Jain A, Brody D, Hamad I, Rishi N, Kanal E, Fung J
Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Transplantation. 2000 Jan 15;69(1):172-6. doi: 10.1097/00007890-200001150-00029.
Neurological complications after orthotopic liver transplantation (OLTX) have remained a major concern in a small proportion of patients. The etiology of these complications is often thought to be multifactorial: the influence of calcineurin inhibitors is occasionally thought to play an important role. When neurotoxicity occurs after OLTX under tacrolimus, it is usually a minor complication and responds readily to a reduction in the dosage of or a temporary withdrawal of tacrolimus. However, neurotoxic complications occasionally do not respond to this conventional process. Neoral is a microemulsion formulation of cyclosporine. It has more consistent pharmacokinetic parameters and improved bioavailability when compared with conventional cyclosporine. The aim of the present report was to evaluate the role of Neoral in OLTX recipients with neurotoxic complication who failed to respond to a reduction in the dosage of tacrolimus.
Between August 1995 and November 1997, 330 adults (age >18 years) received primary OLTX under tacrolimus-based immunosuppression (mean age 52.6+/-11.4 years). There were 190 men and 140 women. Twenty-three (7%) patients (mean age 53.2+/-11.8 years; 17 men, 6 women) were converted to Neoral (mean 35+/-41 days after OLTX). These patients were followed until June 1998 (mean follow-up 22.7+/-7.8 months).
Four (17.4%) patients died during the follow-up period, and two patients underwent retransplantation. Neurological symptoms improved in all patients who survived. Adequate trough concentrations were achieved in all patients with p.o. Neoral. Nine (39%) patients experienced rejection episodes after conversion. Six (26.1%) patients were converted back to tacrolimus because of ongoing rejection (n=3), retransplantation (n=2), or persistent nausea and vomiting (n=1) without recurrence of the original neurological complication.
Neurological complications after OLTX disorders that occur under tacrolimus and that fail to respond to a reduction in the dosage can be treated safely by conversion to Neoral. However, the rate of rejection is up to 39%, and patients can often be converted back to tacrolimus without recurrence of the original neurological complication.
原位肝移植（OLTX）后的神经并发症一直是一小部分患者的主要担忧。这些并发症的病因通常被认为是多因素的：钙调神经磷酸酶抑制剂的影响偶尔被认为起着重要作用。在使用他克莫司进行OLTX后发生神经毒性时，通常是一种轻微并发症，减少他克莫司剂量或暂时停用他克莫司后反应良好。然而，神经毒性并发症偶尔对这种常规处理无反应。新山地明是环孢素的微乳剂剂型。与传统环孢素相比，它具有更一致的药代动力学参数和更高的生物利用度。本报告的目的是评估新山地明在对减少他克莫司剂量无反应的OLTX神经毒性并发症受者中的作用。
1995年8月至1997年11月期间，330名成年人（年龄>18岁）在基于他克莫司的免疫抑制下接受了原位肝移植（平均年龄52.6±11.4岁）。其中男性190名，女性140名。23名（7%）患者（平均年龄53.2±11.8岁；男性17名，女性6名）转换为新山地明（OLTX后平均35±41天）。这些患者随访至1998年6月（平均随访22.7±7.8个月）。
随访期间4名（17.4%）患者死亡，2名患者接受了再次移植。所有存活患者的神经症状均有改善。所有口服新山地明的患者均达到了足够的谷浓度。9名（39%）患者在转换后发生排斥反应。6名（26.1%）患者因持续排斥（n = 3）、再次移植（n = 2）或持续恶心和呕吐（n = 1）而转回他克莫司，原神经并发症未复发。
在他克莫司治疗下发生且对减少剂量无反应的OLTX神经并发症可以通过转换为新山地明安全治疗。然而，排斥反应发生率高达39%，且患者通常可转回他克莫司，原神经并发症不复发。
