{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:16:09Z","timestamp":1787030169169,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Previous studies reported that the hepatitis C virus (HCV) could help disseminate the hepatitis D virus (HDV) in vivo through the unrelated hepatitis B virus (HBV), but with essentially inconclusive results. To try to shed light on this still-debated topic, 146 anti-HCV-positive subjects (of whom 91 HCV\/HIV co-infected, and 43 with prior HCV eradication) were screened for anti-HDV antibodies (anti-HD), after careful selection for negativity to any serologic or virologic marker of current or past HBV infection. One single HCV\/HIV co-infected patient (0.7%) tested highly positive for anti-HD, but with no positive HDV-RNA. Her husband, in turn, was a HCV\/HIV co-infected subject with a previous contact with HBV. While conducting a thorough review of the relevant literature, the authors attempted to exhaustively describe the medical history of both the anti-HD-positive patient and her partner, believing it to be the key to dissecting the possible complex mechanisms of HDV transmission from one subject to another, and speculating that in the present case, it may have been HCV itself that behaved as an HDV helper virus. In conclusion, this preliminary research, while needing further validation in large prospective studies, provided some further evidence of a role of HCV in HDV dissemination in humans.<\/jats:p>","DOI":"10.3390\/v16060992","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T11:10:28Z","timestamp":1718968228000},"page":"992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hepatitis C Virus as a Possible Helper Virus in Human Hepatitis Delta Virus Infection"],"prefix":"10.3390","volume":"16","author":[{"given":"Maria Grazia","family":"Crobu","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"},{"name":"Clinical Biochemistry Laboratory, Department of Laboratory Medicine, AOU Citt\u00e0 della Salute e della Scienza di Torino, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Ravanini","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7694-0740","authenticated-orcid":false,"given":"Clotilde","family":"Impaloni","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Martello","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Bargiacchi","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Di Domenico","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4558-3230","authenticated-orcid":false,"given":"Giulia","family":"Faolotto","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Macaluso","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Mercandino","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Riggi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Quaglia","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Andreoni","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Pirisi","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3338-5416","authenticated-orcid":false,"given":"Carlo","family":"Smirne","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tseligka, E.D., Cl\u00e9ment, S., and Negro, F. (2021). HDV Pathogenesis: Unravelling Ariadne\u2019s Thread. Viruses, 13.","DOI":"10.3390\/v13050778"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/hep.30922","article-title":"Master of Disguise: Hepatitis Delta Virus Packaging and Spread Facilitated by Diverse Viral Envelope Proteins","volume":"71","author":"Maya","year":"2020","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1038\/s41467-019-10117-z","article-title":"Enveloped Viruses Distinct from HBV Induce Dissemination of Hepatitis D Virus in Vivo","volume":"10","author":"Amirache","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"se03250-19","DOI":"10.1128\/mBio.03250-19","article-title":"Snake Deltavirus Utilizes Envelope Proteins of Different Viruses to Generate Infectious Particles","volume":"11","author":"Szirovicza","year":"2020","journal-title":"mBio"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1002\/hep.31453","article-title":"Preliminary Evidence for Hepatitis Delta Virus Exposure in Patients Who Are Apparently Not Infected with Hepatitis B Virus","volume":"73","author":"Chemin","year":"2021","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jare.2021.02.009","article-title":"The Hepatitis D Virus in Italy. A Vanishing Infection, not yet a Vanished Disease","volume":"33","author":"Caviglia","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijid.2023.11.005","article-title":"Prevalence of Hepatitis D Virus Infection in Central Italy Has Remained Stable across the Last 2 Decades with Dominance of Subgenotypes 1 and Characterized by Elevated Viral Replication","volume":"138","author":"Salpini","year":"2024","journal-title":"Int. J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/20477724.2022.2047551","article-title":"Hepatitis Delta Coinfection in Persons with HIV: Misdiagnosis