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Wranke A, Wedemeyer H. Hepatitis D virus-still the devil! Hepatology 2025; 81:1643-1646. [PMID: 39471056 DOI: 10.1097/hep.0000000000001144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 10/23/2024] [Indexed: 11/01/2024]
Affiliation(s)
- Anika Wranke
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Centre for Infection Research (DZIF), HepNet Study-House, German Liver Foundation, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Centre for Infection Research (DZIF), HepNet Study-House, German Liver Foundation, Hannover, Germany
- D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D
- Hannover Medical School, Excellence Cluster RESIST, Hannover, Germany
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2
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John BV, Bastaich D, Amoli MM, Wong RJ, Evon DM, Rogal SS, Ross DB, Morgan TR, Spector SA, Villada G, Chao HH, Dahman B. Association of HDV infection and HCC, hepatic decompensation, and all-cause and liver-related death in a national cohort. Hepatology 2025; 81:1822-1835. [PMID: 39255517 DOI: 10.1097/hep.0000000000001092] [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: 03/17/2024] [Accepted: 08/23/2024] [Indexed: 09/12/2024]
Abstract
BACKGROUND AND AIMS HDV infection is the most severe form of chronic hepatitis. However, studies on outcomes and causes of death in a US-born population, with primarily horizontal transmission of HDV, are lacking. The aim of this study was to conduct a national study of patients with hepatitis D to understand the natural history and outcomes compared to patients with HBV infection. APPROACH AND RESULTS In a national cohort of 4817 veterans infected with HBV tested for HDV (99.6% US-born, 3.3% HDV-positive) over a 23-year period, we used multivariable models to identify the factors associated with a composite outcome of HCC, decompensation, and liver-related mortality, and all-cause mortality of patients with HDV compared to HBV mono-infection. HDV coinfection (vs. HBV mono-infection) was associated with a significantly higher incidence of composite liver-related outcomes at both 5 (23.84 vs. 7.98, p < 0.001) and 10 years (19.14 vs. 10.18, p < 0.001), respectively. The most common cause of death was liver-related (33.8% for HDV vs. 24.7% for HBV), followed by nonhepatic malignancies (15.6% vs. 14.8%), cardiac (11.7% vs. 15.2%), and lung disease (5.2% vs. 3.7%). In multivariable models, HDV was associated with an increased risk of composite liver outcomes (adjusted hazard ratio: 2.57, 95% CI: 1.87-3.52, p < 0.001) and all-cause mortality (adjusted hazard ratio: 1.52, 95% CI: 1.20-1.93, p < 0.001). CONCLUSIONS In a predominantly US-born cohort of veterans, HDV coinfection was associated with an increased risk of liver-related outcomes and all-cause mortality. Our findings support widespread testing for early identification of HDV.
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Affiliation(s)
- Binu V John
- Division of Gastroenterology and Hepatology, Department of Medicine, Miami VA Medical System, Miami, Florida, USA
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Dustin Bastaich
- Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia, USA
| | | | - Robert J Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, Palo Alto VA Health System, Palo Alto, California, USA
- Division of Gastroenterology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - Donna M Evon
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Shari S Rogal
- Center for Health Equity Research and Promotion, Pittsburgh VA Health System, Pittsburgh, Pennsylvania, USA
- Division of Gastroenterology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - David B Ross
- Division of Infectious Diseases, Department of Medicine, VA Washington DC Health Care, Washington, Columbia, USA
- Department of Medicine, George Washington University School of Medicine, Washington, Columbia, USA
| | - Timothy R Morgan
- Division of Gastroenterology and Hepatology, Department of Medicine, Long Beach VA Health System, Irvine, California, USA
- Division of Gastroenterology, Department of Medicine, University of California, Irvine, California, USA
| | - Seth A Spector
- Department of Surgery, Miami VA Health System, and University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Gabriel Villada
- Department of Pathology, Miami VA Medical System, Miami, Florida, USA
| | - Hann-Hsiang Chao
- Department of Radiation Oncology, Richmond VA Medical Center and Virginia Commonwealth University, Richmond, Virginia
| | - Bassam Dahman
- Department of Health Policy, Virginia Commonwealth University, Richmond, Virginia
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Fuentes A, Estévez-Escobar M, De Salazar A, Escolano ER, Montiel N, Macías M, Alados JC, Aguilar JC, Pérez AB, Baena PB, Cabezas T, Camelo-Castillo A, Palop B, Grande RG, Viciana I, Bandera JMP, Sánchez FF, Lozano MDC, Giráldez Á, Domínguez MDC, Maté CJ, Arellano ER, Cordero P, De Luna FFÁ, Del Pino P, Salgado ADLI, Pérez D, Sampedro A, Garrido MÁL, Luzón-García MP, Salas-Coronas J, Roldán C, García F, Freyre C, Rodríguez GS, Rosales-Zabal JM, Domínguez-Hernández R, Casado M, García F. Double reflex testing improves the efficacy and cost effectiveness of hepatitis delta diagnosis in southern Spain. Sci Rep 2025; 15:15413. [PMID: 40316581 PMCID: PMC12048655 DOI: 10.1038/s41598-025-00101-7] [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: 12/22/2024] [Accepted: 04/24/2025] [Indexed: 05/04/2025] Open
Abstract
This study aims to evaluate the prevalence of undiagnosed hepatitis delta in southern Spain (Andalusia) and assess the effectiveness and cost-efficiency of implementing reflex testing for hepatitis D detection in HBsAg-positive patients. A multicenter ambispective study was conducted in 17 Andalusian hospitals. The retrospective phase (January 2018-June 2022) analyzed diagnostic processes for hepatitis delta in HBsAg-positive patients. The prospective phase (October 2022-March 2023) implemented reflex testing, performing anti-HDV serology on all HBsAg-positive patients without prior testing. HDV RNA testing followed for those who tested anti-HDV-positive. In the retrospective phase, out of 18,583 HBsAg-positive patients, anti-HDV tests were performed on 3,436 (18%), identifying 205 (6%) positive cases. HDV RNA was tested in 158 (77%) anti-HDV-positive patients, with 69 (44%) testing positive. In the prospective phase, out of 2,384 HBsAg-positive patients without prior anti-HDV testing, 2,293 (96%) were tested, identifying 109 (4.7%) positive cases. HDV RNA was analyzed in 97 (89%) anti-HDV-positive patients, with 30 (31%) testing positive. Reflex testing increased anti-HDV detection by 77%, resulting in a fourfold increase in detecting anti-HDV-positive patients and a threefold increase in detecting HDV RNA-positive patients, reducing undiagnosed HDV RNA-positive cases to 4% compared to 45% with clinical practice. Cost analysis indicated a saving of €265,954 with reflex testing. Reflex testing improves HDV detection, reduces costs, and simplifies diagnosis, making it an efficient strategy for managing chronic hepatitis D patients.
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Affiliation(s)
- Ana Fuentes
- Instituto de Investigación Biosanitaria de Granada. Hospital Universitario de San Cecilio, Granada, Spain
- Centro de Investigación Biomédica en Red Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
| | | | - Adolfo De Salazar
- Instituto de Investigación Biosanitaria de Granada. Hospital Universitario de San Cecilio, Granada, Spain
- Centro de Investigación Biomédica en Red Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
| | | | | | | | - Juan Carlos Alados
- Hospital Universitario de Jerez de La Frontera, Cádiz, Spain
- Biomedical Research and Innovation Institute of Cádiz (INiBICA), Cádiz, Spain
| | | | - Ana Belén Pérez
- Centro de Investigación Biomédica en Red Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
- Hospital Universitario Reina Sofía, Córdoba, Spain
| | | | | | | | - Begoña Palop
- Hospital Regional Universitario Carlos Haya, Málaga, Spain
| | | | - Isabel Viciana
- Hospital Clínico Universitario Virgen de La Victoria, Málaga, Spain
| | | | | | | | | | | | | | | | | | | | - Pilar Del Pino
- Hospital Universitario Juan Ramón Jiménez, Huelva, Spain
| | | | | | | | | | - María Pilar Luzón-García
- Centro de Investigación Biomédica en Red Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
- Biotechnology Unit. Hospital Universitario de Poniente, Almería, Spain
| | - Joaquín Salas-Coronas
- Centro de Investigación Biomédica en Red Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
- International Health Research Group of Almería (GISIA), Faculty of Health Sciences, University of Almería, Almería, Spain
| | | | - Fernando García
- Instituto de Investigación Biosanitaria de Granada. Hospital Universitario de San Cecilio, Granada, Spain
| | | | | | | | | | | | - Federico García
- Instituto de Investigación Biosanitaria de Granada. Hospital Universitario de San Cecilio, Granada, Spain.
