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Viability Testing and Transplantation of Marginal Donor Livers (VITTAL) Trial: Metabolomics of Ex Vivo Normothermically Machine Perfused Livers Discloses Molecular Signatures Predictive of Graft Viability and Post Transplant Outcomes

J. Attard1, W. Dunn2, L. Wallace1, R. Laing1, Y. Boteon1, H. Mergental3, D. Mirza3, T. Perera3, S. Afford1

1CLGR, University of Birmingham and NIHR Biomedical Research Centre, Birmingham, United Kingdom, 2Phenome Centre Birmingham, University of Birmingham, Birmingham, United Kingdom, 3Liver Unit, Queen Elizabeth University Hospital, Birmingham, United Kingdom

Meeting: 2019 American Transplant Congress

Abstract number: 60

Keywords: Liver metabolism, Liver transplantation, Machine preservation

Session Information

Date: Sunday, June 2, 2019

Session Name: Concurrent Session: Biomarkers, Immune Monitoring and Outcomes I

Session Time: 2:30pm-4:00pm

 Presentation Time: 3:42pm-3:54pm

Location: Room 306

Related Abstracts
  • Viability Testing and Transplantation of Marginal Donor Livers (VITTAL) Trial Outcomes: Proteomic Analysis of Perfusates from Livers Undergoing Normothermic Machine Liver Perfusion Reveals Biomarkers Predictive of Graft Viability and Post-Transplant Complications
  • Resuscitation and Viability Testing of Initially Declined Livers Using Sequential Hypo- and Normothermic Machine Perfusion with an Acellular Fluid

*Purpose: Donor organ shortage has led to increased reliance on high-risk livers for transplantation. Furthermore, emergence of machine perfusion has led to a paradigm shift in organ preservation from functional suppression in static cold storage to full ex vivo metabolic support. The recently completed VITTAL trial demonstrated that normothermic machine perfusion (NMP-L) provides an opportunity to objectively assess graft quality and functional integrity pre-transplantation in order to safely transplant high-risk livers turned down by all transplant centres. This study investigated the potential of metabolic profiling to elucidate molecular signatures during NMP-L predictive of graft viability, post-reperfusion syndrome (PRS) and early allograft dysfunction (EAD) in these discarded livers.

*Methods: All livers were deemed marginal according to established high-risk criteria, and had been discarded by all transplant centres. 31 livers underwent NMP-L for a minimum of four hours, at which point a decision was made to transplant based on established viability criteria. Perfusate aliquots from commencement of graft perfusion to 4-hour time point were collected from all livers. Samples were centrifuged and the supernatant subjected to an untargeted metabolomics analysis using Ultra High Performance Liquid Chromatography-Mass Spectrometry.

*Results: 22 livers were transplanted after achieving viability criteria. Univariate statistical analyses revealed more than 20 metabolites (q<0.05) differentiating liver metabolic profiles according to viability criteria fulfilment following 4 hours of perfusion. Key changes were detected in metabolites relating to lipid, phospholipid and sphingolipid metabolism, notably upregulated in the non-viable group. In the transplanted cohort; 52 metabolites distinguished EAD (n=7) from non-EAD livers (n=15) after 4 hours of perfusion. The PRS group (n=10) revealed changes in 36 metabolites after 4 hours of perfusion compared to non-PRS group (n=12).

*Conclusions: This study reveals a metabolic signature of high-risk livers that correlates with VITTAL criteria for graft viability for transplantation during NMP-L. It also demonstrates the potential of NMP-L metabolic profiling as a clinical tool to objectively assess the quality and predict functional integrity of these livers pre-implantation.

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To cite this abstract in AMA style:

Attard J, Dunn W, Wallace L, Laing R, Boteon Y, Mergental H, Mirza D, Perera T, Afford S. Viability Testing and Transplantation of Marginal Donor Livers (VITTAL) Trial: Metabolomics of Ex Vivo Normothermically Machine Perfused Livers Discloses Molecular Signatures Predictive of Graft Viability and Post Transplant Outcomes [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/viability-testing-and-transplantation-of-marginal-donor-livers-vittal-trial-metabolomics-of-ex-vivo-normothermically-machine-perfused-livers-discloses-molecular-signatures-predictive-of-graft-viabi/. Accessed December 6, 2019.

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