霉酚酸酯作为肝移植后免疫抑制诱导治疗一部分的长期结果。

Long-term results of mycophenolate mofetil as part of immunosuppressive induction therapy after liver transplantation.

作者信息

Langrehr Jan M, Klupp Jochen, Glanemann Matthias, Junge Guido, Pfitzmann Robert, Bahra Marcus, Radtke Cornelia, Neumann Ulf, Neuhaus Ruth, Neuhaus Peter

机构信息

Department of General-, Visceral- and Transplantation Surgery, Charité, Campus Virchow Klinikum, Universitätsmedizin Berlin, Germany.

出版信息

Clin Transplant. 2006 May-Jun;20(3):272-83. doi: 10.1111/j.1399-0012.2005.00485.x.

DOI:10.1111/j.1399-0012.2005.00485.x

PMID:16824141

Abstract

BACKGROUND

The addition of mycophenolate mofetil (MMF) to the induction protocol resulted in a lower incidence of rejection episodes. However, the question whether MMF should be administered in combination with tacrolimus or cyclosporine has not been answered yet. In our study, we report on the long-term results of triple induction therapy after orthotopic liver transplantation (OLT), consisting of MMF and low-dose corticosteroids, in combination with either tacrolimus or cyclosporine.

METHODS

Between March 1996 and April 1997, 120 consecutive patients, who underwent OLT at our institution, were enrolled in this study. Of these patients, 80 received triple induction therapy consisting of cyclosporine and MMF (40) or tacrolimus and MMF (40), in combination with low-dose corticosteroids, whereas the remaining 40 patients served as 'MMF-free' control group receiving dual induction therapy with tacrolimus and corticosteroids. Besides the eight-yr follow-up of patient and graft survival, clinical data were also reviewed for episodes of rejection and infection. Additionally, the early post-operative pharmacokinetics of mycophenolic acid (MPA, immunological active metabolite of MMF) were evaluated.

RESULTS

Long-term results provided higher patient and graft survival after tacrolimus/MMF-based induction therapy than after cyclosporine/MMF-based induction therapy. However, the tacrolimus-based control protocol yielded similar results and, therefore, no significantly superior effect was observed when MMF was added. The same observation was made for incidence of rejection and infection episodes. AUC and C(max) of MPA increased in combination with tacrolimus compared with cyclosporine.

CONCLUSIONS

Although pharmacological synergy between tacrolimus and MMF was observed, MMF showed no significant beneficial effects in the immunosuppressive induction protocol, neither in combination with tacrolimus nor with cyclosporine.

摘要

背景

在诱导方案中添加霉酚酸酯（MMF）可降低排斥反应的发生率。然而，MMF是否应与他克莫司或环孢素联合使用的问题尚未得到解答。在我们的研究中，我们报告了原位肝移植（OLT）后三联诱导治疗的长期结果，该治疗由MMF和低剂量皮质类固醇组成，并与他克莫司或环孢素联合使用。

方法

1996年3月至1997年4月期间，在我们机构接受OLT的120例连续患者被纳入本研究。在这些患者中，80例接受了由环孢素和MMF（40例）或他克莫司和MMF（40例）组成的三联诱导治疗，并与低剂量皮质类固醇联合使用，而其余40例患者作为“无MMF”对照组，接受他克莫司和皮质类固醇的双联诱导治疗。除了对患者和移植物存活进行八年随访外，还对排斥反应和感染事件的临床数据进行了回顾。此外，还评估了术后早期霉酚酸（MPA，MMF的免疫活性代谢产物）的药代动力学。

结果

基于他克莫司/MMF的诱导治疗后的长期结果显示，患者和移植物存活率高于基于环孢素/MMF的诱导治疗。然而，基于他克莫司的对照方案产生了相似的结果，因此，添加MMF时未观察到明显的优越效果。排斥反应和感染事件的发生率也有相同的观察结果。与环孢素相比，MPA的AUC和C(max)与他克莫司联合使用时增加。