Millis J M, Woodle E S, Piper J B, Bruce D S, Newell K A, Seaman D S, Baker A L, Hart J, Dasgupta K, Thistlethwaite J R
Department of Surgery, University of Chicago, Illinois 60637, USA.
Transplantation. 1996 May 15;61(9):1365-9. doi: 10.1097/00007890-199605150-00014.
Twelve patients who experienced steroid-resistant rejection after primary liver transplantation while receiving cyclosporine-based therapy were converted to tacrolimus without receiving OKT3 or additional steroids. The indications for conversion were ongoing biopsy-confirmed rejection. All patients had received one course of high-dose intravenous steroids, which failed to reverse the rejection episode. No other antirejection therapy was given. Tacrolimus was initiated to reverse rejection and for maintenance therapy. The tacrolimus target level was 15-20 ng/ml (whole blood, IMX). All 12 patients had rapid reversal of the rejection episode and did not experience recurrent rejection (mean follow-up: 8.2 +/- 1.2 months). The mean bilirubin level dropped from 6.1 mg/dl at the initiation of tacrolimus therapy to 4.4 mg/dl by day 7 of therapy, 2.5 mg/dl by day 14, and 1.5 mg/dl by day 21 (P < 0.003). Serum glutamic pyruvic transaminase demonstrated a similar response. The serum creatinine level was unchanged at 1.5 mg/dl. No major adverse reactions were noted in this group of patients. Patient and graft survival rates were 100%. Four of the eight patients with a follow-up of >4 months are no longer receiving steroid therapy. Tacrolimus is effective as the primary therapy for the treatment of steroid-resistant rejection and provides a rapid and sustained biochemical response. Patients with mild to moderate rejection may be safely converted from cyclosporine to tacrolimus without an additional steroid bolus or OKT3 therapy. Early "preemptive" conversion to tacrolimus prior to the use of additional steroids or OKT3 may decrease overall rejection therapy requirements. This approach has promise for improved graft survival and fewer infectious and immunologic complications.
12例在接受以环孢素为基础的治疗时，初次肝移植后发生激素抵抗性排斥反应的患者，在未接受OKT3或额外激素的情况下转换为使用他克莫司。转换的指征是持续的活检证实的排斥反应。所有患者均接受过一个疗程的大剂量静脉注射激素，但未能逆转排斥反应。未给予其他抗排斥治疗。开始使用他克莫司以逆转排斥反应并进行维持治疗。他克莫司的目标水平为15 - 20 ng/ml（全血，IMX）。所有12例患者的排斥反应均迅速逆转，且未发生复发性排斥反应（平均随访时间：8.2±1.2个月）。他克莫司治疗开始时平均胆红素水平为6.1 mg/dl，治疗第7天降至4.4 mg/dl，第14天降至2.5 mg/dl，第21天降至1.5 mg/dl（P<0.003）。血清谷丙转氨酶也有类似反应。血清肌酐水平在1.5 mg/dl时保持不变。该组患者未观察到重大不良反应。患者和移植物存活率均为100%。随访时间>4个月的8例患者中有4例不再接受激素治疗。他克莫司作为治疗激素抵抗性排斥反应的一线治疗有效，并能提供快速且持续的生化反应。轻度至中度排斥反应的患者可安全地从环孢素转换为他克莫司，无需额外的激素冲击或OKT3治疗。在使用额外激素或OKT3之前早期“抢先”转换为他克莫司可能会减少总体排斥治疗需求。这种方法有望提高移植物存活率，并减少感染和免疫并发症。