- Centro de Investigación Biomédica en Red Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
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van de Laar TJW, Patmore LA, Molier MM, Sonneveld MJ, Voermans JJC, Slot E, Feltkamp MCW, van der Eijk AA, Zaaijer HL. Low rate of hepatitis Delta virus co-infection in first-time blood donors diagnosed with chronic hepatitis B virus infection in the Netherlands. Transfusion 2025; 65:841-847. [PMID: 40186395 DOI: 10.1111/trf.18238] [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: 02/19/2025] [Revised: 03/16/2025] [Accepted: 03/20/2025] [Indexed: 04/07/2025]
Abstract
BACKGROUND Hepatitis Delta virus (HDV) requires co-infection with hepatitis B virus (HBV) and increases the risk of hepatitis-related morbidity and mortality compared to HBV mono-infection. HBV/HDV co-infected patients will likely benefit from new HDV antiviral drugs, but reliable estimates of co-infection rates are lacking due to limited HDV testing of HBV-infected patients. STUDY DESIGN AND METHODS First-time blood and bone tissue donors in the Netherlands (2006-2023) with a newly diagnosed chronic HBV infection were retrospectively tested for HDV antibodies, and for HDV RNA if HDV antibodies were detected. HBV genotyping using phylogenetic analysis was performed to determine the most likely origin of HBV infection. RESULTS HBV-DNA was detected in 254/758.081 (0.034%) first-time donors in the Netherlands. HBsAg-positive first-time donors had a median age of 43 years (IQR: 33-52), were predominantly male (67%), mostly first- or second-generation migrants (76%) and HBV (sub)genotype strongly correlated with the country of birth. HDV testing was performed for 200 first-time donors with chronic (HBsAg-positive) HBV infection: 5 donors (2.5%) had HDV antibodies, and 1 donor (0.5%) also had detectable HDV RNA. None of the 17 donors with occult (HBsAg-negative) HBV infection had experienced HDV infection. DISCUSSION Chronic HBV/HDV co-infection in first-time donors in the Netherlands is extremely rare, affecting 0.00013% of all first-time donors, and only 0.5% of HBsAg-positive first-time donors consisting predominantly of migrants from high(er) HDV-endemic countries. Despite low HBV/HDV co-infection rates, a one-time HDV reflex testing strategy for HBsAg-positive patients remains essential to identify patients and to initiate antiviral treatment if needed to reduce the risk of serious liver disease.
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Affiliation(s)
- Thijs J W van de Laar
- Department of Donor Medicine Research, Sanquin Research, Amsterdam, The Netherlands
- Department of Medical Microbiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - Lesley A Patmore
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
| | - Michel M Molier
- Department of Donor Medicine Research, Sanquin Research, Amsterdam, The Netherlands
| | - Milan J Sonneveld
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
| | - Jolanda J C Voermans
- Department of Viroscience, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
| | - Ed Slot
- Department of Medical Affairs, Sanquin Corporate Staff, Amsterdam, The Netherlands
| | - Mariet C W Feltkamp
- Department of Donor Medicine Research, Sanquin Research, Amsterdam, The Netherlands
- Department of Medical Microbiology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Annemiek A van der Eijk
- Department of Viroscience, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
| | - Hans L Zaaijer
- Department of Donor Medicine Research, Sanquin Research, Amsterdam, The Netherlands
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Pisaturo M, Russo A, Grimaldi P, Martini S, Coppola N. Current and future therapeutic options for chronic hepatitis D virus infection. Front Cell Infect Microbiol 2025; 14:1382017. [PMID: 40008233 PMCID: PMC11850310 DOI: 10.3389/fcimb.2024.1382017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 11/19/2024] [Indexed: 02/27/2025] Open
Abstract
In the last few years there have been innovations in HDV therapy which have brought new excitement in the scientific community also considering the few therapeutic opportunities. Recently, new molecular targets have been identified, both in monotherapy and in combination with peginterferon alpha (PegIFNα). Evaluating this review of the literature of the last ten years, HDV-related chronic hepatitis seems to have become a potentially curable disease, a statement that was unthinkable a few years ago. There are old and new weapons at our disposal. The old weapons are PegIFNα and recently PegIFN-lambda (PegIFNλ). PegIFNα, for which there are more data, appears to be an excellent combination regimen, if not contraindicated, both for Bulevirtide (BLV), data supported by important clinical trials and real-world studies, and probably for lonarfanib, although in the latter case the results are not yet definitive as the studies are fewer. However, data on long-term follow-up are needed.
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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
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6
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Rodríguez-Tajes S, Palom A, Giráldez-Gallego Á, Moreno A, Urquijo JJ, Rodríguez M, Alvarez-Argüelles M, Diago M, García-Eliz M, Fuentes J, Martínez-Sapiña AM, Castillo P, Casado M, Pérez-Campos E, Muñoz R, Hernández-Conde M, Morillas RM, Granados R, Miquel M, Morillas MJ, García-Retortillo M, Carrión JA, Moreno JM, Montón C, González-Santiago JM, Lorente S, Cabezas J, Mateos B, Vázquez-Rodríguez S, Díaz-Fontenla F, Pinazo JM, Delgado M, Pérez-Palacios D, Horta D, Fernández-Marcos C, López C, Calleja JL, Fernández I, García-Samaniego J, Forns X, Buti M, Lens S. Characterizing Hepatitis Delta in Spain and the gaps in its management. GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502222. [PMID: 38908682 DOI: 10.1016/j.gastrohep.2024.502222] [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: 05/28/2024] [Accepted: 06/18/2024] [Indexed: 06/24/2024]
Abstract
BACKGROUND AND AIMS Chronic hepatitis D (CHD) is a severe form of chronic viral hepatitis. The estimated hepatitis delta prevalence in Spain is around 5% of patients with hepatitis B. Reimbursement of new antiviral therapies (Bulevirtide, BLV) was delayed in our country until February 2024. We aimed to characterize the clinical profile of patients with HDV/HBV infection in Spain and current barriers in their management at the time of BLV approval. METHOD Multicenter registry including patients with positive anti-HDV serology actively monitored in 30 Spanish centers. Epidemiological, clinical and virological variables were recorded at the start of follow-up and at the last visit. RESULTS We identified 329 anti-HDV patients, 41% were female with median age 51 years. The most common geographical origin was Spain (53%) and East Europe (24%). Patients from Spain were older and had HCV and HIV coinfection probably associated to past drug injection (p<0.01). HDV-RNA was positive in 138 of 221 assessed (62%). Liver cirrhosis was present at diagnosis in 33% and it was more frequent among viremic patients (58% vs 25%, p<0.01). After a median follow-up of 6 (3-12) years, 44 (16%) resolved infection (18 spontaneously and 26 after Peg-INF). An additional 10% of patients developed cirrhosis (n=137) during follow-up (45% had portal hypertension and 14% liver decompensation). Liver disease progression was associated to persisting viremia. CONCLUSION One-third of the patients with CHD already have cirrhosis at diagnosis. Persistence of positive viremia is associated to rapid liver disease progression. Importantly, barriers to locally determine/quantify HDV-RNA were present.
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Affiliation(s)
| | - Adriana Palom
- Hospital Universitari Vall d'Hebron, CIBEREHD, Barcelona, Spain
| | | | | | | | | | | | | | | | | | | | | | - Marta Casado
- Hospital Universitario Torrecárdenas, Almería, Spain
| | | | | | | | | | | | | | | | | | | | | | | | | | - Sara Lorente
- Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
| | - Joaquín Cabezas
- Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | | | | | | | | | - Mercè Delgado
- Hospital de Mataró Consorci Sanitari del Maresme, Mataró, Spain
| | | | | | | | | | | | | | | | - Xavier Forns
- Hospital Clínic, Universitat de Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain
| | - María Buti
- Hospital Universitari Vall d'Hebron, CIBEREHD, Barcelona, Spain
| | - Sabela Lens
- Hospital Clínic, Universitat de Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain.
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Herta T, Joachim‐Richter A, Petroff D, Wölk B, Wolffram I, Berg T, Kramer J, Bätz O, Wiegand J. Successful Amendment of an Existing Hepatitis B Screening Programme by a Guideline Recommended Hepatitis D Screening in the Primary Care Setting. Aliment Pharmacol Ther 2025; 61:651-657. [PMID: 39628411 PMCID: PMC11754924 DOI: 10.1111/apt.18424] [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: 08/16/2024] [Revised: 09/09/2024] [Accepted: 11/21/2024] [Indexed: 01/02/2025]
Abstract
BACKGROUND Despite European guidelines recommending anti-hepatitis D virus (HDV) screening for all hepatitis B surface antigen (HBsAg)-positive cases, screening rates remain insufficient. AIMS We analysed anti-HDV screening rates in primary care and implemented prospective HDV screening in HBsAg-positive cases identified in the preventive medical examination from the age of 35 ("Check-Up 35+"). METHODS From 2012 to 2021, we reviewed anti-HDV and HDV RNA test rates in HBsAg-positive patients at 11 sites of a large German laboratory group. From 2022 to 2023, we prospectively screened HBsAg-positive samples from the "Check-Up 35+" for anti-HDV. Anti-HDV positive patients were then contacted again for HDV RNA testing. RESULTS Retrospectively, 2792/13,905 (20%) HBsAg-positive cases were tested for anti-HDV, with 142/2792 (5.1%) being positive. HDV RNA was tested in 57/142 (40%) anti-HDV-positive cases, with 26/57 (46%) being positive. In the prospective screening, 1159/225,901 (0.51%) individuals were HBsAg-positive. Of these, 700 (60%) were tested for anti-HDV, with 18/700 (2.6%) positive test results. 4/18 (22%) were successfully contacted again for HDV RNA analysis, with one case testing positive. Neither the HBsAg nor the anti-HDV positive result was known prior to screening in these cases. Anti-HDV testing could not be performed in 459/1159 (40%) HBsAg-positive cases, primarily due to insufficient blood sample volume (310/459 cases, 68%), with others missed due to logistical errors. CONCLUSIONS Retrospective data show insufficient anti-HDV screening in clinical routine. The prospective anti-HDV screening provides a blueprint for using existing hepatitis B virus screening programms for population-based HDV double reflex testing, provided that adequate logistical prerequisites are established. TRIAL REGISTRATION German Clinical Trial Register: DRKS00029180.
