MOLECULAR SIGNALING NETWORKS AND PHARMACOLOGICAL MODULATION IN LIVER CIRRHOSIS: FROM FIBROGENIC MECHANISMS TO THERAPEUTIC TARGETING

Liver cirrhosis represents the advanced pathological stage of chronic liver diseases and is characterized by progressive fibrosis, architectural distortion, and irreversible functional impairment. Contemporary research has demonstrated that cirrhosis is driven by highly coordinated molecular signaling pathways regulating hepatic stellate cell activation, inflammatory cascades, immune dysregulation, and extracellular matrix accumulation. Key pathways such as transforming growth factor-β (TGF-β)/Smad, platelet-derived growth factor (PDGF), Wnt/β-catenin, nuclear factor-κB (NF-κB), phosphoinositide-3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), and inflammasome signaling collectively orchestrate fibrogenesis and disease progression. Pharmacological interventions targeting these pathways, including kinase inhibitors, antifibrotic agents, immunomodulators, and regenerative therapies, have shown encouraging preclinical and early clinical outcomes. This review critically examines the molecular basis of cirrhosis-related signaling pathways and evaluates current and emerging pharmacological strategies, highlighting translational challenges and future therapeutic directions.