Hepatic organoids as a platform for liver disease modeling and the development of novel therapies

• Liver diseases are a significant global health burden, yet traditional 2D cultures and animal models poorly replicate human liver physiology. Hepatic organoids offer a more accurate, human-relevant model for studying liver function, disease, and treatment development. • Hepatic organoids successfully mimic key liver functions and disease phenotypes, enabling accurate modeling of monogenic and complex liver disorders, drug screening, and regenerative therapy applications. Limitations remain in vascularization, immune integration, and standardization. • Organoids could revolutionize liver disease diagnosis and treatment by supporting personalized drug testing, regenerative therapy development, and improved predictions of patient-specific responses, advancing the precision hepatology field. Liver diseases pose a major global health burden, and progress in understanding liver pathophysiology and therapeutic development is hampered by the lack of predictive human models. Hepatic organoids ( i.e 3D in vitro structures derived from primary, progenitor, or pluripotent stem cells) offer a physiologically relevant alternative to traditional 2D cultures and animal models. This review provides a comprehensive overview of hepatic organoid systems and their translational potential. We reviewed recent advances in the generation, culture, and characterization of hepatic organoids. The discussion covers the diversity of cell sources, 3D matrix-based and microfluidic culture platforms, and analytical approaches used to assess organoid structure, function, and heterogeneity. Applications in disease modeling, drug development, and regenerative therapies were also examined. Hepatic organoids recapitulate key liver-specific functions, including albumin secretion, CYP450 activity, and bile canaliculi formation. They have been used to model monogenic and complex liver diseases (e.g., MAFLD, viral hepatitis, cancer) and to predict patient-specific drug responses. Integration into organ-on-chip systems enhances maturation and functional fidelity. Transplantation studies in bile duct ligation and hepatotoxic injury models demonstrated functional engraftment and regeneration. Limitations persist, notably in vascularization, immune integration, and standardization, but emerging solutions such as 3D bioprinting, defined matrices, co-culture strategies, and complementary approaches like bioartificial liver (BAL) systems, are advancing organoids toward clinical applicability. Hepatic organoids are transformative platforms in hepatology, bridging experimental modeling and personalized medicine. Their continued development promises to redefine liver disease research, precision pharmacology, and regenerative therapies.