Chronic Hepatitis B Infection: New Approaches Towards Cure

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2023 Aug 26

PMID 37627273

Authors

Mojisola Ogunnaike

Srijanee Das

Samiksha S Raut

Ashrafi Sultana

Mohammad Ullah Nayan

Murali Ganesan

Benson J Edagwa

Natalia A Osna

Larisa Y Poluektova

Affiliations

Soon will be listed here.

Abstract

Chronic hepatitis B virus (HBV) infection leads to the development of cirrhosis and hepatocellular carcinoma. Lifelong treatment with nucleotides/nucleoside antiviral agents is effective at suppressing HBV replication, however, adherence to daily therapy can be challenging. This review discusses recent advances in the development of long-acting formulations for HBV treatment and prevention, which could potentially improve adherence. Promising new compounds that target distinct steps of the virus life cycle are summarized. In addition to treatments that suppress viral replication, curative strategies are focused on the elimination of covalently closed circular DNA and the inactivation of the integrated viral DNA from infected hepatocytes. We highlight promising long-acting antivirals and genome editing strategies for the elimination or deactivation of persistent viral DNA products in development.

Citing Articles

Long-term inhibition of Hepatitis B virus gene expression by a primary microrna expressing ancestral adeno-associated viral vector.

Mnyandu N, Limani S, Ely A, Wadee R, Arbuthnot P, Maepa M Virol J. 2025; 22(1):41.

PMID: 39962472 PMC: 11834259. DOI: 10.1186/s12985-025-02662-5.

Surveillance Following Hepatitis B Surface Antigen Loss: An Issue Requiring Attention.

Huang S, Long H, Huang J Pathogens. 2025; 14(1).

PMID: 39860969 PMC: 11768139. DOI: 10.3390/pathogens14010008.

Pharmacophore modeling and QSAR analysis of anti-HBV flavonols.

Baei B, Askari P, Askari F, Kiani S, Mohebbi A PLoS One. 2025; 20(1):e0316765.

PMID: 39804828 PMC: 11730388. DOI: 10.1371/journal.pone.0316765.

Hepatitis B and D virus entry.

Watashi K, Shionoya K, Kobayashi C, Morita T Nat Rev Microbiol. 2024; .

PMID: 39572840 DOI: 10.1038/s41579-024-01121-2.

Applications of CRISPR/Cas as a Toolbox for Hepatitis B Virus Detection and Therapeutics.

Kumar A, Combe E, Mougene L, Zoulim F, Testoni B Viruses. 2024; 16(10).

PMID: 39459899 PMC: 11512240. DOI: 10.3390/v16101565.

References

Perrillo R . Benefits and risks of interferon therapy for hepatitis B. Hepatology. 2009; 49(5 Suppl):S103-11. DOI: 10.1002/hep.22956. View

Wang M, Bian Q, Zhu Y, Pang Q, Chang L, Li R . Real-world study of tenofovir disoproxil fumarate to prevent hepatitis B transmission in mothers with high viral load. Aliment Pharmacol Ther. 2018; 49(2):211-217. DOI: 10.1111/apt.15064. View

Lee M, Wu P, Chen T, Chan C, Lin H, Huang Y . Tenofovir use is associated with a decreased risk of hepatocellular carcinoma among men with HIV irrespective of coinfection status. JHEP Rep. 2023; 5(3):100634. PMC: 9852951. DOI: 10.1016/j.jhepr.2022.100634. View

Yang Y, Chen Y, Kao J, Ching C, Liu I, Wang C . Permanent Inactivation of HBV Genomes by CRISPR/Cas9-Mediated Non-cleavage Base Editing. Mol Ther Nucleic Acids. 2020; 20:480-490. PMC: 7150432. DOI: 10.1016/j.omtn.2020.03.005. View

Pickar-Oliver A, Gersbach C . The next generation of CRISPR-Cas technologies and applications. Nat Rev Mol Cell Biol. 2019; 20(8):490-507. PMC: 7079207. DOI: 10.1038/s41580-019-0131-5. View

Mizushima D, Takano M, Aoki T, Ando N, Uemura H, Yanagawa Y . Effect of tenofovir-based HIV pre-exposure prophylaxis against HBV infection in men who have sex with men. Hepatology. 2023; 77(6):2084-2092. PMC: 10187616. DOI: 10.1097/HEP.0000000000000384. View

