Jain A, Mazariegos G, Kashyap R, Marsh W, Khanna A, Iurlano K, Fung J, Reyes J
Thomas E. Starzl Transplantation Institute, Department of Surgery and Department of Pharmaceutical Sciences, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Pediatr Transplant. 2001 Apr;5(2):93-8. doi: 10.1034/j.1399-3046.2001.005002093.x.
Tacrolimus is a potent immunosuppressive agent and has been used in liver transplantation (LTx) for nearly a decade. More than 70% of children can be maintained on tacrolimus monotherapy, without steroids, by the end of 1 yr post-Tx. This freedom from steroids does not appear to change significantly in subsequent years. The use of steroids has obvious metabolic and cosmetic disadvantages, besides affecting linear growth in children. The present study identifies why some children still require steroid therapy after successful LTx. One hundred and sixty-six consecutive pediatric patients who had undergone primary LTx between October 1989 and December 1992, were included in this study. Follow-up ranged from 6 to 9 yr (mean 7.5 +/- 0.8 yr). One hundred and forty-one children were alive in November 1998 and these patients constituted the study group. Their current rate of prednisone use, reason for prednisone use, and prednisone dose were examined retrospectively. Of the 141 patients, 139 (98.5%) had stopped taking steroids at some time-point after LTx. Thirteen patients (9%) were off immunosuppression altogether (group I), 97 were undergoing tacrolimus monotherapy (group II), and the remaining 31 were receiving therapy with steroids and tacrolimus (group III). The mean prednisone dose at the last follow-up was 6.5 +/- 4.9 mg/day (median 5.0 mg/day). In group III, two children were never weaned off steroids because of inadequate follow-up (both lived outside the country), and the remaining 29 children completely stopped steroid therapy at some time-point after LTx; however, prednisone was re-introduced for clinically suspected or biopsy-proven rejection in 24. Seven children in group III had completely stopped immunosuppressive therapy either as part of an immunosuppression reduction protocol (n = 3) or for suspected or proven post-transplant lymphoproliferative disorder (PTLD) (n = 4). In eleven of the 18 children in group III, requirement of steroid for rejection was thought to be related, in part, to non-compliance. In three children in group III, steroids were re-introduced for renal dysfunction, and two of these patients subsequently received a kidney Tx. In one child with cerebral ischemia, steroids were used to reduce brain edema, and another child had features of auto-immune hepatitis. Hence, almost all children can be weaned off steroids when tacrolimus is used as primary immunosuppression after primary LTx. However, approximately 22% of children may need re-institution of steroids because of late acute rejection or renal dysfunction. The concomitant use of other non-steroidal immunosuppressive agents with tacrolimus may further reduce the dose and rate of steroid use.
他克莫司是一种强效免疫抑制剂，已在肝移植（LTx）中使用了近十年。超过70%的儿童在肝移植术后1年末可仅使用他克莫司进行单药治疗，无需使用类固醇。在随后几年中，这种不使用类固醇的情况似乎没有显著变化。除了影响儿童的线性生长外，使用类固醇还有明显的代谢和美容方面的缺点。本研究确定了为什么有些儿童在肝移植成功后仍需要类固醇治疗。本研究纳入了1989年10月至1992年12月期间连续接受首次肝移植的166例儿科患者。随访时间为6至9年（平均7.5±0.8年）。1998年11月，141名儿童存活，这些患者构成了研究组。回顾性检查了他们目前使用泼尼松的情况、使用泼尼松的原因以及泼尼松的剂量。在141例患者中，139例（98.5%）在肝移植后的某个时间点停止了服用类固醇。13例患者（9%）完全停用了免疫抑制剂（I组），97例接受他克莫司单药治疗（II组），其余31例接受类固醇和他克莫司联合治疗（III组）。最后一次随访时泼尼松的平均剂量为6.5±4.9毫克/天（中位数5.0毫克/天）。在III组中，两名儿童因随访不足从未停用类固醇（两人都住在国外），其余29名儿童在肝移植后的某个时间点完全停止了类固醇治疗；然而，24例因临床怀疑或活检证实的排斥反应而重新使用了泼尼松。III组中有7名儿童作为免疫抑制减量方案的一部分（n = 3）或因怀疑或证实的移植后淋巴增殖性疾病（PTLD）（n = 4）而完全停止了免疫抑制治疗。在III组的18名儿童中，有11名儿童因排斥反应需要使用类固醇，部分原因被认为与不依从有关。在III组的3名儿童中，因肾功能不全重新使用了类固醇，其中2名患者随后接受了肾移植。在1名患有脑缺血的儿童中，使用类固醇来减轻脑水肿，另1名儿童有自身免疫性肝炎的特征。因此，当他克莫司作为首次肝移植后的主要免疫抑制剂使用时，几乎所有儿童都可以停用类固醇。然而，约22%的儿童可能因晚期急性排斥反应或肾功能不全而需要重新使用类固醇。他克莫司与其他非类固醇免疫抑制剂联合使用可能会进一步降低类固醇的使用剂量和使用率。
