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机器灌注与肝移植后缺血性 B 型胆损伤的预防:有何证据?

Machine perfusion and the prevention of ischemic type biliary lesions following liver transplant: What is the evidence?

机构信息

Department of Liver Transplantation, Reina Sofía University Hospital, Córdoba 14004, Spain.

The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom.

出版信息

World J Gastroenterol. 2023 May 28;29(20):3066-3083. doi: 10.3748/wjg.v29.i20.3066.

DOI:10.3748/wjg.v29.i20.3066
PMID:37346149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10280793/
Abstract

The widespread uptake of different machine perfusion (MP) strategies for liver transplant has been driven by an effort to minimize graft injury. Damage to the cholangiocytes during the liver donation, preservation, or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage. This problem continues to trouble clinicians, and may have catastrophic consequences for the graft and patient. Ischemic injury, as a result of compromised hepatic artery flow, is a well-known cause of biliary strictures, sepsis, and graft failure. However, very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions (ITBL) that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise. Both the warm and cold ischemic period duration appear to influence the onset of ITBL. All of the commonly used MP techniques deliver oxygen to the graft cells, and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL. As clinical experience and published evidence grows for these modalities, the impact they have on ITBL rates is important to consider. In this review, the evidence for the three commonly used MP strategies (abdominal normothermic regional perfusion [A-NRP], hypothermic oxygenated perfusion [HOPE], and normothermic machine perfusion [NMP] for ITBL prevention has been critically reviewed. Inconsistencies with ITBL definitions used in trials, coupled with variations in techniques of MP, make interpretation challenging. Overall, the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage. The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.

摘要

不同的机器灌注 (MP) 策略在肝移植中的广泛应用是为了尽量减少移植物损伤。在肝脏捐献、保存或移植后早期,胆管细胞的损伤可能导致胆管狭窄和胆汁引流不足。这个问题一直困扰着临床医生,可能对移植物和患者造成灾难性的后果。由于肝动脉血流受损导致的缺血性损伤是胆管狭窄、脓毒症和移植物失功的已知原因。然而,在肝动脉通畅的情况下,也会出现非常相似的病变,这些病变被称为缺血性胆管病变 (ITBL),归因于微循环功能障碍而不是主要肝动脉损伤。无论是热缺血还是冷缺血时间,似乎都会影响 ITBL 的发生。所有常用的 MP 技术都向移植物细胞输送氧气,因此可以最大限度地减少胆管细胞损伤,从而降低 ITBL 的发生率。随着这些方法的临床经验和已发表证据的增加,考虑它们对 ITBL 发生率的影响非常重要。在这篇综述中,对三种常用的 MP 策略(腹部常温区域性灌注 [A-NRP]、低温氧合灌注 [HOPE] 和常温机器灌注 [NMP])预防 ITBL 的证据进行了批判性评估。临床试验中使用的 ITBL 定义不一致,加上 MP 技术的差异,使得解释变得具有挑战性。总的来说,有证据表明,与冷藏相比,HOPE 和 A-NRP 可预防循环死亡供体的 ITBL。任何 MP 技术预防脑死亡供体 ITBL 的证据都很薄弱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b4/10280793/19430c30311a/WJG-29-3066-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b4/10280793/19430c30311a/WJG-29-3066-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b4/10280793/19430c30311a/WJG-29-3066-g001.jpg

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本文引用的文献

1
A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation.多中心随机对照试验研究低温氧合灌注(HOPE)在人类肝移植前对供体肝脏的作用。
J Hepatol. 2023 Apr;78(4):783-793. doi: 10.1016/j.jhep.2022.12.030. Epub 2023 Jan 19.
2
Predicting Early Allograft Function After Normothermic Machine Perfusion.预测常温机械灌注后早期移植物功能。
Transplantation. 2022 Dec 1;106(12):2391-2398. doi: 10.1097/TP.0000000000004263. Epub 2022 Aug 29.
3
Salvage of Declined Extended-criteria DCD Livers Using In Situ Normothermic Regional Perfusion.
使用原位常温区域性灌注抢救不达标准的边缘供体肝脏。
Ann Surg. 2022 Oct 1;276(4):e223-e230. doi: 10.1097/SLA.0000000000005611. Epub 2022 Jul 21.
4
Normothermic regional perfusion in liver transplantation from donation after cardiocirculatory death: Technical, biochemical, and regulatory aspects and review of literature.心脏死亡后捐献供肝肝移植中常温区域灌注:技术、生化和监管方面及文献复习。
Artif Organs. 2022 Sep;46(9):1727-1740. doi: 10.1111/aor.14330. Epub 2022 Jun 22.
5
Normothermic Machine Perfusion-Improving the Supply of Transplantable Livers for High-Risk Recipients.常温机械灌注——提高高危受体可移植肝脏的供应。
Transpl Int. 2022 May 31;35:10460. doi: 10.3389/ti.2022.10460. eCollection 2022.
6
Hypothermic oxygenated perfusion in extended criteria donor liver transplantation-A randomized clinical trial.扩展标准供肝肝移植中低温氧合灌注:一项随机临床试验。
Am J Transplant. 2022 Oct;22(10):2401-2408. doi: 10.1111/ajt.17115. Epub 2022 Jun 21.
7
In situ normothermic regional perfusion versus ex situ normothermic machine perfusion in liver transplantation from donation after circulatory death.在心脏死亡后捐献供体肝移植中,原位常温区域性灌注与体外常温机器灌注的比较。
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Protective mechanisms and current clinical evidence of hypothermic oxygenated machine perfusion (HOPE) in preventing post-transplant cholangiopathy.低温氧合机器灌注(HOPE)在预防移植后胆管病中的保护机制和临床证据。
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