Necroptosis in ischemia-reperfusion injury of lean and steatotic livers

Abstract Hepatic ischemia-reperfusion (IR) injury is a major complication during liver transplantation, liver resection, and other clinical situations. Increased hepatic IR injury in steatotic livers is a major reason for rejecting the use of steatotic livers for liver transplantation. Necroptosis is implicated in the pathogenesis of fatty liver diseases, including non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Necroptosis is one type of regulated cell death and is regulated by three key proteins: receptor-interacting protein 1 (RIP1), receptor-interacting protein 3 (RIP3), and mixed-lineage kinase domain-like protein (MLKL). In this review, we examine the necroptosis status in the steatotic liver diseases NAFLD and ALD as well as its role in hepatic IR injury of lean and steatotic livers.