ArticleLiver international : official journal of the International Association for the Study of the Liver2026
Proteomic Trajectories of Metabolic and Proteostatic Adaptation During Normothermic Liver Perfusion.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Proteomic Trajectories of Metabolic and Proteostatic Adaptation During Normothermic Liver Perfusion.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
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11 authors.
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Abstract
backgroundNormothermic machine perfusion (NMP) enables metabolic restoration and viability testing of liver grafts, but current viability criteria incompletely predict post-transplant outcomes. The molecular basis of graft resilience or biliary vulnerability remains unclear. This study aimed to characterise tissue-level proteomic trajectories during NMP and early reperfusion to identify molecular signatures associated with biliary complications after liver transplantation (LT).
methodsThis prospective, single-centre study was conducted at Rennes University Hospital. Twenty donation-after-brain-death (DBD) livers underwent NMP; sixteen transplanted grafts with complete sequential biopsies and ≥ 6 months of follow-up were analysed. Biopsies were collected after cold storage (B1), at the end of NMP (B2), and 1 h after graft reperfusion (B3). Proteins were quantified by high-resolution LC-MS/MS and analysed with Proteome Discoverer 3.1/Chimerys. Pathway enrichment used Ingenuity Pathway Analysis to compare grafts with and without biliary complications.
resultsPrincipal 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-reticulum-stress pathways, while resilient grafts maintained proteasome-related protein turnover and enrichment of a hypoxia-response signature driven by ELOC and proteasome subunits.
conclusionsSequential 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-stress programmes predominate in complicated ones. These insights may refine viability assessment beyond biochemical criteria.
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