Present and Future Therapies of Hepatitis B: From Discovery to Cure

Overview

Journal Hepatology

Specialty Gastroenterology

Date 2015 Aug 5

PMID 26239691

Citations 144

Authors

T Jake Liang

Timothy M Block

Brian J McMahon

Marc G Ghany

Stephan Urban

Ju-Tao Guo

Stephen Locarnini

Fabien Zoulim

Kyong-Mi Chang

Anna S Lok

Affiliations

Soon will be listed here.

Abstract

Unlabelled: Hepatitis B virus (HBV) is a significant global pathogen, infecting more than 240 million people worldwide. While treatment for HBV has improved, HBV patients often require lifelong therapies and cure is still a challenging goal. Recent advances in technologies and pharmaceutical sciences have heralded a new horizon of innovative therapeutic approaches that are bringing us closer to the possibility of a functional cure of chronic HBV infection. In this article, we review the current state of science in HBV therapy and highlight new and exciting therapeutic strategies spurred by recent scientific advances. Some of these therapies have already entered into clinical phase, and we will likely see more of them moving along the development pipeline.

Conclusion: With growing interest in developing and efforts to develop more effective therapies for HBV, the challenging goal of a cure may be well within reach in the near future.

Citing Articles

Host 3' flap endonuclease Mus81 plays a critical role in trimming the terminal redundancy of hepatitis B virus relaxed circular DNA during covalently closed circular DNA formation.

Zhang H, Long Q, Liu Y, Marchetti A, Liu C, Sun N PLoS Pathog. 2025; 21(2):e1012918.

PMID: 39913382 PMC: 11801639. DOI: 10.1371/journal.ppat.1012918.

The potential of HBV cure: an overview of CRISPR-mediated HBV gene disruption.

Yao Z, Schank M, Zhao J, El Gazzar M, Wang L, Zhang Y Front Genome Ed. 2024; 6:1467449.

PMID: 39444780 PMC: 11496132. DOI: 10.3389/fgeed.2024.1467449.

Exploring the tolerable region for HiBiT tag insertion in the hepatitis B virus genome.

Murayama A, Igarashi H, Yamada N, Aly H, Toyama M, Isogawa M mSphere. 2024; 9(10):e0051824.

PMID: 39345122 PMC: 11520284. DOI: 10.1128/msphere.00518-24.

mTOR Signaling: Roles in Hepatitis B Virus Infection and Hepatocellular Carcinoma.

Mei L, Sun H, Yan Y, Ji H, Su Q, Chang L Int J Biol Sci. 2024; 20(11):4178-4189.

PMID: 39247820 PMC: 11379076. DOI: 10.7150/ijbs.95894.

Cloning and Functional Characterization of Novel Human Neutralizing Anti-IFN-α and Anti-IFN-β Antibodies.

Papasavvas E, Lu L, Fair M, Oliva I, Cassel J, Majumdar S J Immunol. 2024; 213(6):808-822.

PMID: 39109927 PMC: 11575944. DOI: 10.4049/jimmunol.2400265.

References

Fontaine H, Kahi S, Chazallon C, Bourgine M, Varaut A, Buffet C . Anti-HBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a randomised trial--ANRS HB02 VAC-ADN. Gut. 2014; 64(1):139-47. DOI: 10.1136/gutjnl-2013-305707. View

Menendez-Arias L, Alvarez M, Pacheco B . Nucleoside/nucleotide analog inhibitors of hepatitis B virus polymerase: mechanism of action and resistance. Curr Opin Virol. 2014; 8:1-9. DOI: 10.1016/j.coviro.2014.04.005. View

Xu D, Fu J, Jin L, Zhang H, Zhou C, Zou Z . Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. J Immunol. 2006; 177(1):739-47. DOI: 10.4049/jimmunol.177.1.739. View

Gehring A, Haniffa M, Kennedy P, Ho Z, Boni C, Shin A . Mobilizing monocytes to cross-present circulating viral antigen in chronic infection. J Clin Invest. 2013; 123(9):3766-76. PMC: 3754243. DOI: 10.1172/JCI66043. View

