Dharesh Raj Amarnath, Samuel J. Tingle, Georgios Kourounis, Chris Freise, Garrett R. Roll, Seiji Yamaguchi, Charles Rickert, Colin H. Wilson
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We analyzed the impact of PDCA occurrence and downtime duration on liver transplantation.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 9","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70309","citationCount":"0","resultStr":"{\"title\":\"Pre-Donation Cardiac Arrest and Liver Transplantation Outcomes: Implications for Ischemic Preconditioning\",\"authors\":\"Dharesh Raj Amarnath, Samuel J. Tingle, Georgios Kourounis, Chris Freise, Garrett R. Roll, Seiji Yamaguchi, Charles Rickert, Colin H. Wilson\",\"doi\":\"10.1111/ctr.70309\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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). 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Pre-Donation Cardiac Arrest and Liver Transplantation Outcomes: Implications for Ischemic Preconditioning
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.
期刊介绍：
Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored.
Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include:
Immunology and immunosuppression;
Patient preparation;
Social, ethical, and psychological issues;
Complications, short- and long-term results;
Artificial organs;
Donation and preservation of organ and tissue;
Translational studies;
Advances in tissue typing;
Updates on transplant pathology;.
Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries.
Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.
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