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Pre-Donation Cardiac Arrest and Liver Transplantation Outcomes: Implications for Ischemic Preconditioning

Lookup NU author(s): Dr Sam Tingle, Dr George KourounisORCiD, Professor Colin Wilson

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2025 The Author(s). Clinical Transplantation published by John Wiley & Sons Ltd.Background: Liver transplantation is the definitive treatment for end-stage liver disease and some cancers. The use of livers from donors following pre-donation cardiac arrest (PDCA), especially with prolonged downtime duration, has been limited outside of the US due to fears over inferior outcomes from ischemic injury. However, PDCA may induce ischemic preconditioning, paradoxically improving post-transplant outcomes. We analyzed the impact of PDCA occurrence and downtime duration on liver transplantation. Methods: We used the UNOS registry on adult liver transplantation (2010–2023), and included both donation after brain death (DBD) and donation after circulatory death (DCD) donors. Multivariable regression models were used to analyze the associations. Multiple imputation was used for missing data, and restricted cubic spline modelling to account for non-linear relationships. Results: Among 74,592 recipients, 32,631 (43.7%) received a liver from a PDCA donor. PDCA occurrence was associated with a small improvement in graft survival (aHR = 0.914, 95% Cl = 0.851–0.982). Interaction terms revealed this benefit was more pronounced among the following donor groups: DCD, moderately raised alanine aminotransferase (ALT), short admission-to-donation time and older donors. These novel associations are all in keeping with a preconditioning effect. Increasing PDCA downtime duration was also associated with a small improvement in graft survival (aHR per doubling = 0.953, 95% Cl = 0.917–0.991). Similar associations were seen with secondary outcomes. Conclusions: The use of livers from donors with PDCA, including those with prolonged downtime duration, is a safe and simple approach to expand the donor pool internationally. Interaction terms and non-linear modelling provided clinical evidence for ischemic preconditioning from PDCA, which represents the largest real-world demonstration of this phenomenon.


Publication metadata

Author(s): Amarnath DR, Tingle SJ, Kourounis G, Freise C, Roll GR, Yamaguchi S, Rickert C, Wilson CH

Publication type: Article

Publication status: Published

Journal: Clinical Transplantation

Year: 2025

Volume: 39

Issue: 9

Print publication date: 01/09/2025

Online publication date: 09/09/2025

Acceptance date: 29/08/2025

Date deposited: 30/09/2025

ISSN (print): 0902-0063

ISSN (electronic): 1399-0012

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1111/ctr.70309

DOI: 10.1111/ctr.70309

Data Access Statement: The data used in the analysis are available from OPTN/UNOS. Data can be requested from OPTN/UNOS through the following website: https://optn.transplant.hrsa.gov/data/view-data-reports/request-data/.

PubMed id: 40924859


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Funding

Funder referenceFunder name
Kidney Research UK
MRC/Y000676/1
Medical Research Council
National Institute for Health and Care Research (NIHR) Blood and Transplant Research Unit in Organ Donation and Transplantation (NIHR203332)

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