Pharmacological strategies targeting hepatocyte-mediated crosstalk in liver fibrosis.

Liver fibrosis is a common pathological outcome of chronic liver injury. Many therapeutic agents show limited clinical efficacy or significant adverse effects due to the complex pathogenesis of liver fibrosis. This challenge underscores the urgent need to identify potential therapeutic targets and improve existing therapies. Hepatocytes serve as pivotal initiators of liver fibrosis that actively engage in signaling crosstalk with other hepatic cell types to promote fibrogenesis. Advances in understanding hepatocyte-centered signaling crosstalk have enabled the identification of potential therapeutic targets. Furthermore, combination therapies that regulate multiple pathways and drug modifications that improve pharmacological properties may help to minimize adverse effects and enhance the efficacy of existing treatments. This review highlights recent advances in hepatocyte-focused mechanisms underlying liver fibrosis and their translational potential. It provides a timely and comprehensive overview of current antifibrotic strategies.