Kim H, Kim J . A guide to genome engineering with programmable nucleases. Nat Rev Genet. 2014; 15(5):321-34. DOI: 10.1038/nrg3686. View

Tang K, Cheng H, Wang H, Guo Y . Meta-analysis of the occurrence of hepatocellular carcinoma after the treatment of entecavir and tenofovir for chronic hepatitis B. Medicine (Baltimore). 2023; 102(6):e32894. PMC: 9907921. DOI: 10.1097/MD.0000000000032894. View

Ricco G, Coco B, Colombatto P, Oliveri F, Cavallone D, Bleve P . Highly dynamic changes of regional HBV epidemiology over two decades. Dig Liver Dis. 2022; 55(4):519-526. DOI: 10.1016/j.dld.2022.11.003. View

10.

Mao Q, Liang H, Yin Y, Tang J, Yang J, Wu C . Comparison of Interferon-α-based therapy and nucleos(t)ide analogs in preventing adverse outcomes in patients with chronic hepatitis B. Clin Res Hepatol Gastroenterol. 2021; 46(1):101758. DOI: 10.1016/j.clinre.2021.101758. View

11.

Blank A, Markert C, Hohmann N, Carls A, Mikus G, Lehr T . First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol. 2016; 65(3):483-9. DOI: 10.1016/j.jhep.2016.04.013. View

12.

Higashi-Kuwata N, Hayashi S, Kumamoto H, Ogata-Aoki H, Das D, Venzon D . Identification of a novel long-acting 4'-modified nucleoside reverse transcriptase inhibitor against HBV. J Hepatol. 2020; 74(5):1075-1086. PMC: 9703152. DOI: 10.1016/j.jhep.2020.12.006. View

13.

Tang A, Hallouch O, Chernyak V, Kamaya A, Sirlin C . Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis. Abdom Radiol (NY). 2017; 43(1):13-25. DOI: 10.1007/s00261-017-1209-1. View

14.

Yuen M, Seto W, Chow D, Tsui K, Wong D, Ngai V . Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease. Antivir Ther. 2008; 12(8):1295-303. View

15.

Rathbone T, Ates I, Fernando L, Addlestone E, Lee C, Richards V . Electroporation-Mediated Delivery of Cas9 Ribonucleoproteins Results in High Levels of Gene Editing in Primary Hepatocytes. CRISPR J. 2022; 5(3):397-409. PMC: 9233506. DOI: 10.1089/crispr.2021.0134. View

16.

Zeng Q, Yu Z, Ji F, Li G, Zhang G, Xu J . Tenofovir Alafenamide to Prevent Perinatal Hepatitis B Transmission: A Multicenter, Prospective, Observational Study. Clin Infect Dis. 2021; 73(9):e3324-e3332. DOI: 10.1093/cid/ciaa1939. View

17.

Shi H, Xiao G, Liao M, Zheng L, Jie Y, Lin G . Inappropriate cessation of nucleos(t)ide analog associated with reduced liver transplant-free survival in patients with HBV-related acute on chronic liver failure. Biomed Pharmacother. 2020; 134:111118. DOI: 10.1016/j.biopha.2020.111118. View

18.

Ho M, Lee D, Im S, Yoon J, Shin C, Kim H . Design and in vivo evaluation of entecavir-3-palmitate microcrystals for subcutaneous sustained delivery. Eur J Pharm Biopharm. 2018; 130:143-151. DOI: 10.1016/j.ejpb.2018.06.024. View

19.

Freeling J, Koehn J, Shu C, Sun J, Ho R . Anti-HIV drug-combination nanoparticles enhance plasma drug exposure duration as well as triple-drug combination levels in cells within lymph nodes and blood in primates. AIDS Res Hum Retroviruses. 2014; 31(1):107-14. PMC: 4287118. DOI: 10.1089/aid.2014.0210. View

20.

Cobb D, Smith N, Deodhar S, Bade A, Gautam N, Shetty B . Transformation of tenofovir into stable ProTide nanocrystals with long-acting pharmacokinetic profiles. Nat Commun. 2021; 12(1):5458. PMC: 8445934. DOI: 10.1038/s41467-021-25690-5. View