基于终末期肝病模型（MELD）评分的肝移植术后使用Advagraf®进行延迟的基于钙调神经磷酸酶抑制剂（CNI）的免疫抑制对肝功能的影响[IMUTECT研究]

Effect of delayed CNI-based immunosuppression with Advagraf® on liver function after MELD-based liver transplantation [IMUTECT].

作者信息

Richter Susanne, Polychronidis Georg, Gotthardt Daniel N, Houben Philipp, Giese Thomas, Sander Anja, Dörr-Harim Colette, Diener Markus K, Schemmer Peter

机构信息

Department of General, Visceral and Transplant Surgery, Heidelberg, Germany.

出版信息

BMC Surg. 2014 Sep 1;14:64. doi: 10.1186/1471-2482-14-64.

DOI:10.1186/1471-2482-14-64

PMID:25178675

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4160448/

Abstract

BACKGROUND

MELD-based allocation for liver transplantation follows the "sickest-patient-first" strategy. The latter patients present with both, decreased immune competence and poor kidney function which is further impaired by immunosuppressants.

METHODS/DESIGN: In this prospective observational study, 50 patients with de novo low-dose standard Advagraf®-based immunosuppression consisting of Advagraf®, Mycophenolat-mofetil and Corticosteroids after liver transplantation will be evaluated. Advagraf® trough levels of 7-10 μg/l will be reached at the end of the first postoperative week. Immunostatus, infectious complications, graft and kidney function are compared between patients with a pretransplant calculated MELD-score of ≤20 and >20. Each group comprises of 25 consecutive patients. Prior to liver transplantation and on the postoperative days 1, 3 and 7, the patients' graft function (LiMAx test) will be evaluated. On the postoperative days 3, 5 and 7 the patients' immune status will be evaluated by the measurement of their monocytic HLA-DR status.Infectious complications (CMV-reactivation, wound infection, urinary tract infection, and pneumonia), graft- and kidney function will be analysed on day 0, within the first week, and 1, 3, 6, 9 and 12 months after liver transplantation.

DISCUSSION

This study was designed to assess the effect of a standard low-dose Calcineurin inhibitor-based immunosuppression regime with Advagraf® on the rate of infectious complications, graft and renal function after liver transplantation.

TRIAL REGISTRATION

The trial is registered at "Clinical Trials" (http://www.clinicaltrials.gov), NCT01781195.

摘要

背景

基于终末期肝病模型（MELD）的肝移植分配遵循“病情最重者优先”策略。后一类患者免疫功能下降且肾功能不佳，免疫抑制剂会进一步损害其肾功能。

方法/设计：在这项前瞻性观察性研究中，将评估50例肝移植后采用基于低剂量标准Advagraf®的免疫抑制方案（包括Advagraf®、霉酚酸酯和皮质类固醇）的初治患者。术后第一周结束时，Advagraf®的谷浓度将达到7 - 10μg/l。比较移植前计算的MELD评分≤20和>20的患者的免疫状态、感染并发症、移植肝功能和肾功能。每组由25例连续患者组成。在肝移植前以及术后第1、3和7天，将评估患者的移植肝功能（LiMAx试验）。在术后第3、5和7天，通过测量单核细胞HLA - DR状态来评估患者的免疫状态。将在肝移植后第0天、第一周内以及1、3、6、9和12个月分析感染并发症（巨细胞病毒再激活、伤口感染、尿路感染和肺炎）、移植肝功能和肾功能。