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Affiliation(s)
- Toni Herta
- Division of Hepatology, Department of Medicine IILeipzig University Medical CenterLeipzigGermany
- Department of Hepatology and Gastroenterology, Campus Virchow‐Klinikum and Campus Charité MitteCharité‐Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité—Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Clinician Scientist ProgramBerlinGermany
| | | | - David Petroff
- Clinical Trial Centre LeipzigUniversity of LeipzigLeipzigGermany
| | - Benno Wölk
- LADR Laboratory Group Dr. Kramer & ColleaguesGeesthachtGermany
| | | | - Thomas Berg
- Division of Hepatology, Department of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Jan Kramer
- LADR Laboratory Group Dr. Kramer & ColleaguesGeesthachtGermany
| | - Olaf Bätz
- LADR Laboratory Group Dr. Kramer & ColleaguesGeesthachtGermany
| | - Johannes Wiegand
- Division of Hepatology, Department of Medicine IILeipzig University Medical CenterLeipzigGermany
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Boyd A, Smit C, van der Eijk AA, Zaaijer H, Rijnders BJ, van Welzen B, Claassen MA, Pogány K, de Vries-Sluijs TE, de Coul EO, van der Valk M. Low coverage of hepatitis D virus testing in individuals with hepatitis B virus and HIV, the Netherlands, 2000 to 2022. Euro Surveill 2025; 30:2400344. [PMID: 39980422 PMCID: PMC11843617 DOI: 10.2807/1560-7917.es.2025.30.7.2400344] [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: 05/31/2024] [Accepted: 11/28/2024] [Indexed: 02/22/2025] Open
Abstract
BackgroundSince 2009, European guidelines recommend individuals with hepatitis B virus (HBV) and HIV be tested for hepatitis D virus (HDV).AimTo analyse HDV testing in individuals with HBV/HIV during routine practice in the Netherlands.MethodsWe assessed data from the ATHENA cohort of people with HIV who were ever HBV surface antigen-positive, aged ≥ 18 years and attended one of 24 HIV treatment centres in the Netherlands during 2000-22. Using longitudinal analysis, we estimated the percentage of individuals ever tested for HDV (antibody or RNA test) over time. In cross-sectional analysis, determinants for ever being tested by end of follow-up were assessed using relative risk regression.ResultsWe identified 1,715 individuals with HBV/HIV; 1,460 (85.1%) and 255 (14.9%) were male and female at birth, respectively (median age: 52 years; IQR: 42-59). Only 249 (14.5%) had an HDV test. The percentage tested increased from 5.0% (95% CI: 3.4-7.3) in 2000 to 17.0% (95% CI: 14.9-19.3) in 2022. In 2022, 16.2% (95% CI: 13.7-19.1) of men who have sex with men, 25.0% (95% CI: 9.7-50.9) of persons who inject(ed) drugs and 18.1% (95% CI: 14.6-22.3) of heterosexual/others were tested. In multivariable analysis, ever having an HDV test was associated with detectable HBV DNA viral load (p < 0.001), ever presenting with elevated alanine aminotransferase (ALT) levels (p = 0.023), advanced fibrosis/cirrhosis (p = 0.001) and being overweight/obese (p = 0.043).ConclusionsHDV testing coverage in the Netherlands is low for individuals with HBV/HIV. Although testing was more common in those with advanced liver disease, a considerable proportion at risk of HDV still need testing.
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Affiliation(s)
- Anders Boyd
- Stichting hiv monitoring, Amsterdam, the Netherlands
- Amsterdam UMC, location University of Amsterdam, Infectious Diseases, Amsterdam, the Netherlands
- Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands
| | - Colette Smit
- Stichting hiv monitoring, Amsterdam, the Netherlands
| | | | - Hans Zaaijer
- Amsterdam UMC, location University of Amsterdam, Department of Clinical Virology, Meibergdreef 9, Amsterdam, the Netherlands
| | - Bart Ja Rijnders
- Department of Internal Medicine, Section of Infectious Diseases and Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Berend van Welzen
- Department of Infectious Diseases, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - Mark Aa Claassen
- Department of Internal Medicine and Infectious Diseases, Rijnstate Ziekenhuis, Arnhem, Netherlands
| | - Katalin Pogány
- Department of Internal Medicine, Maasstad Hospital, Rotterdam, the Netherlands
| | - Theodora Ems de Vries-Sluijs
- Department of Internal Medicine, Section of Infectious Diseases and Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Eline Op de Coul
- Centre for Infectious Disease Control, Epidemiology and Surveillance, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
| | - Marc van der Valk
- Stichting hiv monitoring, Amsterdam, the Netherlands
- Amsterdam UMC, location University of Amsterdam, Infectious Diseases, Amsterdam, the Netherlands
- Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
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9
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Zhang Z, Wu Y, Xu J, Meng Z, Chen Q, Yin S. Quantitative Analysis of Hepatitis D Virus Using gRNA-Sensitive Semiconducting Polymer Dots. Anal Chem 2025; 97:1575-1583. [PMID: 39807540 DOI: 10.1021/acs.analchem.4c04147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
Hepatitis D virus (HDV) significantly influences the progression of liver diseases. Through clinical observations and database analyses, it has been established that patients coinfected with HDV and hepatitis B virus (HBV) experience accelerated progression toward cirrhosis, hepatocellular carcinoma (HCC), and liver failure compared to those infected solely with HBV. A higher viral load correlates with increased replicative activity, enhanced infectivity, and more severe disease manifestations. In this study, we use HDV gRNA-sensitive semiconducting polymer dots (Pdots) as the nanoprobes for the quantitative analysis of HDV copy number variations. The surface of the Pdots is engineered with a clamp design that includes a pair of reporter sequences, protection sequences, and capture sequences tailored to the conserved sequence length of the HDV genome. The capture sequence, comprising leading and trailing chains, specifically binds to the gRNA of the target virus. The protection sequence shields the Pdots from external interference, while the reporter sequence detects the presence of target gRNA through the degradation of fluorescent dye Cy5.5dt. We demonstrate the effectiveness of this assay in a stably transfected cell line derived from HepG2-HDV cells and its translational application in clinical samples from patients. Additionally, this nanobiosensor can accurately detect gRNA at femtomolar (fM) levels, a sensitivity unachievable by previously reported methods. This novel virus quantification system offers significant potential for clinical and virological applications, enhancing screening, early diagnosis, and personalized treatment strategies.
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Affiliation(s)
- Ze Zhang
- Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin 130012, P. R. China
- State Key Laboratory of Integrated Optoelectronics, College of Electronics Science and Engineering, Jilin University, No. 2699 Qianjin Street, Changchun, Jilin 130012, P. R. China
| | - Yuyang Wu
- State Key Laboratory of Integrated Optoelectronics, College of Electronics Science and Engineering, Jilin University, No. 2699 Qianjin Street, Changchun, Jilin 130012, P. R. China
| | - Jinglun Xu
- Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P. R. China
| | - Zihui Meng
- Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P. R. China
| | - Qingmin Chen
- Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin 130012, P. R. China
| | - Shengyan Yin
- State Key Laboratory of Integrated Optoelectronics, College of Electronics Science and Engineering, Jilin University, No. 2699 Qianjin Street, Changchun, Jilin 130012, P. R. China
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Alqahtani SA, Sanai FM, Banama MA, Alghamdi MY, Altarrah MY, Abaalkhail FA. Multisociety consensus recommendations on hepatitis delta virus infection. Saudi J Gastroenterol 2025; 31:5-13. [PMID: 39644161 PMCID: PMC11804964 DOI: 10.4103/sjg.sjg_322_24] [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: 09/04/2024] [Revised: 10/22/2024] [Accepted: 10/30/2024] [Indexed: 12/09/2024] Open
Abstract
ABSTRACT Hepatitis D virus (HDV) prevalence data and country-specific HDV guidelines are not widely available in the Gulf Cooperation Council (GCC) states. We developed consensus recommendations to guide healthcare professionals, policymakers, and researchers in improving HDV management and patient health outcomes in three GCC states: Kuwait, Saudi Arabia, and the United Arab Emirates. A consensus panel comprising hepatology experts (n = 6) from the three GCC societies was formed. The panel identified two broader areas related to clinical practice (screening and diagnosis, and treatment and management), addressed critical questions, and developed draft recommendations in February 2024. The strength of the final set of recommendations was subjected to consensus voting in March 2024. A majority was defined apriori with a two-thirds vote (67%). The paper outlines those recommendations alongside showcasing the current epidemiology of HDV in the GCC states, emphasizing the variability in prevalence, demographic patterns, and region-specific risk factors. It also highlights the current state of screening and diagnosis practices, identifying key obstacles, such as access to advanced screening protocols and diagnostic tools. Furthermore, HDV treatment landscape and preventative strategies are outlined, focusing on vaccination, public health initiatives, and the crucial role of public awareness and education. Ethical and sociocultural considerations are discussed, underscoring the importance of culturally sensitive healthcare practices. These recommendations present a comprehensive overview of the challenges and strategies for managing HDV in these states. Policy recommendations are provided to support HDV management, including standardizing care protocols and promoting public health measures.
