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M.J. Copray
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Journal article
(2026)
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Meryl J. Copray, Martin Pabst, Puck C. Groen, Jorke Willemse, Jeroen de Jonge, Marcel Ottens
Extended criteria donor (ECD) livers are increasingly used to mitigate organ shortage, yet they carry a higher risk of post-transplant complications. Normothermic machine perfusion (NMP) enables functional assessment, but current viability criteria cannot always distinguish transplantable from non-transplantable grafts. Here, we identify proteomic signatures and propose underlying mechanisms that determine ECD liver suitability during NMP. Using label-free shotgun proteomics, we analysed 72 perfusate samples collected during hypothermic oxygenated perfusion, controlled rewarming, and NMP of 24 human ECD livers. Non-transplanted grafts were consistently enriched in oxidative stress–related proteins, associated with disrupted glutathione metabolism and severe ischemia–reperfusion injury. In contrast, transplanted livers maintained balanced antioxidant responses and progressively upregulated functional and regenerative pathways. Oxidative stress proteins distinguished transplantable from non-transplantable grafts within 60 minutes of NMP (AUC≥0.94), while prolonged perfusion supported recovery in moderate livers. These findings propose a mechanistic basis for graft viability and demonstrate how oxidative stress and regeneration markers can refine organ assessment during machine perfusion.
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Extended criteria donor (ECD) livers are increasingly used to mitigate organ shortage, yet they carry a higher risk of post-transplant complications. Normothermic machine perfusion (NMP) enables functional assessment, but current viability criteria cannot always distinguish transplantable from non-transplantable grafts. Here, we identify proteomic signatures and propose underlying mechanisms that determine ECD liver suitability during NMP. Using label-free shotgun proteomics, we analysed 72 perfusate samples collected during hypothermic oxygenated perfusion, controlled rewarming, and NMP of 24 human ECD livers. Non-transplanted grafts were consistently enriched in oxidative stress–related proteins, associated with disrupted glutathione metabolism and severe ischemia–reperfusion injury. In contrast, transplanted livers maintained balanced antioxidant responses and progressively upregulated functional and regenerative pathways. Oxidative stress proteins distinguished transplantable from non-transplantable grafts within 60 minutes of NMP (AUC≥0.94), while prolonged perfusion supported recovery in moderate livers. These findings propose a mechanistic basis for graft viability and demonstrate how oxidative stress and regeneration markers can refine organ assessment during machine perfusion.