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Hepatic Ischemia-Reperfusion Injury in Liver Transplantation: Molecular Mechanisms
Eduardo Montalvo-Javé1, Natalia Nuño-Lámbarri2, Timothy Pawlik3
1Department of Surgery, Faculty of Medicine, The National Autonomous University of Mexico (UNAM). Mexico City, Mexico; Hepato Pancreato and Biliary Clinic, Department of General Surgery, "Hospital General de Mexico", Dr. Eduardo Liceaga. Mexico City, Mexico; Traslational Research Unit and Department of Surgery Medica Sur Clinic & Foundation. Mexico City, Mexico.
Background:
Hepatic ischemia-reperfusion injury (HIRI) remains a major determinant of graft dysfunction and adverse outcomes in liver transplantation, particularly in the context of extended criteria donors. The complex interplay between metabolic disruption, oxidative stress, endothelial dysfunction, and immune activation underlies the pathogenesis of HIRI, yet effective therapeutic strategies remain limited.
Aim:
To systematically evaluate the molecular mechanisms involved in HIRI and to analyze emerging therapeutic approaches aimed at mitigating liver injury and improving graft outcomes in transplantation settings.
Methods:
A systematic review of the literature was conducted focusing on experimental and clinical studies addressing the pathophysiology and treatment of HIRI.
Results:
HIRI is characterized by a biphasic process involving ischemic metabolic failure and reperfusion-induced oxidative and inflammatory injury. Central mechanisms include ATP depletion, calcium overload, ROS and reactive nitrogen species production, endothelial dysfunction, and activation of innate immune responses. Emerging therapies such as activated protein C, complement inhibitors (e.g., C1-esterase inhibitor), and endothelial-protective strategies have demonstrated promise in reducing tissue injury and improving microcirculatory integrity. However, the translation of these findings into consistent clinical benefit remains limited.
Conclusions:
HIRI is a multifactorial process requiring integrated therapeutic approaches targeting metabolic, inflammatory, and vascular pathways. Future research should focus on identifying primary drivers of injury and optimizing targeted interventions to improve outcomes in liver transplantation.