{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:56:14Z","timestamp":1792461374519,"version":"4.5.0"},"reference-count":80,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Chronic hepatitis B virus (HBV) infection remains a major global health burden, affecting millions and contributing significantly to liver-related morbidity and mortality. While substantial progress has been made in elucidating the virology and natural history of HBV, the management of chronic hepatitis B (CHB) continues to present clinical challenges. The development of potent nucleos(t)ide analogs and pegylated interferon has improved viral suppression and delayed disease progression, yet a definitive cure remains elusive due to the persistence of covalently closed circular DNA (cccDNA). Recent research has focused on novel antiviral agents, immunomodulatory therapies, and combination strategies aimed at achieving a functional cure. This review summarizes current therapeutic approaches, recent advancements, and emerging directions in CHB management.<\/jats:p>","DOI":"10.3390\/diseases13100311","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:09:42Z","timestamp":1758614982000},"page":"311","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Chronic Hepatitis B: Current Management and Future Directions"],"prefix":"10.3390","volume":"13","author":[{"given":"Hamza","family":"Ertugrul","sequence":"first","affiliation":[{"name":"Trinity Health of New England, St. Mary\u2019s Hospital, 56 Franklin Street, Waterbury, CT 06706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Ekiz","sequence":"additional","affiliation":[{"name":"Trinity Health of New England, St. Mary\u2019s Hospital, 56 Franklin Street, Waterbury, CT 06706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2392-0910","authenticated-orcid":false,"given":"Sibel","family":"Islak Mutcali","sequence":"additional","affiliation":[{"name":"Vandalia Health, Charleston Area Medical Center (CAMC), 3100 MacCorkle Ave. SE, Charleston, WV 25304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6796-9359","authenticated-orcid":false,"given":"Veysel","family":"Tahan","sequence":"additional","affiliation":[{"name":"Vandalia Health, Charleston Area Medical Center (CAMC), 3100 MacCorkle Ave. SE, Charleston, WV 25304, USA"},{"name":"Department of Internal Medicine, Division of Gastroenterology, Northeastern Ohio Medical University (NEOMED), 4209 OH-44, Rootstown, OH 44272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-1704","authenticated-orcid":false,"given":"Ebubekir","family":"Daglilar","sequence":"additional","affiliation":[{"name":"Vandalia Health, Charleston Area Medical Center (CAMC), 3100 MacCorkle Ave. SE, Charleston, WV 25304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s40264-024-01399-4","article-title":"Consensus Guidelines: Best Practices for the Prevention, Detection and Management of Hepatitis B Virus Reactivation in Clinical Trials with Immunosuppressive\/Immunomodulatory Therapy","volume":"47","author":"Cohen","year":"2024","journal-title":"Drug Saf."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Boonstra, A., and Sari, G. (2025). HBV cccDNA: The Molecular Reservoir of Hepatitis B Persistence and Challenges to Achieve Viral Eradication. Biomolecules, 15.","DOI":"10.3390\/biom15010062"},{"key":"ref_3","unstructured":"World Health Organization (2024). Guidelines for the Prevention, Care and the Treatment of Persons with Chronic Hepatitis B Infection."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mendenhall, M.A., Hong, X., and Hu, J. (2023). Hepatitis B Virus Capsid: The Core in Productive Entry and Covalently Closed Circular DNA Formation. Viruses, 15.","DOI":"10.3390\/v15030642"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"199507","DOI":"10.1016\/j.virusres.2024.199507","article-title":"Achieving Chronic Hepatitis B Functional Cure: Factors and Potential Mechanisms","volume":"351","author":"Zheng","year":"2025","journal-title":"Virus Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1097\/HEP.0000000000000431","article-title":"Guidance on Treatment Endpoints and Study Design for Clinical Trials Aiming to Achieve Cure in Chronic Hepatitis B and D: Report from the 2022 AASLD-EASL HBV-HDV Treatment Endpoints Conference","volume":"78","author":"Ghany","year":"2023","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"a021436","DOI":"10.1101\/cshperspect.a021436","article-title":"Hepatitis B Virus Genotypes and Variants","volume":"5","author":"Lin","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bpg.2017.04.012","article-title":"Current Treatment Guidelines of Chronic Hepatitis B: The Role of Nucleos(t)Ide Analogues and Peginterferon","volume":"31","author":"Ghany","year":"2017","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ozaras, R., and Tahan, V. (2018). Viral Hepatitis: Chronic Hepatitis B, Springer International Publishing.","DOI":"10.1007\/978-3-319-93449-5"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1016\/j.cgh.2020.09.004","article-title":"Ultra-Long-Term Follow-up of Interferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B Virus Infection","volume":"19","author":"Choi","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_11","first-page":"e14899","article-title":"Role of Hepatosteatosis in HBsAg Seroconversion in HBeAg-negative Chronic Hepatitis B Patients","volume":"75","author":"Kacar","year":"2021","journal-title":"Int. J. Clin. