Normothermic Machine Perfusion of Extended Criteria Donor Livers: Identification of Protein Biomarkers Predictive of Graft Viability and Post-Transplant Complications
1Centre for Liver and Gastrointestinal Research, University of Birmingham and the NIHR Biomedical Research Centre, UHB NHS Foundation Trust, Birmingham, United Kingdom, 2School of Biosciences, Advanced Mass Spectrometry Facility, University of Birmingham, Birmingham, United Kingdom, 3Liver Unit, The Queen Elizabeth Hospital, Birmingham, United Kingdom
Meeting: 2020 American Transplant Congress
Abstract number: B-328
Keywords: Donors, marginal, Graft function, Machine preservation, Post-operative complications
Session Information
Session Name: Poster Session B: Biomarker Discovery and Immune Modulation
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: The Viability Testing and Transplantation of mArginal donor Livers Clinical Trial (VITTAL) demonstrated the capacity of Normothermic Machine Perfusion (NMP) to increase the proportion of marginal donor livers for transplantation using viability criteria developed in Birmingham. The aim of this study was to quantify proteins previously identified using non quantitative untargeted proteomics in order to determine their potential as a point of use tests of marginal donor liver transplantability and post-transplant complications (PTCs).
*Methods: Sequential samples of perfusate from the 31 VITTAL perfusions were analysed. Untargeted Liquid Chromatography/Mass Spec. proteomic analysis was initially used to reveal any potential protein targets for quantification. ELISA analysis of the same perfusates was then undertaken to provide empirical data for the individual proteins using commercially available assays.
*Results: Of the eight proteins selected for investigation, Aminoacylase-1 (ACY1), Signal recognition particle alpha (SRPRA) and C – Reactive Protein (CRP) demonstrated statistically significant differences that differentiated between viable and non-viable livers. In addition, Glial cell line-derived neurotrophic factor (GNDF) and Heat Shock Protein 7-0 (HSP70) identified the organs which developed Early Allograft Dysfunction and Post Reperfusion Syndrome, respectively. Aldo-Keto Reductase Family 7 Member A3 (AKR7A3) and Plasminogen activator inhibitor-1 (PAI1) failed to predict any differences.
*Conclusions: Untargeted proteomics was able to identify clusters of proteins which when quantified showed statistical differentiation between viable and non-viable organs and those likely to develop post-transplant complications. These findings show that these protein biomarkers may be used as point of use tests during NMP to assess organ viability, quality and hence suitability for transplantation. To our knowledge this study is also the first to report a simple pre transplant test predictive of post -transplant complications which could be useful in post-transplant recipient care. The next phase of the project will involve clinical validation.
To cite this abstract in AMA style:
Wallace LL, Attard J, Boteon Y, Laing R, Yu J, Perera T, Mirza D, Mergental H, Afford S. Normothermic Machine Perfusion of Extended Criteria Donor Livers: Identification of Protein Biomarkers Predictive of Graft Viability and Post-Transplant Complications [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/normothermic-machine-perfusion-of-extended-criteria-donor-livers-identification-of-protein-biomarkers-predictive-of-graft-viability-and-post-transplant-complications/. Accessed May 16, 2025.« Back to 2020 American Transplant Congress