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Affiliation(s)
- Saleh A. Alqahtani
- Liver, Digestive, and Lifestyle Health Research Section, and Organ Transplant Center of Excellence, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, USA
| | - Faisal M. Sanai
- Department of Medicine, Gastroenterology Section, King Abdulaziz Medical City, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Center, Ministry of National Guard – Health Affairs, Jeddah, Saudi Arabia
| | - Mohammed A. Banama
- Gastroenterology Unit, Rashid Hospital, Dubai Academic Health Corporation, Dubai, UAE
| | - Mohammed Y. Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahd Military Complex, Dhahran, Saudi Arabia
| | - Munira Y. Altarrah
- Gastroenterology and Transplant Hepatology Unit, Thunayan Al Ghanim Gastroenterology Center, Al Amiri Hospital, Kuwait
| | - Faisal A. Abaalkhail
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
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11
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Eyi ASA, Komba OM, Chambellant C, Boussoukou IPM, Moukambi L, Moukambi KMWA, Boukani EI, Ndjindji OM, Siawaya ACM, Bignoumba PEI, Chemin I, Siawaya JFD, Ndeboko B. Triple burden of hepatitis B, hepatitis Delta viruses, and Plasmodium falciparum to pregnant women. IJID REGIONS 2024; 13:100447. [PMID: 39399128 PMCID: PMC11471226 DOI: 10.1016/j.ijregi.2024.100447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 09/06/2024] [Accepted: 09/06/2024] [Indexed: 10/15/2024]
Abstract
OBJECTIVES Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. This infection is more severe when combined with hepatitis Delta virus (HDV). Moreover, Plasmodium falciparum (Pf) malaria infection during pregnancy can have severe consequences for the mother and the newborn. Importantly, the manifestation of these three infections has never been described to date. METHODS Thus, we conducted a prospective study, between May 27, 2022, and April 15, 2023, and we investigated these three infections in 260 pregnant women aged 24 to 46 years, in Gabon and evaluated the impact on newborns. The sera were used to screen hepatitis B surface antigen (HBsAg) and Pf by determining HBsAg® ALERE rapid diagnostic test and malaria rapid diagnostic test kits. The positive sample was confirmed using MINI VIDAS® for HBV and Lambaréné method for "Pf". The real-time-polymerase chain reaction assay was used to amplify HBV DNA and HDV RNA on Roche instrument. RESULTS Our results showed that the prevalences of HBV and (Pf) infection were 4.23% (n = 11) and 34.62% (n = 90), respectively. Moreover, we found that 3.46 % (n = 9) of pregnant women infected with HBV were coinfected with HDV. The prevalence of triple infection was 1.15% (n = 3). In addition, the leukocytes and lymphocytes absolute count were significantly lower for the triple-infected pregnant women. CONCLUSIONS We describe for the first time the triple coinfection by HBV, HDV, and Pf, which could induce a great inflammatory reaction and high liver disorder in newborns.
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Affiliation(s)
- Aude Sandrine Andeme Eyi
- Laboratoire du Centre Hospitalier Universitaire Mère-Enfant Fondation Jeanne Ebori, Libreville, Gabon
| | - Opheelia Makoyo Komba
- Service de Gynécologie du Centre Hospitalier Universitaire Mère-Enfant Fondation Jeanne Ebori, Libreville, Gabon
| | | | | | - Lydie Moukambi
- Laboratoire du Centre Hospitalier Universitaire Mère-Enfant Fondation Jeanne Ebori, Libreville, Gabon
| | | | - Enide Iroungou Boukani
- Laboratoire du Centre Hospitalier Universitaire Mère-Enfant Fondation Jeanne Ebori, Libreville, Gabon
| | - Ofilia Mvoundza Ndjindji
- Laboratoire du Centre Hospitalier Universitaire Mère-Enfant Fondation Jeanne Ebori, Libreville, Gabon
| | | | | | | | - Joel Fleury Djoba Siawaya
- Laboratoire du Centre Hospitalier Universitaire Mère-Enfant Fondation Jeanne Ebori, Libreville, Gabon
| | - Bénédicte Ndeboko
- Laboratoire du Centre Hospitalier Universitaire Mère-Enfant Fondation Jeanne Ebori, Libreville, Gabon
- Département de Biologie Cellulaire & Moléculaire-Génétique, Faculté de Médecine, Université des sciences de la Santé, Libreville, Gabon
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12
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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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13
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Osiowy C, Day J, Lee ER. Laboratory development of an RNA quantitative RT-PCR assay reporting in international units for hepatitis D virus. Front Microbiol 2024; 15:1472826. [PMID: 39633803 PMCID: PMC11615724 DOI: 10.3389/fmicb.2024.1472826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 10/29/2024] [Indexed: 12/07/2024] Open
Abstract
Introduction Chronic hepatitis D virus (HDV) is associated with rapid progression to severe liver disease. Co-infection with HDV and hepatitis B virus is likely underdiagnosed due to challenges in diagnostic test availability and standardization. With new HDV antiviral options, HDV RNA quantification is essential for understanding the patient response to treatment. To this end, a quantitative real-time reverse transcription PCR (qRT-PCR) assay utilizing synthetic RNA calibrators and a conversion factor to quantify HDV RNA in WHO international standard units (IU/mL) was developed and validated. Methods qRT-PCR primers and probes were selected within the ribozyme region. Thermocycling conditions and reactions were optimized. Synthetic RNA transcripts were prepared as quantification standards and calibrators. Transcript dilutions (log10 8 to log10 1 copies/μL) were calibrated against the WHO standard and a conversion factor calculated to convert copies/μL to IU/mL. Assay validation and evaluation was conducted, including use of specimens from 8 HDV genotypes and comparison to a commercial assay. Results The assay lower limit of detection was determined by probit analysis to be 11 IU/mL (8.63-15.78 95% CI). Inter- and intra-assay coefficient of variation analysis showed 96.6% precision and 90.6% accuracy. A conversion factor of 16.5 was used to convert copies/μL to IU/mL. All 8 HDV genotypes were quantified by the assay and commercial assay comparison showed good agreement. Discussion The developed assay has clinical utility for the sensitive and specific quantitative monitoring of HDV RNA, appropriate for medium to high throughput laboratories.
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Affiliation(s)
- Carla Osiowy
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
| | - Jacqueline Day
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Emma R. Lee
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
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Bernhard J, Schwarz M, Balcar L, Hofer B, Dominik N, Strassl R, Aberle S, Munda P, Mandorfer M, Trauner M, Reiberger T, Jachs M. Reflex testing for anti-HDV in HBsAg-positive patients offers high diagnostic yield in a large Central European tertiary care center. Sci Rep 2024; 14:25921. [PMID: 39472518 PMCID: PMC11522309 DOI: 10.1038/s41598-024-77737-4] [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: 02/28/2024] [Accepted: 10/24/2024] [Indexed: 11/02/2024] Open
Abstract
Current guidelines recommend reflex testing for hepatitis D virus (HDV) coinfection in hepatitis B surface antigen (HBsAg)-positive patients over risk-factor based screening. We aimed to evaluate the feasibility and diagnostic yield of reflex anti-HDV testing at a Central European tertiary care center. We retrospectively included 560 consecutive patients who had a recorded (first) positive HBsAg test result at the Vienna General Hospital between 2018 and 2022. While reflex anti-HDV testing had been implemented in our hepatitis outpatient clinic (n = 153, 'reflex testing cohort'), HDV screening needed to be manually ordered in the remaining patients (n = 407, 'standard testing cohort'). Overall, 98.0% and 65.1% of patients in the reflex and standard testing cohort were screened for anti-HDV, respectively, and the overall seroprevalence of anti-HDV among screened patients was 6.7% (n = 28, reflex testing cohort: 9.3%, standard testing cohort: 5.3%). Risk factors for HDV were present in 49.1% of all included and in 89.3% of anti-HDV positive patients, respectively. Anti-HDV positive patients showed higher ALT (54 [33-83] vs. 29 [19-49] U/L; p = 0.005) and a higher proportion of low-to-undetectable HBV-DNA (61.5% vs. 33.2%; p < 0.001), as compared to anti-HDV negative patients. HDV-RNA PCR was ordered in n = 21/28 (75.0%) of anti-HDV positive patients, and 76.2% had detectable HDV-RNA. Among viremic patients, 75% and 37.5% had significant fibrosis (≥ F2) or cirrhosis (F4), respectively. The prevalence of anti-HDV among HBsAg-positive patients is considerable in a large hospital located in Central Europe. Double reflex testing, i.e., anti-HDV being triggered by the presence of HBsAg and HDV-PCR bring triggered by the presence of anti-HDV, seems warranted to increase the diagnostic yield.
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Affiliation(s)
- Johannes Bernhard
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Währinger Guertel 18-20, 1090, Vienna, Austria
| | - Michael Schwarz
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Währinger Guertel 18-20, 1090, Vienna, Austria
| | - Lorenz Balcar
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Währinger Guertel 18-20, 1090, Vienna, Austria
| | - Benedikt Hofer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Währinger Guertel 18-20, 1090, Vienna, Austria
| | - Nina Dominik
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Währinger Guertel 18-20, 1090, Vienna, Austria
| | - Robert Strassl
- Division of Clinical Virology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Stephan Aberle
- Center for Virology, Medical University of Vienna, Vienna, Austria
| | - Petra Munda
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Währinger Guertel 18-20, 1090, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Währinger Guertel 18-20, 1090, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Währinger Guertel 18-20, 1090, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Währinger Guertel 18-20, 1090, Vienna, Austria.
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Währinger Guertel 18-20, 1090, Vienna, Austria.
