{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:48:16Z","timestamp":1789541296073,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T00:00:00Z","timestamp":1757116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The burden of hepatitis delta virus (HDV) infection is currently unknown and may affect 12 to 72 million people distributed across various hot spots in different regions of the globe. Screening for antibodies to HDV infection in patients positive for the hepatitis B surface antigen (HBsAg) is generally available in most parts of the world, but systematic testing for HDV is needed. Chronic HDV infection is associated with a higher risk of progression to cirrhosis, liver failure, and hepatocellular carcinoma compared to hepatitis B virus (HBV) mono-infection. Bulevirtide is the recently available treatment against hepatitis delta. The results of efficacy studies and new drugs (lonafarnib) are under discussion. New therapeutic strategies are in development, revealing a critical need for valid next-generation treatments to cure HDV.<\/jats:p>","DOI":"10.3390\/pathogens14090899","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:27:12Z","timestamp":1757500032000},"page":"899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hepatitis Delta Virus Infection: An Overview"],"prefix":"10.3390","volume":"14","author":[{"given":"Vitor","family":"Duque","sequence":"first","affiliation":[{"name":"Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0239-507X","authenticated-orcid":false,"given":"Diana","family":"Duque","sequence":"additional","affiliation":[{"name":"Department of Marketing, HEC Lausanne (UNIL), 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,6]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.coviro.2016.01.022","article-title":"Pathogenesis by subviral agents: Viroids and hepatitis delta virus","volume":"17","author":"Flores","year":"2016","journal-title":"Curr. Opin. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"001963","DOI":"10.1099\/jgv.0.001963","article-title":"ICTV Virus Taxonomy Profile: Kolmioviridae 2024","volume":"105","author":"Kuhn","year":"2024","journal-title":"J. Gen. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1055\/a-2133-8614","article-title":"Hepatitis Delta Infection: A Clinical Review","volume":"43","author":"Pearlman","year":"2023","journal-title":"Semin. Liver Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1056\/NEJMra2212151","article-title":"Hepatitis D Virus Infection","volume":"389","author":"Asselah","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Herrscher, C., Roingeard, P., and Blanchard, E. (2020). Hepatitis B Virus Entry into Cells. Cells, 9.","DOI":"10.3390\/cells9061486"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.jhep.2022.05.023","article-title":"Hepatitis D virus-induced interferon response and administered interferons control cell division-mediated virus spread","volume":"77","author":"Zhang","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1001\/jama.2023.23242","article-title":"Hepatitis D: A Review","volume":"330","author":"Negro","year":"2023","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5742","DOI":"10.1128\/JVI.00430-14","article-title":"Envelope proteins derived from naturally integrated hepatitis B virus DNA support assembly and release of infectious hepatitis delta virus particles","volume":"88","author":"Freitas","year":"2014","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.jhep.2020.04.008","article-title":"The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis","volume":"73","author":"Stockdale","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Montoya-Guzman, M., Martinez, J., Castro-Arroyave, D., Rojas, C., and Navas, M.-C. (2023). Epidemiology and Genetic Diversity of Hepatitis B Virus and Hepatitis Delta Virus Infection in Indigenous Communities in Colombia. Microorganisms, 11.","DOI":"10.3390\/microorganisms11071739"},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1111\/jvh.13310","article-title":"Migratory flow and hepatitis delta infection in Italy: A new challenge at the beginning of the third millennium","volume":"27","author":"Stroffolini","year":"2020","journal-title":"J. Viral. Hepat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/liv.15519","article-title":"Hepatitis delta infection among persons living with HIV in Europe","volume":"43","author":"Atkinson","year":"2023","journal-title":"Liver Int."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mello, F., Barros, T.M., Angelice, G.P., Costa, V.P., Mello, V.M., Pardini, M., Lampe, E., Lago, B.V., Villar, L.M., and Chao, D.