Maeda Akinori, Starkey Graham, Spano Sofia, Chaba Anis, Eastwood Glenn, Yoshino Osamu, Perini Marcos Vinicius, Fink Michael, Bellomo Rinaldo, Jones Robert
Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia.
Department of Emergency and Critical Care Medicine, The University of Tokyo, Tokyo, Japan.
Artif Organs. 2025 Jan;49(1):108-118. doi: 10.1111/aor.14862. Epub 2024 Sep 18.
Normothermic machine perfusion (NMP) aims to reduce ischemia-reperfusion injury in donor livers and its clinical manifestation, early allograft dysfunction (EAD) by maintaining perfusion and oxygenation. However, there is limited data on which NMP perfusate biomarkers might be associated with such EAD and the role of perfusate hemoglobin has not been assessed.
We performed a pilot retrospective analysis of adult donor livers undergoing NMP between 2020 and 2022 at our center. NMP was commenced at the recipient hospital after initial static cold storage. All NMP circuits were primed in the same manner according to the manufacturer's instructions. Livers were stratified by initial perfusate hemoglobin below (≤5.2 mmol/L) or above (>5.2 mmol/L) the median. The association between hemoglobin levels and EAD or recipient peak transaminase levels was assessed.
Among 23 livers, eight were considered unsuitable for transplantation, leaving 15 livers for assessment. Higher initial hemoglobin was associated with a lower risk of EAD (0% vs. 55.6%, p = 0.04). Perfusate hemoglobin decreased after NMP initiation (p = 0.003) and negatively correlated with recipient peak transaminase levels (ALT: ρ = -0.72, p = 0.002; AST: ρ = -0.79, p < 0.001). Consistently, higher hemoglobin livers also demonstrated lower perfusate liver enzymes.
Perfusate hemoglobin levels decreased during NMP, and lower perfusate hemoglobin levels were associated with a higher incidence of EAD and higher levels of liver injury markers. Maintaining higher hemoglobin levels during NMP may help reduce ischemia-reperfusion injury and prevent or attenuate EAD. Larger prospective studies are needed to validate the findings of this pilot study.
常温机器灌注（NMP）旨在通过维持灌注和氧合来减少供体肝脏的缺血再灌注损伤及其临床表现，即早期移植物功能障碍（EAD）。然而，关于哪些NMP灌注液生物标志物可能与这种EAD相关的数据有限，并且尚未评估灌注液血红蛋白的作用。
我们对2020年至2022年在我们中心接受NMP的成年供体肝脏进行了一项初步回顾性分析。在最初的静态冷藏后，在受者医院开始NMP。所有NMP回路均按照制造商的说明以相同方式预充。根据初始灌注液血红蛋白低于（≤5.2 mmol/L）或高于（>5.2 mmol/L）中位数对肝脏进行分层。评估血红蛋白水平与EAD或受者转氨酶峰值水平之间的关联。
在23个肝脏中，8个被认为不适合移植，其余15个肝脏用于评估。较高的初始血红蛋白与较低的EAD风险相关（0%对55.6%，p = 0.04）。NMP开始后灌注液血红蛋白下降（p = 0.003），并且与受者转氨酶峰值水平呈负相关（ALT：ρ = -0.72，p = 0.002；AST：ρ = -0.79，p < 0.001）。同样，血红蛋白水平较高的肝脏灌注液肝酶也较低。
NMP期间灌注液血红蛋白水平下降，较低的灌注液血红蛋白水平与较高的EAD发生率和较高的肝损伤标志物水平相关。在NMP期间维持较高的血红蛋白水平可能有助于减少缺血再灌注损伤并预防或减轻EAD。需要更大规模的前瞻性研究来验证这项初步研究的结果。
