Highlight
• Butyrylcholinesterase (BuChE) expression and activity are markedly reduced in fibrotic liver disease, correlating with fibrosis severity.
• Hepatocyte-derived BuChE enzymatic activity limits hepatic stellate cell (HSC) activation by metabolizing acetylcholine (ACh), preventing paracrine cholinergic signaling.
• Loss of BuChE leads to ACh accumulation, triggering HSC activation through muscarinic receptor M3 (ChRM3)-NF-κB signaling and promoting fibrogenesis.
• Targeting BuChE-ACh-ChRM3 axis presents a promising therapeutic strategy to modulate fibrosis progression in chronic liver diseases.
