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Gheorghe L, Iacob S, Csiki IE, Ghioca M, Iacob R, Constantinescu I, Chiper B, Huiban L, Muzica C, Girleanu I, Tiuca N, Diaconu S, Sandulescu DL, Rogoveanu I, Suceveanu AI, Furtunescu F, Pop C, Trifan A. Unveiling Prevalence, Risk Factors, and Outcomes of Hepatitis D Among Vulnerable Communities in Romania. Viruses 2024; 17:52. [PMID: 39861841 PMCID: PMC11769301 DOI: 10.3390/v17010052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 12/26/2024] [Accepted: 12/27/2024] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Hepatitis B (HBV) and Delta (HDV) virus infections pose critical public health challenges, particularly in Romania, where HDV co-infection is underdiagnosed. METHODS This study investigates the epidemiology, risk factors, and clinical outcomes of HBV/HDV co-infection in vulnerable populations, leveraging data from the LIVE(RO2) program. Conducted between July 2021 and November 2023, the program screened 320,000 individuals across 24 counties, targeting socially disadvantaged groups such as rural residents, the Roma community, and those lacking health insurance. RESULTS Among 6813 hepatitis B surface antigen (HBsAg)-positive individuals, HDV antibody prevalence was 4.87%, with active replication confirmed in 75.6% of HDV-positive cases. Regional disparities emerged, with higher HDV prevalence and replication rates in the Eastern region compared to the South. HDV-positive individuals were more likely to be younger, male, and from rural or socioeconomically disadvantaged backgrounds. Clinically, HDV co-infection correlated with increased liver stiffness, advanced fibrosis stages, and lower steatosis levels compared to HBV mono-infection. Psychiatric comorbidities were more prevalent among HDV-positive patients, highlighting the need for integrated care. CONCLUSIONS This study underscores the urgent need for targeted public health interventions, including enhanced screening, education, and access to novel antiviral therapies like bulevirtide to address the significant burden of HBV/HDV co-infection in Romania.
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Affiliation(s)
- Liana Gheorghe
- Fundeni Clinical Institute, 022328 Bucharest, Romania; (L.G.); (I.E.C.); (M.G.); (R.I.); (I.C.); (B.C.)
- “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (N.T.); (S.D.); (F.F.); (C.P.)
| | - Speranta Iacob
- Fundeni Clinical Institute, 022328 Bucharest, Romania; (L.G.); (I.E.C.); (M.G.); (R.I.); (I.C.); (B.C.)
- “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (N.T.); (S.D.); (F.F.); (C.P.)
| | - Irma Eva Csiki
- Fundeni Clinical Institute, 022328 Bucharest, Romania; (L.G.); (I.E.C.); (M.G.); (R.I.); (I.C.); (B.C.)
| | - Mihaela Ghioca
- Fundeni Clinical Institute, 022328 Bucharest, Romania; (L.G.); (I.E.C.); (M.G.); (R.I.); (I.C.); (B.C.)
- “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (N.T.); (S.D.); (F.F.); (C.P.)
| | - Razvan Iacob
- Fundeni Clinical Institute, 022328 Bucharest, Romania; (L.G.); (I.E.C.); (M.G.); (R.I.); (I.C.); (B.C.)
- “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (N.T.); (S.D.); (F.F.); (C.P.)
| | - Ileana Constantinescu
- Fundeni Clinical Institute, 022328 Bucharest, Romania; (L.G.); (I.E.C.); (M.G.); (R.I.); (I.C.); (B.C.)
- “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (N.T.); (S.D.); (F.F.); (C.P.)
- Academy of Romanian Scientists (AOSR), 030016 Bucharest, Romania
| | - Bogdan Chiper
- Fundeni Clinical Institute, 022328 Bucharest, Romania; (L.G.); (I.E.C.); (M.G.); (R.I.); (I.C.); (B.C.)
- Fundeni Clinical Institute, University of Economic Studies, 70167 Bucharest, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.H.); (C.M.); (I.G.); (A.T.)
- St. Spiridon Emergency Hospital, 700111 Iasi, Romania
| | - Cristina Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.H.); (C.M.); (I.G.); (A.T.)
- St. Spiridon Emergency Hospital, 700111 Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.H.); (C.M.); (I.G.); (A.T.)
- St. Spiridon Emergency Hospital, 700111 Iasi, Romania
| | - Nicoleta Tiuca
- “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (N.T.); (S.D.); (F.F.); (C.P.)
- Department of Internal Medicine II and Gastroenterology, University Emergency Hospital, 050098 Bucharest, Romania
| | - Sorina Diaconu
- “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (N.T.); (S.D.); (F.F.); (C.P.)
- Department of Internal Medicine II and Gastroenterology, University Emergency Hospital, 050098 Bucharest, Romania
| | - Daniela Larisa Sandulescu
- Department of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy, 200349 Craiova, Romania; (D.L.S.); (I.R.)
- Department of Gastroenterology, Emergency County Hospital, 200642 Craiova, Romania
| | - Ion Rogoveanu
- Department of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy, 200349 Craiova, Romania; (D.L.S.); (I.R.)
- Department of Gastroenterology, Emergency County Hospital, 200642 Craiova, Romania
| | | | - Florentina Furtunescu
- “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (N.T.); (S.D.); (F.F.); (C.P.)
- Department of Public Health and Management, National Institute of Public Health, 050463 Bucharest, Romania
| | - Corina Pop
- “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (N.T.); (S.D.); (F.F.); (C.P.)
- Department of Internal Medicine II and Gastroenterology, University Emergency Hospital, 050098 Bucharest, Romania
| | - Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.H.); (C.M.); (I.G.); (A.T.)
- St. Spiridon Emergency Hospital, 700111 Iasi, Romania
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Palom A, Rando-Segura A, Fernandez G, Calatayud L, Sellés-Sánchez A, Pérez del Campo D, Mormeneo Bayo S, Perez Moreno MMO, Tabernero D, Ayats J, Llopis MA, Quer JC, Buti M. OPTI-HEP-D: a protocol for an intervention study comprising screening and linkage to care of people living with hepatitis D in Catalonia. BMJ Open 2024; 14:e086961. [PMID: 39581731 PMCID: PMC11590785 DOI: 10.1136/bmjopen-2024-086961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 10/25/2024] [Indexed: 11/26/2024] Open
Abstract
INTRODUCTION Hepatitis B virus (HBV) affects 296 million people globally, causing 780 000 annual deaths. It has been estimated that 12-43 million individuals are co-infected with hepatitis D virus (HDV). In Spain, the prevalence of HBsAg in adults is 0.22%, with an anti-HDV prevalence of 7.7%, although not extensively documented since many HBsAg-positive cases are not tested for anti-HDV. The primary objective of this project is to optimise hepatitis D care by implementing a screening programme for anti-HDV in all HBsAg-positive individuals over a 1 year period in Catalonia. Secondary objectives include evaluating hepatitis D prevalence, establishing a digital registry for all anti-HDV positive cases, testing them for HDV-RNA in a centralised laboratory and offering linkage to care. METHODS AND ANALYSIS This prospective study will be performed in seven hospital centres in Catalonia, which attend to more than 95% of the adult population. Approximately, 9290 HBsAg-positive individuals are expected to be screened for anti-HDV in 1 year. All anti-HDV positive samples will be sent to a centralised laboratory for HDV-RNA quantification. All individuals testing positive for anti-HDV will be registered on an electronic platform and linked to care. The registry will collect data on demographics, infection stage, risk factors, disease awareness and previous diagnoses. No additional interventions will be conducted for those with adequate follow-up. ETHICS AND DISSEMINATION The Vall d'Hebron Hospital Ethics Committee (PR(AG)628/2023) and the Spanish Agency of Medicines and Medical Devices approved this study. These findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION STUDY Grant number: IN-ES-980-7058.
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Affiliation(s)
- Adriana Palom
- Liver Unit, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Ariadna Rando-Segura
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | - Gema Fernandez
- Microbiology Department, Clinical Laboratory North Metropolitan Area, Hospital Universitari Germans Trias i Pujol. Department of Genetics and Microbiology, Autonomous University of Barcelona, Badalona, Spain
| | - Laura Calatayud
- Microbiology Department, Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Alicia Sellés-Sánchez
- Molecular Biology Department, Clinical Laboratory ICS Camp de Tarragona-Terres de l'Ebre Hospital Universitari Joan XXIII de Tarragona, Tarragona, Spain
| | - Dúnia Pérez del Campo
- Clinical Analysis Department, Clinical Laboratory ICS Girona, Hospital Universitari Doctor Josep Trueta, Girona, Spain
| | - Saray Mormeneo Bayo
- Microbiology Department, Hospital Universitari Arnau de Vilanova, Lleida, Spain
| | | | - David Tabernero
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | - Josefina Ayats
- Microbiology Area of the Clinical Laboratories Directorate, Catalan Institute of Health (ICS), Barcelona, Spain
| | - Maria Antonia Llopis
- Clinical Laboratories Corporate Manager, Catalan Institute of Health (ICS), Barcelona, Spain
| | - Juan Carlos Quer
- Gastroenterology Department, Hospital Universitari Joan XXIII de Tarragona, Universitat Rovira i Virgili, Tarragona, Spain
| | - Maria Buti
- Liver Unit, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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Grecu LI, Pavel-Tanasa M, Matei L, Sultana C, Ruta SM, Grecu RI, Ursu RG, Cianga P, Iancu LS. Molecular Epidemiology of Hepatitis D Virus in the North-East Region of Romania. Pathogens 2024; 13:793. [PMID: 39338984 PMCID: PMC11435033 DOI: 10.3390/pathogens13090793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/07/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
The hepatitis D virus (HDV) superinfection of individuals with chronic hepatitis B virus (HBV) infection causes severe liver damage and the poorest long-term prognosis among viral hepatitis. This is attributed to the unique pathogenic mechanisms of HDV characterized by a direct cytopathic effect on hepatocytes and a significant impairment of the host immune response. The HDV genotype largely influences the extent of the pathogenic mechanisms with consequences on disease progression towards cirrhosis, liver decompensation, or hepatocellular carcinoma. In this context, identifying the circulating HDV genotypes in European regions with high prevalence, such as Romania, is crucial for effectively managing the long-term liver health. Here, we report the first comprehensive HDV study in Romania that clinically characterizes 82 patients and performs HDV genotyping by combining the nested-PCR reaction with sequencing analysis in 49 samples with an HDV-RNA load higher than 5000 IU/mL. While all isolates in our study belong to the HDV-1 genotype, the phylogenetic analysis based on sequence data from GenBank reveals the presence of the following potential three groups: (i) Italy and France; (ii) Spain; and (iii) Turkey, Iran, Pakistan, and Germany. This broad clustering highlights the recent surge in migration to and from Western Europe and the Middle East. Equally important, no differences in viral markers, clinical and paraclinical parameters, or treatment options were observed between these identified clusters. Nevertheless, this study considerably advances the understanding of hepatitis D epidemiology and clinical aspects in Romania.
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Affiliation(s)
- Laura Iulia Grecu
- Department of Preventive Medicine and Interdisciplinarity Microbiology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.I.G.); (R.I.G.); (R.G.U.); (L.S.I.)
- Department of Emerging Viral Diseases, “Stefan S. Nicolau” Institute of Virology, 030304 Bucharest, Romania; (C.S.); (S.M.R.)
| | - Mariana Pavel-Tanasa
- Department of Immunology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
- Laboratory of Immunology, St. Spiridon County Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Lilia Matei
- Department of Cellular and Molecular Pathology, “Stefan S. Nicolau” Institute of Virology, 030304 Bucharest, Romania
| | - Camelia Sultana
- Department of Emerging Viral Diseases, “Stefan S. Nicolau” Institute of Virology, 030304 Bucharest, Romania; (C.S.); (S.M.R.)
| | - Simona Maria Ruta
- Department of Emerging Viral Diseases, “Stefan S. Nicolau” Institute of Virology, 030304 Bucharest, Romania; (C.S.); (S.M.R.)
| | - Razvan Ioan Grecu
- Department of Preventive Medicine and Interdisciplinarity Microbiology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.I.G.); (R.I.G.); (R.G.U.); (L.S.I.)
- Diaverum Romania, 011857 Bucharest, Romania
| | - Ramona Gabriela Ursu
- Department of Preventive Medicine and Interdisciplinarity Microbiology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.I.G.); (R.I.G.); (R.G.U.); (L.S.I.)
- Microbiology Department, Gynecology and Obstetrics Hospital-Cuza Voda, 700038 Iasi, Romania
| | - Petru Cianga
- Department of Immunology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
- Laboratory of Immunology, St. Spiridon County Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Luminita Smaranda Iancu
- Department of Preventive Medicine and Interdisciplinarity Microbiology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.I.G.); (R.I.G.); (R.G.U.); (L.S.I.)
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Khalfi P, Denis Z, McKellar J, Merolla G, Chavey C, Ursic-Bedoya J, Soppa L, Szirovicza L, Hetzel U, Dufourt J, Leyrat C, Goldmann N, Goto K, Verrier E, Baumert TF, Glebe D, Courgnaud V, Gregoire D, Hepojoki J, Majzoub K. Comparative analysis of human, rodent and snake deltavirus replication. PLoS Pathog 2024; 20:e1012060. [PMID: 38442126 PMCID: PMC10942263 DOI: 10.1371/journal.ppat.1012060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 03/15/2024] [Accepted: 02/19/2024] [Indexed: 03/07/2024] Open
Abstract
The recent discovery of Hepatitis D (HDV)-like viruses across a wide range of taxa led to the establishment of the Kolmioviridae family. Recent studies suggest that kolmiovirids can be satellites of viruses other than Hepatitis B virus (HBV), challenging the strict HBV/HDV-association dogma. Studying whether kolmiovirids are able to replicate in any animal cell they enter is essential to assess their zoonotic potential. Here, we compared replication of three kolmiovirids: HDV, rodent (RDeV) and snake (SDeV) deltavirus in vitro and in vivo. We show that SDeV has the narrowest and RDeV the broadest host cell range. High resolution imaging of cells persistently replicating these viruses revealed nuclear viral hubs with a peculiar RNA-protein organization. Finally, in vivo hydrodynamic delivery of viral replicons showed that both HDV and RDeV, but not SDeV, efficiently replicate in mouse liver, forming massive nuclear viral hubs. Our comparative analysis lays the foundation for the discovery of specific host factors controlling Kolmioviridae host-shifting.