Vaz F, Paulusma C, Huidekoper H, de Ru M, Lim C, Koster J . Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: conjugated hypercholanemia without a clear clinical phenotype. Hepatology. 2014; 61(1):260-7. DOI: 10.1002/hep.27240. View

Hao J, Jin W, Li X, Wang S, Zhang X, Fan H . Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α. J Virol. 2012; 87(1):137-47. PMC: 3536426. DOI: 10.1128/JVI.01710-12. View

Heermann K, Goldmann U, Schwartz W, Seyffarth T, Baumgarten H, Gerlich W . Large surface proteins of hepatitis B virus containing the pre-s sequence. J Virol. 1984; 52(2):396-402. PMC: 254539. DOI: 10.1128/JVI.52.2.396-402.1984. View

Doring B, Lutteke T, Geyer J, Petzinger E . The SLC10 carrier family: transport functions and molecular structure. Curr Top Membr. 2012; 70:105-68. DOI: 10.1016/B978-0-12-394316-3.00004-1. View

Bengsch B, Martin B, Thimme R . Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation. J Hepatol. 2014; 61(6):1212-9. DOI: 10.1016/j.jhep.2014.07.005. View

10.

Liang G, Kitamura K, Wang Z, Liu G, Chowdhury S, Fu W . RNA editing of hepatitis B virus transcripts by activation-induced cytidine deaminase. Proc Natl Acad Sci U S A. 2013; 110(6):2246-51. PMC: 3568302. DOI: 10.1073/pnas.1221921110. View

11.

Vanderlinden E, Naesens L . Emerging antiviral strategies to interfere with influenza virus entry. Med Res Rev. 2013; 34(2):301-39. PMC: 7168512. DOI: 10.1002/med.21289. View

12.

Das A, Hoare M, Davies N, Lopes A, Dunn C, Kennedy P . Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection. J Exp Med. 2008; 205(9):2111-24. PMC: 2526205. DOI: 10.1084/jem.20072076. View

13.

Baxevanis C, Voutsas I, Tsitsilonis O . Toll-like receptor agonists: current status and future perspective on their utility as adjuvants in improving anticancer vaccination strategies. Immunotherapy. 2013; 5(5):497-511. DOI: 10.2217/imt.13.24. View

14.

Lucifora J, Arzberger S, Durantel D, Belloni L, Strubin M, Levrero M . Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection. J Hepatol. 2011; 55(5):996-1003. DOI: 10.1016/j.jhep.2011.02.015. View

15.

. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2011; 55(2):245-64. DOI: 10.1016/j.jhep.2011.02.023. View

16.

Yapali S, Talaat N, Lok A . Management of hepatitis B: our practice and how it relates to the guidelines. Clin Gastroenterol Hepatol. 2013; 12(1):16-26. DOI: 10.1016/j.cgh.2013.04.036. View

17.

Schulze A, Gripon P, Urban S . Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. Hepatology. 2007; 46(6):1759-68. DOI: 10.1002/hep.21896. View

18.

Thimme R, Dandri M . Dissecting the divergent effects of interferon-alpha on immune cells: time to rethink combination therapy in chronic hepatitis B?. J Hepatol. 2012; 58(2):205-9. DOI: 10.1016/j.jhep.2012.11.007. View

19.

Yang S, Lee C, Park S, Im S, Kim Y, Son J . Correlation of antiviral T-cell responses with suppression of viral rebound in chronic hepatitis B carriers: a proof-of-concept study. Gene Ther. 2006; 13(14):1110-7. DOI: 10.1038/sj.gt.3302751. View

20.

Hirsch I, Caux C, Hasan U, Bendriss-Vermare N, Olive D . Impaired Toll-like receptor 7 and 9 signaling: from chronic viral infections to cancer. Trends Immunol. 2010; 31(10):391-7. DOI: 10.1016/j.it.2010.07.004. View