Molecular fingerprints linked to graft viability in extended criteria donor livers during normothermic machine perfusion

Abstract Background Donor organ shortage has led to increased reliance on extended-criteria donor (ECD) livers for transplantation. Normothermic machine perfusion (NMP) has led to a paradigm shift in organ preservation from cold storage to full ex-situ metabolic support. This study investigated ECD liver metabolic profiling to elucidate NMP molecular signatures and whether signatures were predictive of graft viability and clinical outcome. Methods Thirty-one livers underwent NMP for a minimum of four hours and 23 livers fulfilled NMP viability criteria. Perfusate from graft perfusion commencement to 4-h time point were collected at 0.25, 2 and 4 h. Samples underwent untargeted metabolomics analysis using Ultra High Performance Liquid Chromatography-Mass Spectrometry. Univariate statistical analyses revealed dynamic changes in metabolic profiles across the perfusion period and differences in water-soluble and lipid-based metabolites between viable and non-viable livers. Results Pathway enrichment analysis highlights pathways relating to amino acid and energy metabolism differing between viable and non-viable livers. Metabolic changes are not observed for ECD livers based on post-transplant clinical outcome. Conclusions This study revealed metabolic signatures of ECD livers that may define metabolic differences related to graft viability which can be targeted for improved viability.