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Affiliation(s)
- Pierre Khalfi
- Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France
| | - Zoé Denis
- Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France
| | - Joe McKellar
- Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France
| | - Giovanni Merolla
- Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France
| | - Carine Chavey
- Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France
| | - José Ursic-Bedoya
- Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France
- Department of hepato-gastroenterology, Hepatology and Liver Transplantation Unit, Saint Eloi University Hospital, Montpellier, France
| | - Lena Soppa
- Institute of Medical Virology, National Reference Centre for Hepatitis B Viruses and Hepatitis D Viruses, German Center for Infection Research (DZIF, Partner Site Giessen-Marburg-Langen), Justus Liebig University Giessen, Giessen, Germany
| | - Leonora Szirovicza
- Medicum, Department of Virology, University of Helsinki, Helsinki, Finland
| | - Udo Hetzel
- Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland
| | - Jeremy Dufourt
- Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France
- Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, CNRS UMR9004, Montpellier, France
| | - Cedric Leyrat
- Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France
| | - Nora Goldmann
- Institute of Medical Virology, National Reference Centre for Hepatitis B Viruses and Hepatitis D Viruses, German Center for Infection Research (DZIF, Partner Site Giessen-Marburg-Langen), Justus Liebig University Giessen, Giessen, Germany
| | - Kaku Goto
- Université de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMR_S1110, Strasbourg, France
- Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Nouvel Hôpital Civil, Strasbourg, France
| | - Eloi Verrier
- Université de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMR_S1110, Strasbourg, France
- Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Nouvel Hôpital Civil, Strasbourg, France
| | - Thomas F. Baumert
- Université de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMR_S1110, Strasbourg, France
- Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Nouvel Hôpital Civil, Strasbourg, France
| | - Dieter Glebe
- Institute of Medical Virology, National Reference Centre for Hepatitis B Viruses and Hepatitis D Viruses, German Center for Infection Research (DZIF, Partner Site Giessen-Marburg-Langen), Justus Liebig University Giessen, Giessen, Germany
| | - Valérie Courgnaud
- Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France
| | - Damien Gregoire
- Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France
| | - Jussi Hepojoki
- Medicum, Department of Virology, University of Helsinki, Helsinki, Finland
- Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland
| | - Karim Majzoub
- Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France
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Cossiga V, Brusa S, Montalti R, De Conte A, Jannuzzi G, Ranieri L, Sorrentino R, Vallefuoco L, Pignata L, Guarino M, Portella G, Morisco F. Anti-HDV reflex testing in HBsAg-positive subjects: An efficacious strategy to identify HDV infection. Liver Int 2024; 44:148-154. [PMID: 37789576 DOI: 10.1111/liv.15746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 09/02/2023] [Accepted: 09/11/2023] [Indexed: 10/05/2023]
Abstract
BACKGROUND AND AIMS The prevalence of HDV infection in HBsAg carriers is about 9.9% in Italy. However, the real prevalence is underestimated because the anti-HDV test is not performed routinely in all HBsAg carriers. The aim of this study was to compare the prevalence and the absolute number of HDV infection identified in HBsAg-positive subjects tested at University Hospital Federico II before and after the introduction of anti-HDV reflex testing. METHODS From January to December 2022, reflex test for the detection of total HDV antibodies was performed in all HBsAg-positive subjects tested at University Hospital Federico II. The control group consisted of all the HBsAg-positive subjects tested at the same laboratory in 2019, before the implementation of anti-HDV reflex testing. Sera were evaluated with ADVIA Centaur HBsAgII Qualitative, Liaison Murex HBsAg Quantitative and Liaison Murex Total Anti-HDV Qualitative. RESULTS Before reflex testing, anti-HDV had been tested in 16.4% (84/512) of HBsAg-positive subjects, while after its implementation, 100% (484/484) of HBsAg-positive patients was tested for anti-HDV. The anti-HDV positive prevalence was lower than before the introduction of reflex test (10.7% vs. 16.6%) but the absolute number of anti-HDV positive patients increased (14 vs. 52 subjects). HDV-RNA was detectable in 26 (53%) of 49 tested subjects. CONCLUSIONS Our data showed that the implementation of anti-HDV reflex testing increased the diagnoses of HDV infection. In this setting, due to the approval of specific anti-HDV drugs, a reflex test for anti-HDV should be implemented to early identify patients with HBV/HDV infection.
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Affiliation(s)
- Valentina Cossiga
- Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Naples "Federico II", Naples, Italy
| | - Stefano Brusa
- Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
| | - Roberto Montalti
- Department of Public Health, Division of Hepato-Bilio-Pancreatic, Minimally Invasive and Robotic Surgery, University of Naples "Federico II", Naples, Italy
| | - Annachiara De Conte
- Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Naples "Federico II", Naples, Italy
| | - Giuseppe Jannuzzi
- Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
| | - Luisa Ranieri
- Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Naples "Federico II", Naples, Italy
| | - Rosanna Sorrentino
- Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
| | - Luca Vallefuoco
- Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
| | - Luca Pignata
- Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Naples "Federico II", Naples, Italy
| | - Maria Guarino
- Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Naples "Federico II", Naples, Italy
| | - Giuseppe Portella
- Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Naples "Federico II", Naples, Italy
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Hsu CW, Hsu HY, Chen CH, Chao M. Unbranched rod-like RNA is required for RNA editing of hepatitis delta virus genotype 2 and genotype 4. Virus Res 2023; 338:199239. [PMID: 37827303 PMCID: PMC10590747 DOI: 10.1016/j.virusres.2023.199239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 10/09/2023] [Accepted: 10/09/2023] [Indexed: 10/14/2023]
Abstract
RNA editing of the hepatitis delta virus (HDV) is essential for generating the large delta antigen, which is crucial for virion assembly. In HDV genotype 1 (HDV-1), editing occurs within the context of the unbranched rod-like structure characteristic of HDV RNA, while RNA editing in HDV-3 requires a branched double-hairpin structure. The regulation of RNA editing in HDV-2 and HDV-4 remains uncertain. Based on predictions of the unbranched rod-like RNA structures of HDV-2 and HDV-4, the editing site occurs as an A.C mismatch pair, surrounded by four base pairs upstream and two base pairs downstream of the editing site, respectively. To investigate HDV-2 and HDV-4 RNA editing, cultured cells were transfected with non-replicating editing reporters carrying wild-type sequences or specific mutations. The results revealed that the editing rates observed for wild-type HDV-2 and HDV-4 were fairly similar, albeit lower than that of HDV-1. Like HDV-1, both HDV-2 and HDV-4 showed a reduction in editing rate when the A.C mismatch pair and the immediately upstream base-paired region were disturbed. Notably, extending the downstream base-paired region from two to three or four (forming a structure identical to that of HDV-1) base pairs increased editing rate. Furthermore, we presented novel evidence that indicates the importance of the first bulge's size, located upstream of the editing site, and the base-pairing length within 7-13 and 28-39 nucleotides downstream of the editing site in influencing the HDV-4 editing rate. To summarize, our analyses suggest that the unbranched rod-like structures surrounding the editing site of HDV-2 and HDV-4 play a crucial role in regulating their RNA editing rates.
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Affiliation(s)
- Chao-Wei Hsu
- Liver Research Center, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Guishan, Taoyang 33302, Taiwan
| | - Hsueh-Ying Hsu
- Liver Research Center, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Guishan, Taoyang 33302, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
| | - Mei Chao
- Liver Research Center, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Guishan, Taoyang 33302, Taiwan; Department of Microbiology and Immunology and Division of Microbiology, Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyang 33302, Taiwan.
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Abbas Z, Abbas M. An Insight Into the Factors Affecting the Prevalence and Natural History of Hepatitis D. Cureus 2023; 15:e43362. [PMID: 37593072 PMCID: PMC10427805 DOI: 10.7759/cureus.43362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/11/2023] [Indexed: 08/19/2023] Open
Abstract
Epidemiological studies and recent metanalyses addressing hepatitis D have reported a wide variation in the prevalence of the disease. Between 4.5% to 15% of all hepatitis B surface antigen (HBsAg) positive patients are thought to harbor the hepatitis D virus. The emergent variation in prevalence can be attributed to several factors. Unsurprisingly, published literature shows that the prevalence of the disease is higher in areas where aggregate viral hepatitis infections are endemic and amongst groups with high-risk practices facilitating the horizontal transfer. Meanwhile, the natural history of the disease is influenced by the genotype of the virus, the hepatitis D virus (HDV) RNA levels, HBV-HDV codominance, HBsAg titers, HBV genotype, nutritional status, HIV co-infection, and prior treatment. Together these factors contribute to the accelerated development of fibrosis and the increased risk of hepatocellular carcinoma. Superinfection with genotype 1 results in rapid progression to cirrhosis with lower rates of remission. Genotype 3 follows an aggressive course but shows a good response to interferon therapy. Other genotypes have better outcomes. The course of the disease leading to these outcomes can be tracked by HDV-specific models integrating clinical surrogate markers and epidemiological factors such as age, region, alanine aminotransferase (ALT), gamma-glutamyl transferase, albumin, platelets and cholinesterase, and liver stiffness.
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Affiliation(s)
- Zaigham Abbas
- Gastroenterology and Hepatology, Dr. Ziauddin University Hospital, Karachi, PAK
| | - Minaam Abbas
- Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, GBR
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Souza Campos M, Villalobos-Salcedo JM, Vieira Dallacqua DS, Lopes Borges Andrade C, Meyer Nascimento RJ, Menezes Freire S, Paraná R, Schinoni MI. Systemic Inflammatory Molecules Are Associated with Advanced Fibrosis in Patients from Brazil Infected with Hepatitis Delta Virus Genotype 3 (HDV-3). Microorganisms 2023; 11:1270. [PMID: 37317244 DOI: 10.3390/microorganisms11051270] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 05/03/2023] [Accepted: 05/03/2023] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND AND AIMS Hepatitis Delta virus (HDV) genotype 3 is responsible for outbreaks of fulminant hepatitis in Northeastern South America. This study investigates if systemic inflammatory molecules are differentially expressed in patients with advanced fibrosis chronically infected with Hepatitis Delta virusgenotype 3(HDV-3). METHODS Sixty-one patients from the north of Brazil coinfected with hepatitis B virus (HBV)/HDV-3 were analyzed. HDV quantification and genotyping were performed by semi-nested real-time polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) methodologies. Ninety-two systemic inflammatory molecules (SIMs) were measured by Proximity Extension Assay (PEA) technology. The Shapiro-Wilk, Student's t-test, Mann-Whitney tests, and logistic regression analysis were used when appropriate. RESULTS The median age was 41 years, and all patients were HBeAg negative. Advanced fibrosis or cirrhosis was diagnosed by histological staging in 17 patients, while 44 presented with minimal or no fibrosis. Advanced necroinflammatory activity correlated positively with serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Established non-invasive fibrosis scores (APRI, FIB-4, and AST/ALT ratio) revealed low sensitivities and positive predictive values (PPVs) with an AUROC maximum of 0.586. Among the 92 SIMs analyzed, MCP.4, CCL19, EN.RAGE, SCF, and IL18 showed a positive correlation with fibrosis stage. A combined score including CCL19 and MCP.4 revealed a sensitivity of 81% and an odds ratio of 2.202 for advanced fibrosis. CONCLUSIONS Standard non-invasive fibrosis scores showed poor performance in HDV-3 infection. We here suggest that the determination of CCL19 and MCP.4 may be used to identify patients with advanced fibrosis. Moreover, this study gives novel insights into the immunopathogenesis of HDV-3 infection.
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Affiliation(s)
- Mauricio Souza Campos
- Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil
- Programa de Pós-Graduação em Processos Interativos de Órgãos e Sistemas, Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil
| | | | | | - Caio Lopes Borges Andrade
- Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil
- Programa de Pós-Graduação em Imunologia, Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil
- Laboratório de Imunologia e Biologia Molecular, Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300,Brazil
| | - Roberto José Meyer Nascimento
- Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil
- Programa de Pós-Graduação em Imunologia, Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil
- Laboratório de Imunologia e Biologia Molecular, Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300,Brazil
| | - Songeli Menezes Freire
- Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil
- Programa de Pós-Graduação em Imunologia, Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil
- Laboratório de Imunologia e Biologia Molecular, Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300,Brazil
| | - Raymundo Paraná
- Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil
- Hospital Universitario Professor Edgard Santos, Universidade Federal da Bahia, Salvador 40110-060, Brazil
| | - Maria Isabel Schinoni
- Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil
- Programa de Pós-Graduação em Processos Interativos de Órgãos e Sistemas, Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil
- Hospital Universitario Professor Edgard Santos, Universidade Federal da Bahia, Salvador 40110-060, Brazil
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de los Ángeles Rodríguez Lay L, Tan Z, Villalba MCM, Suárez MS, Corredor MB, Hernández DL, Sánchez BM, Alonso LV, Sausy A, Hübschen JM. Low prevalence of hepatitis delta infection in Cuban HBsAg carriers: Prospect for elimination. Front Med (Lausanne) 2023; 9:1069372. [PMID: 36816726 PMCID: PMC9928864 DOI: 10.3389/fmed.2022.1069372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 12/16/2022] [Indexed: 02/04/2023] Open
Abstract
Introduction Infection with hepatitis delta virus (HDV) is one of the most severe hepatitis B virus (HBV) complications, with a more rapid progression to cirrhosis and an increased risk of hepatic decompensation and death. Data on HDV infection in Cuba are limited. The aims of our study were to determine the HDV prevalence in HBsAg carriers and to characterize the HDV strains circulating. The data were used to assess the possibility of HDV elimination in the Cuban HBV epidemiological setting. Methods Five hundred and two serum samples from the same number of HBsAg carriers collected in the period 2006-2019 from all over the country were tested for anti-HDV total antibodies. If positive, the samples were analyzed for HDV-RNA using Real-Time RT-PCR targeting the ribozyme and HD antigen domains followed by genotyping based on phylogenetic analysis. Results Two samples were anti-HDV positive [0.39% (95% CI 0.11-1.44)]. One of them was also HDV-RNA positive. Clinically, the patient with active HDV infection had compensated liver cirrhosis. Phylogenetic analysis showed that the virus belonged to genotype 1 and thus clustered with contemporary strains from North America, Europe, Middle East, and Asia. Discussion This is the first HDV study, including molecular detection and virus characterization, done after the introduction of the universal childhood anti-hepatitis B vaccination. The very low prevalence of HDV infection in HBsAg carriers combined with the high HBV vaccination coverage of all newborn children, of previously identified risk groups, and of the general population currently under 40 years of age suggests that HDV elimination is feasible in Cuba if the success in HBV control is maintained.
