Neuhaus P, Blumhardt G, Bechstein W O, Platz K P, Jonas S, Mueller A R, Langrehr J M, Lohmann R, Schattenfroh N, Knoop M
Department of Surgery, Free University of Berlin, Germany.
Transplantation. 1995 Jan 15;59(1):31-40. doi: 10.1097/00007890-199501150-00007.
FK506 has been proven effective for prevention and treatment of liver allograft rejection. Herein, we compare FK506-based immunosuppression with an effective quadruple immunosuppressive regimen, including cyclosporine and antithymocyte globulin. The results of a single center participating in the European multicenter FK506 study are reported, including immunosuppressive efficacy as well as toxicity. One-year patient and graft survival was 96.7% and 90.0% for the CsA group and 90.2% and 88.5% for the FK506 group, which is not statistically different. The incidence and severity of acute rejection episodes during the first postoperative year was similar in both treatment groups with 34.4% and 33.3% for the FK506 and CsA treatment group, respectively. Immunosuppressive potency was better for the FK506 group compared with the CsA group according to the incidence of chronic rejection. Furthermore, 5 patients (8.3%) required conversion to FK506 for immunological reasons, i.e., refractory acute or chronic rejection. The incidence of moderate and severe neurotoxicity during the early postoperative period was higher in the FK506 group (21.3%) compared with the CsA group (11.7%), while the incidence of renal insufficiency and acute renal failure was similar (18.0% and 18.3% for the FK506 and CsA treatment groups, respectively). The incidence of CMV infection was significantly higher under treatment with CsA (25.0%) than with FK506 (6.6%) (P < or = 0.05), while the incidence of pneumonia (13.1% and 13.3%), cholangitis (29.5% and 26.7%), and urinary tract infection (39.3% and 28.3% for the FK506 and CsA treatment groups, respectively) was similar in both treatment groups. However, infection was more serious in some cases treated with FK506, and evolved as the main cause of death in the FK506 treatment group. Therefore, caution should be paid to over immunosuppression and toxicity in FK506-treated patients. Regarding the monitoring of FK506, FK506 plasma level failed to be a reliable indicator, and therefore we recommend measurement of whole blood FK506 levels. Our data indicate that immunosuppressive potency of FK506 is greater than that of CsA, especially concerning the incidence of chronic rejection.
FK506已被证明对预防和治疗肝移植排斥反应有效。在此，我们将基于FK506的免疫抑制与一种有效的四联免疫抑制方案进行比较，该方案包括环孢素和抗胸腺细胞球蛋白。报告了一个参与欧洲多中心FK506研究的单中心结果，包括免疫抑制效果以及毒性。环孢素组的1年患者和移植物存活率分别为96.7%和90.0%，FK506组为90.2%和88.5%，差异无统计学意义。两个治疗组术后第一年急性排斥反应的发生率和严重程度相似，FK506治疗组和环孢素治疗组分别为34.4%和33.3%。根据慢性排斥反应的发生率，FK506组的免疫抑制效力优于环孢素组。此外，5例患者（8.3%）因免疫原因，即难治性急性或慢性排斥反应，需要转换为FK506治疗。术后早期FK506组中度和重度神经毒性的发生率（21.3%）高于环孢素组（11.7%），而肾功能不全和急性肾衰竭的发生率相似（FK506和环孢素治疗组分别为18.0%和18.3%）。环孢素治疗下巨细胞病毒感染的发生率（25.0%）显著高于FK506治疗（6.6%）（P≤0.05），而肺炎（13.1%和13.3%）、胆管炎（29.5%和26.7%）和尿路感染（FK506和环孢素治疗组分别为39.3%和28.3%）的发生率在两个治疗组中相似。然而，在一些接受FK506治疗的病例中感染更严重，并成为FK506治疗组的主要死亡原因。因此，对于接受FK506治疗的患者，应注意过度免疫抑制和毒性。关于FK506的监测，FK506血浆水平不是一个可靠的指标，因此我们建议检测全血FK506水平。我们的数据表明，FK506的免疫抑制效力大于环孢素，尤其是在慢性排斥反应的发生率方面。
