Liver Fibrosis: Molecular Pathogenesis and Therapeutic Interventions

Liver fibrosis is a common pathological process, leading to the development of end-stage liver diseases. It is triggered by various etiological drivers including viral hepatitis, metabolic-associated steatotic liver disease (MASLD), and cholestasis. Given the substantial impact of liver fibrosis on individuals and its associated mortality rates, effective management of this condition is crucial for improving public health. Despite a growing number of preclinical studies and clinical trials, a systematic synthesis remains lacking. In this review, the molecular panorama of liver fibrogenesis is summarized at first, encompassing etiological drivers of chronic liver injury, key cellular players, core signaling pathways, and extracellular matrix dynamics. Therapeutic interventions in preclinical or clinical stages are systematically classified into two main categories: etiological treatment as the foundational approach and mechanism-based antifibrotic therapies. Emerging and future therapeutic strategies, including those targeting gut-liver axis, gut microbiota, and cell-based therapies, are also addressed along with inherent challenges. Furthermore, future perspectives centered on precision medicine, combination therapies, novel target discovery, and advanced drug delivery systems are emphasized. This review offers a comprehensive overview of the etiologies, diagnostic approaches, pathogenic mechanisms, current development of antifibrotic agents, and prospects for future therapeutic directions of liver fibrosis.