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Affiliation(s)
- Licel de los Ángeles Rodríguez Lay
- National Reference Laboratory of Viral Hepatitis, Department of Virology, Institute of Tropical Medicine “Pedro Kourí”, Havana, Cuba,*Correspondence: Licel de los Ángeles Rodríguez Lay, ; orcid.org/0000-0002-7742-3146
| | - Zexi Tan
- National Reference Laboratory of Viral Hepatitis, Department of Virology, Institute of Tropical Medicine “Pedro Kourí”, Havana, Cuba
| | - Maria Caridad Montalvo Villalba
- National Reference Laboratory of Viral Hepatitis, Department of Virology, Institute of Tropical Medicine “Pedro Kourí”, Havana, Cuba
| | | | - Marité Bello Corredor
- National Reference Laboratory of Viral Hepatitis, Department of Virology, Institute of Tropical Medicine “Pedro Kourí”, Havana, Cuba
| | - Dayesi López Hernández
- National Reference Laboratory of Viral Hepatitis, Department of Virology, Institute of Tropical Medicine “Pedro Kourí”, Havana, Cuba
| | - Barbara Marrero Sánchez
- National Reference Laboratory of Viral Hepatitis, Department of Virology, Institute of Tropical Medicine “Pedro Kourí”, Havana, Cuba
| | - Lidunka Valdés Alonso
- National Reference Laboratory of Viral Hepatitis, Department of Virology, Institute of Tropical Medicine “Pedro Kourí”, Havana, Cuba
| | - Aurélie Sausy
- Clinical and Applied Virology Group, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - Judith M. Hübschen
- Clinical and Applied Virology Group, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
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Pisaturo M, Alessio L, Di Fraia A, Macera M, Minichini C, Cordua E, Onorato L, Scotto G, Di Caprio G, Calò F, Sagnelli C, Coppola N. Hepatitis D virus infection in a large cohort of immigrants in southern Italy: a multicenter, prospective study. Infection 2022; 50:1565-1572. [PMID: 36222979 PMCID: PMC9554856 DOI: 10.1007/s15010-022-01938-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 09/30/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Since few data are available in the literature on the prevalence of anti-Delta-positive subjects in immigrant populations, the aim of the present study was to evaluate the demographic and virological characteristics of HDV infection in a large cohort of immigrants living in southern Italy. METHODS Between January 2012 and February 2020 all immigrants attending one of the 5 first- level centers were enrolled and screened for HBsAg, the HBsAg-positive for anti-Delta and if positive, for HDV-RNA and HDV genotype. RESULTS Of the 3521 immigrants observed in the study period, 3417 (97.0%) agreed to be screened; they were mainly males (61%), with a median age of 27 years (IQR 8-74) and came prevalently (58%) from sub-Saharan Africa. Of the 3417 patients enrolled, 319 (9%) subjects were HBsAg-positive, and of those, 8 (2.5%) were anti-Delta-positive. No difference in the demographic and epidemiological characteristics was observed between the anti-Delta-negative vs -positive. Of the 8 anti-Delta-positive subjects, only one was HDV-RNA-positive (viral load: 7050 IU/mL), genotype 1, with clinical signs of cirrhosis. CONCLUSIONS the present study showed a prevalence of HDV of 2.5% in a large cohort of asymptomatic immigrants, suggesting the need for screening campaigns for viral infections including delta hepatitis in this population.
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Affiliation(s)
- Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Centro Sociale ex Canapificio, Caserta, Italy
| | - Loredana Alessio
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Centro di Accoglienza "La Tenda di Abramo", Caserta, Italy
| | - Alessandra Di Fraia
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Margherita Macera
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Centro per la Tutela Della Salute Degli Immigrati, Naples, Italy
| | - Carmine Minichini
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Emanuele Cordua
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Centro Suore Missionarie Della Carità, Naples, Italy
| | - Gaetano Scotto
- Medical Center, Centro Borgoroma, Foggia, Italy
- Infectious Diseases Unit, Foggia, Italy
| | - Giovanni Di Caprio
- Medical Center, Centro Sociale ex Canapificio, Caserta, Italy
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Federica Calò
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Centro per la Tutela Della Salute Degli Immigrati, Naples, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Centro Suore Missionarie Della Carità, Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy.
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Palom A, Rando-Segura A, Vico J, Pacín B, Vargas E, Barreira-Díaz A, Rodríguez-Frías F, Riveiro-Barciela M, Esteban R, Buti M. Implementation of anti-HDV reflex testing among HBsAg-positive individuals increases testing for hepatitis D. JHEP Rep 2022; 4:100547. [PMID: 36052219 PMCID: PMC9425021 DOI: 10.1016/j.jhepr.2022.100547] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 06/28/2022] [Accepted: 07/08/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND & AIMS Although EASL guidelines recommend anti-HDV testing in all HBsAg-positive individuals, HDV infection remains an underdiagnosed condition. We describe the impact of an HDV screening program by reflex anti-HDV testing in all HBsAg-positive samples and compare the results before and after its implementation. METHODS In total, 2,236 HBsAg-positive determinations were included from January 2018 to December 2021. Only the first sample from each participant was evaluated: 1,492 samples before reflex anti-HDV testing (2018-2020) and 744 samples after (2021). Demographic and clinical characteristics of anti-HDV-positive patients were collected. RESULTS Before reflex testing, anti-HDV had been tested in 7.6% (114/1492) of HBsAg-positive individuals: 23% (91/390) attended in an academic hospital and only 2% (23/1,102) in primary care centres. After reflex testing was established, 93% (691/744) of HBsAg-positive cases were evaluated for anti-HDV: 91% (533/586) in the academic hospital and 100% (158/158) in primary care. The anti-HDV-positive prevalence was similar before and after reflex testing: 9.6% (11/114) and 8.1% (56/691), respectively. However, the absolute number of anti-HDV-positive patients increased. Most anti-HDV-positive patients were young, HBeAg-negative, Caucasian males. HDV-RNA was detectable in 35 (65%) of 54 tested, HBV-DNA was undetectable in 64%, and alanine aminotransferase levels were normal in 48%. CONCLUSIONS Anti-HDV reflex testing quintupled the absolute number of diagnoses of chronic hepatitis D infection. Before the reflex test, a large percentage of HBsAg-positive individuals had not undergone any anti-HDV determination. Implementation of reflex testing increases the diagnosis of patients with chronic hepatitis D. LAY SUMMARY Chronic hepatitis delta (CHD) is a viral disease caused by HDV, which requires the presence of HBV to propagate. HDV infection can cause rapid progression to cirrhosis, among other severe complications. The prevalence of CHD worldwide is controversial, and the infection often goes unrecognised, mainly because of unawareness among physicians. Use of reflex testing in other viral hepatitis has proven to increase detection and linking-to-care of infected patients. Implementation of anti-HDV testing in all HBsAg-positive patients has led to a 5-fold increase in the number of HDV diagnoses in an academic hospital and primary care centres.
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Affiliation(s)
- Adriana Palom
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Ariadna Rando-Segura
- Microbiology Department, Clinical Laboratories, Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | - Judit Vico
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | - Beatriz Pacín
- Microbiology Department, Clinical Laboratories, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Elena Vargas
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Ana Barreira-Díaz
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Francisco Rodríguez-Frías
- Microbiology Department, Clinical Laboratories, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Rafael Esteban
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Maria Buti
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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Yang Y, Delcourte L, Fogeron ML, Böckmann A, Lecoq L. 1H, 15N and 13C backbone and side chain solution NMR assignments of the truncated small hepatitis delta antigen Δ60-S-HDAg. BIOMOLECULAR NMR ASSIGNMENTS 2022; 16:311-316. [PMID: 35749039 DOI: 10.1007/s12104-022-10096-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 05/30/2022] [Indexed: 06/15/2023]
Abstract
Hepatitis D virus (HDV) is a defective virus that relies on hepatitis B virus envelope proteins to complete its replication cycle. The HDV genome contains two isoforms of hepatitis delta antigen: the small and the large hepatitis delta antigens (S- and L-HDAg). Here we report the 1H, 13C and 15 N backbone and side chain resonance assignments of an N-terminally truncated form of S-HDAg (SΔ60), which lacks the 1-60 oligomerization domain. We derived secondary structures based on NMR chemical shifts, which will be used in further structural and functional studies. We show that SΔ60 is partially disordered, and that the central structured part contains two well-defined α-helices of 22 and 17 residues, respectively. A temperature titration allowed to identify the residues involved in hydrogen bonds.
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Affiliation(s)
- Yang Yang
- Molecular Microbiology and Structural Biochemistry (MMSB), UMR 5086, CNRS, Université de Lyon, Labex Ecofect, 7 passage du Vercors, 69367, Lyon, France
| | - Loïc Delcourte
- Molecular Microbiology and Structural Biochemistry (MMSB), UMR 5086, CNRS, Université de Lyon, Labex Ecofect, 7 passage du Vercors, 69367, Lyon, France
| | - Marie-Laure Fogeron
- Molecular Microbiology and Structural Biochemistry (MMSB), UMR 5086, CNRS, Université de Lyon, Labex Ecofect, 7 passage du Vercors, 69367, Lyon, France
| | - Anja Böckmann
- Molecular Microbiology and Structural Biochemistry (MMSB), UMR 5086, CNRS, Université de Lyon, Labex Ecofect, 7 passage du Vercors, 69367, Lyon, France.
| | - Lauriane Lecoq
- Molecular Microbiology and Structural Biochemistry (MMSB), UMR 5086, CNRS, Université de Lyon, Labex Ecofect, 7 passage du Vercors, 69367, Lyon, France.
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Liver Transplantation in Hepatitis B/Hepatitis D (Delta) Virus Coinfected Recipients. Transplantation 2022; 106:1935-1939. [DOI: 10.1097/tp.0000000000004138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Yardeni D, Heller T, Koh C. Chronic hepatitis D-What is changing? J Viral Hepat 2022; 29:240-251. [PMID: 35122369 DOI: 10.1111/jvh.13651] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 01/03/2022] [Indexed: 01/04/2023]
Abstract
Hepatitis D virus (HDV) infection is a chronic viral disease of the liver that is still largely considered to be incurable due to lack of effective treatment options. Without treatment, the risk for the development of advanced liver disease, cirrhosis and hepatocellular carcinoma is significantly high. Currently, new therapeutic options are emerging out of ongoing phase 3 clinical trials, promising a new hope of cure for this devastating liver infection. Recently, bulevirtide, a first in its class HDV entry inhibitor, has received conditional authorization of use from the European Medicines Agency (EMA) and was also submitted for approval in the United States. Other novel therapeutic options in clincal trials include interferon lambda, the prenylation inhibitor lonafarnib and nucleic acidic polymers (NAPs). This review describes all recent advances and ongoing changes to the field of HDV therpaeutics.
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Affiliation(s)
- David Yardeni
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Caviglia GP, Martini S, Ciancio A, Niro GA, Olivero A, Fontana R, Tandoi F, Rosso C, Romagnoli R, Saracco GM, Smedile A, Rizzetto M. The hepatitis D virus in Italy. A vanishing infection, not yet a vanished disease. J Adv Res 2021; 33:183-187. [PMID: 34603788 PMCID: PMC8463926 DOI: 10.1016/j.jare.2021.02.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 02/18/2021] [Accepted: 02/25/2021] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION Hepatitis D Virus (HDV) infection is vanishing in Italy. It is therefore believed that hepatitis D is no longer a medical problem in the domestic population of the country but remains of concern only in migrants from HDV-endemic areas. OBJECTIVES To report the clinical features and the medical impact of the residual domestic HDV infections in Italy. METHODS From 2010 to 2019, one hundred ninety-three first-time patients with chronic HDV liver disease attended gastroenterology units in Torino and San Giovanni Rotondo (Apulia); 121 were native Italians and 72 were immigrants born abroad. For this study, we considered the 121 native Italians in order to determine their clinical features and the impact of HDV disease in liver transplant programs. RESULTS At the last observation the median age of the 121 native Italians was 58 years. At the end of the follow-up, the median liver stiffness was 12.0 kPa (95% CI 11.2-17.4), 86 patients (71.1%) had a diagnosis of cirrhosis; 80 patients (66.1%) remained HDV viremic. The ratio of HDV to total HBsAg transplants varied from 38.5% (139/361) in 2000-2009 to 50.2% (130/259) in 2010-2019, indicating a disproportionate role of hepatitis D in liver transplants compared to the minor prevalence of HDV infections in the current scenario of HBsAg-positive liver disorders in Italy. CONCLUSION Though HDV is vanishing in Italy, a legacy of ageing native-Italian patients with advanced HDV liver disease still represents an important medical issue and maintains an impact on liver transplantation.
