Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction

终末缺血机器灌注后灌注液肝精氨酸酶 1 水平与早期同种异体移植功能障碍相关

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作者:Giuseppina Basta, Serena Babboni, Daniele Pezzati, Serena Del Turco, Emanuele Balzano, Gabriele Catalano, Lara Russo, Giovanni Tincani, Paola Carrai, Stefania Petruccelli, Jessica Bronzoni, Caterina Martinelli, Simona Palladino, Arianna Trizzino, Lorenzo Petagna, Renato Romagnoli, Damiano Patrono, G

Conclusions

ARG-1 demonstrates strong potential as an early biomarker for assessing liver graft viability during perfusion, supporting timely and effective decision-making in transplantation.

Methods

Among 57 DCD donors, 32 liver grafts were transplanted, and recipients were monitored for one week post-transplant. Biomarkers linked with oxidative stress, hepatic injury, mitochondrial dysfunction, inflammation, regeneration, and autophagy were measured during NRP, end-ischemic MP, and one week post-transplant.

Results

Arginase-1 (ARG-1) levels were consistently higher in discarded grafts and in recipients who later developed early allograft dysfunction (EAD). Specifically, ARG-1 levels at the end of MP correlated with markers of hepatic injury. Receiver operating characteristic analysis indicated that ARG-1 at the end of MP had a good predictive accuracy for EAD (AUC = 0.713; p = 0.02). Lipid peroxidation (TBARS) elevated at the start of NRP, declined over time, with higher levels in D-HOPE than in NMP, suggesting a more oxidative environment in D-HOPE. 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, increased during NRP and NMP and normalized post-transplant. Conclusions: 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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