Jonas S, Bechstein W O, Lemmens H P, Kling N, Grauhan O, Lobeck H, Neuhaus P
Chirurgische Klinik, Virchow Klinikum, Humboldt Universität, Berlin, Germany.
Transpl Int. 1996;9(1):23-31. doi: 10.1007/BF00336808.
We have reviewed our experience with conversion to tacrolimus after 435 liver transplantations. Tacrolimus was administered as a rescue agent in 33 patients until October 1993. Indications for rescue therapy were: cholestatic forms of severe, steroid-resistant cellular rejection (n = 8), OKT3-resistant cellular rejections (n = 6), cellular rejections in patients suffering from cyclosporin malabsorption (n = 4), late onset cellular rejections (n = 4), early chronic rejections (n = 3), and chronic vascular or ductopenic rejections (n = 8). Response was evident in 29 of the 33 patients (88%), whereas 4 patients (12%) were nonresponsive. Patient and graft survival were 76% and 70%, respectively. Graft loss with or without patient death occurred in three of eight patients suffering from severe, steroid-resistant cellular rejection, in two of six patients with OKT3-resistant cellular rejections, and in five of eight patients undergoing chronic rejection. In severe steroid-resistant cellular rejection, successful tacrolimus rescue therapy corresponded to a significantly lower total serum bilirubin than unsuccessful therapy (12.0 +/- 5.6 mg% vs 29.7 +/- 5.9 mg%, P < 0.05). We conclude that tacrolimus rescue therapy is a safe and efficient alternative for high-risk cases that do not respond to conservative treatment. In severe, steroid-resistant cellular rejection and in chronic ductopenic rejection, conversion to tacrolimus is beneficial only in a limited number of cases. A predictive parameter, which total serum bilirubin may prove to be in severe, steroid-resistant cellular rejection, is needed to select those cases that might benefit more from retransplantation than from conversion to tacrolimus.
我们回顾了435例肝移植术后转换为使用他克莫司的经验。1993年10月前，33例患者将他克莫司作为挽救药物使用。挽救治疗的指征包括：严重的胆汁淤积型、对类固醇耐药的细胞性排斥反应（n = 8）、对OKT3耐药的细胞性排斥反应（n = 6）、环孢素吸收不良患者的细胞性排斥反应（n = 4）、迟发性细胞性排斥反应（n = 4）、早期慢性排斥反应（n = 3）以及慢性血管性或胆管闭塞性排斥反应（n = 8）。33例患者中有29例（88%）反应明显，而4例患者（12%）无反应。患者和移植物存活率分别为76%和70%。在8例严重的、对类固醇耐药的细胞性排斥反应患者中，有3例发生了移植物丢失，无论患者是否死亡；在6例对OKT3耐药的细胞性排斥反应患者中，有2例发生了移植物丢失；在8例接受慢性排斥反应的患者中，有5例发生了移植物丢失。在严重的、对类固醇耐药的细胞性排斥反应中，他克莫司挽救治疗成功组的总血清胆红素显著低于未成功组（12.0±5.6mg% 对29.7±5.9mg%，P < 0.05）。我们得出结论，对于对保守治疗无反应的高危病例，他克莫司挽救治疗是一种安全有效的替代方法。在严重的、对类固醇耐药的细胞性排斥反应和慢性胆管闭塞性排斥反应中，转换为使用他克莫司仅在少数病例中有益。需要一个预测参数，总血清胆红素可能被证明是严重的、对类固醇耐药的细胞性排斥反应中的预测参数，以选择那些可能从再次移植中比从转换为使用他克莫司中获益更多的病例。