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Affiliation(s)
| | - Silvia Martini
- Division of Gastroenterology, Città della Salute e della Scienza - Molinette Hospital, Torino, Italy
| | - Alessia Ciancio
- Department of Medical Sciences, University of Turin, Torino, Italy
- Division of Gastroenterology, Città della Salute e della Scienza - Molinette Hospital, Torino, Italy
| | - Grazia Anna Niro
- Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy
| | | | - Rossana Fontana
- Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy
| | - Francesco Tandoi
- Liver Transplant Unit, Città della Salute e della Scienza - Molinette Hospital, Torino, Italy
| | - Chiara Rosso
- Department of Medical Sciences, University of Turin, Torino, Italy
| | - Renato Romagnoli
- Liver Transplant Unit, Città della Salute e della Scienza - Molinette Hospital, Torino, Italy
- Department of Surgical Sciences, University of Turin, Torino, Italy
| | - Giorgio Maria Saracco
- Department of Medical Sciences, University of Turin, Torino, Italy
- Division of Gastroenterology, Città della Salute e della Scienza - Molinette Hospital, Torino, Italy
| | - Antonina Smedile
- Department of Medical Sciences, University of Turin, Torino, Italy
- Division of Gastroenterology, Città della Salute e della Scienza - Molinette Hospital, Torino, Italy
| | - Mario Rizzetto
- Department of Medical Sciences, University of Turin, Torino, Italy
- Division of Gastroenterology, Città della Salute e della Scienza - Molinette Hospital, Torino, Italy
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16
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Hayashi T, Takeshita Y, Hutin YJF, Harmanci H, Easterbrook P, Hess S, van Holten J, Oru EO, Kaneko S, Yurdaydin C, Bulterys M. The global hepatitis delta virus (HDV) epidemic: what gaps to address in order to mount a public health response? Arch Public Health 2021; 79:180. [PMID: 34663473 PMCID: PMC8525025 DOI: 10.1186/s13690-021-00693-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 09/13/2021] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Co-infection between hepatitis B virus (HBV) and hepatitis delta virus (HDV) causes the severest chronic hepatitis and is associated with a high risk of cirrhosis and hepatocellular carcinoma (HCC). The Global Health Sector Strategy on Viral Hepatitis called for the elimination of hepatitis (- 65% mortality and - 90% incidence) by 2030. Our aims were to summarize key points of knowledge and to identify the gaps that need to be addressed to mount a public health response to HDV. METHODS We performed a current literature review in terms of epidemiology by WHO regions, genotypes distribution and their pathogenicity, factors associated with HDV infection, mortality due to HDV infection, testing strategies and treatment. RESULTS Prevalence of infection and genotypes are heterogeneous distributed, with highest prevalence in foci around the Mediterranean, in the Middle East, and in Central, Northern Asia and Eastern Asia. Persons who inject drugs (PWID) and migrants from highly endemic areas are highly affected. While antibody detection tests are available, HDV RNA tests of current infection are not standardized nor widely available. The few therapeutic options, including lofartinib, are not widely available; however several new and promising agents have entered clinical trials. CONCLUSION HDV infection is an poorly known cause of chronic liver disease. To mount a public health response, we need a better description of the HDV epidemic, standardized testing strategies and better treatment options.
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Affiliation(s)
- Tomoyuki Hayashi
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland.
- Department of Gastroenterology, Kanazawa University and WHO Collaborating Center for Chronic Hepatitis and Liver Cancer, Kanazawa, Ishikawa, Japan.
| | - Yumie Takeshita
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
- Department of Gastroenterology, Kanazawa University and WHO Collaborating Center for Chronic Hepatitis and Liver Cancer, Kanazawa, Ishikawa, Japan
| | - Yvan J-F Hutin
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
| | - Hande Harmanci
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
| | | | - Sarah Hess
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
| | - Judith van Holten
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
| | - Ena Oghenekaro Oru
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
| | - Shuichi Kaneko
- Department of Gastroenterology, Kanazawa University and WHO Collaborating Center for Chronic Hepatitis and Liver Cancer, Kanazawa, Ishikawa, Japan
| | - Cihan Yurdaydin
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
- Hepatology Institute, University of Ankara, Ankara, Turkey
| | - Marc Bulterys
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
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17
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Higuera-de-la-Tijera F, Castro-Narro GE, Velarde-Ruiz Velasco JA, Cerda-Reyes E, Moreno-Alcántar R, Aiza-Haddad I, Castillo-Barradas M, Cisneros-Garza LE, Dehesa-Violante M, Flores-Calderón J, González-Huezo MS, Márquez-Guillén E, Muñóz-Espinosa LE, Pérez-Hernández JL, Ramos-Gómez MV, Sierra-Madero J, Sánchez-Ávila JF, Torre-Delgadillo A, Torres R, Marín-López ER, Kershenobich D, Wolpert-Barraza E. Asociación Mexicana de Hepatología A.C. Clinical guideline on hepatitis B. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2021; 86:403-432. [PMID: 34483073 DOI: 10.1016/j.rgmxen.2021.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 04/14/2021] [Indexed: 12/24/2022]
Abstract
Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.
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Affiliation(s)
- F Higuera-de-la-Tijera
- Departamento de Gastroenterología, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico
| | - G E Castro-Narro
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico.
| | - J A Velarde-Ruiz Velasco
- Departamento de Gastroenterología, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, Jalisco, Mexico
| | - E Cerda-Reyes
- Departamento de Gastroenterología, Hospital Central Militar, Mexico City, Mexico
| | - R Moreno-Alcántar
- Departamento de Gastroenterología, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico
| | - I Aiza-Haddad
- Clínica de Enfermedades Hepáticas, Hospital Ángeles Lomas, Mexico City, Mexico
| | - M Castillo-Barradas
- Departamento de Gastroenterología, Hospital de Especialidades del Centro Médico Nacional "La Raza", IMSS, Mexico City, Mexico
| | - L E Cisneros-Garza
- Centro de Enfermedades Hepáticas, Hospital San José, Nuevo León, Monterrey, Mexico
| | - M Dehesa-Violante
- Fundación Mexicana para la Salud Hepática A.C. (FUNDHEPA), Mexico City, Mexico
| | - J Flores-Calderón
- Departamento de Gastroenterología, Hospital de Pediatría del Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico
| | - M S González-Huezo
- Servicio de Gastroenterología y Endoscopia Gastrointestinal, ISSSEMYM, Metepec, Estado de México, Mexico
| | - E Márquez-Guillén
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico
| | - L E Muñóz-Espinosa
- Clínica de Hígado, Departamento de Medicina Interna, Hospital Universitario "Dr. José E. González", Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
| | - J L Pérez-Hernández
- Departamento de Gastroenterología, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico
| | - M V Ramos-Gómez
- Departamento de Gastroenterología, Centro Médico Nacional "20 de Noviembre", ISSSTE, Mexico City, Mexico
| | - J Sierra-Madero
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico
| | - J F Sánchez-Ávila
- Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
| | - A Torre-Delgadillo
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico
| | - R Torres
- Hospital de Infectología del Centro Médico Nacional "La Raza", IMSS, Mexico City, Mexico
| | | | - D Kershenobich
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico
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18
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Higuera-de-la-Tijera F, Castro-Narro GE, Velarde-Ruiz Velasco JA, Cerda-Reyes E, Moreno-Alcántar R, Aiza-Haddad I, Castillo-Barradas M, Cisneros-Garza LE, Dehesa-Violante M, Flores-Calderón J, González-Huezo MS, Márquez-Guillén E, Muñóz-Espinosa LE, Pérez-Hernández JL, Ramos-Gómez MV, Sierra-Madero J, Sánchez-Ávila JF, Torre-Delgadillo A, Torres R, Marín-López ER, Kershenobich D, Wolpert-Barraza E. Asociación Mexicana de Hepatología A.C. Clinical guideline on hepatitis B. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2021; 86:S0375-0906(21)00061-6. [PMID: 34384668 DOI: 10.1016/j.rgmx.2021.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 04/11/2021] [Accepted: 04/14/2021] [Indexed: 02/07/2023]
Abstract
Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.
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Affiliation(s)
- F Higuera-de-la-Tijera
- Departamento de Gastroenterología, Hospital General de México «Dr. Eduardo Liceaga», Ciudad de México, México
| | - G E Castro-Narro
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México.
| | - J A Velarde-Ruiz Velasco
- Departamento de Gastroenterología, Hospital Civil de Guadalajara «Fray Antonio Alcalde», Guadalajara, Jalisco, México
| | - E Cerda-Reyes
- Departamento de Gastroenterología, Hospital Central Militar, Ciudad de México, México
| | - R Moreno-Alcántar
- Departamento de Gastroenterología, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - I Aiza-Haddad
- Clínica de Enfermedades Hepáticas, Hospital Ángeles Lomas, Ciudad de México, México
| | - M Castillo-Barradas
- Departamento de Gastroenterología, Hospital de Especialidades del Centro Médico Nacional «La Raza», IMSS, Ciudad de México, México
| | - L E Cisneros-Garza
- Centro de Enfermedades Hepáticas, Hospital San José, Nuevo León, Monterrey, México
| | - M Dehesa-Violante
- Fundación Mexicana para la Salud Hepática A.C. (FUNDHEPA), Ciudad de México, México
| | - J Flores-Calderón
- Departamento de Gastroenterología, Hospital de Pediatría del Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - M S González-Huezo
- Servicio de Gastroenterología y Endoscopia Gastrointestinal, ISSSEMYM, Metepec, Estado de México, México
| | - E Márquez-Guillén
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - L E Muñóz-Espinosa
- Clínica de Hígado, Departamento de Medicina Interna, Hospital Universitario «Dr. José E. González», Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México
| | - J L Pérez-Hernández
- Departamento de Gastroenterología, Hospital General de México «Dr. Eduardo Liceaga», Ciudad de México, México
| | - M V Ramos-Gómez
- Departamento de Gastroenterología, Centro Médico Nacional «20 de Noviembre», ISSSTE, Ciudad de México, México
| | - J Sierra-Madero
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - J F Sánchez-Ávila
- Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Ciudad de México, México
| | - A Torre-Delgadillo
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - R Torres
- Hospital de Infectología del Centro Médico Nacional «La Raza», IMSS, Ciudad de México, México
| | | | - D Kershenobich
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
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19
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Papatheodoridi M, Papatheodoridis GV. Is hepatitis delta underestimated? Liver Int 2021; 41 Suppl 1:38-44. [PMID: 34155795 DOI: 10.1111/liv.14833] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 02/22/2021] [Indexed: 01/08/2023]
Abstract
Hepatitis D virus may be underestimated because it is a significant problem in HBsAg-positive patients, especially those who inject drugs, have HIV or HCV co-infections and/or live in certain endemic regions. In the past few decades, the prevalence of HDV was expected to have decreased as a result of improvements in public healthcare policies and universal HBV vaccination programs. However, HDV has continued to spread in low-income countries, with local outbreaks and migration to less endemic areas, so that its prevalence has remained stable or even increased in certain regions. As a result, research has been focused on the epidemiology of HDV. Contradicting data from three large recent meta-analyses have reported that the prevalence of HDV may be between 0.16% and 1.00% in the global general population, and 4.5% and 14.6% in HBsAg-positive patients, with an estimated 12 to 70 million HDV patients worldwide. The exact prevalence and estimated number of HDV patients is still a subject of debate for several reasons, including the unreliable assessment of the infection and a lack of real-world screening. HDV infection is associated with an increased risk of progression to cirrhosis and the development of HCC compared to patients with HBV mono-infection, a risk which is even higher in patients with HIV co-infection. Morbidity and mortality from HDV-related cirrhosis should not be overlooked. In conclusion, hepatitis D virus is probably underestimated and certainly underdiagnosed, and screening for HDV should be performed in all HBsAg-positive patients in clinical practice.
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Affiliation(s)
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
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20
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Rizzetto M, Hamid S, Negro F. The changing context of hepatitis D. J Hepatol 2021; 74:1200-1211. [PMID: 33484770 DOI: 10.1016/j.jhep.2021.01.014] [Citation(s) in RCA: 113] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 01/04/2021] [Accepted: 01/09/2021] [Indexed: 12/18/2022]
Abstract
The global epidemiology of hepatitis D is changing with the widespread implementation of vaccination against hepatitis B. In high-income countries that achieved optimal control of HBV, the epidemiology of hepatitis D is dual, consisting of an ageing cohort of domestic patients with advanced liver fibrosis who represent the end stage of the natural history of HDV, and of a younger generation of immigrants from endemic countries who account for the majority of new infections. As observed in Europe in the 1980s, the distinctive clinical characteristic of chronic hepatitis D in endemic countries is the accelerated progression to cirrhosis and hepatocellular carcinoma. Despite some recent progress, the therapeutic management of HDV remains unsatisfactory, as most patients are not cured of HDV with currently available medicines. This review article describes the current epidemiology and clinical features of chronic hepatitis D, based on the literature published in the last 10 years.
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Affiliation(s)
- Mario Rizzetto
- Department of Medical Sciences, University of Turin, Turin, Italy.
| | - Saeed Hamid
- Department of Medicine, The Aga Khan University, Karachi, Pakistan
| | - Franco Negro
- Division of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva, Switzerland; Division of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland
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21
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Yurdaydin C, Toy M. Hepatitis Delta Virus Infection: A Large Burden After All? J Infect Dis 2021; 221:1573-1575. [PMID: 31778169 DOI: 10.1093/infdis/jiz634] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 11/27/2019] [Indexed: 12/15/2022] Open
Affiliation(s)
- Cihan Yurdaydin
- Department of Gastroenterology and Hepatology, Koç University Medical School, Istanbul, Turkey
| | - Mehlika Toy
- Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA
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22
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Cappy P, Lucas Q, Kankarafou N, Sureau C, Laperche S. No Evidence of Hepatitis C Virus (HCV)-Assisted Hepatitis D Virus Propagation in a Large Cohort of HCV-Positive Blood Donors. J Infect Dis 2020; 223:1376-1380. [PMID: 32804999 DOI: 10.1093/infdis/jiaa517] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 08/11/2020] [Indexed: 12/18/2022] Open
Abstract
A study reported in 2019 showed that hepatitis C virus (HCV) could help disseminate hepatitis D virus (HDV). To test this finding, 2123 plasma samples positive for anti-HCV antibody were screened for anti-HDV antibodies, and HDV-RNA was searched for in samples positive for anti-HDV antibody. Of 41 samples (1.9%) that tested positive for anti-HDV antibody, 27 (65.9%) were positive and 14 (34.1%) negative for antibody to hepatitis B core antigen (anti-HBc). Anti-HDV antibodies were significantly more present in samples positive for anti-HBc (6.21% vs 0.8% in negative samples; P < .001) and in samples negative for HCV RNA (2.9% vs 1.5% for positive samples; P = .03). Serological ratios were significantly higher in samples positive for anti-HBc (P < .01). No anti-HDV-positive sample was HDV RNA positive. In conclusion, this study found no evidence suggesting a role for HCV in HDV dissemination in humans.
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Affiliation(s)
- Pierre Cappy
- Institut National de la Transfusion Sanguine, Département des Agents Transmissibles par le Sang, Centre National de Référence Risques Infectieux Transfusionnels, Paris, France
| | - Quentin Lucas
- Institut National de la Transfusion Sanguine, Département des Agents Transmissibles par le Sang, Centre National de Référence Risques Infectieux Transfusionnels, Paris, France
| | - Nakourogou Kankarafou
- Institut National de la Transfusion Sanguine, Département des Agents Transmissibles par le Sang, Centre National de Référence Risques Infectieux Transfusionnels, Paris, France
| | - Camille Sureau
- Institut National de la Transfusion Sanguine, Département des Agents Transmissibles par le Sang, Centre National de Référence Risques Infectieux Transfusionnels, Paris, France
| | - Syria Laperche
- Institut National de la Transfusion Sanguine, Département des Agents Transmissibles par le Sang, Centre National de Référence Risques Infectieux Transfusionnels, Paris, France
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23
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Daw MA, Daw AM, Sifennasr NEM, Draha A, Daw A, Daw A, Ahmed M, Mokhtar E, El-Bouzedi A, Daw I, Adam S, Warrag S. The epidemiological characterization and geographic distribution of hepatitis D virus infection in Libya. Pan Afr Med J 2020; 35:120. [PMID: 32637018 PMCID: PMC7320781 DOI: 10.11604/pamj.2020.35.120.20055] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 03/03/2020] [Indexed: 12/20/2022] Open
Abstract
Introduction North Africa is known to be endemic for hepatitis D virus. However, data one the prevalence of this virus in Libya are scanty. This study aimed to determine the prevalence of hepatitis D virus infection in Libya and analyze the demographic factors associated with the infection, and also to assess the variations across the regions and districts. Methods A total of 1873 samples collected from all over the country were tested for antibodies against hepatitis B surface antigen and the results were correlated with demographic and geographic variables. Results The overall prevalence of hepatitis D virus infection was 1.7%. The prevalence rate was significantly high among those aged over 40 years (P < 0.001) and it was associated with intravenous drug use and coinfection with human immunodeficiency virus and/or hepatitis C virus infection (P < 0.001). The prevalence rates varied with geographic location and differed markedly within the regions the country. The highest rate reported was in the central region of Libya, followed by the western and eastern regions. Conclusion Hepatitis D virus infection rate in Libya is considered to be low but is of some concern in some districts. This has been propagated by population displacement and African immigrants, indicating that a continuous epidemiological surveillance program should be implemented.
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Affiliation(s)
- Mohamed Ali Daw
- Department of Medical Microbiology & Immunology, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Amina Mohamed Daw
- Department of General Medicine, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | | | - Aisha Draha
- Department of Pharmacology, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Ahmed Daw
- Tripoli Medical Centre, Faculty of Medicine, Tripoli, CC 82668, Tripoli, Libya
| | - Ali Daw
- Tripoli Medical Centre, Faculty of Medicine, Tripoli, CC 82668, Tripoli, Libya
| | - Mohamed Ahmed
- Department of Microbiology & Parasitology, Faculty of Veterinary Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Ebtisam Mokhtar
- Department of Medical Microbiology & Immunology, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Abdallah El-Bouzedi
- Department of Laboratory Medicine, Faculty of Biotechnology, Tripoli University, CC 82668, Tripoli, Libya
| | - Ibrahem Daw
- Department of Electric Engineering, Faculty of Engineering, University of Tripoli, CC 82668Libya
| | - Samia Adam
- Department of Medical Microbiology & Immunology, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Saed Warrag
- Department of Laboratory Medicine, Faculty of Biotechnology, Aljabel-Agarbi University, Nalot, Libya
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24
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Pouri AA, Ghojazadeh M, Baiaz B, Hamzavi FS, Pourasghari B, Somi MH. Prevalence of hepatitis D virus among HBsAg-positive individuals, 2015-2016: Azar cohort study. Health Promot Perspect 2020; 10:38-42. [PMID: 32104655 PMCID: PMC7036205 DOI: 10.15171/hpp.2020.07] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Accepted: 12/30/2019] [Indexed: 12/17/2022] Open
Abstract
Background: Hepatitis D virus (HDV) is a defective RNA pathogen that requires the presence of the hepatitis B virus (HBV) for infection. Middle East countries are endemic areas for HDV infection. So, it is important to estimate the prevalence of HDV in these countries. This study aimed to estimate the prevalence of HDV in HBsAg positive patients participated in Azar cohort study, North-west of Iran. Methods: In this cross-sectional study, out of 4949 participants of the Azar cohort study, 51 HBsAg positive patients were selected. Five participants did not consent to HDV testing. The presence of anti-HDV IgG was checked in 46 patients (13 chronic hepatitis B and 33 inactive chronic hepatitis B) using enzyme-linked immunosorbent assay (ELISA) kit. The serum level of liver enzymes was measured and a questionnaire about risk factors was completed. Results: In this study, the mean age of HBsAg positive patients was 50.06 (SD 9.14) years and 41.3% were female. Only one out of 46 patients was positive for HDV infection. Thus, the prevalence of HDV infection among hepatitis B virus surface antigen (HBsAg) positive patients was 2.17% (95% CI: 0.1-11.5). The positive anti-HDV patient was in the inactive chronic hepatitis B state and she had a history of hospitalization and dental procedures. Conclusion: The results showed that the prevalence of HDV infection in HBsAg positive patients was 2.1% that was lower than the reported prevalence in many other regions of Iran. Health policymakers and healthcare providers should design coherent and orderly epidemiological studies for planning and monitoring HDV infection.
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Affiliation(s)
- Ali Asghar Pouri
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Morteza Ghojazadeh
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Babak Baiaz
- Laborathory Department Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Soghra Hamzavi
- Laborathory Department Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behrouz Pourasghari
- Laborathory Department Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Hossein Somi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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25
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Rizzetto M. Epidemiology of the Hepatitis D virus. WIKIJOURNAL OF MEDICINE 2020; 7:1. [DOI: 10.15347/wjm/2020.001.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/02/2023] Open
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26
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Coppola N, Alessio L, Onorato L, Sagnelli C, Sagnelli E, Pisaturo M. HDV infection in immigrant populations. J Med Virol 2019; 91:2049-2058. [PMID: 31429940 DOI: 10.1002/jmv.25570] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 08/10/2019] [Indexed: 12/16/2022]
Abstract
AIMS Little data have been published so far on the epidemiological aspects of hepatitis D virus (HDV) infection in immigrant populations and even poorer is the information on the virological, phylogenetic, and clinical aspects of this infection in these populations. This review article, aimed primarily at physicians caring for immigrants, summarizes the information available on HDV infection and analyzes data on this topic concerning the immigrant populations. METHODS AND RESULTS The prevalence of HDV infection in HBsAg-positive immigrants varies according to the country of origin. For example, in immigrants from sub-Saharan Africa, this prevalence is higher in those born in Equatorial Guinea (24.4%) than those from other African countries (10.3%). The epidemiological impact of HDV infection linked to migratory flows is a function of the different endemicity between countries of origin and countries in which a new existence has been established. This impact is high when immigrants from areas endemic to HDV infection (eg, Equatorial Guinea) settle in areas of low endemicity (eg, Germany or England, with a prevalence of around 4%), while the impact is lesser or nonexistent if the migratory flows are directed toward countries with intermediate endemicity (eg, Italy and Greece, with a prevalence of around 10%). CONCLUSION This impact of immigration on HDV epidemiology can be strong when HDV endemicity is high in the country of origin and low in the host country and slight when immigrants move to high or medium endemic countries.
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Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
- Infectious Disease Unit, AORN Caserta, Caserta, Italy
| | | | - Lorenzo Onorato
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
- Infectious Disease Unit, AORN Caserta, Caserta, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
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27
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Hardikar W. Viral hepatitis. J Paediatr Child Health 2019; 55:1038-1043. [PMID: 31317618 DOI: 10.1111/jpc.14562] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 06/25/2019] [Accepted: 06/26/2019] [Indexed: 12/14/2022]
Abstract
Hepatitis viruses A to E can cause abnormal liver function tests in children. Although, overall, they are relatively uncommon in children in Australia, epidemiology diagnosis and treatment modalities for these viruses have evolved over the last decade. This review provides an update on the diagnosis and treatment of viral hepatitis in children.
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Affiliation(s)
- Winita Hardikar
- Department of Gastroenterology, Royal Children's Hospital, Melbourne, Victoria, Australia
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28
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Brovold M, Almeida JI, Pla-Palacín I, Sainz-Arnal P, Sánchez-Romero N, Rivas JJ, Almeida H, Dachary PR, Serrano-Aulló T, Soker S, Baptista PM. Naturally-Derived Biomaterials for Tissue Engineering Applications. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1077:421-449. [PMID: 30357702 PMCID: PMC7526297 DOI: 10.1007/978-981-13-0947-2_23] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Naturally-derived biomaterials have been used for decades in multiple regenerative medicine applications. From the simplest cell microcarriers made of collagen or alginate, to highly complex decellularized whole-organ scaffolds, these biomaterials represent a class of substances that is usually first in choice at the time of electing a functional and useful biomaterial. Hence, in this chapter we describe the several naturally-derived biomaterials used in tissue engineering applications and their classification, based on composition. We will also describe some of the present uses of the generated tissues like drug discovery, developmental biology, bioprinting and transplantation.
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Affiliation(s)
- Matthew Brovold
- Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA
| | - Joana I Almeida
- Health Research Institute of Aragón (IIS Aragón), Zaragoza, Spain
| | - Iris Pla-Palacín
- Health Research Institute of Aragón (IIS Aragón), Zaragoza, Spain
| | - Pilar Sainz-Arnal
- Health Research Institute of Aragón (IIS Aragón), Zaragoza, Spain
- Aragon Health Sciences Institute (IACS), Zaragoza, Spain
| | | | - Jesus J Rivas
- Health Research Institute of Aragón (IIS Aragón), Zaragoza, Spain
| | - Helen Almeida
- Health Research Institute of Aragón (IIS Aragón), Zaragoza, Spain
| | - Pablo Royo Dachary
- Instituto de Investigación Sanitária de Aragón (IIS Aragón), Zaragoza, Spain
- Liver Transplant Unit, Gastroenterology Department, Lozano Blesa University Hospital, Zaragoza, Spain
| | - Trinidad Serrano-Aulló
- Instituto de Investigación Sanitária de Aragón (IIS Aragón), Zaragoza, Spain
- Liver Transplant Unit, Gastroenterology Department, Lozano Blesa University Hospital, Zaragoza, Spain
| | - Shay Soker
- Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA.
| | - Pedro M Baptista
- Instituto de Investigación Sanitária de Aragón (IIS Aragón), Zaragoza, Spain.
- Center for Biomedical Research Network Liver and Digestive Diseases (CIBERehd), Zaragoza, Spain.
- Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid, Spain.
- Biomedical and Aerospace Engineering Department, Universidad Carlos III de Madrid, Madrid, Spain.
- Fundación ARAID, Zaragoza, Spain.
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29
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Marino Q, Cisse M, Gerber A, Dolo O, Sayon S, Ba A, Brichler S, Traore FT, Gordien E, Togo J, Calvez V, Marcelin AG, Maiga AI, Todesco E. Low hepatitis D seroprevalence in blood donors of Bamako, Mali. Infect Dis (Lond) 2019; 51:622-624. [PMID: 31165648 DOI: 10.1080/23744235.2019.1620963] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Affiliation(s)
- Quentin Marino
- a Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie , Paris , France
| | - Moussa Cisse
- b Centre National de Transfusion Sanguine , Bamako , Mali
| | - Athenaïs Gerber
- c Laboratoire de Microbiologie Clinique, Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Université Sorbonne Paris Cité , Bobigny , France.,d Centre national de référence des virus des hépatites B, C et Delta, Laboratoire de Virologie , Bobigny , France.,e Unité INSERM U955, Equipe 18 , Créteil , France
| | - Oumar Dolo
- f SEREFO/UCRC, FMOS, Université des Sciences Techniques et des Technologies de Bamako , Bamako , Mali
| | - Sophie Sayon
- a Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie , Paris , France
| | - Alhassane Ba
- b Centre National de Transfusion Sanguine , Bamako , Mali.,g Service de santé des armées , Kati , Mali
| | - Ségolène Brichler
- c Laboratoire de Microbiologie Clinique, Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Université Sorbonne Paris Cité , Bobigny , France.,d Centre national de référence des virus des hépatites B, C et Delta, Laboratoire de Virologie , Bobigny , France.,e Unité INSERM U955, Equipe 18 , Créteil , France
| | - Fatoumata Tata Traore
- f SEREFO/UCRC, FMOS, Université des Sciences Techniques et des Technologies de Bamako , Bamako , Mali
| | - Emmanuel Gordien
- c Laboratoire de Microbiologie Clinique, Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Université Sorbonne Paris Cité , Bobigny , France.,d Centre national de référence des virus des hépatites B, C et Delta, Laboratoire de Virologie , Bobigny , France.,e Unité INSERM U955, Equipe 18 , Créteil , France
| | - Josue Togo
- f SEREFO/UCRC, FMOS, Université des Sciences Techniques et des Technologies de Bamako , Bamako , Mali
| | - Vincent Calvez
- a Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie , Paris , France
| | - Anne-Geneviève Marcelin
- a Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie , Paris , France
| | - Almoustapha Issiaka Maiga
- f SEREFO/UCRC, FMOS, Université des Sciences Techniques et des Technologies de Bamako , Bamako , Mali.,h Clinical and Microbiology Department , University Hospital Gabriel Toure , Bamako , Mali
| | - Eve Todesco
- a Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie , Paris , France
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30
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Puigvehí M, Moctezuma-Velázquez C, Villanueva A, Llovet JM. The oncogenic role of hepatitis delta virus in hepatocellular carcinoma. JHEP Rep 2019; 1:120-130. [PMID: 32039360 PMCID: PMC7001537 DOI: 10.1016/j.jhepr.2019.05.001] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Revised: 04/18/2019] [Accepted: 05/05/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis delta virus (HDV) is a small defective virus that needs hepatitis B virus (HBV) to replicate and propagate. HDV infection affects 20-40 million people worldwide and pegylated interferon (PegIFN) is the only recommended therapy. There is limited data on the contribution of HDV infection to HBV-related liver disease or liver cancer. Evidence from retrospective and cohort studies suggests that HBV/HDV coinfection accelerates progression to cirrhosis and is associated with an increased risk of hepatocellular carcinoma (HCC) development compared to HBV monoinfection. Although the life cycle of HDV is relatively well known, there is only ancillary information on the molecular mechanisms that can drive specific HDV-related oncogenesis. No thorough reports on the specific landscape of mutations or molecular classes of HDV-related HCC have been published. This information could be critical to better understand the uniqueness, if any, of HDV-related HCC and help identify novel targetable mutations. Herein, we review the evidence supporting an oncogenic role of HDV, the main reported mechanisms of HDV involvement and their impact on HCC development.