-Y. (2023). Circulation of HDV Genotypes in Brazil: Identification of a Putative Novel HDV-8 Subgenotype. Microbiol. Spectr., 11.","DOI":"10.1128\/spectrum.03965-22"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.cld.2023.05.007","article-title":"Maternal-to-Child Transmission of Hepatitis B Virus and Hepatitis Delta Virus","volume":"27","author":"Worthington","year":"2023","journal-title":"Clin. Liver Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1093\/infdis\/162.5.1170","article-title":"Heterosexual transmission of hepatitis delta virus in the general population of an area endemic for hepatitis B virus infection: A prospective study","volume":"162","author":"Liaw","year":"1990","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/apt.16485","article-title":"One-quarter of chronic hepatitis D patients reach HDV-RNA decline or undetectability during the natural course of the disease","volume":"54","author":"Palom","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_19","unstructured":"WHO 2024 (2025, July 18). Guidelines for the Prevention, Diagnosis, Care and Treatment for People with Chronic Hepatitis B Infection. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240090903."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.jhep.2018.12.022","article-title":"Treating chronic hepatitis delta: The need for surrogate markers of treatment efficacy","volume":"70","author":"Yurdaydin","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_21","unstructured":"European Medicines Agency (2025, July 18). Hepcludex (Bulevirtide). Product Information. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/hepcludex-epar-product-information_en.pdf."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1056\/NEJMoa2213429","article-title":"A phase 3, randomized trial of bulevirtide in chronic hepatitis D","volume":"389","author":"Wedemeyer","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S1473-3099(22)00318-8","article-title":"Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): A multicentre, randomised, parallel-group, open-label, phase 2 trial","volume":"23","author":"Wedemeyer","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1056\/NEJMoa2314134","article-title":"Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D","volume":"391","author":"Asselah","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101070","DOI":"10.1016\/j.jhepr.2024.101070","article-title":"Effect of Peg-IFN on the viral kinetics of patients with HDV infection treated with bulevirtide","volume":"6","author":"Messaoudi","year":"2024","journal-title":"JHEP Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.jhep.2024.01.035","article-title":"Blocking viral entry with bulevirtide reduces the number of HDV-infected hepatocytes in human liver biopsies","volume":"80","author":"Allweiss","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/S1473-3099(15)00074-2","article-title":"Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: A proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial","volume":"15","author":"Koh","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1002\/hep.32259","article-title":"A phase 2 dose-finding study of lonafarnib and ritonavir with or without interferon alpha for chronic delta hepatitis","volume":"75","author":"Yurdaydin","year":"2022","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/S0168-8278(23)00451-8","article-title":"Week 48 results of the phase 3 D-LIVR study, a randomized double-blind, placebo-controlled trial evaluating the safety and efficacy of Lonafarnib-boosted with Ritonavir with or without Peginterferon Alfa in patients with chronic hepatitis delta","volume":"78","author":"Etzion","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Vaillant, A. (2022). Oligonucleotide-Based Therapies for Chronic HBV Infection: A Primer on Biochemistry, Mechanisms and Antiviral Effects. Viruses, 14.","DOI":"10.3390\/v14092052"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Collotta, D., Bertocchi, I., Chiapello, E., and Collino, M. (2023). Antisense Oligonucleotides: A Novel Frontier in Pharmacological Strategy. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1304342"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"104853","DOI":"10.1016\/j.antiviral.2020.104853","article-title":"Characterization of the Antiviral Effects of REP 2139 on the HBV Lifecycle In Vitro","volume":"183","author":"Boulon","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/hep4.1633","article-title":"Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139-Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus\/Hepatitis Delta Virus Coinfection","volume":"5","author":"Bazinet","year":"2021","journal-title":"Hepatol. