{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:31:13Z","timestamp":1760149873588,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Chronic delta hepatitis is a global health problem. Although a smaller percentage of chronic HBV-infected patients are coinfected with the hepatitis delta virus, these patients have a higher risk of an accelerated progression to fulminant \u201cdelta hepatitis\u201d, cirrhosis, hepatic decompensation, and hepatocellular carcinoma, putting a financial strain on the healthcare system and increasing the need for a liver transplant. Since its discovery, tremendous efforts have been directed toward understanding the intricate pathogenic mechanisms, discovering the complex viral replication process, the essential replicative intermediates, and cell division-mediated viral spread, which enables virion viability. The consideration of the interaction between HBV and HDV is crucial in the process of developing novel pharmaceuticals. Until just recently, interferon-based therapy was the only treatment available worldwide. This review aims to present the recent advancements in understanding the life cycle of HDV, which have consequently facilitated the development of innovative drug classes. Additionally, we will examine the antiviral strategies currently in phases II and III of development, including bulevirtide (an entry inhibitor), lonafarnib (a prenylation inhibitor), and REP 2139 (an HBsAg release inhibitor).<\/jats:p>","DOI":"10.3390\/cimb45100498","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T08:24:44Z","timestamp":1695889484000},"page":"7878-7890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Interferon-Free Regimens and Direct-Acting Antiviral Agents for Delta Hepatitis: Are We There Yet?"],"prefix":"10.3390","volume":"45","author":[{"given":"Roxana","family":"Nemteanu","sequence":"first","affiliation":[{"name":"Medical I Department, Grigore T. Popa University of Medicine and Pharmacy, 700100 Iasi, Romania"},{"name":"Institute of Gastroenterology and Hepatology, \u201cSfantul. Spiridon\u201d University Hospital, 700111 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreea","family":"Clim","sequence":"additional","affiliation":[{"name":"Medical I Department, Grigore T. Popa University of Medicine and Pharmacy, 700100 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corina Elena","family":"Hincu","sequence":"additional","affiliation":[{"name":"Department of Radiology, \u201cSfantul Spiridon\u201d Hospital, 700111 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8770-9340","authenticated-orcid":false,"given":"Liliana","family":"Gheorghe","sequence":"additional","affiliation":[{"name":"Medical I Department, Grigore T. Popa University of Medicine and Pharmacy, 700100 Iasi, Romania"},{"name":"Department of Radiology, \u201cSfantul Spiridon\u201d Hospital, 700111 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Ciortescu","sequence":"additional","affiliation":[{"name":"Medical I Department, Grigore T. Popa University of Medicine and Pharmacy, 700100 Iasi, Romania"},{"name":"Institute of Gastroenterology and Hepatology, \u201cSfantul. Spiridon\u201d University Hospital, 700111 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Plesa","sequence":"additional","affiliation":[{"name":"Medical I Department, Grigore T. Popa University of Medicine and Pharmacy, 700100 Iasi, Romania"},{"name":"Institute of Gastroenterology and Hepatology, \u201cSfantul. 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Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1136\/gut.18.12.997","article-title":"Immunofluorescence detection of new antigen-antibody system (delta\/anti-delta) associated to hepatitis B virus in liver and in serum of HBsAg carriers","volume":"18","author":"Rizzetto","year":"1977","journal-title":"Gut"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/jvh.13777","article-title":"Hepatitis delta virus: Disease assessment and stratification","volume":"30","author":"Koffas","year":"2023","journal-title":"J. Viral Hepat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7271","DOI":"10.3748\/wjg.v27.i42.7271","article-title":"Hepatitis B virus\/hepatitis D virus epidemiology: Changes over time and possible future influence of the SARS-CoV-2 pandemic","volume":"27","author":"Sagnelli","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1136\/gutjnl-2020-323888","article-title":"Hepatitis D virus in 2021: Virology, immunology and new treatment approaches for a difficult-to-treat disease","volume":"70","author":"Urban","year":"2021","journal-title":"Gut"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1002\/hep.29574","article-title":"Genetic diversity and worldwide distribution of the deltavirus genus: A study of 2,152 clinical strains","volume":"66","author":"Brichler","year":"2017","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/j.jhep.2021.01.014","article-title":"The changing context of hepatitis