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15
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Brichler S, Trimoulet P, Roque-Afonso AM, Izopet J, Thibault V, Roudot-Thoraval F, Chevaliez S. The diagnostic cascade for patients with hepatitis delta infection in France, 2018-2022: A cross-sectional study. Liver Int 2024; 44:2858-2865. [PMID: 39115174 DOI: 10.1111/liv.16031] [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: 03/06/2024] [Revised: 05/28/2024] [Accepted: 06/26/2024] [Indexed: 10/10/2024]
Abstract
BACKGROUND AND AIMS Chronic hepatitis D infection is the most severe form of viral hepatitis and can rapidly progress to cirrhosis or hepatocellular carcinoma. Despite recommendations for systematic screening of hepatitis B surface antigen (HBsAg)-positive individuals, data from real-world studies have reported a low frequency of hepatitis D (or delta) virus (HDV) screening. Our cross-sectional analysis evaluated the diagnostic cascade for hepatitis D infection in tertiary centres and described the characteristics of HDV-positive patients. METHODS A total of 6772 individuals who tested HBsAg positive for the first time between 2018 and 2022 were retrospectively included. Demographic, clinical and laboratory data were analysed. RESULTS A total of 5748 HBsAg-positive individuals (84.9%) were screened for HDV infection. The screening rate varied from 63% to 97% according to the screening strategy used in the centres including or not HDV reflex testing. The prevalence of HDV infection was 6.3%. HDV RNA levels were determined in 285 of the 364 (78.3%) HDV antibody screening-positive patients, and 167 (58.6%) had active HDV infection. 66.8% were males, with a mean age of 44.9 years. A total of 97.5% were born abroad, and 92.9% were HBeAg negative. At the time of diagnosis, HDV RNA levels were 6.0 Log UI/mL; 60.1% had alanine aminotransferase >40 U/L, and 56.3% had significant fibrosis (≥F2), including 41.6% with cirrhosis. The most common genotype was HDV-1 (75.4%). Coinfections were not uncommon: 7.4% were HIV positive, and 15.0% were HCV antibody positive. CONCLUSIONS The present study highlights the need for increased screening and monitoring of HDV infection. Reflex testing helps to identify HDV-infected individuals.
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Affiliation(s)
- Ségolène Brichler
- French National Reference Center for Hepatitis B, C and D Viruses, Laboratoire de Microbiologie Clinique, Hôpital Avicenne, Bobigny, France
- "Team Viruses, Hepatology, Cancer", Institut de Recherche Biomédicale INSERM U955, Créteil, France
| | - Pascale Trimoulet
- Laboratoire de Virologie, CHU Bordeaux, Groupe Hospitalier Pellegrin, Bordeaux, France
| | - Anne-Marie Roque-Afonso
- Department of Virology, Hopital Paul Brousse, Université Paris Saclay, Villejuif, France
- INSERM U1193, Villejuif, France
| | - Jacques Izopet
- Laboratoire de Virologie, CHU Toulouse, Hôpital Purpan, Toulouse, France
- INSERM UMR 1291-CNRS UMR 5051, Université Toulouse III, Toulouse, France
| | - Vincent Thibault
- Department of Virology, Pontchaillou University Hospital, Rennes, France
- INSERM EHESP, Irset-UMR_S 1085, Rennes, France
| | - Françoise Roudot-Thoraval
- "Team Viruses, Hepatology, Cancer", Institut de Recherche Biomédicale INSERM U955, Créteil, France
- Department of Hepatology, Créteil, France
| | - Stéphane Chevaliez
- "Team Viruses, Hepatology, Cancer", Institut de Recherche Biomédicale INSERM U955, Créteil, France
- Department of Virology, French National Reference Center for Hepatitis B, C and D Viruses, Hôpital Henri Mondor (AP-HP), Créteil, France
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16
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Wranke A, Lobato C, Ceausu E, Dalekos GN, Rizzetto M, Turcanu A, Niro GA, Keskin O, Gherlan G, Abbas M, Ingiliz P, Muche M, Buti M, Jachs M, Vanwolleghem T, Cornberg M, Abbas Z, Yurdaydin C, Dörge P, Wedemeyer H. Long-term outcome of hepatitis delta in different regions world-wide: Results of the Hepatitis Delta International Network. Liver Int 2024; 44:2442-2457. [PMID: 38888267 DOI: 10.1111/liv.16006] [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: 02/13/2024] [Revised: 04/23/2024] [Accepted: 05/23/2024] [Indexed: 06/20/2024]
Abstract
BACKGROUND AND AIMS Chronic hepatitis delta represents a major global health burden. Clinical features of hepatitis D virus (HDV) infection vary largely between different regions worldwide. Treatment approaches are dependent on the approval status of distinct drugs and financial resources. METHODS The Hepatitis Delta International Network (HDIN) registry involves researchers from all continents (Wranke, Liver International 2018). We here report long-term follow-up data of 648 hepatitis D patients recruited by 14 centres in 11 countries. Liver-related clinical endpoints were defined as hepatic decompensation (ascites, encephalopathy and variceal bleeding), liver transplantation, hepatocellular carcinoma or liver-related death. RESULTS Patient data were available from all continents but Africa: 22% from Eastern Mediterranean, 32% from Eastern Europe and Central Asia, 13% from Central and Southern Europe, 14% from South Asia (mainly Pakistan) and 19% from South America (mainly Brazil). The mean follow-up was 6.4 (.6-28) years. During follow-up, 195 patients (32%) developed a liver-related clinical event after 3.5 (±3.3) years. Liver cirrhosis at baseline and a detectable HDV RNA test during follow-up were associated with a worse clinical outcome in multivariate regression analysis while patients receiving interferon alfa-based therapies developed clinical endpoints less frequently. Patients from South Asia developed endpoints earlier and had the highest mortality. CONCLUSIONS The HDIN registry confirms the severity of hepatitis D and provides further evidence for HDV viraemia as a main risk factor for disease progression. Hepatitis D seems to take a particularly severe course in patients born in Pakistan. There is an urgent need to extend access to antiviral therapies and to provide appropriate education about HDV infection.
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Affiliation(s)
- Anika Wranke
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany
| | - Cirley Lobato
- Centro de Ciências de Saúde e do Desporto, Universidade Federal do Acre, Rio Branco, Brazil
| | - Emanoil Ceausu
- Infectious Diseases, Dr. Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest, Romania
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
| | - Mario Rizzetto
- Department of Internal Medicine-Gastroenterology, University of Torino, Torino, Italy
| | - Adela Turcanu
- Department of Gastroenterology, State University of Medicine "Nicolae Testemitanu", Chisinau, Republic of Moldova
| | - Grazia A Niro
- Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Onur Keskin
- Medical Faculty, Ankara University, Ankara, Turkey
| | - George Gherlan
- Infectious Diseases, Dr. Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest, Romania
| | - Minaam Abbas
- Department of Hepatogastroenterology and Liver Transplantation, Ziauddin University Hospital Karachi, Karachi, Pakistan
| | | | - Marion Muche
- Department of Gastroenterology, Infectious Diseases and Rheumatology (including Clinical Nutrition), Charité, Berlin, Germany
| | - Maria Buti
- Liver Unit, Valle d'Hebron University Hospital and Ciberhed del Instituto CarlosIII, Barcelona, Spain
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Vanwolleghem
- Faculty of Medicine and Health Sciences, Laboratory of Experimental Medicine and Pediatrics, Viral Hepatitis Research group, University of Antwerp, Antwerp, Belgium
- European Reference Network RARE-LIVER
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany
- D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D
- Centre for Individualized Infection Medicine (CiiM), c/o CRC, Hannover, Germany
| | - Zaigham Abbas
- Department of Hepatogastroenterology and Liver Transplantation, Ziauddin University Hospital Karachi, Karachi, Pakistan
| | - Cihan Yurdaydin
- Medical Faculty, Ankara University, Ankara, Turkey
- Department of Gastroenterology & Hepatology, Koc University Medical School, Istanbul, Turkey
| | - Petra Dörge
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany
- D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D
- Centre for Individualized Infection Medicine (CiiM), c/o CRC, Hannover, Germany
- Hannover Medical School, Excellence Cluster RESIST, Hannover, Germany
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Cardoso MF, Coelho H, Branco JCE, Bragança S, Alexandrino G, Costa MN, Carvalho R, Pádua E, Martins A. Predominance of Genotype 5 Hepatitis Delta Virus Infection in a Portuguese Hepatology Unit. LIVERS 2024; 4:388-397. [DOI: 10.3390/livers4030028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2025] Open
Abstract
Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Genotype 1 (HDV-1) is by far the most prevalent in Europe and globally, while HDV-5 predominates in Western Africa. Data about HDV seroprevalence in Portugal are scarce and genotyping studies have not been performed yet. We aimed to assess the seroprevalence and genotypes of HDV in a large cohort of HBsAg-positive patients followed in our Hepatology Unit between 2012 and 2022. The anti-HDV-positive patients were subjected to a cross-sectional analysis, including blood sample collection for HDV RNA testing and genotype determination. In the cohort of HBsAg-positive patients, 57.5% (480/835) were born in African countries and 665/835 (79.6%) had been screened for anti-HDV antibodies. The HDV seroprevalence obtained was 6.5% (43/665). Twenty-one patients (age 41.2 ± 9.9 years; 57.1% male) were included in further molecular analyses. HDV RNA was positive in 8/21 (38.0%) and classified as HDV-5 in 7 patients (6 from Guinea-Bissau and 1 from Cape Verde) and HDV-1 in 1 patient (from Ukraine). In the largest and most comprehensive study performed in Portugal regarding HDV epidemiology to date, seroprevalence and genotype distribution of HDV (with predominance of HDV-5) were strongly influenced by immigration, notably from African countries.
