Hepatic stellate cells in liver fibrosis: From biology to pathology

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. HSCs remain dormant in a healthy liver, effectively storing vitamin A and ensuring ECM stability. However, when faced with injuries from viral hepatitis, alcohol abuse, or nonalcoholic steatohepatitis, these cells are activated and transform into proliferative, ECM-producing myofibroblasts. This review provides a comprehensive overview of the biology of HSCs and their transition from a quiescent to an activated state. The key signaling pathways (e.g., transforming growth factor-beta, platelet-derived growth factor, Wnt/β-catenin) and cellular interactions that drive hepatocyte stem cell (HSC) activation are examined, with a special emphasis on emerging themes such as metabolic reprogramming and epigenetic control. Furthermore, the landscape of antifibrotic therapies targeting HSCs, from pathway inhibitors and epigenetic drugs to ribonucleic acid based strategies, is critically evaluated, and their translational potential and challenges are discussed. 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.