGROUND

Steroid-resistant rejection (SRR) results in significant morbidity and mortality from the adverse effects of rescue therapy and in graft loss from chronic rejection. In our knowledge, the efficacy and safety of anti-interleukin (IL) 2r antibodies (daclizumab and basiliximab) for the treatment of SRR in adult liver transplantation has not previously been evaluated.

METHODS

Twenty-five patients received either daclizumab or basiliximab as rescue therapy for SRR. Outcome and biochemical parameters were recorded before and after treatment with an anti-IL-2r antibody.

RESULTS

The median time from transplantation to SRR was 25 days. Secondary immunosuppression included mycophenolate mofetil in 18 patients. Twelve patients (48%) had complete resolution of SRR. Aspartate transaminase levels normalized at a median of 37 days (range, 1-168 days). In 13 patients (52%) progressive hepatic dysfunction developed. Four of these patients received another transplant, and 6 patients had chronic rejection. Three patients died with graft failure. Of 16 patients with acute cellular rejection, 12 (75%) had resolution, 2 had chronic rejection, 1 required a repeat transplantation, and 1 died with graft failure. In contrast, all 9 patients with established chronic rejection in their pretreatment biopsy continued to have significant graft dysfunction, with 4 having persistent chronic graft dysfunction, 3 requiring repeat transplantation, and 2 dying with graft failure.

CONCLUSION

Twelve (48%) of 25 patients who received an anti-IL-2r antibody because of SRR were successfully treated. All successfully treated patients had ongoing acute cellular rejection at liver biopsy (75%), whereas patients with histologic evidence of chronic rejection responded poorly.

摘要

背景

类固醇抵抗性排斥反应(SRR)因挽救治疗的不良反应导致显著的发病率和死亡率,并因慢性排斥反应导致移植物丢失。据我们所知,抗白细胞介素(IL)-2r抗体(达利珠单抗和巴利昔单抗)在成人肝移植中治疗SRR的疗效和安全性此前尚未得到评估。

方法

25例患者接受达利珠单抗或巴利昔单抗作为SRR的挽救治疗。在使用抗IL-2r抗体治疗前后记录结果和生化参数。

结果

从移植到SRR的中位时间为25天。二线免疫抑制包括18例患者使用霉酚酸酯。12例患者(48%)的SRR完全缓解。天冬氨酸转氨酶水平在中位时间37天(范围1-168天)恢复正常。13例患者(52%)出现进行性肝功能障碍。其中4例患者接受了再次移植,6例患者发生慢性排斥反应。3例患者死于移植物功能衰竭。16例急性细胞性排斥反应患者中,12例(75%)缓解,2例发生慢性排斥反应,1例需要再次移植,1例死于移植物功能衰竭。相比之下,预处理活检中确诊为慢性排斥反应的所有9例患者仍有明显的移植物功能障碍,4例持续存在慢性移植物功能障碍,3例需要再次移植,2例死于移植物功能衰竭。

结论

25例因SRR接受抗IL-2r抗体治疗的患者中有12例(48%)得到成功治疗。所有成功治疗的患者在肝活检时均存在持续的急性细胞性排斥反应(75%),而有慢性排斥反应组织学证据的患者反应不佳。

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