Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

New potent HBV replication inhibitors for the management of chronic hepatitis B are needed

Nature Reviews Gastroenterology & Hepatology volume 22, pages 150–151 (2025)Cite this article

Subjects

With several drugs in use that inhibit the hepatitis B virus polymerases (nucleos(t)ide analogues (or NUCs)), some argue that new direct-acting antiviral drugs, and new NUCs in particular, are not necessary. Here, we make the counter-argument that additional direct-acting antiviral drugs that can potently suppress hepatitis B virus replication, ideally via distinct mechanisms, are still needed and can provide additional therapeutic benefits.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Clinical phase investigational HBV drugs and drug programmes that have been discontinued since 2017.

References

  1. Block, T. M., Chang, K.-M. & Guo, J.-T. Prospects for the global elimination of hepatitis B. Annu. Rev. Virol. 8, 437–458 (2021).

    Article  CAS  PubMed  Google Scholar 

  2. Desai, A., Sandhu, S., Lai, J.-P. & Sandhu, D. S. Hepatocellular carcinoma in non-cirrhotic liver: a comprehensive review. World J. Hepatol. 11, 1–18 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Terrault, N. A. et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 67, 1560–1599 (2018).

    Article  PubMed  Google Scholar 

  4. Choi, H. S., Tonthat, A., Janssen, H. L. A. & Terrault, N. A. Aiming for functional cure with established and novel therapies for chronic hepatitis B. Hepatol. Commun. 6, 935–949 (2022).

    Article  PubMed  Google Scholar 

  5. Ibrahim, Y., Umstead, M., Wang, S. & Cohen, C. The impact of living with chronic hepatitis B on quality of life: implications for clinical management. J. Patient Exp. 10, 23743735231211069 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Choi, W.-M. et al. Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: a multinational cohort study of HBeAg-positive patients. Hepatology 80, 428–439 (2024).

    Article  PubMed  Google Scholar 

  7. Tseng, T.-C. & Kao, J.-H. Treating immune-tolerant hepatitis B. J. Viral Hepat. 22, 77–84 (2015).

    Article  CAS  PubMed  Google Scholar 

  8. Brahmania, M. et al. Prevalence and risk factors for viral blipping in chronic hepatitis B patients treated with nucleos (t) ide analogues. J. Viral Hepat. 23, 1003–1008 (2016).

    Article  CAS  PubMed  Google Scholar 

  9. Burdette, D. L. et al. Ongoing viral replication and production of infectious virus in patients with chronic hepatitis B virus suppressed below the limit of quantitation on long-term nucleos(t)ide therapy. PLoS ONE 17, e0262516 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zoulim, F., Chen, P.-J., Dandri, M., Kennedy, P. T. & Seeger, C. Hepatitis B virus DNA integration: implications for diagnostics, therapy, and outcome. J. Hepatol. 81, 2087–1099 (2024).

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank J. Marchand for help in manuscript preparation. The authors also thank X. Hong and C. Freije for helpful feedback.

Author information

Authors and Affiliations

  1. Baruch S. Blumberg Institute, Doylestown, PA, USA

    Timothy M. Block & Ju-Tao Guo

  2. Viral Hepatitis Research Laboratory of INSERM Unit 1052, Hepatology Department, Hospices Civils de Lyon, University of Lyon, Lyon, France

    Fabien Zoulim

  3. Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA

    Charles M. Rice & William M. Schneider

  4. Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Chloe L. Thio & Mark Sulkowski