and Disease Burden in Italy","volume":"117","author":"Brancaccio","year":"2023","journal-title":"Pathog. Glob. Health"},{"key":"ref_9","first-page":"50","article-title":"IL28B Polymorphism, Blood Interferon-Alpha Concentration, and Disease Stage of HCV Mono-Infected and HCV-HIV Co-Infected Patients","volume":"11","author":"Burlone","year":"2013","journal-title":"Curr. HIV Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Fasano, M., Poliseno, M.C., Fiore, J.R., Lo Caputo, S., D\u2019Arminio Monforte, A., and Santantonio, T.A. (2022). Management of Chronic Hepatitis B in HIV-Coinfected Patients. Viruses, 14.","DOI":"10.3390\/v14092022"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Saitta, C., Pollicino, T., and Raimondo, G. (2022). Occult Hepatitis B Virus Infection: An Update. Viruses, 14.","DOI":"10.3390\/v14071504"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1086\/520752","article-title":"Impact of Highly Active Antiretroviral Therapy (HAART) on the Natural History of Hepatitis B Virus (HBV) and HIV Coinfection: Relationship between Prolonged Efficacy of HAART and HBV Surface and Early Antigen Seroconversion","volume":"45","author":"Miailhes","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gantner, P., Cotte, L., Allavena, C., Bani-Sadr, F., Huleux, T., Duvivier, C., Valantin, M.A., Jacomet, C., Joly, V., and Ch\u00e9ret, A. (2019). Higher Rates of HBsAg Clearance with Tenofovir-Containing Therapy in HBV\/HIV Co-Infection. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215464"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"a021550","DOI":"10.1101\/cshperspect.a021550","article-title":"Hepatitis D Virus Coinfection and Superinfection","volume":"4","author":"Negro","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.jhep.2013.11.010","article-title":"Persistent Hepatitis D Virus Mono-Infection in Humanized Mice Is Efficiently Converted by Hepatitis B Virus to a Productive Co-Infection","volume":"60","author":"Giersch","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1055\/s-0032-1323628","article-title":"Clinical Features of Hepatitis D","volume":"32","author":"Farci","year":"2012","journal-title":"Semin. Liver Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1128\/jvi.63.5.1945-1950.1989","article-title":"Initiation of Replication of the Human Hepatitis Delta Virus Genome from Cloned DNA: Role of Delta Antigen","volume":"63","author":"Kuo","year":"1989","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3469","DOI":"10.1128\/JVI.75.7.3469-3473.2001","article-title":"Replication of the Human Hepatitis Delta Virus Genome Is Initiated in Mouse Hepatocytes Following Intravenous Injection of Naked DNA or RNA Sequences","volume":"75","author":"Chang","year":"2001","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jim.2014.03.002","article-title":"Mouse Models of Hepatitis B and Delta Virus Infection","volume":"410","author":"Dandri","year":"2014","journal-title":"J. Immunol. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Taylor, J.M. (2020). Infection by Hepatitis Delta Virus. Viruses, 12.","DOI":"10.3390\/v12060648"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.20411\/pai.v1i1.72","article-title":"Hepatitis Delta Virus Detected in Salivary Glands of Sj\u00f6gren\u2019s Syndrome Patients and Recapitulates a Sj\u00f6gren\u2019s Syndrome-like Phenotype in Vivo","volume":"1","author":"Weller","year":"2016","journal-title":"Pathog. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1177\/00220345231186394","article-title":"Analysis of Hepatitis D Virus in Minor Salivary Gland of Sj\u00f6gren\u2019s Disease","volume":"102","author":"Hesterman","year":"2023","journal-title":"J. Dent. Res."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1016\/0016-5085(91)90404-9","article-title":"Patterns of Hepatitis Delta Virus Reinfection and Disease in Liver Transplantation","volume":"101","author":"Ottobrelli","year":"1991","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/jvh.13825","article-title":"Hepatitis D Virus Infection: Progress on the Path toward Disease Control and Cure","volume":"30","author":"Sulkowski","year":"2023","journal-title":"J. Viral Hepat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101395","DOI":"10.1016\/j.jceh.2024.101395","article-title":"The Forgotten Virus, Hepatitis D: A Review of Epidemiology, Diagnosis, and Current Treatment Strategies","volume":"14","author":"Khattak","year":"2024","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1097\/QAD.0b013e32834babb3","article-title":"Hepatitis Delta in HIV-Infected Individuals in Europe","volume":"25","author":"Soriano","year":"2011","journal-title":"AIDS"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1093\/cid\/ciu167","article-title":"Hepatitis Delta Is a Major Determinant of Liver Decompensation Events and Death in HIV-Infected Patients","volume":"58","author":"Vispo","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1002\/hep.27742","article-title":"Changing