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.
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BibTeX
@article{attard2026molecular,
title = {{Molecular fingerprints linked to graft viability in extended criteria donor livers during normothermic machine perfusion}},
author = {Joseph A. Attard and Richard Laing and Lorraine Wallace and Lukas Najdekr and Gavin R. Lloyd and Andris Jankevics and Amanda Kirkham and Yuri L. Boteon and Darren Barton and Stuart Curbishley and Manpreet Wilkhu and Desley A. H. Neil and Paolo Muiesan and John R. Isaac and Keith J. Roberts and Manuel Abradelo and Andrea Schlegel and James Ferguson and Hentie Cilliers and Chris Morris and Peter J. Friend and Christina Yap and Hynek Mergental and Darius F. Mirza and M. Thamara P. R. Perera and Warwick B. Dunn and Simon C. Afford},
journal = {Communications Medicine},
year = {2026},
month = oct,
doi = {10.1038/s43856-025-00737-6},
url = {https://www.nature.com/articles/s43856-025-00737-6},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular fingerprints linked to graft viability in extended criteria donor livers during normothermic machine perfusion
AU - Joseph A. Attard
AU - Richard Laing
AU - Lorraine Wallace
AU - Lukas Najdekr
AU - Gavin R. Lloyd
AU - Andris Jankevics
AU - Amanda Kirkham
AU - Yuri L. Boteon
AU - Darren Barton
AU - Stuart Curbishley
AU - Manpreet Wilkhu
AU - Desley A. H. Neil
AU - Paolo Muiesan
AU - John R. Isaac
AU - Keith J. Roberts
AU - Manuel Abradelo
AU - Andrea Schlegel
AU - James Ferguson
AU - Hentie Cilliers
AU - Chris Morris
AU - Peter J. Friend
AU - Christina Yap
AU - Hynek Mergental
AU - Darius F. Mirza
AU - M. Thamara P. R. Perera
AU - Warwick B. Dunn
AU - Simon C. Afford
PY - 2026
DA - 2026/10/13
JO - Communications Medicine
DO - 10.1038/s43856-025-00737-6
UR - https://www.nature.com/articles/s43856-025-00737-6
AB - 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.
SN - 2730-664X
ER -