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/apt.14362","article-title":"HBeAg Levels at Week 24 Predict Response to 8 Years of Tenofovir in HBeAg-Positive Chronic Hepatitis B Patients","volume":"47","author":"Wong","year":"2018","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.4254\/wjh.v7.i8.1030","article-title":"Current and Future Antiviral Drug Therapies of Hepatitis B Chronic Infection","volume":"7","author":"Koumbi","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3908","DOI":"10.3892\/etm.2017.4963","article-title":"Effect of Entecavir in the Treatment of Patients with Hepatitis B Virus-Related Compensated and Decompensated Cirrhosis","volume":"14","author":"Gai","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.jhep.2022.12.018","article-title":"A Multicenter Randomized-Controlled Trial of Nucleos(t)Ide Analogue Cessation in HBeAg-Negative Chronic Hepatitis B","volume":"78","author":"Stein","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.jhep.2025.03.018","article-title":"EASL Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection","volume":"83","author":"Cornberg","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/hep.28156","article-title":"AASLD Guidelines for Treatment of Chronic Hepatitis B","volume":"63","author":"Terrault","year":"2016","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4960","DOI":"10.3390\/v7092854","article-title":"Anti-HBV Drugs: Progress, Unmet Needs, and New Hope","volume":"7","author":"Kang","year":"2015","journal-title":"Viruses"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.3748\/wjg.v21.i7.2116","article-title":"Predictors of Kidney Tubular Dysfunction Induced by Adefovir Treatment for Chronic Hepatitis B","volume":"21","author":"Shimizu","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"334","DOI":"10.21037\/atm.2016.09.19","article-title":"Treatment for Hepatitis B in Patients with Drug Resistance","volume":"4","author":"Tacke","year":"2016","journal-title":"Ann. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"305","DOI":"10.5009\/gnl220390","article-title":"Noninferiority Outcomes of Besifovir Compared to Tenofovir Alafenamide in Treatment-Na\u00efve Patients with Chronic Hepatitis B","volume":"18","author":"Kim","year":"2024","journal-title":"Gut Liver"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.jhep.2014.10.026","article-title":"Two-Year Treatment Outcome of Chronic Hepatitis B Infection Treated with Besifovir vs. Entecavir: Results from a Multicentre Study","volume":"62","author":"Yuen","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1136\/gutjnl-2014-308943","article-title":"Towards an HBV Cure: State-of-the-Art and Unresolved Questions\u2014Report of the ANRS Workshop on HBV Cure","volume":"64","author":"Zeisel","year":"2015","journal-title":"Gut"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e16202","DOI":"10.1111\/liv.16202","article-title":"HBV-Induced Carcinogenesis: Mechanisms, Correlation with Viral Suppression, and Implications for Treatment","volume":"45","author":"Tu","year":"2025","journal-title":"Liver Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jcmgh.2018.10.010","article-title":"Inhibition of HBV Transcription From cccDNA With Nitazoxanide by Targeting the HBx\u2013DDB1 Interaction","volume":"7","author":"Sekiba","year":"2019","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1002\/hep4.1339","article-title":"A Pilot Clinical Trial of Nitazoxanide in the Treatment of Chronic Hepatitis B","volume":"3","author":"Rossignol","year":"2019","journal-title":"Hepatol. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1007\/s00018-019-03021-8","article-title":"Orthologous CRISPR\/Cas9 Systems for Specific and Efficient Degradation of Covalently Closed Circular DNA of Hepatitis B Virus","volume":"76","author":"Kostyushev","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kayesh, M.E.H., Hashem, M.A., Kohara, M., and Tsukiyama-Kohara, K. (2022). In Vivo Delivery Tools for Clustered Regularly Interspaced Short Palindromic Repeat\/Associated Protein 9-Mediated Inhibition of Hepatitis B Virus Infection: An Update. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.953218"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.coph.2016.08.015","article-title":"Antiviral Strategies to Eliminate Hepatitis B Virus Covalently Closed Circular DNA (cccDNA)","volume":"30","author":"Revill","year":"2016","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1093\/infdis\/jiz143","article-title":"Comparative Analysis of the Antiviral Effects Mediated by Type I and III Interferons in Hepatitis B Virus\u2013Infected Hepatocytes","volume":"220","author":"Bockmann","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.omtn.2023.04.016","article-title":"Transient and Tunable CRISPRa Regulation of APOBEC\/AID Genes for Targeting Hepatitis B Virus","volume":"32","author":"Kostyushev","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1002\/hep.31902","article-title":"Hypoxia-Inducible Factor 1 Alpha\u2013Mediated RelB\/APOBEC3B Down-regulation Allows Hepatitis B Virus Persistence","volume":"74","author":"Riedl","year":"2021","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Morrish, E., Mackiewicz, L., Silke, N., Pellegrini, M., Silke, J., Brumatti, G., and Ebert, G. (2020). Combinatorial Treatment of Birinapant and Zosuquidar Enhances Effective Control of HBV Replication In Vivo. Viruses, 12.","DOI":"10.3390\/v12080901"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5803","DOI":"10.1073\/pnas.1502400112","article-title":"Eliminating Hepatitis B by Antagonizing Cellular Inhibitors of Apoptosis","volume":"112","author":"Ebert","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Guo, F., Zhao, Q., Sheraz, M., Cheng, J., Qi, Y., Su, Q., Cuconati, A., Wei, L., Du, Y., and Li, W. (2017). HBV Core Protein Allosteric Modulators Differentially Alter cccDNA Biosynthesis from de Novo Infection and Intracellular Amplification Pathways. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006658"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e00835-18","DOI":"10.1128\/AAC.00835-18","article-title":"Novel Potent Capsid Assembly Modulators Regulate Multiple Steps of the Hepatitis B Virus Life Cycle","volume":"62","author":"Lahlali","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1021\/acsinfecdis.8b00337","article-title":"Treatment of Chronic Hepatitis B Virus Infection Using Small Molecule Modulators of Nucleocapsid Assembly: Recent Advances and Perspectives","volume":"5","author":"Yang","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/S2468-1253(21)00176-X","article-title":"Safety, Pharmacokinetics, and Antiviral Activity of RO7049389, a Core Protein Allosteric Modulator, in Patients with Chronic Hepatitis B Virus Infection: A Multicentre, Randomised, Placebo-Controlled, Phase 1 Trial","volume":"6","author":"Yuen","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e01323-20","DOI":"10.1128\/AAC.01323-20","article-title":"A Five-in-One First-in-Human Study To Assess Safety, Tolerability, and Pharmacokinetics of RO7049389, an Inhibitor of Hepatitis B Virus Capsid Assembly, after Single and Multiple Ascending Doses in Healthy Participants","volume":"64","author":"Feng","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/cid\/ciaa961","article-title":"Antiviral Activity and Pharmacokinetics of the Hepatitis B Virus (HBV) Capsid Assembly Modulator GLS4 in Patients With Chronic HBV Infection","volume":"73","author":"Zhang","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e01686-19","DOI":"10.1128\/AAC.01686-19","article-title":"A First-in-Human Trial of GLS4, a Novel Inhibitor of Hepatitis B Virus Capsid Assembly, Following Single- and Multiple-Ascending-Oral-Dose Studies with or without Ritonavir in Healthy Adult Volunteers","volume":"64","author":"Zhao","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"104557","DOI":"10.1016\/j.antiviral.2019.104557","article-title":"BAY 41-4109-Mediated Aggregation of Assembled and Misassembled HBV Capsids in Cells Revealed by Electron Microscopy","volume":"169","author":"Rat","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1053\/j.gastro.2018.12.023","article-title":"Antiviral Activity, Safety, and Pharmacokinetics of Capsid Assembly Modulator NVR 3-778 in Patients with Chronic HBV Infection","volume":"156","author":"Yuen","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1002\/cpdd.1164","article-title":"Drug-Drug Interactions with the Hepatitis B Virus Capsid Assembly Modulator JNJ-56136379 (Bersacapavir)","volume":"11","author":"Vandenbossche","year":"2022","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1053\/j.gastro.2020.04.036","article-title":"JNJ-56136379, an HBV Capsid Assembly Modulator, Is Well-Tolerated and Has Antiviral Activity in a Phase 1 Study of Patients with Chronic Infection","volume":"159","author":"Zoulim","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.jhep.2022.05.027","article-title":"Safety and Efficacy of Vebicorvir Administered with Entecavir in Treatment-Na\u00efve Patients with Chronic Hepatitis B Virus Infection","volume":"77","author":"Sulkowski","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1080\/21505594.2022.2093444","article-title":"Novel Therapeutic Strategies for Chronic Hepatitis B","volume":"13","author":"Phillips","year":"2022","journal-title":"Virulence"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"eaan0241","DOI":"10.1126\/scitranslmed.aan0241","article-title":"RNAi-Based Treatment of Chronically Infected Patients and Chimpanzees Reveals That Integrated Hepatitis B Virus DNA Is a Source of HBsAg","volume":"9","author":"Wooddell","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wooddell, C.I., Mak, L.Y., Seto, W.