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Affiliation(s)
- Marc Puigvehí
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Hepatology Section, Gastroenterology Department, Hospital del Mar, IMIM, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
| | - Carlos Moctezuma-Velázquez
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Augusto Villanueva
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.,Denotes co-senior authorship
| | - Josep M Llovet
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain.,Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain.,Denotes co-senior authorship
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31
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White SL, Rawlinson W, Boan P, Sheppeard V, Wong G, Waller K, Opdam H, Kaldor J, Fink M, Verran D, Webster A, Wyburn K, Grayson L, Glanville A, Cross N, Irish A, Coates T, Griffin A, Snell G, Alexander SI, Campbell S, Chadban S, Macdonald P, Manley P, Mehakovic E, Ramachandran V, Mitchell A, Ison M. Infectious Disease Transmission in Solid Organ Transplantation: Donor Evaluation, Recipient Risk, and Outcomes of Transmission. Transplant Direct 2019; 5:e416. [PMID: 30656214 PMCID: PMC6324914 DOI: 10.1097/txd.0000000000000852] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 08/15/2018] [Indexed: 12/11/2022] Open
Abstract
In 2016, the Transplantation Society of Australia and New Zealand, with the support of the Australian Government Organ and Tissue authority, commissioned a literature review on the topic of infectious disease transmission from deceased donors to recipients of solid organ transplants. The purpose of this review was to synthesize evidence on transmission risks, diagnostic test characteristics, and recipient management to inform best-practice clinical guidelines. The final review, presented as a special supplement in Transplantation Direct, collates case reports of transmission events and other peer-reviewed literature, and summarizes current (as of June 2017) international guidelines on donor screening and recipient management. Of particular interest at the time of writing was how to maximize utilization of donors at increased risk for transmission of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus, given the recent developments, including the availability of direct-acting antivirals for hepatitis C virus and improvements in donor screening technologies. The review also covers emerging risks associated with recent epidemics (eg, Zika virus) and the risk of transmission of nonendemic pathogens related to donor travel history or country of origin. Lastly, the implications for recipient consent of expanded utilization of donors at increased risk of blood-borne viral disease transmission are considered.
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Affiliation(s)
- Sarah L White
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
| | - William Rawlinson
- Serology and Virology Division, NSW Health Pathology Prince of Wales Hospital, Sydney, Australia
- Women's and Children's Health and Biotechnology and Biomolecular Sciences, University of New South Wales Schools of Medicine, Sydney, Australia
| | - Peter Boan
- Departments of Infectious Diseases and Microbiology, Fiona Stanley Hospital, Perth, Australia
- PathWest Laboratory Medicine, Perth, Australia
| | - Vicky Sheppeard
- Communicable Diseases Network Australia, New South Wales Health, Sydney, Australia
| | - Germaine Wong
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Karen Waller
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
| | - Helen Opdam
- Austin Health, Melbourne, Australia
- The Organ and Tissue Authority, Australian Government, Canberra, Australia
| | - John Kaldor
- Kirby Institute, University of New South Wales, Sydney, Australia
| | - Michael Fink
- Austin Health, Melbourne, Australia
- Department of Surgery, Melbourne Medical School, The University of Melbourne, Melbourne, Australia
| | - Deborah Verran
- Transplantation Services, Royal Prince Alfred Hospital, Sydney, Australia
| | - Angela Webster
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, Australia
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Kate Wyburn
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
- Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia
| | - Lindsay Grayson
- Austin Health, Melbourne, Australia
- Department of Surgery, Melbourne Medical School, The University of Melbourne, Melbourne, Australia
| | - Allan Glanville
- Department of Thoracic Medicine and Lung Transplantation, St Vincent's Hospital, Sydney, Australia
| | - Nick Cross
- Department of Nephrology, Canterbury District Health Board, Christchurch Hospital, Christchurch, New Zealand
| | - Ashley Irish
- Department of Nephrology, Fiona Stanley Hospital, Perth, Australia
- Faculty of Health and Medical Sciences, UWA Medical School, The University of Western Australia, Crawley, Australia
| | - Toby Coates
- Renal and Transplantation, Royal Adelaide Hospital, Adelaide, Australia
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
| | - Anthony Griffin
- Renal Transplantation, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
| | - Greg Snell
- Lung Transplant, Alfred Health, Melbourne, Victoria, Australia
| | - Stephen I Alexander
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
| | - Scott Campbell
- Department of Renal Medicine, University of Queensland at Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
| | - Steven Chadban
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
- Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia
| | - Peter Macdonald
- Department of Cardiology, St Vincent's Hospital, Sydney, Australia
- St Vincent's Hospital Victor Chang Cardiac Research Institute, University of New South Wales, Sydney, Australia
| | - Paul Manley
- Kidney Disorders, Auckland District Health Board, Auckland City Hospital, Auckland, New Zealand
| | - Eva Mehakovic
- The Organ and Tissue Authority, Australian Government, Canberra, Australia
| | - Vidya Ramachandran
- Serology and Virology Division, NSW Health Pathology Prince of Wales Hospital, Sydney, Australia
| | - Alicia Mitchell
- Department of Thoracic Medicine and Lung Transplantation, St Vincent's Hospital, Sydney, Australia
- Woolcock Institute of Medical Research, Sydney, Australia
- School of Medical and Molecular Biosciences, University of Technology, Sydney, Australia
| | - Michael Ison
- Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL
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33
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Goodrum G, Pelchat M. Insight into the Contribution and Disruption of Host Processes during HDV Replication. Viruses 2018; 11:v11010021. [PMID: 30602655 PMCID: PMC6356607 DOI: 10.3390/v11010021] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 12/18/2018] [Accepted: 12/30/2018] [Indexed: 02/07/2023] Open
Abstract
Hepatitis delta virus (HDV) is unique among animal viruses. HDV is a satellite virus of the hepatitis B virus (HBV), however it shares no sequence similarity with its helper virus and replicates independently in infected cells. HDV is the smallest human pathogenic RNA virus and shares numerous characteristics with viroids. Like viroids, HDV has a circular RNA genome which adopts a rod-like secondary structure, possesses ribozyme domains, replicates in the nucleus of infected cells by redirecting host DNA-dependent RNA polymerases (RNAP), and relies heavily on host proteins for its replication due to its small size and limited protein coding capacity. These similarities suggest an evolutionary relationship between HDV and viroids, and information on HDV could allow a better understanding of viroids and might globally help understanding the pathogenesis and molecular biology of these subviral RNAs. In this review, we discuss the host involvement in HDV replication and its implication for HDV pathogenesis.
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Affiliation(s)
- Gabrielle Goodrum
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
| | - Martin Pelchat
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
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34
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Daw MA, Daw AM, Sifennasr NEM, Draha AM, Daw AM, Daw AM, Ahmed MO, Mokhtar ES, El-Bouzedi A, Daw IM. The Epidemiology of Hepatitis D Virus in North Africa: A Systematic Review and Meta-Analysis. ScientificWorldJournal 2018; 2018:9312650. [PMID: 30356409 PMCID: PMC6178169 DOI: 10.1155/2018/9312650] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 07/25/2018] [Accepted: 08/27/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Hepatitis D virus (HDV) infection has been considered a serious neglected pandemic, particularly in developing countries. The virus causes a more severe disease than mono infection with hepatitis B virus (HBV). The epidemiology of HDV is not well documented in North Africa, which is known to be endemic for HBV. In this study, we explored the prevalence of HDV infection and also attempted to identify factors associated with hepatitis D positive status among chronic hepatitis B patients in North Africa. METHODS The electronic databases PubMed, Embase, Scopus, Science Direct, Web of Science, and Google Scholar were comprehensively searched for all papers published between January 1, 1998, and December 31, 2017, using appropriate strategies containing all related keywords, including North Africa, names of countries in the region, and all permutations of hepatitis D virus. The estimated prevalence of HDV in North Africa was calculated as an average of the pooled infection prevalence in each country weighted by the ratio of the country's hepatitis D virus population to the study's sample size in the survey data analysis. FINDINGS A total of 312 studies were identified and 32 were included in this study, with a total sample of 4907 individuals screened for HDV. There was considerable variability in the prevalence estimates of HDV within the countries of the region. The overall prevalence of HDV in the general population of North Africa was 5·01% (95% CI: 1·25-8·27) and in liver disease patients it was 20.7% (95% CI:9.87-44.53). Genotype-1 was the most prominent genotype reported in five published studies. Ten studies reported on HDV RNA in participants who were seropositive for HDV, and four studies highlighted the impact of demographic factors (sex and age). No study showed the impact of risk factors on the prevalence of HDV in North Africa. INTERPRETATION This review provides a comprehensive assessment of the burden of HDV in Northern Africa. There were significant differences in seroprevalence, study population, and diagnostic testing between the countries in the region. The results presented here will alert health professionals to implement clear policies based on evidence to diminish the burden of HDV infection. Such measures may include but are not restricted to improving the laboratory diagnostic tests and initiating patient data registries and blood screening. Further epidemiological and research studies are needed to explore the risk factors, coinfections, and approaches to increase testing for HDV, particularly in high-risk subpopulations, such as intravenous drug users and immigrants, and to define the consequences of HDV infection in North Africa.
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Affiliation(s)
- Mohamed A. Daw
- Department of Medical Microbiology & Immunology, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Amina M. Daw
- Department of General Medicine, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Nadia E. M. Sifennasr
- Department of Medical Microbiology & Immunology, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Aisha M. Draha
- Department of Pharmacology, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Ahmed M. Daw
- Tripoli Medical Centre, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Ali M. Daw
- Tripoli Medical Centre, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Mohamed O. Ahmed
- Department of Microbiology and Parasitology, Faculty of Veterinary Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Ebtisam S. Mokhtar
- Department of Medical Microbiology & Immunology, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Abdallah El-Bouzedi
- Department of Laboratory Medicine, Faculty of Biotechnology, University of Tripoli, CC 82668, Tripoli, Libya
| | - Ibrahem M. Daw
- Department of Planning, Faculty of Engineering, University of Tripoli, CC 82668, Tripoli, Libya
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Ricco G, Popa DC, Cavallone D, Iacob S, Salvati A, Tabacelia D, Oliveri F, Mascolo G, Bonino F, Yuan Q, Xia NS, Gheorghe L, Brunetto MR. Quantification of serum markers of hepatitis B (HBV) and Delta virus (HDV) infections in patients with chronic HDV infection. J Viral Hepat 2018; 25:911-919. [PMID: 29577518 DOI: 10.1111/jvh.12895] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 02/28/2018] [Indexed: 12/31/2022]
Abstract
The interplay between hepatitis B (HBV) and delta (HDV) viruses is complex and not always characterized during chronic HDV infection. We assessed the clinical usefulness of new quantitative assays for HBV and HDV serum markers in a retrospective cross-sectional study. Sera obtained from 122 HDV genotype 1 and HBV genotype D coinfected, anti-HIV-negative patients (71 males; median age 49.8 [21.7-66.9] years), recruited consecutively in two geographical areas (Italy 69 patients, Romania 53 patients) with different HBV and HDV epidemiology, were tested for HBsAg, HBV-DNA, HBcrAg, total anti-HBc, HDV-RNA, IgM and total anti-HDV using quantitative assays. Cirrhosis, which showed comparable prevalence in the two cohorts, was diagnosed in 97 of 122 (79.5%) patients. At multivariate analysis, cirrhosis was associated with lower total anti-HBc/IgM anti-HDV ratio (OR 0.990, 95% CI 0.981-0.999, P = .038), whereas disease activity was associated with higher total anti-HDV (OR 10.105, 95% CI 1.671-61.107, P = .012) and HDV-RNA levels (OR 2.366, 95% CI 1.456-3.844, P = .001). HDV-RNA serum levels showed a positive correlation with HBV-DNA (ρ = 0.276, P = .005), HBsAg (ρ = 0.404, P < .001) and HBcrAg (ρ = 0.332, P < .001). The combined quantitative profiling of HBV and HDV serum markers identifies specific patterns associated with activity and stage of chronic hepatitis D (CHD). HDV pathogenicity depends on the underlying active HBV infection in spite of the inhibition of its replication. HDV-RNA, IgM anti-HDV, total anti-HDV, total anti-HBc, HBsAg and HBcrAg serum levels qualify for prospective studies to predict progressive CHD and identify candidates to antiviral therapy.
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Affiliation(s)
- G Ricco
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy
- Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - D C Popa
- Department of Biochemistry, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Bone Marrow Transplant Laboratory, Fundeni Clinical Institute, Bucharest, Romania
| | - D Cavallone
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy
| | - S Iacob
- Department of Gastroenterology and Hepatology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Center for Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - A Salvati
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy
| | - D Tabacelia
- Center for Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - F Oliveri
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy
| | - G Mascolo
- Dia.Pro Diagnostic Bioprobes Srl, Sesto San Giovanni, Milan, Italy
| | - F Bonino
- University of Pittsburgh Medical Center (UPMC) Institute for Health, Chianciano Terme, Siena and Fondazione Italiana Fegato (FIF), AREA Science Park, Trieste, Italy
| | - Q Yuan
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
| | - N-S Xia
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
| | - L Gheorghe
- Department of Gastroenterology and Hepatology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Center for Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - M R Brunetto
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy
- Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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Coghill S, McNamara J, Woods M, Hajkowicz K. Epidemiology and clinical outcomes of hepatitis delta (D) virus infection in Queensland, Australia. Int J Infect Dis 2018; 74:123-127. [PMID: 30003953 DOI: 10.1016/j.ijid.2018.07.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 07/03/2018] [Accepted: 07/04/2018] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVES To investigate the epidemiology, clinical characteristics and outcomes of those with hepatitis delta virus (HDV) infection in Queensland, Australia. DESIGN Retrospective cohort study of individuals tested for HDV between 1997 and 2016 in the public healthcare system in Queensland. RESULTS 179 individuals recorded positive HDV serology between 1997 and 2016, with a total of 4407 individuals undergoing testing (seroprevalence 4.1%). The majority of HDV positive individuals were male and were born overseas. Those born in Africa had a higher risk ratio (RR) for HDV infection (RR, 1.55; 95% CI, 1.14-2.09); being born in Asia was associated with a relatively lower risk of HDV infection (RR, 0.36; 95% CI, 0.27-0.58). Positive hepatitis C virus (HCV) serology was significantly associated with positive HDV serology (RR, 2.98; 95% CI, 2.36-3.78). Of the HDV positive individuals born in Australia, the majority were HCV positive (69.8%). HDV positive individuals were less likely to be Hepatitis B e antigen (HBeAg) positive (RR, 0.64; 95% CI, 0.45-0.93) and recorded lower hepatitis B virus (HBV) viral loads. Positive HDV serology was associated with increased risk of liver cirrhosis (RR, 2.3; 95% CI 1.73-3.07) and liver transplantation (RR, 1.93; CI 1.31-2.85). Only 8% of HDV positive individuals underwent HDV treatment. CONCLUSIONS In Queensland, HDV seropositivity is associated with overseas birth, particularly in Africa. HDV infection is associated with decreased HBV viraemia and more advanced liver disease.