D","volume":"74","author":"Rizzetto","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Karlsen, A.A., Kyuregyan, K.K., Isaeva, O.V., Kichatova, V.S., Mobarkhan, F.A.A., Bezuglova, L.V., Netesova, I.G., Manuylov, V.A., Pochtovyi, A.A., and Gushchin, V.A. (2022). Different evolutionary dynamics of hepatitis B virus genotypes A and D, and hepatitis D virus genotypes 1 and 2 in an endemic area of Yakutia, Russia. BMC Infect. Dis., 22.","DOI":"10.1186\/s12879-022-07444-w"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Usman, Z., Velkov, S., Protzer, U., Roggendorf, M., Frishman, D., and Karimzadeh, H. (2020). HDVdb: A Comprehensive Hepatitis D Virus Database. Viruses, 12.","DOI":"10.3390\/v12050538"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Souza Campos, M., Villalobos-Salcedo, J.M., Vieira Dallacqua, D.S., Lopes Borges Andrade, C., Meyer Nascimento, R.J., Menezes Freire, S., Paran\u00e1, R., and Schinoni, M.I. (2023). Systemic Inflammatory Molecules Are Associated with Advanced Fibrosis in Patients from Brazil Infected with Hepatitis Delta Virus Genotype 3 (HDV-3). Microorganisms, 11.","DOI":"10.3390\/microorganisms11051270"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s12985-017-0845-y","article-title":"Hepatitis delta: Virological and clinical aspects","volume":"14","author":"Vasconcelos","year":"2017","journal-title":"Virol. J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wu, S., Zhang, Y., Tang, Y., Yao, T., Lv, M., Tang, Z., Zang, G., Yu, Y., and Chen, X. (2020). Molecular epidemiology and clinical characteristics of hepatitis delta virus (HDV) infected patients with elevated transaminases in Shanghai, China. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-05275-1"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sant\u2019Anna, T.B., and Araujo, N.M. (2023). Hepatitis B Virus Genotype D: An Overview of Molecular Epidemiology, Evolutionary History, and Clinical Characteristics. Microorganisms, 11.","DOI":"10.3390\/microorganisms11051101"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e718","DOI":"10.1016\/S0618-8278(19)31437-9","article-title":"Endogenous and exogenous IFN responses suppress HDV persistence during proliferation of hepatocytes in vitro","volume":"70","author":"Zhang","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Netter, H.J., Barrios, M.H., Littlejohn, M., and Yuen, L.K.W. (2021). Hepatitis Delta Virus (HDV) and Delta-Like Agents: Insights into Their Origin. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.652962"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1126\/science.3704630","article-title":"Cloned fragment of the hepatitis delta virus RNA genome: Sequence and diagnostic application","volume":"232","author":"Denniston","year":"1986","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Venkataraman, S., Badar, U., Shoeb, E., Hashim, G., AbouHaidar, M., and Hefferon, K. (2021). An Inside Look into Biological Miniatures: Molecular Mechanisms of Viroids. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062795"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4161\/rna.8.5.16226","article-title":"HDV-like self-cleaving ribozymes","volume":"8","author":"Webb","year":"2011","journal-title":"RNA Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S102","DOI":"10.1016\/j.jhep.2016.02.013","article-title":"The hepatitis delta virus: Replication and pathogenesis","volume":"64","author":"Sureau","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sausen, D.G., Shechter, O., Bietsch, W., Shi, Z., Miller, S.M., Gallo, E.S., Dahari, H., and Borenstein, R. (2022). Hepatitis B and Hepatitis D Viruses: A Comprehensive Update with an Immunological Focus. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415973"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cld.1033","article-title":"The Discovery of the Hepatitis D Virus: Three Princes of Serendip and the Recognition of Autoantibodies to Liver-Kidney Microsomes","volume":"16","author":"Rizzetto","year":"2020","journal-title":"Clin. Liver Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1053\/j.gastro.2018.09.058","article-title":"Pathogenesis of and New Therapies for Hepatitis D","volume":"156","author":"Koh","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhang, Z., and Urban, S. (2020). Interplay between Hepatitis D Virus and the Interferon Response. Viruses, 12.","DOI":"10.3390\/v12111334"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00049","DOI":"10.7554\/eLife.00049","article-title":"Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus","volume":"1","author":"Yan","year":"2012","journal-title":"eLife"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Shen, C., Jiang, X., Li, M., and Luo, Y. (2023). Hepatitis Virus and Hepatocellular Carcinoma: Recent Advances. Cancers, 15.","DOI":"10.3390\/cancers15020533"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1080\/22221751.2019.1625728","article-title":"Down-regulation of cell membrane localized NTCP expression in proliferating hepatocytes prevents hepatitis B virus infection","volume":"8","author":"Yan","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zi, J., Gao, X., Du, J., Xu, H., Niu, J., and Chi, X. (2022). Multiple Regions Drive Hepatitis Delta Virus Proliferation and Are Therapeutic Targets. