Abdulrazzak E, Kallwitz ER. Hepatic ischemia reperfusion injury: Understanding the little components of the larger picture. World J Hepatol 2026; 18(8): 117012 [DOI: 10.4254/wjh.117012]
Corresponding Author of This Article
Eric R Kallwitz, MD, Associate Professor, Division of Hepatology, Department of Medicine, Loyola University Medical Center, 2160 S First Ave, Maywood, IL 60153, United States. ekallwitz@lumc.edu
Research Domain of This Article
Transplantation
Article-Type of This Article
editorial
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Abdulrazzak E, Kallwitz ER. Hepatic ischemia reperfusion injury: Understanding the little components of the larger picture. World J Hepatol 2026; 18(8): 117012 [DOI: 10.4254/wjh.117012]
World J Hepatol. Aug 27, 2026; 18(8): 117012 Published online Aug 27, 2026. doi: 10.4254/wjh.117012
Hepatic ischemia reperfusion injury: Understanding the little components of the larger picture
Eyad Abdulrazzak, Eric R Kallwitz
Eyad Abdulrazzak, Eric R Kallwitz, Division of Hepatology, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, United States
Author contributions: Abdulrazzak E conducted the literature review, developed the outline, and drafted the initial manuscript; Kallwitz ER critically revised the outline and manuscript drafts, contributed to the development of the final version, and ensured scientific accuracy. Both authors reviewed and approved the final manuscript.
AI contribution statement: An AI tool (ChatGPT) was used solely for language polishing and grammar review to improve clarity and readability. This tool was not used to generate any portion of the manuscript content, nor did they contribute to the study design, data analysis, interpretation of results, or inferences. All scientific content, analyses, and conclusions were developed independently by the authors.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Eric R Kallwitz, MD, Associate Professor, Division of Hepatology, Department of Medicine, Loyola University Medical Center, 2160 S First Ave, Maywood, IL 60153, United States. ekallwitz@lumc.edu
Received: November 26, 2025 Revised: January 2, 2026 Accepted: April 1, 2026 Published online: August 27, 2026 Processing time: 265 Days and 7.9 Hours
Abstract
Hepatic ischemia reperfusion injury is especially relevant in the field of liver surgery and transplantation. In the most severe cases, significant liver dysfunction and liver failure can occur, resulting in death or re-transplantation. The mechanisms are complex; however, the most basic concept is that the restoration of blood flow to an ischemic organ can lead to an inflammatory response. The mechanisms that trigger this immune response are not completely understood; however, multiple factors were found to contribute. These include the release of inflammatory cytokines/chemokines, hepatocellular apoptosis, and oxidative stress. Multiple studies, mainly animal models, have examined the potential for various therapies, including pharmacotherapy, to ameliorate ischemia-reperfusion injury. The study by Kelleni et al recently published in the recent issue of the World Journal of Hepatology examines the potential hepatoprotective effect of aprepitant, an antiemetic agent commonly used for nausea related to chemotherapy. In an animal model of ischemia-reperfusion injury, the authors found improved inflammatory markers and survival in rats treated with aprepitant. There have been multiple animal models suggesting various pharmacotherapies to reduce the severity of ischemia-reperfusion injury. The use of aprepitant is unique as it is currently available for use in humans, although further data is needed, side effects need to be monitored, and significant drug interactions could occur.
Core Tip: Despite advancements in surgical techniques and preservation, hepatic ischemia-reperfusion injury (H-IRI) remains a critical hurdle in liver transplantation, contributing to early allograft dysfunction. While machine perfusion represents a major macro-level advancement, pharmacological strategies targeting specific molecular pathways remain an important avenue for mitigating H-IRI. This editorial briefly outlines the complexity of H-IRI mechanisms, discusses emerging pharmacological and mechanical interventions, and highlights recent findings on the neurokinin-1 receptor antagonist aprepitant as a potential therapeutic agent.
