ArticleeLife2021
Application of human liver organoids as a patient-derived primary model for HBV infection and related hepatocellular carcinoma.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
90 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Liver organoids: From fabrication to application in liver diseases.Frontiers in physiology · 2022Pooled it
- Cell-based platforms for antiviral screening against hepatitis B virus: advantages, limitations, and future perspectives.Antiviral research · 2026Review
- Planar neural organoids as an advanced in vitro model to study patient-derived melanoma metastasis.Scientific reports · 2026Article
- Human 3D liver spheroids support productive infection of a novel tick-borne phenuivirus.One health (Amsterdam, Netherlands) · 2026Article
- Organoids: From Bench to Bedside Applications.MedComm · 2026Review
- The evolution of in vitro culture systems for the study of hepatitis E virus infection.Virology · 2026Review
- Exposure to fibrillar proteins leads to widespread infiltration but only mild tau pathology in cortical organoids.iScience · 2026Article
- [Advances in the construction and application of a novel liver organoid model for hepatitis B virus infection].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Organoids Gone Viral: A Comprehensive Review on Human Organoid Models to Study Viral Pathogenesis.Viruses · 2026Review
- Patient-derived organoids predict responses to chemotherapy and PARP inhibitors in advanced ovarian cancer.Journal of translational medicine · 2026Article
- Advances in liver and pancreas organoids: how far we have come and where we go next.Nature reviews. Gastroenterology & hepatology · 2026Review
- Human organoids and organ-on-chip systems for AI-guided therapeutic discovery against emerging and re-emerging infections.Frontiers in pharmacology · 2026Review
- Review
- Experimental models of liver-stage malaria: Progress, gaps, and challenges.PLoS pathogens · 2025Review
- Organoid Models to Study Human Infectious Diseases.Cell proliferation · 2025Review
- Organoids: physiologically relevantJournal of virology · 2025Review
- Article
- Review
- Review
- Unraveling the advances of non-coding RNAs on the tumor microenvironment: innovative strategies for cancer therapies.Journal of translational medicine · 2025Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular events that drive hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system. Here we propose the use of human liver organoids as a platform for modeling HBV infection and related tumorigenesis. We first describe a primary ex vivo HBV-infection model derived from healthy donor liver organoids after challenge with recombinant virus or HBV-infected patient serum. HBV-infected organoids produced covalently closed circular DNA (cccDNA) and HBV early antigen (HBeAg), expressed intracellular HBV RNA and proteins, and produced infectious HBV. This ex vivo HBV-infected primary differentiated hepatocyte organoid platform was amenable to drug screening for both anti-HBV activity and drug-induced toxicity. We also studied HBV replication in transgenically modified organoids; liver organoids exogenously overexpressing the HBV receptor sodium taurocholate co-transporting polypeptide (NTCP) after lentiviral transduction were not more susceptible to HBV, suggesting the necessity for additional host factors for efficient infection. We also generated transgenic organoids harboring integrated HBV, representing a long-term culture system also suitable for viral production and the study of HBV transcription. Finally, we generated HBV-infected patient-derived liver organoids from non-tumor cirrhotic tissue of explants from liver transplant patients. Interestingly, transcriptomic analysis of patient-derived liver organoids indicated the presence of an aberrant early cancer gene signature, which clustered with the hepatocellular carcinoma (HCC) cohort on The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset and away from healthy liver tissue, and may provide invaluable novel biomarkers for the development of HCC and surveillance in HBV-infected patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.