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S2468-1253(24)00237-1","article-title":"VIR-2218 (Elebsiran) plus Pegylated Interferon-Alfa-2a in Participants with Chronic Hepatitis B Virus Infection: A Phase 2 Study","volume":"9","author":"Yuen","year":"2024","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1016\/S0168-8278(24)00565-8","article-title":"OS-127 Efficacy and Safety of Tobevibart (VIR-3434) Alone or in Combination with Elebsiran (VIR-2218) in Participants with Chronic Hepatitis Delta Virus Infection: Preliminary Results from the Phase 2 SOLSTICE Trial in Non-Cirrhotic and Compensated Cirrhotic Participants","volume":"80","author":"Asselah","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jhep.2024.03.046","article-title":"JNJ-73763989 and Bersacapavir Treatment in Nucleos(t)ide Analogue-Suppressed Patients with Chronic Hepatitis B: REEF-2","volume":"81","author":"Agarwal","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S34","DOI":"10.1016\/S0168-8278(23)00487-7","article-title":"Treatment with siRNA JNJ-73763989 plus Nucleos(t)ide Analogue (NA) Decreases HBsAg and HDV RNA Levels in Patients with Chronic Hepatitis D (CHD): Part 1 of the REEF-D Study","volume":"78","author":"Wedemeyer","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S100","DOI":"10.1016\/S0168-8278(24)00611-1","article-title":"LBP-044 Robust Reduction of HBsAg and HDV RNA Levels with Low Risk for ALT Elevations in JNJ-73763989 Treated Patients with Chronic Hepatitis D (CHD) and Baseline HBsAg Levels below 10,000 IU\/mL: Part 2 of the REEF-D Study","volume":"80","author":"Wedemeyer","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.jhep.2023.07.003","article-title":"Potent Broadly Neutralizing Antibody VIR-3434 Controls Hepatitis B and D Virus Infection and Reduces HBsAg in Humanized Mice","volume":"79","author":"Lempp","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"101400","DOI":"10.1016\/j.jhepr.2025.101400","article-title":"Therapy with Murinized Tobevibart and Elebsiran Is Efficacious in a Liver-Chimeric Mouse Model of HDV Infection","volume":"7","author":"Zhou","year":"2025","journal-title":"JHEP Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S829","DOI":"10.1016\/S0168-8278(25)02132-4","article-title":"THU-243 SOLSTICE Week 24 Subgroup Analysis: Impact of Baseline Viral Parameters and Cirrhosis Status on Virological and Biochemical Responses in Participants with Chronic Hepatitis Delta Virus Infection Treated with Tobevibart and Elebsiran","volume":"82","author":"Jucov","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_46","unstructured":"(2025, August 18). A Global, Randomized, Open-Label, Multicenter, Phase 2b\/3 Trial Evaluating BJT-778 vs. Delayed Treatment for the Treatment of Chronic Hepatitis Delta Infection (AZURE-1), Available online: https:\/\/clinicaltrials.gov\/study\/NCT06907290."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/S0168-8278(23)00606-2","article-title":"Safety and Efficacy of Anti-Pre-S1 Domain Monoclonal Antibody (HH-003) Treatment in Patients with Co-Infection of Chronic Hepatitis B Virus (HBV) and Hepatitis D Virus (HDV): A Single Center, Open-Label, Phase 2 Trial","volume":"78","author":"Wang","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1016\/S0168-8278(25)00389-7","article-title":"OS-074 Recombinant Polyclonal Antibody GIGA-2339 Potently Neutralizes Hepatitis B and Hepatitis D Virus","volume":"82","author":"Keating","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1097\/HEP.0000000000000642","article-title":"Association of hepatitis delta virus with liver morbidity and mortality: A systematic literature review and meta-analysis","volume":"79","author":"Gish","year":"2024","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1097\/TP.0000000000004138","article-title":"Liver Transplantation in Hepatitis B\/Hepatitis D (Delta) Virus Coinfected Recipients","volume":"106","author":"Martini","year":"2022","journal-title":"Transplantation"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/apt.16374","article-title":"2020 position statement and recommendations of the European Liver and Intestine Transplantation Association (ELITA): Management of hepatitis B virus-related infection before and after liver transplantation","volume":"54","author":"Duvoux","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e14971","DOI":"10.1111\/ctr.14971","article-title":"Successful clinical and virological outcomes of liver transplantation for HDV\/HBV-related disease after long-term discontinuation of hepatitis B immunoglobulins","volume":"37","author":"Lenci","year":"2023","journal-title":"Clin. Transplant."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/9\/899\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:41:13Z","timestamp":1760035273000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/9\/899"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,6]]},"references-count":52,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["pathogens14090899"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14090899","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,6]]}}}