Mouratidou C, Pavlidis ET, Katsanos G, Kofinas A, Marneri AG, Stavrati KE, Tsoulfas G, Pavlidis TE. Pathophysiological mechanisms of cell death affecting graft survival in liver transplantation. World J Transplant 2026; 16(3): 124992 [DOI: 10.5500/wjt.124992]
Corresponding Author of This Article
Theodoros E Pavlidis, MD, PhD, Professor Emeritus, The Second Department of Propaedeutic Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Konstantinoupoleos 49, Thessaloniki 54642, Greece. pavlidth@auth.gr
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Transplantation
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review-article
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World J Transplant. Sep 18, 2026; 16(3): 124992 Published online Sep 18, 2026. doi: 10.5500/wjt.124992
Pathophysiological mechanisms of cell death affecting graft survival in liver transplantation
Christina Mouratidou, Efstathios T Pavlidis, Georgios Katsanos, Athanasios Kofinas, Alexandra G Marneri, Kalliopi E Stavrati, Georgios Tsoulfas, Theodoros E Pavlidis
Christina Mouratidou, Alexandra G Marneri, Department of Intensive Care Unit, Hippokration General Hospital, Thessaloniki 54642, Greece
Efstathios T Pavlidis, Theodoros E Pavlidis, The Second Department of Propaedeutic Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
Georgios Katsanos, Athanasios Kofinas, Georgios Tsoulfas, Department of Transplantation Surgery, Center for Research and Innovation in Solid Organ Transplantation, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki 54642, Greece
Kalliopi E Stavrati, Department of Surgical, Eugenideio Hospital, Athens 11528, Greece
Co-corresponding authors: Efstathios T Pavlidis and Theodoros E Pavlidis.
Author contributions: Mouratidou C, Pavlidis ET conceived the study design and carried out data analysis; Marneri AG, Stavrati KE, Tsoulfas G developed analytical tools, assessed the data, and contributed to manuscript revision; Katsanos G, Kofinas A, assisted with data collection and interpretation; Pavlidis TE, supervised data analysis, reviewed the manuscript, and approved the paper; Pavlidis ET and Pavlidis TE contributed equally to this manuscript as co-corresponding authors; all authors have read and approved the final manuscript.
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Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
Corresponding author: Theodoros E Pavlidis, MD, PhD, Professor Emeritus, The Second Department of Propaedeutic Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Konstantinoupoleos 49, Thessaloniki 54642, Greece. pavlidth@auth.gr
Received: June 29, 2026 Revised: July 24, 2026 Accepted: August 10, 2026 Published online: September 18, 2026 Processing time: 62 Days and 19.4 Hours
Abstract
Early allograft dysfunction (EAD) is a significant complication of liver transplantation (LT). LT remains the sole curative treatment for patients with end-stage liver disease. EAD is correlated with heightened morbidity, extended stays in intensive care units, and decreased graft survival rates. Within the clinical practice, EAD presents a substantial challenge, necessitating vigilant monitoring, heightened clinical awareness, and prompt multidisciplinary intervention to prevent progression to primary graft nonfunction and multiorgan failure. Multiple forms of programmed cell death, including necrosis, apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy, PANoptosis, and NETosis, have been implicated in graft injury. Apoptosis facilitates the regulated elimination of damaged or senescent hepatocytes via caspase-dependent pathways, whereas necroptosis and other necrotic mechanisms exacerbate caspase-independent tissue injury through membrane disruption and the release of inflammatory mediators. Pyroptosis, driven by inflammasome activation and gasdermin-mediated pore formation, further amplifies inflammatory signaling within the graft. Moreover, ferroptosis, characterized by iron-dependent lipid peroxidation, has emerged as a pivotal contributor to hepatocellular injury during hepatic ischemia–reperfusion events. Failure of hepatocellular protective mechanisms to adequately counteract energy depletion and oxidative stress during ischemia results in cell death, which subsequently activates immune and contributing to acute graft rejection.
Core Tip: The incidence of end-stage liver disease and its associated mortality have increased substantially in recent years, with liver transplantation remaining the sole definitive therapeutic intervention for affected patients. Hepatic ischemia-reperfusion injury is implicated strongly in early allograft dysfunction (EAD), increased postoperative complications, and unfavorable long-term prognoses. It affects nearly all grafts to varying extents, with the severity of injury being correlated with elevated morbidity, primary graft dysfunction, and potential graft loss. The prevention and immediate recognition of EAD, along with a thorough understanding of its pathophysiological processes, are crucial for optimal transplant function.