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Affiliation(s)
| | - Henrique Coelho
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, 2720-276 Amadora, Portugal
| | - Joana Carvalho e Branco
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, 2720-276 Amadora, Portugal
| | - Sofia Bragança
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, 2720-276 Amadora, Portugal
| | - Gonçalo Alexandrino
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, 2720-276 Amadora, Portugal
| | - Mariana Nuno Costa
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, 2720-276 Amadora, Portugal
| | - Rita Carvalho
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, 2720-276 Amadora, Portugal
| | - Elizabeth Pádua
- Infectious Disease Department, National Institute of Health, 1649-016 Lisbon, Portugal
| | - Alexandra Martins
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, 2720-276 Amadora, Portugal
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18
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Akuffo GA, Ouoba S, Ko K, Chhoung C, Phyo Z, Mirzaev UK, Sugiyama A, Akita T, Tanaka J. Assessing the diagnostic accuracy of serological tests for hepatitis delta virus diagnosis: a systematic review and meta-analysis. Sci Rep 2024; 14:18475. [PMID: 39122751 PMCID: PMC11316141 DOI: 10.1038/s41598-024-69304-8] [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: 03/22/2024] [Accepted: 08/02/2024] [Indexed: 08/12/2024] Open
Abstract
Hepatitis Delta Virus (HDV), a satellite virus of Hepatitis B virus, exacerbates liver damage in affected individuals. Screening for HDV antibodies in HBsAg positive patients is recommended, but the diagnostic accuracy of serological tests remains uncertain. This review aimed to assess the diagnostic accuracy of serological tests for HDV. We searched PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Scopus etc. for relevant studies. Studies measuring the sensitivity and specificity of serological HDV tests against PCR as a reference standard were included. Pooled sensitivity and specificity for each test method and sero-marker were calculated. The review included six studies with 11 study arms, evaluating ARCHITECT immunoassay, EIA, ELISA, QMAC, RIA, and Western Blot test methods targeting Anti-HDV IgG, Total anti-HDV and Anti-HDV IgM. Sensitivities for Anti-HDV IgG, Total Anti-HDV and Anti-HDV IgM, tests were 97.4%, 51.9%, and 62.0%, respectively, with specificities of 95.3%, 80.0%, and 85.0%. Our findings, with its limited number of studies, suggest that HDV serological tests, particularly those identifying Anti IgG exhibit high accuracy and can serve as effective screening tools for HDV.
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Affiliation(s)
- Golda Ataa Akuffo
- Department of Epidemiology Infectious Diseases Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami, Hiroshima, 734-8551, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Serge Ouoba
- Department of Epidemiology Infectious Diseases Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami, Hiroshima, 734-8551, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | - Ko Ko
- Department of Epidemiology Infectious Diseases Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami, Hiroshima, 734-8551, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Chanroth Chhoung
- Department of Epidemiology Infectious Diseases Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami, Hiroshima, 734-8551, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Zayar Phyo
- Department of Epidemiology Infectious Diseases Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami, Hiroshima, 734-8551, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Ulugbek Khudayberdievich Mirzaev
- Department of Epidemiology Infectious Diseases Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami, Hiroshima, 734-8551, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
- Department of Hepatology, Scientific Research Instutute of Virology, Ministry of Health, Tashkent, Uzbekistan
| | - Aya Sugiyama
- Department of Epidemiology Infectious Diseases Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami, Hiroshima, 734-8551, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Tomoyuki Akita
- Department of Epidemiology Infectious Diseases Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami, Hiroshima, 734-8551, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology Infectious Diseases Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami, Hiroshima, 734-8551, Japan.
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan.
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19
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Qiu X, Hadji A, Olivo A, Hodges A, Beertsen C, Anderson M, Rodgers M, Mbanya D, Elaborot S, Cloherty G. Evaluation of a fully automated high-throughput serology assay for detection of Hepatitis D virus antibodies. J Clin Virol 2024; 173:105689. [PMID: 38781633 DOI: 10.1016/j.jcv.2024.105689] [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: 01/03/2024] [Revised: 04/23/2024] [Accepted: 05/07/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND HDV antibody testing is recommended for universal screening and as the first line in an HDV double reflex testing strategy for effectively identifying patients with active infection for therapeutic treatments. OBJECTIVE The aim of this study is to evaluate the performance of a newly developed ARCHITECT HDV Total Ig (ARCHITECT HDV Ig) prototype assay. STUDY DESIGN Performance characteristics were determined for the ARCHITECT HDV Ig and a reference test, LIAISON XL Anti-HDV using a well-characterized specimen panel, comprising HDV RNA positive (n = 62) and negative (n = 70) samples, and healthy US blood donors. RESULTS Healthy US blood donors (n=200) showed 99.5% (199/200, 95%CI=97.65-99.98) specificity with ARCHITECT HDV Ig and 98.5 % (197/200, 95 %CI = 96.10-99.64) with LIAISON Anti-HDV. Among known HDV RNA positive samples, ARCHITECT HDV Ig detected 59/62 demonstrating 95.2 % sensitivity while LIAISON Anti-HDV sensitivity was 90.3 % (56/62). Among 101 HBV positive samples, 70 were reactive in the ARCHITECT test, 59 of which tested positive for HDV RNA for a positive predictive value (PPV) for the presence of HDV RNA was 84.3 %. For LIAISON Anti-HDV, 79 specimens were reactive and 56 contained HDV RNA: PPV for HDV RNA was 70.9 %. Among 70 HDV RNA negative samples, 39 were HBV positive. ARCHITECT HDV Ig negative predictive value (NPV) was 71.8 % and LIAISON Anti-HDV NPV was 41 % for the HBV positive group, respectively. CONCLUSION When compared to the LIASON Anti-HDV test, the ARCHITECT HDV Ig assay demonstrated enhanced sensitivity and specificity and better NPV and PPV values for HDV RNA status. The ARCHITECT HDV Ig assay represents a promising tool for universal screening of all HBsAg-positive persons.
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Affiliation(s)
- Xiaoxing Qiu
- Infectious Disease Research, Abbott, Core Diagnostics, Abbott Park, IL, United States
| | - Abbas Hadji
- Infectious Disease Research, Abbott, Core Diagnostics, Abbott Park, IL, United States.
| | - Ana Olivo
- Infectious Disease Research, Abbott, Core Diagnostics, Abbott Park, IL, United States
| | - Austin Hodges
- Infectious Disease Research, Abbott, Core Diagnostics, Abbott Park, IL, United States
| | - Carla Beertsen
- Endocrine Laboratory, Amsterdam University Medical Centers, Amsterdam, Netherlands
| | - Mark Anderson
- Infectious Disease Research, Abbott, Core Diagnostics, Abbott Park, IL, United States
| | - Mary Rodgers
- Infectious Disease Research, Abbott, Core Diagnostics, Abbott Park, IL, United States
| | | | | | - Gavin Cloherty
- Infectious Disease Research, Abbott, Core Diagnostics, Abbott Park, IL, United States
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20
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Lai JCT, Wong GLH, Wong VWS, Yip TCF. Unmet need in screening for hepatitis D virus: Time to take action. J Hepatol 2024; 80:e277-e278. [PMID: 38110005 DOI: 10.1016/j.jhep.2023.12.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 12/03/2023] [Accepted: 12/11/2023] [Indexed: 12/20/2023]
Affiliation(s)
- Jimmy Che-To Lai
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Terry Cheuk-Fung Yip
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
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21
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Cadranel JFD, Zougmoré HT, Efole JRN, Hanslik B, Causse X, Rosa I, Lemaitre C, Mokhtari C, Baron A, Thevenot T, Medmoun M, Smadhi R, Fantognon G, Remy AJ, Macaigne G, Arondel Y, Arpurt JP, Bellaiche G, Bourlière M, De Kerguenec C, Heluwaert F, Verlynde J, Halfon P, Roulot D, Carrier P, Loustaud-Ratti V, Lemagoarou T. Hepatitis B Delta: assessment of the knowledge and practices of hepato-gastroenterologists practicing in non-academic settings in France. Eur J Gastroenterol Hepatol 2024; 36:735-741. [PMID: 38683191 DOI: 10.1097/meg.0000000000002707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/01/2024]
Abstract
BACKGROUND Data on the management of Hepatitis B-Delta (HB-D) by hepatogastroenterologists (HGs) practicing in nonacademic hospitals or private practices are unknown in France. OBJECTIVE We aimed to evaluate the knowledge and practices of HGs practicing in nonacademic settings regarding HB-D. METHODS A Google form document was sent to those HGs from May to September 2021. RESULTS A total of 130 HGs (mean age, 45 years) have participated in this survey. Among HBsAg-positive patients, Delta infection was sought in only 89% of cases. Liver fibrosis was assessed using FibroScan in 77% of the cases and by liver biopsy in 81% of the cases. A treatment was proposed for patients with >F2 liver fibrosis in 49% of the cases regardless of transaminase levels and for all the patients by 39% of HGs. Responding HGs proposed a treatment using pegylated interferon in 50% of cases, bulevirtide in 45% of cases and a combination of pegylated interferon and bulevirtide in 40.5% of cases. Among the criteria to evaluate the treatment efficacy, a decrease or a normalization of transaminases was retained by 89% of responding HGs, a reduction of liver fibrosis score for 70% of them, an undetectable delta RNA and HBsAg for 55% of them and a 2 log 10 decline in delta viremia for 62% of the cases. CONCLUSION Hepatitis Delta screening was not systematically performed in HBsAg-positive patients despite the probable awareness and knowledge of the few responders who were able to prescribe treatments of hepatitis delta.
