{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:10:45Z","timestamp":1792797045241,"version":"4.5.0"},"reference-count":171,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Hepatic ischemia\u2013reperfusion injury (HIRI) remains a key contributor to early allograft dysfunction (EAD), post-hepatectomy liver failure, biliary complications, and the underutilization of marginal donor grafts. Damage-associated molecular patterns (DAMPs) are central mediators of sterile inflammation in HIRI; however, their translational relevance extends beyond being upstream inflammatory triggers. In this review, we reframe DAMP biology by considering spatiotemporal release, sampling accessibility, biomarker utility, and therapeutic tractability. Rather than providing another broad overview of sterile inflammation or regulated cell death, we focus on how distinct DAMP classes\u2014including nuclear and nucleic acid-related signals, mitochondrial and metabolic DAMPs, extracellular matrix-derived fragments, and protein-based danger cues\u2014arise from defined cellular sources during cold ischemia, warm ischemia, early reperfusion, and late injury\u2013repair phases. We discuss how these signals are detected by pattern-recognition receptors (PRRs) and intracellular sensing pathways, including Toll-like receptors (TLRs), receptor for advanced glycation end products (RAGE), the P2X purinoceptor 7 (P2X7)\u2013NLR family pyrin domain-containing 3 (NLRP3) inflammasome axis, and cyclic GMP\u2013AMP synthase (cGAS)\u2013stimulator of interferon genes (STING) signaling. We further examine how DAMP-driven sensing coordinates Kupffer cell activation, endothelial dysfunction, neutrophil-mediated amplification, thromboinflammation, and impaired tissue recovery. Particular emphasis is placed on circulating and perfusate-accessible DAMP signatures as minimally invasive tools for injury grading, EAD prediction, biliary complication risk stratification, and donor graft-quality assessment during machine perfusion. We also summarize DAMP-targeted therapeutic strategies, including strategies to limit DAMP release, enhance extracellular DAMP clearance, block dominant sensing pathways, and integrate DAMP modulation with organ-preservation platforms. Finally, we highlight key barriers to clinical translation, including assay heterogeneity, undefined sampling windows, insufficient multicenter validation, and the need to distinguish reparative from pathogenic DAMP signaling. A spatiotemporal, DAMP-centered framework may help connect molecular injury biology with biomarker-guided decision-making and precision interventions in liver transplantation and hepatic surgery.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1789287","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:51:30Z","timestamp":1779943890000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Damage-associated molecular patterns in hepatic ischemia\u2013reperfusion injury: spatiotemporal signatures, biomarker potential, and clinical translation"],"prefix":"10.3389","volume":"17","author":[{"given":"Peng","family":"An","sequence":"first","affiliation":[{"name":"The Gastroenterology Department of Shanxi Provincial People\u2019s Hospital, Shanxi Medical University","place":["Taiyuan, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16219","article-title":"Ischemia-reperfusion injury and its relationship with early allograft dysfunction in liver transplant patients","volume":"21","author":"Ito","year":"2021","journal-title":"Am J Transplant"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2017.5040","article-title":"Evaluation of early allograft function using the Liver Graft Assessment Following Transplantation risk score model","volume":"153","author":"Agopian","year":"2018","journal-title":"JAMA Surg"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.hpb.2016.07.016","article-title":"Postoperative peak transaminases correlate with morbidity and mortality after liver resection","volume":"18","author":"Olthof","year":"2016","journal-title":"HPB 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