Translating Patient‑Specific Liver Organoid Multi‑Omics into Precision Diagnostics and Risk Stratification for Herb‑Induced Liver Injury: A Systematic Review

Background The use of traditional herbal medicines has spread worldwide but herb-induced liver injury (HILI) is one of the unpredictable and often under-diagnosed etiology of acute and chronic liver diseases. Traditional toxicology models cannot account for human-specific metabolic profile, inter-patient differences in vulnerability, and immune-mediated mechanisms of HILI. Latest advancements in patient specific human liver organoids with integrated multiomics profiling is a new avenue of precision toxicology. Methods A PRISMA-compliant systematic review was performed on experimental studies employing organoids(hepatobiliary, multi-lineage and induced pluripotent stem cells-derived models) integrated with transcriptomics, proteomics, metabolomics, lipid omics, spatial and single cell omics to address mechanism(s) of traditional herbal medicine-induced hepatotoxicity. Results Out of 37 selected studies, organoid omics approaches effectively reproduced clinical mechanisms of HILI such as mitochondrial dysfunction, oxidative stress and endoplasmic reticulum stress, cholestasic bile acid abnormalities, immune-mediated damage, fibrogenesis and indirect exosomes-mediated hepatotoxicity. Translation biomarker candidates, such as bile acid patterns, oxidative stress-responsive genes and extracellular vesicle-associated microRNAs, for corresponding human liver injuries and patient specific profiles, were identified via multi omics analysis. Conclusions Patient specific liver organoid multi omics approach provides a human relevant, mechanism-driven platform that links experimental toxicology with clinical hepatology. Aside from a broad discovery mechanism, it allows for early detection of diagnostically relevant markers, patient-specific risk assessment and mechanistically supported safety evaluation of herbal medicine. Organoid omics methods, through systematic standardization and clinical validation, could aid in precision diagnostics, clinical decision-making and risk evaluation for HILI.