-K., Given, B.D., and Yuen, M.-F. (2025). Virological Insights from ARC-520 siRNA and Entecavir Treated Chronically HBV-Infected Patients and Chimpanzees. Microorganisms, 13.","DOI":"10.3390\/microorganisms13081787"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.jhep.2022.07.010","article-title":"Combination Treatments Including the Small-Interfering RNA JNJ-3989 Induce Rapid and Sometimes Prolonged Viral Responses in Patients with CHB","volume":"77","author":"Yuen","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1021\/acsinfecdis.4c00514","article-title":"Control of Hepatitis B Virus with Imdusiran, a Small Interfering RNA Therapeutic","volume":"10","author":"Thi","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1056\/NEJMra2211764","article-title":"New Approaches to Chronic Hepatitis B","volume":"388","author":"Dusheiko","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1056\/NEJMoa2210027","article-title":"Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection","volume":"387","author":"Yuen","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_54","unstructured":"(2025, August 20). GSK Receives US FDA Fast Track Designation for Bepirovirsen in Chronic Hepatitis B. Available online: https:\/\/www.gsk.com\/media\/o22eqbgg\/gsk-receives-us-fda-fast-track-designation-for-bepirovirsen-press-release.pdf."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.12688\/f1000research.8983.1","article-title":"Recent Advances in Understanding and Diagnosing Hepatitis B Virus Infection","volume":"5","author":"Fourati","year":"2016","journal-title":"F1000Research"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.virol.2015.02.031","article-title":"Molecular Biology of Hepatitis B Virus Infection","volume":"479\u2013480","author":"Seeger","year":"2015","journal-title":"Virology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jhep.2016.04.016","article-title":"Treatment of Chronic Hepatitis D with the Entry Inhibitor Myrcludex B: First Results of a Phase Ib\/IIa Study","volume":"65","author":"Bogomolov","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.jhep.2024.05.001","article-title":"Bulevirtide Monotherapy in Patients with Chronic HDV: Efficacy and Safety Results through Week 96 from a Phase III Randomized Trial","volume":"81","author":"Wedemeyer","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"101205","DOI":"10.1016\/j.coviro.2022.101205","article-title":"Advances in Human Monoclonal Antibody Therapy for HBV Infection","volume":"53","author":"Beretta","year":"2022","journal-title":"Curr. Opin. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1002\/hep.26982","article-title":"Cyclosporin A and Its Analogs Inhibit Hepatitis B Virus Entry Into Cultured Hepatocytes Through Targeting a Membrane Transporter, Sodium Taurocholate Cotransporting Polypeptide (NTCP)","volume":"59","author":"Watashi","year":"2014","journal-title":"Hepatology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/S2468-1253(17)30288-1","article-title":"Safety and Efficacy of REP 2139 and Pegylated Interferon Alfa-2a for Treatment-Naive Patients with Chronic Hepatitis B Virus and Hepatitis D Virus Co-Infection (REP 301 and REP 301-LTF): A Non-Randomised, Open-Label, Phase 2 Trial","volume":"2","author":"Bazinet","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1053\/j.gastro.2020.02.058","article-title":"Safety and Efficacy of 48 Weeks REP 2139 or REP 2165, Tenofovir Disoproxil, and Pegylated Interferon Alfa-2a in Patients With Chronic HBV Infection Na\u00efve to Nucleos(t)Ide Therapy","volume":"158","author":"Bazinet","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.cld.2023.05.004","article-title":"Novel Drug Development in Chronic Hepatitis B Infection: Capsid Assembly Modulators and Nucleic Acid Polymers","volume":"27","author":"Mak","year":"2023","journal-title":"Clin. Liver Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.antiviral.2014.04.002","article-title":"Benzimidazole Derivative, BM601, a Novel Inhibitor of Hepatitis B Virus and HBsAg Secretion","volume":"107","author":"Xu","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s11901-024-00652-9","article-title":"Perspective on Emerging Therapies to Achieve Functional Cure of Chronic Hepatitis B","volume":"23","author":"Gopalakrishna","year":"2024","journal-title":"Curr. Hepatol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1007\/s00204-022-03266-6","article-title":"Farnesoid X Receptor (FXR) Agonists Induce Hepatocellular Apoptosis and Impair Hepatic Functions via FXR\/SHP Pathway","volume":"96","author":"Zhang","year":"2022","journal-title":"Arch. Toxicol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1016\/j.celrep.2020.02.100","article-title":"Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5\u03b1 Binding to the Viral Core","volume":"30","author":"Selyutina","year":"2020","journal-title":"Cell Rep."