{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T13:13:50Z","timestamp":1783430030986,"version":"3.54.6"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007525","name":"Universit\u00e9 de Rennes 1","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007525","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Normothermic machine perfusion (NMP) enables metabolic restoration and viability testing of liver grafts, but current viability criteria incompletely predict post\u2010transplant outcomes. The molecular basis of graft resilience or biliary vulnerability remains unclear. This study aimed to characterise tissue\u2010level proteomic trajectories during NMP and early reperfusion to identify molecular signatures associated with biliary complications after liver transplantation (LT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective, single\u2010centre study was conducted at Rennes University Hospital. Twenty donation\u2010after\u2010brain\u2010death (DBD) livers underwent NMP; sixteen transplanted grafts with complete sequential biopsies and \u2265\u20096\u2009months of follow\u2010up were analysed. Biopsies were collected after cold storage (B1), at the end of NMP (B2), and 1\u2009h after graft reperfusion (B3). Proteins were quantified by high\u2010resolution LC\u2013MS\/MS and analysed with Proteome Discoverer 3.1\/Chimerys. Pathway enrichment used Ingenuity Pathway Analysis to compare grafts with and without biliary complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Principal component analysis revealed distinct proteomic profiles between grafts with and without complications at all biopsy time points. During NMP (B2\/B1), uncomplicated grafts showed glycolytic activation with attenuation of oxidative phosphorylation, whereas complicated grafts showed blunted glycolysis and mild OXPHOS upregulation. At reperfusion (B3\/B2), complicated grafts displayed induction of translational and endoplasmic\u2010reticulum\u2010stress pathways, while resilient grafts maintained proteasome\u2010related protein turnover and enrichment of a hypoxia\u2010response signature driven by ELOC and proteasome subunits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sequential tissue proteomics during NMP reveals divergent metabolic and proteostatic adaptations linked to biliary outcomes. Glycolytic activation with preserved protein turnover characterises resilient grafts, whereas translational and ER\u2010stress programmes predominate in complicated ones. These insights may refine viability assessment beyond biochemical criteria.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70629","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:48:16Z","timestamp":1776232096000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic Trajectories of Metabolic and Proteostatic Adaptation During Normothermic Liver Perfusion"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3722-904X","authenticated-orcid":false,"given":"Heithem","family":"Jeddou","sequence":"first","affiliation":[{"name":"Service de Chirurgie H\u00e9patobiliaire et Digestive, CHU Rennes  Rennes France"},{"name":"Inserm, EHESP Universit\u00e9 de Rennes, Irset (Institut de Recherche en Sant\u00e9, Environnement et Travail) \u2013 UMR_S 1085  Rennes 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Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eya Ben","family":"Nejma","sequence":"additional","affiliation":[{"name":"Service de Chirurgie H\u00e9patobiliaire et Digestive, CHU Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stylianos","family":"Tzedakis","sequence":"additional","affiliation":[{"name":"Service de Chirurgie Digestive, H\u00e9patobiliaire et Endocrinienne, H\u00f4pital Cochin, AP\u2010HP Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Turlin","sequence":"additional","affiliation":[{"name":"Service D'anatomie Pathologique, CHU Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6179-3396","authenticated-orcid":false,"given":"Pierre","family":"Allaume","sequence":"additional","affiliation":[{"name":"Service D'anatomie Pathologique, CHU Rennes  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