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Affiliation(s)
- Sarah Coghill
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia; School of Clinical Medicine, University of Queensland, Australia.
| | - John McNamara
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia
| | - Marion Woods
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia; School of Clinical Medicine, University of Queensland, Australia
| | - Krispin Hajkowicz
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia; School of Clinical Medicine, University of Queensland, Australia
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Binh MT, Hoan NX, Van Tong H, Giang DP, Sy BT, Toan NL, Song LH, Bang MH, Wedemeyer H, Meyer CG, Kremsner PG, Bock CT, Velavan TP. HDV infection rates in northern Vietnam. Sci Rep 2018; 8:8047. [PMID: 29795302 PMCID: PMC5966401 DOI: 10.1038/s41598-018-26446-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 05/11/2018] [Indexed: 12/18/2022] Open
Abstract
Hepatitis D caused by the hepatitis delta virus (HDV) is a serious health problem in many regions of the world. A total of 546 HBV-infected patients were enrolled from 2013 to 2015 and classified clinically into the subgroups of chronic hepatitis B (CHB, n = 191), liver cirrhosis (LC, n = 147) and hepatocellular carcinoma (HCC, n = 208). The patients were screened for HDV-RNA by nested PCR assays. HDV genotypes were assessed by direct sequencing, followed by phylogenetic analysis. HDV-RNA was identified in 13% (71/546) of HBV-infected patients. The highest HDV prevalence was found in the LC group (19.7%), followed by the HCC (12%) and CHB (8.9%) groups (P = 0.017). HDV/HBV coinfections were significantly associated with a rather unfavourable clinical outcome, in particular with LC development compared to HBV monoinfection. Phylogenetic analyses indicated that the genotype HDV1 was, with a prevalence of 91%, by far the most common genotype in Vietnam, followed by HDV2 with 9%. Other HDV genotypes were not observed. In accordance with previous data obtained a decade ago, our results confirm a continuing high prevalence of HDV infection in hepatitis B patients in northern Vietnam with the HDV1 genotype still being the predominant genotype. HDV nucleic acid testing to minimize the associated risk should be considered.
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Affiliation(s)
- Mai Thanh Binh
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Excellence in Medical Research, Hanoi, Vietnam
- 108 Military Central Hospital, Hanoi, Vietnam
| | - Nghiem Xuan Hoan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Excellence in Medical Research, Hanoi, Vietnam
- 108 Military Central Hospital, Hanoi, Vietnam
| | - Hoang Van Tong
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Excellence in Medical Research, Hanoi, Vietnam
- Vietnamese Military Medical University, Hanoi, Vietnam
| | - Dao Phuong Giang
- Vietnamese-German Center for Excellence in Medical Research, Hanoi, Vietnam
- 108 Military Central Hospital, Hanoi, Vietnam
| | - Bui Tien Sy
- Vietnamese-German Center for Excellence in Medical Research, Hanoi, Vietnam
- 108 Military Central Hospital, Hanoi, Vietnam
| | - Nguyen Linh Toan
- Vietnamese-German Center for Excellence in Medical Research, Hanoi, Vietnam
- Vietnamese Military Medical University, Hanoi, Vietnam
| | - Le Huu Song
- Vietnamese-German Center for Excellence in Medical Research, Hanoi, Vietnam
- 108 Military Central Hospital, Hanoi, Vietnam
| | | | - Heiner Wedemeyer
- Department. for Gastroenterology and Hepatology Medical Center, University Hospital Essen, Essen, Germany
| | - Christian G Meyer
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Excellence in Medical Research, Hanoi, Vietnam
- Faculty of Medicine, Duy Tan University, Da Nang, Vietnam
| | - Peter G Kremsner
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - C-Thomas Bock
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
| | - Thirumalaisamy P Velavan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
- Vietnamese-German Center for Excellence in Medical Research, Hanoi, Vietnam.
- Faculty of Medicine, Duy Tan University, Da Nang, Vietnam.
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Katwesigye E, Seremba E, Semitala F, Ocama P. Low sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis B co-infected patients attending an urban HIV clinic in Uganda. Afr Health Sci 2017; 17:974-978. [PMID: 29937867 PMCID: PMC5870270 DOI: 10.4314/ahs.v17i4.4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Background Co-infection with hepatitis B (HBV) and hepatitis D (HDV) is common among human immunodeficiency virus (HIV) infected individuals in developing countries and it aggressively accelerates progression of liver disease to cirrhosis and other complications. There is scarcity of data on HDV in sub-Saharan Africa .We investigated the sero-prevalence and factors associated with HDV antibody among HIV/HBV co-infected patients attending a large urban HIV clinic in Uganda. Methods We screened 189 HIV/HBV co-infected individuals for anti-HDV immunoglobulin G (IgG) and performed logistic regression to determine the associated factors. Socio-demographic, clinical data, immunological status, and liver fibrosis (as determined by the Aspartate transaminase to platelet ratio index and transient elastography) were included. Results Participants were predominately young and of sound immunologic status (median age 40 years, median CD4 440 cells/µl). 98% were on ART regimens containing anti-HBV active medications (95.2% were on TDF/3TC while 4.8% on 3TC containing regimen). Median duration on ART was 36 months (IQR 22–72). Anti-HDV was detected in 6/198, 3.2% (95% CI 1.14–6.92%), associated with male gender and a duration of more than 5 years since HIV diagnosis. Conclusions The sero-prevalence of HDV antibodies among the HIV/HBV co-infected patients is low in a Ugandan urban cohort.
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Affiliation(s)
- Elizabeth Katwesigye
- Department of Medicine, Mulago Hospital and Makerere University College of Health Sciences, Kampala, Uganda
| | | | - Fred Semitala
- Department of Medicine, Mulago Hospital and Makerere University College of Health Sciences, Kampala, Uganda
| | - Ponsiano Ocama
- Department of Medicine, Mulago Hospital and Makerere University College of Health Sciences, Kampala, Uganda
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Abstract
Hepatitis D virus (HDV) infection leads to the most severe form of chronic viral hepatitis and requires the attention of a liver specialist. In this review, I will recapitulate recent advances in the management of HDV, present background information on HDV infection as well as current chronic hepatitis D treatment, briefly examine the HDV life cycle and discuss new management strategies.
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Affiliation(s)
- Cihan Yurdaydin
- Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.,Hepatology Institute, University of Ankara, Ankara, Turkey
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40
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Lempp FA, Urban S. Hepatitis Delta Virus: Replication Strategy and Upcoming Therapeutic Options for a Neglected Human Pathogen. Viruses 2017; 9:E172. [PMID: 28677645 PMCID: PMC5537664 DOI: 10.3390/v9070172] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 06/28/2017] [Accepted: 06/29/2017] [Indexed: 12/15/2022] Open
Abstract
The human Hepatitis Delta Virus (HDV) is unique among all viral pathogens. Encoding only one protein (Hepatitis Delta Antigen; HDAg) within its viroid-like self-complementary RNA, HDV constitutes the smallest known virus in the animal kingdom. To disseminate in its host, HDV depends on a helper virus, the human Hepatitis B virus (HBV), which provides the envelope proteins required for HDV assembly. HDV affects an estimated 15-20 million out of the 240 million chronic HBV-carriers and disperses unequally in disparate geographical regions of the world. The disease it causes (chronic Hepatitis D) presents as the most severe form of viral hepatitis, leading to accelerated progression of liver dysfunction including cirrhosis and hepatocellular carcinoma and a high mortality rate. The lack of approved drugs interfering with specific steps of HDV replication poses a high burden for gaining insights into the molecular biology of the virus and, consequently, the development of specific novel medications that resiliently control HDV replication or, in the best case, functionally cure HDV infection or HBV/HDV co-infection. This review summarizes our current knowledge of HBV molecular biology, presents an update on novel cell culture and animal models to study the virus and provides updates on the clinical development of the three developmental drugs Lonafarnib, REP2139-Ca and Myrcludex B.
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Affiliation(s)
- Florian A Lempp
- Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
- German Centre for Infection Research (DZIF), Partner Site Heidelberg, 69120 Heidelberg, Germany.
| | - Stephan Urban
- Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
- German Centre for Infection Research (DZIF), Partner Site Heidelberg, 69120 Heidelberg, Germany.
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41
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Coffie PA, Tchounga BK, Bado G, Kabran M, Minta DK, Wandeler G, Gottlieb GS, Dabis F, Eholie SP, Ekouevi DK. Prevalence of hepatitis B and delta according to HIV-type: a multi-country cross-sectional survey in West Africa. BMC Infect Dis 2017; 17:466. [PMID: 28676076 PMCID: PMC5496401 DOI: 10.1186/s12879-017-2568-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 06/26/2017] [Indexed: 12/22/2022] Open
Abstract
Background In West Africa where HIV-1 and HIV-2 co-circulate, the co-infection with hepatitis B virus (HBV) and hepatitis Delta virus (HDV) is not well described. This study aimed at estimating the prevalence of HBV and HBV/HDV co-infection according to HIV types and risk factors for HBV infection among West African HIV-infected patients. Method A cross-sectional survey was conducted within the IeDEA West Africa cohort from March to December 2012 in Côte d’Ivoire (three sites), Burkina Faso and Mali (one site each). All HIV-infected adult patients on antiretroviral therapy (ART) or not who attended one of the participating HIV clinics during the study period and agreed to participate were included. Blood samples were collected and re-tested for HIV type discrimination, HBV and HDV serology as well as HBV viral load. Logistic regression was used to identify risk factors for HBV infection. Results A total of 791 patients were included: 192 HIV-1, 447 HIV-2 and 152 HIV-1&2 dually reactive. At time of sampling, 555 (70.2%) were on ART and median CD4+ cell count was 472/mm3 (inter-quartile range [IQR]: IQR: 294–644). Sixty-seven (8.5%, 95% CI 6.6–10.6) patients were HBsAg positive without any difference according to HIV type (7.9% in HIV-1, 7.2% in HIV-1&2 dually reactive and 9.4% in HIV-2; p = 0.61). In multivariate logistic analysis, age ≤ 30 years old (adjusted odds ratio [aOR] 5.00, 95% CI 1.96–12.76), age between 31 and 49 years old (aOR 1.78, 95% CI 1.00–2.21) and male gender (aOR 2.15, 95% CI 1.25–3.69) were associated with HBsAg positivity. HBV DNA testing was performed in 36 patients with blood sample available (25 on ART) and 8 (22.2%) had detectable HBV DNA. Among the HBsAg-positive individuals, 14.9% (95% CI 7.4–25.7) were also positive for anti-HDV antibody without any difference according to HIV type (28.6% in HIV-1, 14.3% in HIV-2 and 0.0% in HIV-1&2 dually reactive; p = 0.15). Conclusion HBV and HBV/HDV co-infection are common in West Africa, irrespective of HIV type. Therefore, screening for both viruses should be systematically performed to allow a better management of HIV-infected patients. Follow-up studies are necessary to determine the impact of these two viruses on HIV infection.
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Affiliation(s)
- Patrick A Coffie
- Département de Dermatologie et d'Infectiologie, UFR des Sciences Médicales, Université Félix Houphouët Boigny, BP V3 Abidjan, CHU de Treichville, Abidjan, Côte d'Ivoire. .,Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Treichville, Abidjan, Côte d'Ivoire. .,Programme PACCI, site de recherche ANRS, Abidjan, Côte d'Ivoire.
| | - Boris K Tchounga
- Programme PACCI, site de recherche ANRS, Abidjan, Côte d'Ivoire.,ISPED, Université de Bordeaux & Centre INSERM U1219 - Bordeaux Population Health, Bordeaux, France
| | - Guillaume Bado
- Hôpital de Jour, Service des Maladies Infectieuses et Tropicales, CHU Souro Sanou, Bobo Dioulasso, Burkina Faso
| | - Mathieu Kabran
- Département d'Hématologie, d'immunologie et de biologie cellulaire, UFR des Sciences Pharmaceutiques, Université Félix Houphouët Boigny, Abidjan, Côte d'Ivoire
| | - Daouda K Minta
- Centre de Prise en Charge des Personnes vivant avec le VIH, Service de Maladies Infectieuses, Hôpital du Point G, Bamako, Mali
| | - Gilles Wandeler
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.,Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - Geoffrey S Gottlieb
- Departments of Medicine & Global Health, University of Washington, Seattle, USA
| | - François Dabis
- ISPED, Université de Bordeaux & Centre INSERM U1219 - Bordeaux Population Health, Bordeaux, France
| | - Serge P Eholie
- Département de Dermatologie et d'Infectiologie, UFR des Sciences Médicales, Université Félix Houphouët Boigny, BP V3 Abidjan, CHU de Treichville, Abidjan, Côte d'Ivoire.,Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Treichville, Abidjan, Côte d'Ivoire.,Programme PACCI, site de recherche ANRS, Abidjan, Côte d'Ivoire
| | - Didier K Ekouevi
- Programme PACCI, site de recherche ANRS, Abidjan, Côte d'Ivoire.,ISPED, Université de Bordeaux & Centre INSERM U1219 - Bordeaux Population Health, Bordeaux, France.,Université de Lomé, Département des Sciences Fondamentales et Santé Publique, Lomé, Togo
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Elazar M, Koh C, Glenn JS. Hepatitis delta infection - Current and new treatment options. Best Pract Res Clin Gastroenterol 2017; 31:321-327. [PMID: 28774414 DOI: 10.1016/j.bpg.2017.05.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 05/13/2017] [Indexed: 01/31/2023]
Abstract
In humans, hepatitis D virus (HDV) infection only occurs in the presence of a concomitant hepatitis B virus (HBV) infection, and induces the most severe form of human viral hepatitis. Even though HDV is spread worldwide and is endemic in some regions, screening and treatment has been often neglected in part due to the lack of an effective therapy. Moreover, HDV prevalence rates are increasing in many countries driven by immigration from areas of high endemicity. Currently, no FDA-approved anti-HDV therapy is available, although interferon (IFN) alpha therapy has demonstrated benefit in a minority of patients. In this review, we present a current view of our understanding of the epidemiology, molecular virology and management of HDV infection. We additionally discuss new treatment approaches in development and describe the most promising results of recent and ongoing clinical trials of these new potential agents.