Hepatitis D Virus Epidemiology in a Hepatitis B Virus Endemic Area with a National Vaccination Program","volume":"61","author":"Lin","year":"2015","journal-title":"Hepatology"},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1093\/infdis\/jiaa517","article-title":"No Evidence of Hepatitis C Virus (HCV)-Assisted Hepatitis D Virus Propagation in a Large Cohort of HCV-Positive Blood Donors","volume":"223","author":"Cappy","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/jvh.13385","article-title":"Hepatitis Delta Virus Propagation Enabled by Hepatitis C Virus\u2014Scientifically Intriguing, but Is It Relevant to Clinical Practice?","volume":"28","author":"Polywka","year":"2021","journal-title":"J. Viral Hepat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1365-2893.2007.00903.x","article-title":"Liver Cirrhosis in HIV-Infected Patients: Prevalence, Aetiology and Clinical Outcome","volume":"15","author":"Castellares","year":"2008","journal-title":"J. Viral Hepat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1097\/QAD.0000000000001424","article-title":"Hepatitis Delta and HIV Infection","volume":"31","author":"Soriano","year":"2017","journal-title":"AIDS"},{"key":"ref_36","first-page":"25","article-title":"The Changing Epidemiology of Liver Disease in HIV Patients","volume":"15","author":"Soriano","year":"2013","journal-title":"AIDS Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1097\/MEG.0000000000000795","article-title":"Prevalence and Epidemiology of Hepatitis D among Patients with Chronic Hepatitis B Virus Infection: A Report from Northern Spain","volume":"29","author":"Ordieres","year":"2017","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3851\/IMP3161","article-title":"Decline and Changing Profile of Hepatitis Delta among Injection Drug Users in Spain","volume":"23","author":"Aguilera","year":"2018","journal-title":"Antivir. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Caviglia, G.P., Ciancio, A., and Rizzetto, M. (2022). A Review of HDV Infection. Viruses, 14.","DOI":"10.3390\/v14081749"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1128\/JVI.79.2.1142-1153.2005","article-title":"Roles of Carboxyl-Terminal and Farnesylated Residues in the Functions of the Large Hepatitis Delta Antigen","volume":"79","author":"Lazinski","year":"2005","journal-title":"J. Virol."},{"key":"ref_41","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_42","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s11901-024-00643-w","article-title":"Advances and Challenges in Managing Hepatitis D Virus: Evolving Strategies","volume":"23","author":"Gopalakrishna","year":"2024","journal-title":"Curr. Hepatol. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jhep.2019.03.034","article-title":"Update of the Statements on Biology and Clinical Impact of Occult Hepatitis B Virus Infection","volume":"71","author":"Raimondo","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1111\/j.1537-2995.2008.01701.x","article-title":"Hepatitis B Virus Infection and Transfusion Medicine: Science and the Occult","volume":"48","author":"Hollinger","year":"2008","journal-title":"Transfusion"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"211","DOI":"10.14218\/JCTH.2015.00020","article-title":"Asymptomatic Hepadnaviral Persistence and Its Consequences in the Woodchuck Model of Occult Hepatitis B Virus Infection","volume":"3","author":"Michalak","year":"2015","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jhep.2023.10.030","article-title":"JAK1 Promotes HDV Replication and Is a Potential Target for Antiviral Therapy","volume":"80","author":"Heuschkel","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1126\/science.1152725","article-title":"Identification of Host Proteins Required for HIV Infection through a Functional Genomic Screen","volume":"319","author":"Brass","year":"2008","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.chom.2008.10.004","article-title":"Genome-Scale RNAi Screen for Host Factors Required for HIV Replication","volume":"4","author":"Zhou","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1074\/jbc.M506070200","article-title":"Intracellular versus Cell Surface Assembly of Retroviral Pseudotypes Is Determined by the Cellular Localization of the Viral Glycoprotein, Its Capacity to Interact with Gag, and the Expression of the Nef Protein","volume":"281","author":"Sandrin","year":"2006","journal-title":"J. Biol. Chem."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/6\/992\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:01:40Z","timestamp":1760108500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/6\/992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,20]]},"references-count":49,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["v16060992"],"URL":"https:\/\/doi.org\/10.3390\/v16060992","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,20]]}}}