  5. Department of Transfusion Medicine Clinical Center, The National Institutes of Health Bethesda, Bethesda, MD, USA

    Harvey J. Alter

  6. Department of Medicine, NYU Langone Health, New York, NY, USA

    Ira M. Jacobson

  7. Hepatitis B Foundation, Doylestown, PA, USA

    Robert G. Gish & Chari A. Cohen

  8. Division of Gastroenterology and Hepatology, New York University Langone Hospital, New York, NY, USA

    Peter D. Block

  9. Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada

    Jordan J. Feld

Authors
  1. Timothy M. Block
    View author publications

    Search author on:PubMed Google Scholar

  2. Ju-Tao Guo
    View author publications

    Search author on:PubMed Google Scholar

  3. Fabien Zoulim
    View author publications

    Search author on:PubMed Google Scholar

  4. Charles M. Rice
    View author publications

    Search author on:PubMed Google Scholar

  5. Chloe L. Thio
    View author publications

    Search author on:PubMed Google Scholar

  6. William M. Schneider
    View author publications

    Search author on:PubMed Google Scholar

  7. Harvey J. Alter
    View author publications

    Search author on:PubMed Google Scholar

  8. Ira M. Jacobson
    View author publications

    Search author on:PubMed Google Scholar

  9. Robert G. Gish
    View author publications

    Search author on:PubMed Google Scholar

  10. Peter D. Block
    View author publications

    Search author on:PubMed Google Scholar

  11. Mark Sulkowski
    View author publications

    Search author on:PubMed Google Scholar

  12. Jordan J. Feld
    View author publications

    Search author on:PubMed Google Scholar

  13. Chari A. Cohen
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Timothy M. Block.

Ethics declarations

Competing interests

T.M.B. is co-founder and Chair of the Hepatitis B Foundation and is on the board of Hepion, Harlingene Life Sciences, Cirna Diagnostics and SAB: Excision. C.A.C. is President of the Hepatitis B Foundation, which has received grants from Gilead Sciences, GSK, Roche, Dynavax and Moderna, all outside of the submitted work. J.J.F. declares competing interests with Abbott, Abbvie, Bluejay, Gilead, GSK, Pfizer, Roche and Vir. R.G.G. is the Medical Director at the Hepatitis B Foundation, and has consulted for or received honoraria from Abacus, Aligos, Altimunne, Antios, Dynavax, Enyo, Gilead Sciences, GlaxoSmithKline, Janssen, Precision BioSciences, Tune Therapeutics, Venatorx and Virion. J.-T.G. is co-founder of RimmSting Life Sciences, is a member of the scientific advisory board for GeneLancet Biosciences, and is a scientific consultant for Brii BioSciences, Argo Pharmaceuticals and ARV Technologies. I.M.J. has acted as a consultant or advisor for Aligos Therapeutics, Altimmune, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Biomarin Pharmaceuticals, Bristol Myers Squibb, Gilead Sciences, GSK, Intercept Pharmaceuticals, Janssen Pharmaceuticals, Madrigal Pharmaceuticals, Merck, Moderna, NeuroBo Pharmaceuticals, Novo Nordisk, Precision Biosciences and RedHill Biopharma, and has received grants or research support from Astrazeneca, Assembly Biosciences, AusperBio, Bristol Myers Squibb, Cymabay Therapeutics, Eiger Biopharmaceuticals, Eli Lilly, Enanta Pharmaceuticals, Genfit, Genkyotex, Gilead, GSK, Inventiva, Intercept Pharmaceuticals, Ipsen, Janssen Pharmaceuticals, Madrigal, Merck, Mirum Pharmaceuticals, Novo Nordisk and the Rockefeller Institute (NIH supported). M.S. has received grants from Grifols, GSK, Vir and the National Institutes of Health, and has received personal fees from AbbVie, Aligos, Immunocore, Gilead Sciences, GSK, Pfizer, Virion and Vir. F.Z. consults for Aligos, Antios, Arbutus, Assembly, Enanta, Enochian, Gilead, GSK, Roche, Viravaxx and Zhimeng, and has received research grants from Assembly, Beam, Janssen and Viravaxx. H.J.A., P.D.B., C.M.R., W.M.S. and C.LT. declare no competing interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Block, T.M., Guo, JT., Zoulim, F. et al. New potent HBV replication inhibitors for the management of chronic hepatitis B are needed. Nat Rev Gastroenterol Hepatol 22, 150–151 (2025). https://doi.org/10.1038/s41575-025-01037-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41575-025-01037-z

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing