Organoids as preclinical platforms for metabolic dysfunction-associated steatotic liver disease: Model construction, mechanistic dissection, and therapeutic translation

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global public health challenge, necessitating reliable in vitro models to unravel its complex pathophysiology and accelerate therapeutic development.Organoid systems have revolutionized MASLD research by recapitulating key hepatic structural features, cellular heterogeneity, and pathological processes.This review systematically summarizes liver organoids derived from human pluripotent stem cells, primary tissues, and immortalized cell lines in MASLD research, highlighting their distinct advantages in modeling MASLD pathogenesis, elucidating mechanisms, screening biomarkers, and validating therapeutics.In addition, we elaborate on the progress gained from multitissue organoid systems in deciphering inter-organ crosstalk and systemic metabolic perturbations associated with MASLD.We further discuss the inherent limitations of current organoid models and propose future directions for their development.Collectively, this review highlights the indispensable role of organoid models in unraveling the complex molecular mechanisms of MASLD, in advancing drug discovery, and in identifying diagnostic biomarkers, while also providing insights to accelerate their clinical translation toward precision medicine for MASLD.