Division of Hepatopancreatobiliary Surgery, Department of Surgery, Erasmus MC Transplant Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Intensive Care Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
Sci Rep. 2021 Dec 6;11(1):23444. doi: 10.1038/s41598-021-02641-0.
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.
在体外常温机器灌注（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物功能。LiMAx 测试是一种经过临床验证的细胞色素呼吸测试，基于 13CO2 的产生来测量肝功能。作为一种创新概念，我们旨在将 LiMAx 呼吸测试与 NMP 相结合，以评估器官功能。11 个人肝使用 NMP 进行灌注。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 值范围在 111 到 1838 µg/kg/h 之间，并且在较长的 NMP 期间连续进行 LiMAx 测试是可行的。在灌流液中，未发现 LiMAx 值与 miR-122 和 FMN 水平之间存在相关性。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）之间存在显著的负相关。此外，与乳酸清除率呈显著正相关（R=0.683，P=0.043）。我们证明，作为原理证明，NMP 期间的肝功能可以使用 LiMAx 测试来定量，表明与传统损伤标志物呈正相关。这种新的呼吸测试应用将具有足够细胞色素肝功能的肝脏与功能不足的肝脏区分开来，并可能支持安全利用扩展标准供体移植物的决策。
