The Role of Ischemia/Reperfusion Injury in Early Hepatic Allograft Dysfunction

Liver transplantation (LT) is the only available curative treatment for patients with end-stage liver disease. Early allograft dysfunction (EAD) is a life-threatening complication of LT and is thought to be mediated in large part through ischemia/reperfusion injury (IRI). However, the underlying mechanisms linking IRI and EAD after LT are poorly understood. Most previous studies focused on the clinical features of EAD, but basic research on the underlying mechanisms is insufficient, due, in part, to a lack of suitable animal models of EAD. There is still no consensus on definition of EAD, which hampers comparative analysis of data from different LT centers. IRI is considered as an important risk factor of EAD, which can induce both damage and adaptive responses in liver grafts. IRI and EAD are closely linked and share several common pathways. However, the underlying mechanisms remain largely unclear. Therapeutic interventions against EAD through the amelioration of IRI is a promising strategy, but most approaches are still in preclinical stages. To further study the mechanisms of EAD and promote collaborations between LT centers, optimized animal models and unified definitions of EAD are urgently needed. Because IRI and EAD are closely linked, more attention should be paid to the underlying mechanisms and the fundamental relationship between them. Ischemia/reperfusion-induced adaptive responses may play a crucial role in the prevention of EAD, and more preclinical studies and clinical trials are urgently needed to address the current limitation of available therapeutic interventions.