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Affiliation(s)
| | | | | | | | | | - Isabelle Rosa
- Department of Liver and Digestive Diseases, CHI Créteil
| | | | | | - Aurore Baron
- Department of Liver and Digestive Diseases, Corbeil
| | | | - Mourad Medmoun
- Department of Liver and Digestive Diseases, GHPSO, Creil
| | - Ryad Smadhi
- Department of Liver and Digestive Diseases, GHPSO, Creil
| | | | - André J Remy
- Department of Liver and Digestive Diseases, Perpignan
| | | | - Yves Arondel
- Department of Liver and Digestive Diseases, Haguenau
| | | | - Guy Bellaiche
- Department of Liver and Digestive Diseases, Aulnay-sous-bois
| | | | | | | | | | - Philippe Halfon
- Department of Internal Medicine and Infectious Diseases, Alphabio Laboratory Marseille, Marseille
| | | | - Paul Carrier
- Department of Liver and Digestive Diseases, Limoges
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22
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Zong Q, Zhang H, Liu F, Li J, Liu Q, Duan Z, Duan W, Ruan M, Zhang J, Liu Y, Zhou Q, Wang Q. Activation of the cGAS-STING pathway by viral dsDNA leading to M1 polarization of macrophages mediates antiviral activity against hepatitis B virus. Immunobiology 2024; 229:152810. [PMID: 38772101 DOI: 10.1016/j.imbio.2024.152810] [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: 02/17/2024] [Revised: 05/09/2024] [Accepted: 05/16/2024] [Indexed: 05/23/2024]
Abstract
BACKGROUND AND AIMS Activation of the cGAS-STING pathway induces the production of type I interferons, initiating the antiviral immune response, which contributes to the clearance of pathogens. Previous studies have shown that STING agonists promote hepatitis B virus (HBV) clearance; however, few studies have investigated the effect of activating the cGAS-STING pathway in macrophages on HBV. METHODS The polarization status of HBV particle-stimulated RAW264.7 macrophages was analyzed. After stimulation with HBV particles, the analysis focused on determining whether the DNA sensors in RAW264.7 macrophages recognized the viral double-stranded DNA (dsDNA) and evaluating the activation of the cGAS-STING pathway. Coculture of mouse macrophages and hepatocytes harboring HBV was used to study the antiviral activity of HBV-stimulated RAW264.7 macrophages. RESULTS After stimulation with HBV particles, HBV relaxed circular DNA (rcDNA) was detected in RAW264.7 macrophages, and the protein expression of phospho-STING, phospho-TBK1, and phospho-IRF3 in the STING pathway was increased, as shown by Western blot analysis, which revealed that M1 polarization of macrophages was caused by increased expression of CD86. RT-PCR analyses revealed elevated expression of M1 macrophage polarization-associated cytokines such as TNFα, IL-1β, iNOS, and IFNα/β. In the coculture experiment, both HBsAg and HBeAg expression levels were significantly decreased in AML12-HBV1.3 cells cocultured with the supernatants of HBV-stimulated RAW264.7 macrophages. CONCLUSION The results suggest that macrophages can endocytose HBV particles. Additionally, viral dsDNA can be recognized by DNA pattern recognition receptors, which in turn activate the cGAS-STING pathway, promoting the M1 polarization of macrophages, while no significant M2 polarization is observed. Macrophages stimulated with HBV particles exhibit enhanced antiviral activity against HBV.
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Affiliation(s)
- Qiyin Zong
- Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Hao Zhang
- Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Futing Liu
- Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jianfei Li
- Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qian Liu
- Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhi Duan
- Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wanlu Duan
- Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Mengqi Ruan
- Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jingjing Zhang
- Department of Geriatric Cardiology, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yan Liu
- Department of Microbiology, School of Basic Medical, Anhui Medical University, Hefei, China
| | - Qiang Zhou
- Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China.
| | - Qin Wang
- Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China.
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23
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John BV, Amoli MM, Evon DM, Wong R, Dahman B. Hepatitis delta testing trends in a US national cohort: An analysis of patient and provider-level predictive factors. Hepatol Commun 2024; 8:e0401. [PMID: 38619425 PMCID: PMC11019823 DOI: 10.1097/hc9.0000000000000401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Accepted: 01/29/2024] [Indexed: 04/16/2024] Open
Abstract
BACKGROUND The low prevalence of HDV infection in the United States could be attributed to insufficient testing rate, which can result in an underestimation of the true burden of HDV. The primary objective of this study is to quantify the prevalence of and factors associated with HDV antibody (anti-HDV) or RNA testing, among participants with positive HBsAg in the Veterans Health Administration (VHA). METHODS We conducted a retrospective cohort study of participants who tested positive for HBsAg between January 2000 and December 2022 within the VHA. We identified those who were tested for HDV, and patient and provider-level factors associated with HDV testing. RESULTS Of 41,658 participants with positive HBsAg who had follow-up, 4438 (10.7%) were tested at least once for HDV, of which 135 (3.0%) were positive. Participants in the Northeast (adjusted odds ratio [aOR]: 1.30, 95% CI: 1.17-1.44, p<0.001), and receiving hepatology care (aOR: 1.38, 95% CI: 1.24-1.54, p<0.001) were more likely, while those in the Midwest (aOR: 0.69, 95% CI: 0.60-0.79, p<0.001), under the care of a primary care provider (aOR: 0.61, 95% CI: 0.50-0.74, p<0.001), Blacks (aOR: 0.85, 95% CI: 0.77-0.94, p=0.001), participants who were HCV antibody-positive (aOR: 0.89, 95% CI: 0.81-0.99, p=0.03), and participants who were HIV-positive (aOR: 0.80, 95% CI: 0.71-0.90, p<0.001) were less likely to be tested for HDV. CONCLUSIONS HDV screening rates in the VHA remain low overall. Participants who are Black, living in the Midwest, patients who are HIV-positive, and patients who are HCV-positive are less likely to be tested for HDV. These results suggest that risk-based screening strategies are ineffective in the VHA and highlight the need for refining testing strategies to increase HDV screening rates.
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Affiliation(s)
- Binu V. John
- Department of Medicine, Division of Gastroenterology and Hepatology, Miami VA Medical System, Miami, Florida, USA
- Division of Medical Education, University of Miami Miller School of Medicine, Miami, Florida, USA
| | | | - Donna M. Evon
- Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Robert Wong
- Division of Gastroenterology and Hepatology, Palo Alto VA Health System, Alto, California, USA
- Division of Gastroenterology, Stanford University, Palo Alto, California, USA
| | - Bassam Dahman
- Department of Health Behavior and Policy, Virginia Commonwealth University, Richmond, Virginia, USA
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24
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Soriano V, Moreno-Torres V, Treviño A, de Jesús F, Corral O, de Mendoza C. Prospects for Controlling Hepatitis B Globally. Pathogens 2024; 13:291. [PMID: 38668246 PMCID: PMC11054959 DOI: 10.3390/pathogens13040291] [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: 03/09/2024] [Revised: 03/28/2024] [Accepted: 03/29/2024] [Indexed: 04/29/2024] Open
Abstract
Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic hepatitis B, and more than 800,000 patients die each year due to hepatitis B complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage is suboptimal. In adults, sexual transmission is by far the most frequent route of contagion. The WHO estimates that 1.5 million new HBV infections occur annually. Oral nucleos(t)ide analogues entecavir and tenofovir are the most frequent antivirals prescribed as HBV therapy. Almost all patients adherent to the medication achieve undetectable plasma viremia beyond 6 months of monotherapy. However, less than 5% achieve anti-HBs seroconversion, and viral rebound occurs following drug discontinuation. Therefore, nucleos(t)ide analogues need to be lifelong. New long-acting formulations of tenofovir and entecavir are being developed that will maximize treatment benefit and overcome adherence barriers. Furthermore, new antiviral agents are in development, including entry inhibitors, capside assembly modulators, and RNA interference molecules. The use of combination therapy pursues a functional HBV cure, meaning it is negative for both circulating HBV-DNA and HBsAg. Even when this goal is achieved, the cccDNA reservoir within infected hepatocytes remains a signal of past infection, and HBV can reactivate under immune suppression. Therefore, new gene therapies, including gene editing, are eagerly being pursued to silence or definitively disrupt HBV genomes within infected hepatocytes and, in this way, ultimately cure hepatitis B. At this time, three actions can be taken to push HBV eradication globally: (1) expand universal newborn HBV vaccination; (2) perform once-in-life testing of all adults to identify susceptible HBV persons that could be vaccinated (or re-vaccinated) and unveil asymptomatic carriers that could benefit from treatment; and (3) provide earlier antiviral therapy to chronic HBV carriers, as being aviremic reduces the risk of both clinical progression and transmission.
