Abstract

Hepatic stellate cells (HSCs) are pivotal in the development of liver fibrosis, a serious condition characterized by excessive extracellular matrix (ECM) accumulation and compromised liver function. In a healthy liver, HSCs remain dormant, effectively storing vitamin A and ensuring ECM stability. However, when faced with injuries from viral hepatitis, alcohol abuse, or non-alcoholic steatohepatitis (NASH), these cells activate, transforming into proliferative, ECM-producing myofibroblasts. This review provides a comprehensive synthesis of HSC biology and their transition from a quiescent to an activated state. We delve into the key signaling pathways (e.g., TGF-β, PDGF, Wnt/β-catenin) and cellular interactions that drive HSC activation, with a special emphasis on emerging themes such as metabolic reprogramming and epigenetic control. Furthermore, we critically evaluate the landscape of antifibrotic therapies targeting HSCs, from pathway inhibitors and epigenetic drugs to RNA-based strategies, discussing their translational potential and challenges. By integrating foundational knowledge with recent advances—including insights from single-cell technologies revealing HSC heterogeneity—this review aims to offer a timely and critical perspective on the pathobiology of HSCs and the evolving strategies to combat liver fibrosis.

Key words: Hepatic stellate cells, Extracellular matrix, Liver fibrosis, Fibrosis therapeutics