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低温氧合机器灌注中肝脏移植质量的实时生物标志物

Real-Time Biomarkers of Liver Graft Quality in Hypothermic Oxygenated Machine Perfusion.

作者信息

Zhylko Andriy, Morawski Marcin, Rykowski Paweł, Krasnodębski Maciej, Wyporski Anya, Borkowski Jan, Zhylko Dmytro, Kobryń Konrad, Stankiewicz Rafał, Stypułkowski Jan, Hołówko Wacław, Patkowski Waldemar, Wróblewski Tadeusz, Szczepankiewicz Benedykt, Górnicka Barbara, Mielczarek-Puta Magdalena, Struga Marta, Krawczyk Marek, Grąt Michał

机构信息

Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha 1A, 02-097 Warsaw, Poland.

Doctoral School, Medical University of Warsaw, 02-091 Warsaw, Poland.

出版信息

J Clin Med. 2025 Jan 13;14(2):471. doi: 10.3390/jcm14020471.

DOI:10.3390/jcm14020471
PMID:39860477
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11766178/
Abstract

: Hypothermic oxygenated machine perfusion has emerged as a strategy to alleviate ischemic-reperfusion injury in liver grafts. Nevertheless, there is limited data on the effectiveness of hypothermic liver perfusion in evaluating organ quality. This study aimed to introduce a readily accessible real-time predictive biomarker measured in machine perfusate for post-transplant liver graft function. : The study evaluated perfusate analytes over a 90-day postoperative period in 26 patients randomly assigned to receive a liver graft following dual hypothermic machine perfusion in a prospective randomized controlled trial. Machine perfusion was consistently conducted end-ischemically for at least 120 min, with real-time perfusate assessment at 30-min intervals. Graft functionality was assessed using established metrics, including Early Allograft Dysfunction (EAD). : Perfusate lactate concentration after 120 min of machine perfusion demonstrated significant predictive value for EAD (AUC ROC: 0.841, = 0.009). Additionally, it correlated with post-transplant peak transaminase levels and extended hospital stays. Subgroup analysis revealed significantly higher lactate accumulation in livers with post-transplant EAD. : Liver graft quality can be effectively assessed during hypothermic machine perfusion using simple perfusate lactate measurements. The reliability and accessibility of this evaluation support its potential integration into diverse transplant centers.

摘要

低温氧合机器灌注已成为减轻肝移植缺血再灌注损伤的一种策略。然而,关于低温肝脏灌注在评估器官质量方面有效性的数据有限。本研究旨在引入一种易于获取的实时预测生物标志物,该标志物可在机器灌注液中测量,用于预测移植后肝移植功能。

该研究在一项前瞻性随机对照试验中,对26例随机分配接受双低温机器灌注后肝移植的患者进行了为期90天的术后灌注液分析物评估。机器灌注在缺血末期持续进行至少120分钟,每隔30分钟对灌注液进行实时评估。使用包括早期移植物功能障碍(EAD)在内的既定指标评估移植物功能。

机器灌注120分钟后的灌注液乳酸浓度对EAD具有显著预测价值(AUC ROC:0.841,P = 0.009)。此外,它与移植后转氨酶峰值水平及住院时间延长相关。亚组分析显示,移植后发生EAD的肝脏中乳酸积累显著更高。

通过简单测量灌注液乳酸,可在低温机器灌注期间有效评估肝移植质量。该评估的可靠性和可及性支持其有可能整合到不同的移植中心。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e1/11766178/60e112cacee0/jcm-14-00471-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e1/11766178/74dc3f5ad1a3/jcm-14-00471-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e1/11766178/a02abc7aa1fc/jcm-14-00471-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e1/11766178/c27cac0b0b52/jcm-14-00471-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e1/11766178/60e112cacee0/jcm-14-00471-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e1/11766178/74dc3f5ad1a3/jcm-14-00471-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e1/11766178/a02abc7aa1fc/jcm-14-00471-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e1/11766178/c27cac0b0b52/jcm-14-00471-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e1/11766178/60e112cacee0/jcm-14-00471-g004.jpg

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本文引用的文献

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Routine end-ischemic hypothermic machine perfusion in liver transplantation from donors after brain death: results of 2-year follow-up of a randomized controlled trial.脑死亡后供体肝脏移植中常规缺血后低温机器灌注:一项随机对照试验的2年随访结果
Int J Surg. 2024 Nov 1;110(11):7003-7010. doi: 10.1097/JS9.0000000000001919.
2
Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study).真实世界中1202例供肝低温氧合机器灌注及移植后的长期预后(HOPE-REAL研究)
J Hepatol. 2025 Jan;82(1):97-106. doi: 10.1016/j.jhep.2024.06.035. Epub 2024 Jul 3.
3
The Predictive Value of Graft Viability and Bioenergetics Testing Towards the Outcome in Liver Transplantation.
移植物活力和生物能量学检测对肝移植预后的预测价值
Transpl Int. 2024 Feb 23;37:12380. doi: 10.3389/ti.2024.12380. eCollection 2024.
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Prolonged hypothermic machine perfusion enables daytime liver transplantation - an IDEAL stage 2 prospective clinical trial.延长低温机器灌注可实现日间肝移植——一项IDEAL 2期前瞻性临床试验
EClinicalMedicine. 2024 Jan 5;68:102411. doi: 10.1016/j.eclinm.2023.102411. eCollection 2024 Feb.
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Fecal Microbiota Transplantation in Liver Cirrhosis.粪便微生物群移植治疗肝硬化
Biomedicines. 2023 Oct 30;11(11):2930. doi: 10.3390/biomedicines11112930.
6
Routine End-ischemic Hypothermic Oxygenated Machine Perfusion in Liver Transplantation From Donors After Brain Death: A Randomized Controlled Trial.脑死亡供体肝移植中常规复温缺血期氧合机器灌注:一项随机对照试验。
Ann Surg. 2023 Nov 1;278(5):662-668. doi: 10.1097/SLA.0000000000006055. Epub 2023 Jul 27.
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A Spectrofluorometric Method for Real-Time Graft Assessment and Patient Monitoring.实时移植物评估和患者监测的光谱荧光法。
Adv Sci (Weinh). 2023 Aug;10(23):e2301537. doi: 10.1002/advs.202301537. Epub 2023 Jun 2.
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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.
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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.
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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。
J Hepatol. 2022 Jun;76(6):1330-1347. doi: 10.1016/j.jhep.2022.01.024.