Neutrophil extracellular traps in liver diseases: from molecular mechanisms to therapeutic interventions

Liver diseases are hepatic pathological changes caused by a variety of pathogenic factors, including viral hepatitis, alcoholic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, and hepatocellular carcinoma (HCC), etc. The characteristics of liver diseases are steatosis, hepatocyte ballooning, and immune cell infiltration. Among these immune cells, neutrophils are important immune cells in innate immunity. Under hepatic pathological conditions, neutrophils can produce neutrophil extracellular traps (NETs) under the stimulation of various factors, such as viral infections, metabolic disorders, toxic exposures, etc. Accumulating evidence has shown that NETs can interact with multiple signaling pathways and immune cells, regulate hepatic inflammatory responses, remodel the hepatic immune microenvironment, and promote the activation of hepatic stellate cells (HSCs). This review expounds the mechanism of NETs in various liver diseases, and the compounds or drugs that have been discovered or applied for the treatment of liver diseases by targeting NETs. This review enriches the pathogenesis of liver diseases and provides a theoretical basis and research directions for targeted therapeutic strategies.