The emerging role of neutrophil extracellular traps in liver diseases: a narrative review.

Neutrophil extracellular traps (NETs) are web-like chromatin structures released by neutrophils that play dual roles in host defense and tissue injury. In liver diseases, NETs have emerged as key pathogenic mediators. This narrative review synthesizes current evidence on the involvement of NETs in alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), viral hepatitis, hepatic ischemia-reperfusion injury (HIRI), hepatocellular carcinoma (HCC), and intrahepatic cholangiocarcinoma (iCCA). Mechanistically, NETs amplify sterile inflammation, promote hepatocyte death, activate hepatic stellate cells to drive fibrosis. NETs also promote malignant transformation, sustain an aggressive phenotype, attenuate immunotherapy responses, mediate resistance to targeted therapies, and contribute to poor prognosis in primary liver cancers. Preclinical studies targeting NET formation or degrading existing NETs have shown therapeutic benefits across these liver diseases. Despite promising results, clinical translation remains limited, with challenges including a lack of standardized biomarkers, optimal timing of intervention, and the need for liver-specific delivery. This review highlights NETs as a druggable target in liver diseases, and underscores future directions toward biomarker development and targeted therapies.