Organoid models in viral hepatitis, primary liver cancer, and non-alcoholic fatty liver disease: Advances and challenges.

BACKGROUND

Organoids are advanced to mimic the structural and functional features of native organs. Advances in stem cell research and extracellular matrix technology have enabled the generation of organoids for diverse organs. Liver organoids hold significant relevance due to the liver's critical physiological roles and the high morbidity associated with liver diseases. Organoids offer potential for studying disease mechanisms and therapeutic interventions.

DATA SOURCES: A literature search was conducted in PubMed and Web of Science for relevant articles published up to December 2024. The keywords used for the search included liver organoid, viral hepatitis, primary liver cancer and non-alcoholic fatty liver disease.

RESULTS

Liver organoids have been successfully utilized to model a spectrum of liver diseases, such as viral hepatitis, primary liver cancer, non-alcoholic fatty liver disease, and other hepatic pathologies. By using liver organoids to simulate the pathological environments of different liver diseases, researchers have discovered that molecular (e.g., miR-122) and signaling pathways (e.g., mTOR signaling pathway) are related to liver diseases. Moreover, novel drugs (e.g., regorafenib) have been identified for the treatment of these liver diseases. Their application has significantly enhanced preclinical research by providing a more physiologically relevant platform compared to traditional models.

CONCLUSIONS

Liver organoids represent a transformative tool in hepatology, offering a physiologically relevant platform for disease modeling, drug screening, and regenerative applications. While promising, liver organoids remain limited in replicating native liver complexity. Future efforts should enhance structural maturity, multicellular interactions, and microenvironment integration.