Interferon in Liver Diseases: Recent Advances.

Abstract

Interferons (IFNs) are a pivotal class of cytokines with multifaceted roles in antiviral defense, immune regulation, and antitumor activity. Structural and functional distinctions among IFN types (I, II, and III) underlie their diverse biological effects. IFN production is initiated by pattern recognition receptor signaling, containing Toll-like receptors, RIG-I-like receptors, and the cGAS-STING axis, which activates downstream pathways, such as JAK-STAT, PI3K-AKT, NF-κB, and MAPK signaling pathways. These pathways critically influence the pathogenesis, progression, therapeutic management, and prognosis of liver diseases. This review delineates the mechanistic roles of IFN-associated signaling in viral hepatitis, non-alcoholic fatty liver disease, alcohol-associated liver disease, liver fibrosis, and hepatocellular carcinoma. We further elucidate IFN-mediated regulatory networks in viral defense, metabolic dysregulation, immune responses, and inflammatory activation. By integrating these insights, the review provides a novel therapeutic direction to unravel context-specific IFN dynamics and address unmet needs in the management of liver diseases, thereby fostering personalized approaches to improve clinical outcomes.