Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction
<b>Background/Objectives</b>: 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. We aimed to identify predictive biomarkers in DCD grafts subjected to NR...
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2025-01-01
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| author | 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 Giandomenico Biancofiore Adriano Peris Chiara Lazzeri Davide Ghinolfi |
| author_facet | 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 Giandomenico Biancofiore Adriano Peris Chiara Lazzeri Davide Ghinolfi |
| author_sort | Giuseppina Basta |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: 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. We aimed to identify predictive biomarkers in DCD grafts subjected to NRP, followed by randomization to either normothermic machine perfusion (NMP) or dual hypothermic oxygenated perfusion (D-HOPE). <b>Methods</b>: 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. <b>Results</b>: 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; <i>p</i> = 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. <b>Conclusions</b>: ARG-1 demonstrates strong potential as an early biomarker for assessing liver graft viability during perfusion, supporting timely and effective decision-making in transplantation. |
| format | Article |
| id | doaj-art-19cbd195fb924cf29fc8cb84b0bf809b |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-19cbd195fb924cf29fc8cb84b0bf809b2025-01-24T13:24:31ZengMDPI AGBiomedicines2227-90592025-01-0113124410.3390/biomedicines13010244Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft DysfunctionGiuseppina Basta0Serena Babboni1Daniele Pezzati2Serena Del Turco3Emanuele Balzano4Gabriele Catalano5Lara Russo6Giovanni Tincani7Paola Carrai8Stefania Petruccelli9Jessica Bronzoni10Caterina Martinelli11Simona Palladino12Arianna Trizzino13Lorenzo Petagna14Renato Romagnoli15Damiano Patrono16Giandomenico Biancofiore17Adriano Peris18Chiara Lazzeri19Davide Ghinolfi20Institute of Clinical Physiology, National Research Council (CNR), Via Moruzzi 1, 56124 Pisa, ItalyInstitute of Clinical Physiology, National Research Council (CNR), Via Moruzzi 1, 56124 Pisa, ItalyDivision of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana, Via Paradisa 2, 56124 Pisa, ItalyInstitute of Clinical Physiology, National Research Council (CNR), Via Moruzzi 1, 56124 Pisa, ItalyDivision of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana, Via Paradisa 2, 56124 Pisa, ItalyDivision of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana, Via Paradisa 2, 56124 Pisa, ItalyInstitute of Clinical Physiology, National Research Council (CNR), Via Moruzzi 1, 56124 Pisa, ItalyDivision of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana, Via Paradisa 2, 56124 Pisa, ItalyDivision of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana, Via Paradisa 2, 56124 Pisa, ItalyDivision of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana, Via Paradisa 2, 56124 Pisa, ItalyDivision of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana, Via Paradisa 2, 56124 Pisa, ItalyDivision of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana, Via Paradisa 2, 56124 Pisa, ItalyDivision of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana, Via Paradisa 2, 56124 Pisa, ItalyDivision of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana, Via Paradisa 2, 56124 Pisa, ItalyDivision of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana, Via Paradisa 2, 56124 Pisa, ItalyGeneral Surgery 2U-Liver Transplant Unit, Azienda Ospedaliero Universitaria Città della Salute e Della Scienza di Torino, University of Torino, Corso Bramante 88-90, 10126 Torino, ItalyGeneral Surgery 2U-Liver Transplant Unit, Azienda Ospedaliero Universitaria Città della Salute e Della Scienza di Torino, University of Torino, Corso Bramante 88-90, 10126 Torino, ItalyDepartment of Anesthesia and Critical Care Medicine, Azienda Ospedaliero-Universitaria Pisana, 56124 Pisa, ItalyTuscany Regional Transplant Authority, Centro Regionale Allocazione Organi e Tessuti (CRAOT), 50134 Florence, ItalyTuscany Regional Transplant Authority, Centro Regionale Allocazione Organi e Tessuti (CRAOT), 50134 Florence, ItalyDivision of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana, Via Paradisa 2, 56124 Pisa, Italy<b>Background/Objectives</b>: 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. We aimed to identify predictive biomarkers in DCD grafts subjected to NRP, followed by randomization to either normothermic machine perfusion (NMP) or dual hypothermic oxygenated perfusion (D-HOPE). <b>Methods</b>: 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. <b>Results</b>: 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; <i>p</i> = 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. <b>Conclusions</b>: ARG-1 demonstrates strong potential as an early biomarker for assessing liver graft viability during perfusion, supporting timely and effective decision-making in transplantation.https://www.mdpi.com/2227-9059/13/1/244DCDdonations after circulatory deathD-HOPEdual hypothermic oxygenated machine perfusionNMPnormothermic regional perfusion |
| spellingShingle | 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 Giandomenico Biancofiore Adriano Peris Chiara Lazzeri Davide Ghinolfi Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction Biomedicines DCD donations after circulatory death D-HOPE dual hypothermic oxygenated machine perfusion NMP normothermic regional perfusion |
| title | Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction |
| title_full | Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction |
| title_fullStr | Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction |
| title_full_unstemmed | Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction |
| title_short | Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction |
| title_sort | perfusate liver arginase 1 levels after end ischemic machine perfusion are associated with early allograft dysfunction |
| topic | DCD donations after circulatory death D-HOPE dual hypothermic oxygenated machine perfusion NMP normothermic regional perfusion |
| url | https://www.mdpi.com/2227-9059/13/1/244 |
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