用于脑死亡后捐献（DBD）的扩大标准供体（ECD）的人肝同种异体原位肝移植的低温氧合机器灌注（HOPE）：一项前瞻性多中心随机对照试验（HOPE ECD-DBD）
Hypothermic oxygenated machine perfusion (HOPE) for orthotopic liver transplantation of human liver allografts from extended criteria donors (ECD) in donation after brain death (DBD): a prospective multicentre randomised controlled trial (HOPE ECD-DBD).
作者信息
Czigany Zoltan, Schöning Wenzel, Ulmer Tom Florian, Bednarsch Jan, Amygdalos Iakovos, Cramer Thorsten, Rogiers Xavier, Popescu Irinel, Botea Florin, Froněk Jiří, Kroy Daniela, Koch Alexander, Tacke Frank, Trautwein Christian, Tolba Rene H, Hein Marc, Koek Ger H, Dejong Cornelis H C, Neumann Ulf Peter, Lurje Georg
机构信息
Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
Department of Solid Organ Transplantation, Ghent University Hospital and Medical School, Ghent, Belgium.
出版信息
BMJ Open. 2017 Oct 10;7(10):e017558. doi: 10.1136/bmjopen-2017-017558.
INTRODUCTION
Orthotopic liver transplantation (OLT) has emerged as the mainstay of treatment for end-stage liver disease. In an attempt to improve the availability of donor allografts and reduce waiting list mortality, graft acceptance criteria were extended increasingly over the decades. The use of extended criteria donor (ECD) allografts is associated with a higher incidence of primary graft non-function and/or delayed graft function. As such, several strategies have been developed aiming at reconditioning poor quality ECD liver allografts. Hypothermic oxygenated machine perfusion (HOPE) has been successfully tested in preclinical experiments and in few clinical series of donation after cardiac death OLT.
METHODS AND ANALYSIS
HOPE ECD-DBD is an investigator-initiated, open-label, phase-II, prospective multicentre randomised controlled trial on the effects of HOPE on ECD allografts in donation after brain death (DBD) OLT. Human whole organ liver grafts will be submitted to 1-2 hours of HOPE (n=23) via the portal vein before implantation and are going to be compared with a control group (n=23) of patients transplanted after conventional cold storage. Primary (peak and Δ peak alanine aminotransferase within 7 days) and secondary (aspartate aminotransferase, bilirubin and international normalised ratio, postoperative complications, early allograft dysfunction, duration of hospital and intensive care unit stay, 1-year patient and graft survival) endpoints will be analysed within a 12-month follow-up. Extent of ischaemia-reperfusion (I/R) injury will be assessed using liver tissue, perfusate, bile and serum samples taken during the perioperative phase of OLT.
ETHICS AND DISSEMINATION
The study was approved by the institutional review board of the RWTH Aachen University, Aachen, Germany (EK 049/17). The current paper represent the pre-results phase. First results are expected in 2018.
TRIAL REGISTRATION NUMBER
NCT03124641.
引言
原位肝移植（OLT）已成为终末期肝病治疗的主要手段。为了提高供体同种异体移植物的可用性并降低等待名单上的死亡率，几十年来，移植物接受标准不断放宽。使用边缘供体（ECD）同种异体移植物会导致原发性移植物无功能和/或移植物功能延迟的发生率更高。因此，已经开发了几种策略来修复质量较差的ECD肝同种异体移植物。低温氧合机器灌注（HOPE）已在临床前实验和少数心脏死亡后器官捐献的OLT临床系列中成功进行了测试。
方法与分析
HOPE ECD-DBD是一项由研究者发起的、开放标签、II期、前瞻性多中心随机对照试验，旨在研究HOPE对脑死亡后器官捐献（DBD）OLT中ECD同种异体移植物的影响。人类全器官肝移植物在植入前将通过门静脉接受1-2小时的HOPE（n=23），并与传统冷藏后移植的对照组（n=23）进行比较。主要终点（7天内谷丙转氨酶峰值和Δ峰值）和次要终点（谷草转氨酶、胆红素和国际标准化比值、术后并发症、早期移植物功能障碍、住院和重症监护病房停留时间、1年患者和移植物存活率）将在12个月的随访中进行分析。将使用OLT围手术期采集的肝组织、灌注液、胆汁和血清样本评估缺血再灌注（I/R）损伤的程度。
伦理与传播
该研究已获得德国亚琛工业大学机构审查委员会的批准（EK 049/17）。本文代表预结果阶段。预计2018年得出初步结果。
试验注册号
NCT03124641。
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