Hepatic fibrosis pathway

The hepatic fibrosis pathway is a complex series of molecular and cellular events culminating in the excessive deposition of extracellular matrix proteins, notably fibrillar collagen, in response to chronic liver injury due to various causes (viral hepatitis, NASH, ASH, autoimmune, drug-induced liver injury)[1][5][8]. Key molecular drivers include the activation of hepatic stellate cells (HSCs), mediated by the TGF-β pathway and augmented by receptor tyrosine kinases (e.g., PDGF), various cytokines, and epigenetic modifications[7][3][4][9]. Downstream, activated HSCs differentiate into myofibroblasts, which secrete collagen, fibronectin, and ECM molecules that disrupt liver architecture leading to progressive loss of function and, eventually, cirrhosis[5][4]. Drug targeting is focused on blocking pathways (e.g. TGF-β/SMAD, inflammatory signals, ECM synthesis) or directly suppressing HSC activation. While some anti-fibrotic therapies exist, efficacy is limited especially in advanced fibrosis, and safety concerns include immunosuppression and GI side effects[2][6].

Other names

Liver fibrosis pathwayFibrogenic signaling in the liverFibrosis signaling cascades

TGF-β pathway inhibition; Antifibrotic effects via ECM/collagen synthesis inhibition; Suppression of hepatic stellate cell activation; Inhibition of PDGF signaling; Epigenetic modulation (e.g., DNA methyltransferase inhibition); Suppression of inflammatory signals and immune cell activation