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Gallay, P., Ure, D., Bobardt, M., Chatterji, U., Ou, J., Trepanier, D., and Foster, R. (2019). The Cyclophilin Inhibitor CRV431 Inhibits Liver HBV DNA and HBsAg in Transgenic Mice. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0217433"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1111\/jvh.12942","article-title":"Safety and Efficacy of Vesatolimod (GS-9620) in Patients with Chronic Hepatitis B Who Are Not Currently on Antiviral Treatment","volume":"25","author":"Agarwal","year":"2018","journal-title":"J. Viral Hepat."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.jhep.2022.09.027","article-title":"Safety and Efficacy of the Oral TLR8 Agonist Selgantolimod in Individuals with Chronic Hepatitis B under Viral Suppression","volume":"78","author":"Gane","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Phillips, S., Mistry, S., Riva, A., Cooksley, H., Hadzhiolova-Lebeau, T., Plavova, S., Katzarov, K., Simonova, M., Zeuzem, S., and Woffendin, C. (2017). Peg-Interferon Lambda Treatment Induces Robust Innate and Adaptive Immunity in Chronic Hepatitis B Patients. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00621"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.jhep.2019.06.028","article-title":"Anti-PD-1 Blockade with Nivolumab with and without Therapeutic Vaccination for Virally Suppressed Chronic Hepatitis B: A Pilot Study","volume":"71","author":"Gane","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.jhep.2015.12.018","article-title":"Peginterferon Lambda for the Treatment of HBeAg-Positive Chronic Hepatitis B: A Randomized Phase 2b Study (LIRA-B)","volume":"64","author":"Chan","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Chronopoulou, S., and Tsochantaridis, I. (2025). Interferon Lambda: The Next Frontier in Antiviral Therapy?. Pharmaceuticals, 18.","DOI":"10.3390\/ph18060785"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.jhep.2016.05.016","article-title":"Randomized Phase II Study of GS-4774 as a Therapeutic Vaccine in Virally Suppressed Patients with Chronic Hepatitis B","volume":"65","author":"Lok","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Al Mahtab, M., Akbar, S.M.F., Aguilar, J.C., Guillen, G., Penton, E., Tuero, A., Yoshida, O., Hiasa, Y., and Onji, M. (2018). Treatment of Chronic Hepatitis B Na\u00efve Patients with a Therapeutic Vaccine Containing HBs and HBc Antigens (a Randomized, Open and Treatment Controlled Phase III Clinical Trial). PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201236"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"100361","DOI":"10.1016\/j.jhepr.2021.100361","article-title":"Therapeutic Vaccine BRII-179 Restores HBV-Specific Immune Responses in Patients with Chronic HBV in a Phase Ib\/IIa Study","volume":"3","author":"Ma","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1080\/21645515.2019.1651141","article-title":"Safety and Immunogenicity of the Therapeutic Vaccine TG1050 in Chronic Hepatitis B Patients: A Phase 1b Placebo-Controlled Trial","volume":"16","author":"Zoulim","year":"2020","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.jhep.2024.06.027","article-title":"Phase Ib\/IIa Randomized Study of Heterologous ChAdOx1-HBV\/MVA-HBV Therapeutic Vaccination (VTP-300) as Monotherapy and Combined with Low-Dose Nivolumab in Virally-Suppressed Patients with CHB","volume":"81","author":"Tak","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.jhep.2022.12.013","article-title":"Activation of CD4 T Cells during Prime Immunization Determines the Success of a Therapeutic Hepatitis B Vaccine in HBV-Carrier Mouse Models","volume":"78","author":"Su","year":"2023","journal-title":"J. Hepatol."}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/13\/10\/311\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:47:29Z","timestamp":1760035649000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/13\/10\/311"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,23]]},"references-count":80,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["diseases13100311"],"URL":"https:\/\/doi.org\/10.3390\/diseases13100311","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,23]]}}}