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Affiliation(s)
- Menashe Elazar
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA 94305, USA.
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, NIH, 10 Center Drive, CRC, 5-2740 Bethesda, MD 20892 USA.
| | - Jeffrey S Glenn
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA 94305, USA; Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Veterans Administration Medical Center, Palo Alto, CA, USA.
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Prevalence of Hepatitis D Virus Infection and Associated Factors Among HBsAg-Positive Patients in Birjand, Iran, 2012 - 2014. HEPATITIS MONTHLY 2017. [DOI: 10.5812/hepatmon.42866] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Affiliation(s)
| | - Abdurrahman Sahin
- Department of Gastroenterology, Medicine Faculty, Firat University, Elazig, Turkey
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Takyar V, Surana P, Kleiner DE, Wilkins K, Hoofnagle JH, Liang TJ, Heller T, Koh C. Noninvasive markers for staging fibrosis in chronic delta hepatitis. Aliment Pharmacol Ther 2017; 45:127-138. [PMID: 27813124 PMCID: PMC5135658 DOI: 10.1111/apt.13834] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 08/21/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Serum fibrosis markers are useful in staging chronic hepatitis B (HBV) and C (HCV) virus but have not been evaluated in chronic hepatitis D virus (HDV). AIM To evaluate the utility of serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, aspartate aminotransferase ratio (AAR), age-platelet index (API), AST-to-platelet-ratio-index (APRI) and Hui score] in HDV infection. METHODS Clinical and histologic laboratory data from HBV, HCV and HDV patients were evaluated and serum fibrosis markers were calculated. The ability of fibrosis markers to detect advanced fibrosis (Ishak ≥4) and cirrhosis (Ishak = 6) were evaluated and compared between viral infections. RESULTS A total of 1003 subjects (HCV = 701, HBV = 240 and HDV = 62) with mean age of 46 ± 11 and 66% male were evaluated. HDV subjects had higher ALT and AST than HCV and lower platelets than both HBV and HCV. Histologically, HDV had the greatest percentage of Ishak ≥4 and necroinflammation. FIB-4 performed best in detecting advanced fibrosis and cirrhosis in all viral cohorts. In HDV, area under the receiver operator curve (AUROC) 95% confidence intervals for detecting advanced fibrosis were: FIB-4 = 0.70 (0.55-0.84), API = 0.69 (0.55-0.82), APRI = 0.68 (0.54-0.82), Hui score = 0.63 (0.49-0.78), AAR = 0.63 (0.48-0.77). The AUROC for detecting cirrhosis in HDV were: FIB-4 = 0.83 (0.69-0.97), API = 0.80 (0.66-0.95), APRI = 0.75 (0.61-0.89), Hui score = 0.70 (0.49-0.91) and AAR = 0.70 (0.48-0.93). Adjustment of published cut-offs led to marginal improvements in FIB4 for advanced fibrosis and of APRI for cirrhosis in HDV. CONCLUSIONS Serum fibrosis markers have lower performance accuracy in chronic HDV infected patients compared to HBV and HCV patients. Other noninvasive fibrosis markers should be explored to assist in the management of these patients.
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Affiliation(s)
- Varun Takyar
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Pallavi Surana
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - David E. Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Kenneth Wilkins
- Office of the Director, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Jay H. Hoofnagle
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - T. Jake Liang
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Katwesigye E, Seremba E, Semitala F, Ocama P. Low sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis B co-infected patients attending an urban HIV clinic in Uganda. Afr Health Sci 2016; 16:1089-1093. [PMID: 28479902 DOI: 10.4314/ahs.v16i4.26] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Co-infection with hepatitis B (HBV) and hepatitis D (HDV) is common among human immunodeficiency virus (HIV) infected individuals in developing countries and it aggressively accelerates progression of liver disease to cirrhosis and other complications. There is scarcity of data on HDV in sub-Saharan Africa .We investigated the sero-prevalence and factors associated with HDV antibody among HIV/HBV co-infected patients attending a large urban HIV clinic in Uganda. METHODS We screened 189 HIV/HBV co-infected individuals for anti-HDV immunoglobulin G (IgG) and performed logistic regression to determine the associated factors. Socio-demographic, clinical data, immunological status, and liver fibrosis (as determined by the Aspartate transaminase to platelet ratio index and transient elastography) were included. RESULTS Participants were predominately young and of sound immunologic status (median age 40 years, median CD4 440 cells/µl). 98% were on ART regimens containing anti-HBV active medications (95.2% were on TDF/3TC while 4.8% on 3TC containing regimen). Median duration on ART was 36 months (IQR 22-72). Anti-HDV was detected in 6/198, 3.2% (95% CI 1.14-6.92%), associated with male gender and a duration of more than 5 years since HIV diagnosis. CONCLUSIONS The sero-prevalence of HDV antibodies among the HIV/HBV co-infected patients is low in a Ugandan urban cohort.
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Affiliation(s)
- Elizabeth Katwesigye
- Department of Medicine, Mulago Hospital and Makerere University College of Health Sciences, Kampala, Uganda
| | | | - Fred Semitala
- Department of Medicine, Mulago Hospital and Makerere University College of Health Sciences, Kampala, Uganda
| | - Ponsiano Ocama
- Department of Medicine, Mulago Hospital and Makerere University College of Health Sciences, Kampala, Uganda
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Hsieh MH, Wang SC, Hsieh MY, Huang CF, Yeh ML, Yang JF, Chang K, Lin WR, Lin CY, Chen TC, Huang JF, Dai CY, Tsai JJ, Chuang WL, Yu ML. Hepatitis D virus infections among injecting drug users with and without human immunodeficiency virus infection in Taiwan. Kaohsiung J Med Sci 2016; 32:526-530. [PMID: 27742037 DOI: 10.1016/j.kjms.2016.08.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 08/01/2016] [Accepted: 07/27/2016] [Indexed: 11/19/2022] Open
Abstract
In Taiwan, injecting drug use has been the main route of human immunodeficiency virus (HIV) transmission since 2005, with hepatitis B virus (HBV) and hepatitis D virus (HDV) also having similar transmission routes. This has now become an important public health issue. The aim of this study is to explore the conditions of HDV infections between injecting drug users (IDUs) with and without HIV infection in Southern Taiwan. In this study, 87 IDUs were enrolled, including 27 anti-HDV seronegative IDUs and 60 anti-HDV seropositive IDUs, and the results of their liver function tests, CD4 cell counts, and anti-HIV and HIV RNA levels were analyzed. The prevalence of anti-HDV seropositivity among hepatitis B surface antigen (HBsAg) seropositive IDUs in this study was 68.9% (60/87). The prevalence rate of anti-HDV seropositive IDUs among anti-HIV seronegative and anti-HIV seropositive cases was 40.0% (12/30) and 84.2% (48/57), respectively. Anti-HIV seropositivity was related to anti-HDV seropositivity (odds ratio = 9.34, 95% confidence interval = 2.67-31.59, p < 0.001). Among IDUs with HIV infection, there was no significant difference in CD4 cell counts and HIV RNA viral load between HBsAg-positive patients with anti-HDV seronegativity and those with anti-HDV seropositivity. In conclusion, the prevalence of HDV infection among IDUs is higher among IDUs with HIV infection. Because anti-HIV seropositivity is significantly related to anti-HDV seropositivity, HDV infection among IDUs is still important. We suggest that for IDUs, HBsAg and anti-HDV should be monitored closely.
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Affiliation(s)
- Meng-Hsuan Hsieh
- Health Management Center, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Shu-Chi Wang
- Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Ming-Yen Hsieh
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Chung-Feng Huang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung City, Taiwan
| | - Ming-Lun Yeh
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Jeng-Fu Yang
- Health Management Center, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Ko Chang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung City, Taiwan
| | - Wei-Ru Lin
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Chun-Yu Lin
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Tun-Chieh Chen
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Jee-Fu Huang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Chia-Yen Dai
- Health Management Center, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Jih-Jin Tsai
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan; Tropical Medicine Center, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan.
| | - Wan-Long Chuang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Ming-Lung Yu
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
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48
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Lempp FA, Ni Y, Urban S. Hepatitis delta virus: insights into a peculiar pathogen and novel treatment options. Nat Rev Gastroenterol Hepatol 2016; 13:580-9. [PMID: 27534692 DOI: 10.1038/nrgastro.2016.126] [Citation(s) in RCA: 121] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Chronic hepatitis D is the most severe form of viral hepatitis, affecting ∼20 million HBV-infected people worldwide. The causative agent, hepatitis delta virus (HDV), is a unique human pathogen: it is the smallest known virus; it depends on HBV to disseminate its viroid-like RNA; it encodes only one protein (HDAg), which has both structural and regulatory functions; and it replicates using predominantly host proteins. The failure of HBV-specific nucleoside analogues to suppress the HBV helper function, and the limitations of experimental systems to study the HDV life cycle, have impeded the development of HDV-specific drugs. Thus, the only clinical regimen for HDV is IFNα, which shows some efficacy but long-term virological responses are rare. Insights into the receptor-mediated entry of HDV, and the observation that HDV assembly requires farnesyltransferase, have enabled novel therapeutic strategies to be developed. Interference with entry, for example through blockade of the HBV-HDV-specific receptor sodium/taurocholate cotransporting polypeptide NTCP by Myrcludex B, and inhibition of assembly by blockade of farnesyltransferase using lonafarnib or nucleic acid polymers such as REP 2139-Ca, have shown promising results in phase II studies. In this Review, we summarize our knowledge of HDV epidemiology, pathogenesis and molecular biology, with a particular emphasis on possible future developments.
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Affiliation(s)
- Florian A Lempp
- Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany
| | - Yi Ni
- Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.,German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
| | - Stephan Urban
- Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.,German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
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The hepatitis delta genotype 8 in Northeast Brazil: The North Atlantic slave trade as the potential route for infection. Virus Res 2016; 224:6-11. [PMID: 27515509 DOI: 10.1016/j.virusres.2016.08.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 08/01/2016] [Accepted: 08/03/2016] [Indexed: 12/18/2022]
Abstract
Hepatitis Delta virus (HDV) is not well known, even though HDV and Hepatitis B virus (HBV) co-infection leads to severe forms of acute and chronic liver diseases. HDV is endemic in the Western Amazon region. Recently, the HDV genotype 8 was found in chronic patients followed at the center for liver studies in the Northeast Brazil, Maranhão. Previous studies suggested that this genotype was introduced in Maranhão during the slave trade. The presence of HDV in that study, which was done outside the Amazon region, led us to investigate whether the virus is found infecting individuals in other regions of Maranhão as well. Thus, we screened ninety-two HBsAg positive individuals from five Municipalities of Maranhão for anti-HD antibody and eight were found positive (8.7%). These eight positive individuals were submitted to polymerase chain reaction (PCR) to investigate active HDV infection. Half of them were positive for a fragment sequence of the delta antigen; their sequence samples were submitted to genotype characterization by phylogenetic analysis. All sequences clustered in a unique branch of the tree separated from the other branch described in Africa. Our study confirmed the presence of HDV-8 in Maranhão. These infected individuals had no evidence of contact with African people. Furthermore, we found individuals infected with HDV-8 in two more different municipalities. More studies like ours are urgent because the co-infection HBV/HDV is more difficult to treat. Identification of the endemic regions and implementation of healthy policies for preventing this infection are urgent in this region.
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Chao M, Lin CC, Lin FM, Li HP, Iang SB. Whole-genome analysis of genetic recombination of hepatitis delta virus: molecular domain in delta antigen determining trans-activating efficiency. J Gen Virol 2016; 96:3460-3469. [PMID: 26407543 DOI: 10.1099/jgv.0.000297] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Hepatitis delta virus (HDV) is the only animal RNA virus that has an unbranched rod-like genome with ribozyme activity and is replicated by host RNA polymerase. HDV RNA recombination was previously demonstrated in patients and in cultured cells by analysis of a region corresponding to the C terminus of the delta antigen (HDAg), the only viral-encoded protein. Here, a whole-genome recombination map of HDV was constructed using an experimental system in which two HDV-1 sequences were co-transfected into cultured cells and the recombinants were analysed by sequencing of cloned reverse transcription-PCR products. Fifty homologous recombinants with 60 crossovers mapping to 22 junctions were identified from 200 analysed clones. Small HDAg chimeras harbouring a junction newly detected in the recombination map were then constructed. The results further indicated that the genome-replication level of HDV was sensitive to the sixth amino acid within the N-terminal 22 aa of HDAg. Therefore, the recombination map established in this study provided a tool for not only understanding HDV RNA recombination, but also elucidating the related mechanisms, such as molecular elements responsible for the trans-activation levels of the small HDAg.
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Affiliation(s)
- Mei Chao
- Division of Microbiology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan 33302, Taiwan
- Department of Microbiology and Immunology, Chang Gung University, Guishan, Taoyuan 33302, Taiwan
| | - Chia-Chi Lin
- Division of Microbiology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan 33302, Taiwan
| | - Feng-Ming Lin
- Division of Microbiology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan 33302, Taiwan
| | - Hsin-Pai Li
- Division of Microbiology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan 33302, Taiwan
- Department of Microbiology and Immunology, Chang Gung University, Guishan, Taoyuan 33302, Taiwan
- Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan 33302, Taiwan
| | - Shan-Bei Iang
- Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan 33302, Taiwan
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