Langrehr J M, Nüssler N C, Neumann U, Guckelberger O, Lohmann R, Radtke A, Jonas S, Klupp J, Steinmüller T, Lobeck H, Meuer S, Schlag H, Lemmens H P, Knoop M, Keck H, Bechstein W O, Neuhaus P
Chirurgische Klinik, Virchow-Klinikum, Humboldt Universität, Berlin, Germany.
Transplantation. 1997 Jun 27;63(12):1772-81. doi: 10.1097/00007890-199706270-00012.
Quadruple immunosuppressive induction therapy has been shown to markedly reduce the incidence of acute rejection episodes without increasing the incidence of infectious complications after liver transplantation. However, the use of polyclonal antibody preparations (e.g. antithymocyte globulin [ATG]) is associated with side effects such as fever and tachycardia. To evaluate the efficacy and the safety of a monoclonal antibody directed against the interleukin-2 receptor (BT563) in comparison with ATG as part of a quadruple induction regimen, a prospective, randomized study was conducted.
Eighty consecutive adult recipients of primary orthotopic liver transplants were randomized to receive either BT563 (10 mg/day; days 0-12; n=39) or ATG (5 mg/kg/day; days 0-6; n=41) in addition to the standard immunosuppressive protocol consisting of cyclosporine, and prednisolone, and azathioprine.
Patients treated with BT563 had a significantly lower incidence of steroid-sensitive rejection episodes (3 vs. 11; P<0.025) and also significantly fewer drug-related side effects (4 vs. 18, P<0.038) when compared with patients treated with ATG. The incidence of infectious complications was not different between the two groups. Patient survival did not differ significantly between the two groups (84.6% at 1, 2, and 3 years in the BT563 group and 90.2% at 1 year and 87.8% at 2 and 3 years for the ATG group). Analysis of graft function showed an advantage for the BT563 group in terms of postoperative bilirubin levels. However, no differences were observed in long-term follow-up between the two groups.
Our results indicate that treatment with anti-interleukin-2 receptor antibody as part of quadruple induction therapy after orthotopic liver transplantation is safe and effective and shows fewer steroid-sensitive rejection episodes as well as fewer side effects when compared with quadruple induction therapy including ATG.
四联免疫抑制诱导疗法已被证明可显著降低肝移植后急性排斥反应的发生率，且不会增加感染并发症的发生率。然而，使用多克隆抗体制剂（如抗胸腺细胞球蛋白[ATG]）会伴有发热和心动过速等副作用。为了评估作为四联诱导方案一部分的抗白细胞介素-2受体单克隆抗体（BT563）与ATG相比的疗效和安全性，进行了一项前瞻性随机研究。
80例连续接受原位肝移植的成年受者被随机分为两组，除接受由环孢素、泼尼松龙和硫唑嘌呤组成的标准免疫抑制方案外，一组接受BT563（10毫克/天；第0 - 12天；n = 39），另一组接受ATG（5毫克/千克/天；第0 - 6天；n = 41）。
与接受ATG治疗的患者相比，接受BT563治疗的患者类固醇敏感型排斥反应的发生率显著更低（3例对11例；P < 0.025），药物相关副作用也显著更少（4例对18例，P < 0.038）。两组感染并发症的发生率无差异。两组患者的生存率无显著差异（BT563组1年、2年和3年时为84.6%，ATG组1年时为90.2%，2年和3年时为87.8%）。移植物功能分析显示，BT563组在术后胆红素水平方面具有优势。然而，两组在长期随访中未观察到差异。
我们的结果表明，原位肝移植后作为四联诱导治疗一部分的抗白细胞介素-2受体抗体治疗是安全有效的，与包括ATG的四联诱导治疗相比，类固醇敏感型排斥反应的发生率更低，副作用也更少。
