REVIEW article
Front. Immunol.
Sec. Inflammation
This article is part of the Research TopicMechanisms of cell death in acute liver diseases and the pathobiology of sterile inflammation: The double-edged sword problemView all 4 articles
Exploring Cell Death Mechanisms in Liver Transplantation: Implications for Graft Survival
Provisionally accepted
- 1Department of Surgery, Division of Hepato-Pancreato-Biliary Surgery and Transplantation, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Japan
- 2Lab. of Immunology, Institute for Life and Medical Sciences, Kyoto Daigaku, Kyoto, Japan
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Liver transplantation (LT) has become a life-saving therapy for patients with end-stage liver disease and malignancies. However, graft survival remains a significant challenge because of LT-related stresses. Grafts are subject to several stresses, including cold preservation after procurement and during transportation, as well as warm ischemia until vascular reconstitution, which can trigger hepatic cell death. This review examines the various cell death mechanisms that influence liver graft outcomes, including apoptosis, necrosis, autophagy, and non-apoptotic inflammatory cell death. We discuss how these mechanisms are driven by ischemia-reperfusion injury, which contributes to graft dysfunction. Apoptosis leads to the selective elimination of damaged hepatic cells, while necrosis, resulting from fulminant injury, can provoke inflammatory responses that further jeopardize graft viability. Autophagy emerges as a double-edged sword, promoting cellular repair under stress while potentially leading to cell death in extreme circumstances. Additionally, recent studies have uncovered novel non-apoptotic death pathways, such as necroptosis, pyroptosis, ferroptosis, panoptosis, and netosis, that may also influence transplant outcomes. Understanding the intricate interplay of these cell death mechanisms is vital for developing innovative therapeutic strategies to enhance graft survival. By synthesizing current research findings, this review aims to highlight the potential for targeted interventions to mitigate cell death and improve liver transplant outcomes, ultimately improving patient survival and quality of life.
Keywords: Cell Death, damage-associated molecular pattern, innate immunity, ischemia-reperfusion injury, Liver Transplantation, Sterile Inflammation
Received: 06 Sep 2025; Accepted: 15 Dec 2025.
Copyright: © 2025 Hirao, Watanabe, Uchida and Hatano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Takeshi Watanabe
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