A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion.
A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion.
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DOI：
10.1038/s41598-021-02641-0
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发表时间：
2021-12-06
影响因子：
4.6
通讯作者：
de Jonge J
中科院分区：
文献类型：
--
作者：
Schurink IJ;de Haan JE;Willemse J;Mueller M;Doukas M;Roest H;de Goeij FHC;Polak WG;Ijzermans JNM;Dutkowski P;van der Laan LJW;de Jonge J
在离体常温机器灌注（NMP）期间，没有单一可靠的参数可用于评估扩展标准供体的肝移植功能。肝脏最大容量（LiMAx）测试是一种临床验证的细胞色素呼吸测试，基于13 CO2的产生来测量肝功能。作为一个创新的概念，我们的目标是将LiMAx呼吸测试与NMP相结合，以评估器官功能。使用NMP灌注11个人肝脏。稳定1小时后，进行LiMAx测试。测量损伤标志物（ALT、AST、miR-122、FMN和Suzuki评分）和乳酸清除率，并与LiMAx值相关。LiMAx值范围为111至1838 µg/kg/h，在较长NMP期间进行连续LiMAx测试是可行的。LiMAx值与灌注液中的miR-122和FMN水平之间未发现相关性。然而，LiMAx值与组织学损伤（Suzuki评分，R =-0.874，P < 0.001）、AST（R =-0.812，P = 0.004）和ALT（R =-0.687，P = 0.028）之间存在显著负相关。此外，发现乳酸清除率显著相关（R = 0.683，P = 0.043）。我们证明，作为原则的证明，NMP期间的肝功能可以使用LiMAx测试进行量化，说明与传统损伤标志物呈正相关。这种新的呼吸测试应用程序将具有足够细胞色素肝功能的肝脏与不充分的肝脏区分开来，并可能支持安全使用扩展标准供体移植物的决策。
No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an innovative concept, we aimed to integrate the LiMAx breath test with NMP to assess organ function. Eleven human livers were perfused using NMP. After one hour of stabilization, LiMAx testing was performed. Injury markers (ALT, AST, miR-122, FMN, and Suzuki-score) and lactate clearance were measured and related to LiMAx values. LiMAx values ranged between 111 and 1838 µg/kg/h, and performing consecutive LiMAx tests during longer NMP was feasible. No correlation was found between LiMAx value and miR-122 and FMN levels in the perfusate. However, a significant inverse correlation was found between LiMAx value and histological injury (Suzuki-score, R = − 0.874, P < 0.001), AST (R = − 0.812, P = 0.004) and ALT (R = − 0.687, P = 0.028). Furthermore, a significant correlation was found with lactate clearance (R = 0.683, P = 0.043). We demonstrate, as proof of principle, that liver function during NMP can be quantified using the LiMAx test, illustrating a positive correlation with traditional injury markers. This new breath-test application separates livers with adequate cytochromal liver function from inadequate ones and may support decision-making in the safe utilization of extended criteria donor grafts.
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影响因子：
8.8
作者：
Watson, Christopher J. E.;Kosmoliaptsis, Vasilis;Butler, Andrew J.
通讯作者：
Butler, Andrew J.
影响因子：
4.6
作者：
Lock, Johan Friso;Schwabauer, Eugen;Stockmann, Martin
通讯作者：
Stockmann, Martin
影响因子：
1.9
作者：
Hoppe, Steffi;von Loeffelholz, Christian;Stockmann, Martin
通讯作者：
Stockmann, Martin
DOI：
10.1111/j.1440-1746.2011.06844.x
发表时间：
2012-03-01
影响因子：
4.1
作者：
de Graaf, Esther L.;Kench, James;Verran, Deborah J.
通讯作者：
Verran, Deborah J.
影响因子：
6.2
作者：
Jackson, Kyle R.;Motter, Jennifer D.;Segev, Dorry L.
通讯作者：
Segev, Dorry L.