Abstract
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.
Highlights
No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP)
In donation after circulatory death (DCD) donors, only 35% of the offered grafts are accepted for transplantation; this is in contrast to a utilization rate as high as 82% in donation after brain death (DBD) d onors[3]
By correlating the liver maximum capacity (LiMAx) values as a measure of liver function to hepatocellular injury, we found a negative correlation with the markers ALT (R = − 0.687, P = 0.028) and AST (R = − 0.812, P = 0.004; Fig. 5B,C), indicating a relationship between injury and cytochromal liver function
Summary
No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). 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. Compromised donor organs are increasingly used to resolve this problem These extended criteria donor (ECD) organs bear risk factors, such as high donor body mass index (BMI), older age, prolonged cold ischemia time, donation after circulatory death (DCD), and elevated liver injury parameters. These result in higher complication rates and reduced graft survival after transplantation. In DCD donors, only 35% of the offered grafts are accepted for transplantation; this is in contrast to a utilization rate as high as 82% in donation after brain death (DBD) d onors[3]
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