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.838382"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ma, J., Dissanayaka Mudiyanselage, S.D., Hao, J., and Wang, Y. (Trends Microbiol., 2023). Cellular roadmaps of viroid infection, Trends Microbiol., ahead of print.","DOI":"10.1016\/j.tim.2023.05.014"},{"key":"ref_31","first-page":"508","article-title":"Hepatitis Delta: Current Knowledge and Future Directions","volume":"18","author":"Lange","year":"2022","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Guillot, C., Martel, N., Berby, F., Bordes, I., Hantz, O., Blanchet, M., Sureau, C., Vaillant, A., and Chemin, I. (2017). Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179697"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3530","DOI":"10.3748\/wjg.v27.i24.3530","article-title":"Hepatitis delta virus: From infection to new therapeutic strategies","volume":"27","author":"Niro","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_34","first-page":"0201721","article-title":"Hepatitis Delta Virus Genome RNA Synthesis Initiates at Position 1646 with a Nontemplated Guanosine","volume":"96","author":"Casey","year":"2022","journal-title":"J. Virol."},{"key":"ref_35","first-page":"560105","article-title":"Hepatitis delta virus: A peculiar virus","volume":"12","author":"Alves","year":"2013","journal-title":"Adv. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105461","DOI":"10.1016\/j.antiviral.2022.105461","article-title":"Hepatitis D virus: Improving virological knowledge to develop new treatments","volume":"209","author":"Khalfi","year":"2023","journal-title":"Antivir. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jare.2019.03.009","article-title":"A review on hepatitis D: From virology to new therapies","volume":"17","author":"Mentha","year":"2019","journal-title":"J. Adv. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1128\/CMR.00046-08","article-title":"Pathogen recognition and inflammatory signaling in innate immune defenses","volume":"22","author":"Mogensen","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1002\/hep.31112","article-title":"Hepatitis B Virus Particles Activate Toll-Like Receptor 2 Signaling Initially Upon Infection of Primary Human Hepatocytes","volume":"72","author":"Zhang","year":"2020","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.coviro.2011.10.008","article-title":"Interferon-stimulated genes and their antiviral effector functions","volume":"1","author":"Schoggins","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/hep.30815","article-title":"Analysis of Host Responses to Hepatitis B and Delta Viral Infections in a Micro-scalable Hepatic Co-culture System","volume":"71","author":"Winer","year":"2020","journal-title":"Hepatology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/hep.22654","article-title":"Hepatitis delta virus inhibits alpha interferon signaling","volume":"49","author":"Pugnale","year":"2009","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14218\/JCTH.2018.00022","article-title":"Consensus on Pegylated Interferon Alpha in Treatment of Chronic Hepatitis B","volume":"6","author":"Zhang","year":"2018","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104995","DOI":"10.1016\/j.antiviral.2020.104995","article-title":"Effectiveness of pegylated interferon monotherapy in the treatment of chronic hepatitis D virus infection: A meta-analysis","volume":"185","author":"Abdrakhman","year":"2021","journal-title":"Antivir. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.jfma.2020.10.002","article-title":"Role of hepatitis D virus in persistent alanine aminotransferase abnormality among chronic hepatitis B patients treated with nucleotide\/nucleoside analogues","volume":"120","author":"Jang","year":"2021","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_46","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_47","doi-asserted-by":"crossref","first-page":"S101","DOI":"10.1016\/S0168-8278(18)30422-7","article-title":"LBO-003-RO7049389, a core protein allosteric modulator, demonstrates robust anti-HBV activity in chronic hepatitis B patients and is safe and well tolerated","volume":"68","author":"Gane","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1136\/gutjnl-2018-317065","article-title":"Combined small molecule and loss-of-function screen uncovers estrogen receptor alpha and CAD as host factors for HDV infection and antiviral targets","volume":"69","author":"Verrier","year":"2020","journal-title":"Gut"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Vogt, A., Wohlfart, S., Urban, S., and Mier, W. (2022). Medical Advances in Hepatitis D Therapy: Molecular Targets. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810817"},{"key":"ref_50","first-page":"234","article-title":"A phase 2 randomized clinical trial to evaluate the safety and efficacy of pegylated interferon lambda monotherapy in patients with chronic hepatitis delta virus infection. interim results from the LIMT HDV study","volume":"66","author":"Hamid","year":"2017","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Koh, C., Hercun, J., and Rahman, F. (2020, January 13\u201316). A phase 2 study of peginterferon lambda, lonafarnib, and ritonavir for 24 weeks: End-of-study results from the lift HDV study. Proceedings of the AASLD 2020: The Liver Meeting, Virtual.","DOI":"10.1016\/S0168-8278(20)30774-1"},{"key":"ref_52","first-page":"129","article-title":"Future anti-HDV treatment strategies, including those aimed at HBV functional cure","volume":"3","author":"Tan","year":"2022","journal-title":"Liver Int."},{"key":"ref_53","unstructured":"Wedemeyer, H., Bogomolov, P., Blank, A., Allweiss, L., Dandri-Petersen, M., Bremer, B., Voronkova, N., Schoneweis, K., Pathil, A., and Burhenne, J. (Lancet Infect. Dis., 2022). Final results of a multicenter, open-label phase 2b clinical trial to assess safety and efficacy of myrcludex B in combination with tenofovir in patients with chronic HBV\/HDV co-infection, Lancet Infect. Dis., in press."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.1016\/S0168-8278(20)30651-6","article-title":"48 weeks of high dose (10 mg) bulevirtide as monotherapy or with peginterferon alfa-2a in patients with chronic HBV\/HDV coinfection","volume":"73","author":"Wedemeyer","year":"2020","journal-title":"J Hepatol."},{"key":"ref_55","first-page":"S294","article-title":"Bulevirtide monotherapy at low and high dose in patients with chronic hepatitis delta: 24-week interim data of the phase 3 MYR301 study","volume":"75","author":"Wedemeyer","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/j.jhep.2022.06.010","article-title":"Bulevirtide with or without pegIFN\u03b1 for patients with compensated chronic hepatitis delta: From clinical trials to real-world studies","volume":"77","author":"Lampertico","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"144","DOI":"10.2133\/dmpk.DMPK-12-RG-057","article-title":"Analysis of the pharmacokinetic boosting effects of ritonavir on oral bioavailability of drugs in mice","volume":"28","author":"Tomaru","year":"2013","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/jac\/dkh029","article-title":"Pharmacological and therapeutic properties of ritonavir-boosted protease inhibitor therapy in HIV-infected patients","volume":"53","author":"Zeldin","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1002\/hep.29658","article-title":"Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study","volume":"67","author":"Yurdaydin","year":"2018","journal-title":"Hepatology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1016\/S0168-8278(17)30327-6","article-title":"A phase 2 dose-optimization study of lonafarnib with ritonavir for the treatment of chronic delta hepatitis-end of treatment results from the LOWR HDV-2 study","volume":"66","author":"Yurdaydin","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"S101","DOI":"10.1016\/S0168-8278(17)30464-6","article-title":"A phase 2 study exploring once daily dosing of ritonavir boosted lonafarnib for the treatment of chronic delta hepatitis\u2014End of study results from the LOWR HDV-3 study","volume":"66","author":"Koh","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1016\/S0168-8278(17)30310-0","article-title":"A phase 2 dose-escalation study of lonafarnib plus ritonavir in patients with chronic hepatitis D: Final results from the lonafarnib with ritonavir in HDV-4 (LOWR HDV-4) study","volume":"66","author":"Wedemeyer","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.antiviral.2016.07.004","article-title":"Nucleic acid polymers: Broad spectrum antiviral activity, antiviral mechanisms and optimization for the treatment of hepatitis B and hepatitis D infection","volume":"133","author":"Vaillant","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_64","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_65","unstructured":"European Medicines Agency (2020, August 31). Hepcludex (Bulevirtide) Powder for Solution for Injection: EU Summary of Product Characteristics. Available online: https:\/\/ec.europa.eu."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/45\/10\/498\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:00:29Z","timestamp":1760130029000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/45\/10\/498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,28]]},"references-count":65,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["cimb45100498"],"URL":"https:\/\/doi.org\/10.3390\/cimb45100498","relation":{},"ISSN":["1467-3045"],"issn-type":[{"type":"electronic","value":"1467-3045"}],"subject":[],"published":{"date-parts":[[2023,9,28]]}}}