A narrative review of the role of necroptosis in liver disease: a double-edged sword

Acute and chronic liver injuries lead to hepatocyte death and turnover. When injuries become chronic, continuous cell death and transformation lead to chronic inflammation, fibrosis, cirrhosis, and eventually carcinoma. A therapeutic strategy of great significance for liver disease is to control hepatocyte death in acute and chronic injuries. This strategy prevents hepatocytes from causing liver failure and inhibits both secondary inflammation and fibrosis. Both apoptosis and necrosis have been proven to occur in the liver, but the role of necroptosis in liver diseases is controversial. Necroptosis, which has features of necrosis and apoptosis, is a regulatory process that occurs in some cell types when caspases are inhibited. The signaling pathway of necroptosis is characterized by the activation of receptor-interacting proteins kinase (RIPK) and mixed lineage kinase domain-like (MLKL). Necroptosis is associated with a variety of inflammatory diseases and has been the focus of research in recent years. The incidence of necroptosis in liver tissues has been studied recently in several liver injury models, but the results of the studies are not consistent. The purpose of this review is to summarize the published data on the involvement of necroptosis in liver injury, focusing on the controversies, issues remaining to be discussed, and potential therapeutic applications in this area.