Perfusate Liver Arginase 1 Levels After End-ischemic Machine Perfusion Are Associated With Early Allograft DysfunctionPerfusate Liver Arginase 1 Levels After End-ischemic Machine Perfusion Are Associated With Early Allograft Dysfunction

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The rising use of liver grafts from donation after circulatory death (DCD) has been enabled by advances in normothermic regional perfusion (NRP) and machine perfusion (MP) technologies. Our study aimed to identify predictive biomarkers in DCD liver grafts subjected to NRP, followed by randomization to either normothermic machine perfusion (NMP) or dual hypothermic oxygenated perfusion (D-HOPE). Among 57 DCD donors, 32 liver grafts were transplanted, and recipients were monitored for one week after transplantation. Biomarkers linked with oxidative stress, hepatic injury, mitochondrial dysfunction, inflammation, regeneration, and autophagy gene expression were measured during NRP, end-ischemic MP, and one week post-transplant. Arginase-1(ARG-1) levels were consistently higher in discarded grafts and recipients who later developed early allograft dysfunction (EAD). Specifically, ARG-1 levels at the end of ex-situ machine perfusion correlated significantly with other markers of hepatic injury. Receiver Operating Characteristic analysis indicated that ARG-1 at the end of MP had good predictive accuracy for EAD (AUC = 0.713 [95% CI: 0.538-1]; p = 0.02). Additionally, lipid peroxidation, measured by TBARS, was elevated at the start of NRP but declined over time, with higher levels in D-HOPE than in NMP, suggesting a more sustained oxidative environment. Metabolites like Flavin mononucleotide (FMN) and NADH exhibited significant disparities between perfusion types, due to differences in perfusate compositions. Inflammatory biomarkers rose during NRP and NMP but normalized post-transplantation. Regenerative markers, including osteopontin and hepatocyte growth factor, also increased during NRP and NMP and normalized after transplantation. In conclusion, ARG-1 demonstrates strong potential as an early biomarker for assessing liver graft viability during perfusion, supporting timely and effective decision-making in transplantation.

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