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Affiliation(s)
- Vicente Soriano
- UNIR Health Sciences School & Medical Center, 28010 Madrid, Spain
| | - Víctor Moreno-Torres
- UNIR Health Sciences School & Medical Center, 28010 Madrid, Spain
- Department of Internal Medicine, Puerta de Hierro University Hospital, Majadahonda, 28222 Madrid, Spain
| | - Ana Treviño
- UNIR Health Sciences School & Medical Center, 28010 Madrid, Spain
| | | | - Octavio Corral
- UNIR Health Sciences School & Medical Center, 28010 Madrid, Spain
| | - Carmen de Mendoza
- Department of Internal Medicine, Puerta de Hierro University Hospital, Majadahonda, 28222 Madrid, Spain
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25
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Abbas Z, Abbas M. Is there a need for universal double reflex testing of HBsAg-positive individuals for hepatitis D infection? World J Hepatol 2024; 16:300-303. [PMID: 38577532 PMCID: PMC10989316 DOI: 10.4254/wjh.v16.i3.300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 01/16/2024] [Accepted: 02/22/2024] [Indexed: 03/27/2024] Open
Abstract
Hepatitis D virus (HDV) can infect HBsAg-positive individuals, causing rapid fibrosis progression, early decompensation, increased hepatocellular carcinoma risk, and higher mortality than hepatitis B virus (HBV) mono-infection. Most countries lack high-quality HDV prevalence data, and the collection techniques employed often bias published data. In recent meta-analyses, HDV prevalence in HBsAg-positive patients reaches 5%-15% and is even significantly higher in endemic areas. Since HBV vaccination programs were implemented, HDV prevalence has decreased among younger populations. However, owing to immigrant influx, it has increased in some Western countries. The current practice of HDV screening in HBsAg-positive individuals is stepwise, based on physician's discretion, and limited to at-risk populations and may require numerous visits. Double reflex testing, which includes anti-HDV testing in all HBsAg-positive individuals and then HDV RNA testing for anti-HDV-positive ones, is uncommon. Reflex testing can identify more HDV infection cases and link identified patients to further care and follow-up. Moreover, laboratory-based double reflex screening is less biased than physician-led testing. Therefore, healthcare providers should learn about reflex testing, and federal and provincial hepatitis control programs should implement laboratory-based double reflex testing to obtain reliable HDV prevalence estimates. The test's cost-effectiveness depends on the number of HBV-positive patients screened to identify one HDV-positive patient. Such testing may be viable in areas with low HBsAg but high HDV prevalence. However, its economic impact on areas with low HDV prevalence needs further study.
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Affiliation(s)
- Zaigham Abbas
- Department of Hepatogastroenterology and Liver Transplantation, Dr. Ziauddin University Hospital, Karachi 75600, Sindh, Pakistan.
| | - Minaam Abbas
- Department of Medicine, University of Cambridge, Cambridge CB2 0SP, United Kingdom
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26
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Buti M, Gonzalez A, Riveiro-Barciela M, Bourliere M. Management of chronic HBV-HDV patients chronic HBV-HDV infection: A review on new management options. United European Gastroenterol J 2024; 12:210-218. [PMID: 38041549 PMCID: PMC10954430 DOI: 10.1002/ueg2.12494] [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: 07/21/2023] [Accepted: 09/01/2023] [Indexed: 12/03/2023] Open
Abstract
Hepatitis D virus was first described by Mario Rizzeto in 1977, and it is considered chronic viral hepatitis with the poorest prognosis. Despite its discovery almost 50 years ago, progress in its diagnosis and treatment has been scarce until recent years. The approval of bulevirtide has shed some light for patients with Chronic Hepatitis D, although important gaps regarding its use in therapy as well as about the epidemiology and diagnosis of the disease need to be addressed.
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Affiliation(s)
- María Buti
- Liver Unit, Internal Medicine Department, Hospital Universitari Valld'Hebron, Valld'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBERehd, Instituto Carlos III, Barcelona, Spain
| | | | - Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitari Valld'Hebron, Valld'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBERehd, Instituto Carlos III, Barcelona, Spain
| | - Marc Bourliere
- Liver Unit, Saint Joseph Hopital, Marseille, France
- Aix Marseille University, Inserm, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
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Gopalakrishna H, Mironova M, Dahari H, Koh C, Heller T. Advances and Challenges in Managing Hepatitis D Virus: Evolving Strategies. CURRENT HEPATOLOGY REPORTS 2024; 23:32-44. [PMID: 38533303 PMCID: PMC10965034 DOI: 10.1007/s11901-024-00643-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 01/14/2024] [Indexed: 03/28/2024]
Abstract
Purpose of Review Hepatitis D Virus (HDV), although a small defective virus, poses a substantial public health challenge due to lack of awareness, underrecognized prevalence, and limited treatment options. Universal HDV screening within hepatitis B virus (HBV) cohorts is essential to address this issue. Despite its aggressive nature, effective HDV therapies have remained elusive for over four decades. Recent Findings Advances in understanding HDV's biology and clinical behavior offer potential therapeutic breakthroughs, fostering optimism. As insights grow, effective and targeted therapies are being developed to improve HDV management. Summary This review delves into HDV's intricate structure and biology, highlighting formidable hurdles in antiviral development. It emphasizes the importance of widespread screening, exploring noninvasive diagnostics, and examining current and emerging innovative therapeutic strategies. Moreover, the review explores models for monitoring treatment response. In essence, this review simplifies the complexities of effectively combating HDV.
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Affiliation(s)
- Harish Gopalakrishna
- Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Maria Mironova
- Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Harel Dahari
- The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA
| | - Christopher Koh
- Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Theo Heller
- Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
- Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Building 10, Room 4-5722, Bethesda, MD 20892-1800, USA
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Razavi-Shearer D, Child H, Razavi-Shearer K, Voeller A, Razavi H, Buti M, Tacke F, Terrault N, Zeuzem S, Abbas Z, Aghemo A, Akarca U, Al Masri N, Alalwan A, Blomé MA, Jerkeman A, Aleman S, Kamal H, Alghamdi A, Alghamdi M, Alghamdi S, Al-Hamoudi W, Ali E, Aljumah A, Altraif I, Amarsanaa J, Asselah T, Baatarkhuu O, Babameto A, Ben-Ari Z, Berg T, Biondi M, Braga W, Brandão-Mello C, Brown R, Brunetto M, Cabezas J, Cardoso M, Martins A, Chan H, Cheinquer H, Chen CJ, Yang HI, Chen PJ, Chien CH, Chuang WL, Garza LC, Coco B, Coffin C, Coppola N, Cornberg M, Craxi A, Crespo J, Cuko L, De Ledinghen V, Duberg AS, Etzion O, Ferraz M, Ferreira P, Forns X, Foster G, Fung J, Gaeta G, García-Samaniego J, Genov J, Gheorghe L, Gholam P, Gish R, Glenn J, Hamid S, Hercun J, Hsu YC, Hu CC, Huang JF, Idilman R, Jafri W, Janjua N, Jelev D, Jia J, Kåberg M, Kaita K, Kao JH, Khan A, Kim D, Kondili L, Lagging M, Lampertico P, Lázaro P, Lazarus J, Lee MH, Yang HI, Lim YS, Lobato C, Macedo G, Marinho R, Marotta P, Mendes-Correa M, Méndez-Sánchez N, Navas MC, Ning Q, et alRazavi-Shearer D, Child H, Razavi-Shearer K, Voeller A, Razavi H, Buti M, Tacke F, Terrault N, Zeuzem S, Abbas Z, Aghemo A, Akarca U, Al Masri N, Alalwan A, Blomé MA, Jerkeman A, Aleman S, Kamal H, Alghamdi A, Alghamdi M, Alghamdi S, Al-Hamoudi W, Ali E, Aljumah A, Altraif I, Amarsanaa J, Asselah T, Baatarkhuu O, Babameto A, Ben-Ari Z, Berg T, Biondi M, Braga W, Brandão-Mello C, Brown R, Brunetto M, Cabezas J, Cardoso M, Martins A, Chan H, Cheinquer H, Chen CJ, Yang HI, Chen PJ, Chien CH, Chuang WL, Garza LC, Coco B, Coffin C, Coppola N, Cornberg M, Craxi A, Crespo J, Cuko L, De Ledinghen V, Duberg AS, Etzion O, Ferraz M, Ferreira P, Forns X, Foster G, Fung J, Gaeta G, García-Samaniego J, Genov J, Gheorghe L, Gholam P, Gish R, Glenn J, Hamid S, Hercun J, Hsu YC, Hu CC, Huang JF, Idilman R, Jafri W, Janjua N, Jelev D, Jia J, Kåberg M, Kaita K, Kao JH, Khan A, Kim D, Kondili L, Lagging M, Lampertico P, Lázaro P, Lazarus J, Lee MH, Yang HI, Lim YS, Lobato C, Macedo G, Marinho R, Marotta P, Mendes-Correa M, Méndez-Sánchez N, Navas MC, Ning Q, Örmeci N, Orrego M, Osiowy C, Pan C, Pessoa M, Piracha Z, Pop C, Qureshi H, Raimondo G, Ramji A, Ribeiro S, Ríos-Hincapié C, Rodríguez M, Rosenberg W, Roulot D, Ryder S, Saeed U, Safadi R, Shouval D, Sanai F, Sanchez-Avila J, Santantonio T, Sarrazin C, Seto WK, Seto WK, Simonova M, Tanaka J, Tergast T, Tsendsuren O, Valente C, Villalobos-Salcedo J, Waheed Y, Wong G, Wong V, Yip T, Wong V, Wu JC, Yang HI, Yu ML, Yuen MF, Yurdaydin C, Zuckerman E. Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories. J Hepatol 2024; 80:232-242. [PMID: 38030035 DOI: 10.1016/j.jhep.2023.10.043] [Show More Authors] [Citation(s) in RCA: 29] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 10/13/2023] [Accepted: 10/30/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND & AIMS Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. METHODS We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. RESULTS After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. CONCLUSIONS We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened. IMPACT AND IMPLICATIONS There is a great deal of uncertainty surrounding the prevalence of hepatitis delta virus among people living with hepatitis B virus at the population level. In this study, we aimed to better understand the burden in 25 countries and territories, to refine techniques that can be used in future analyses. We found a lower prevalence in the majority of places studied than had been previously reported. These data can help inform policy makers on the need to screen people living with hepatitis B virus to find those coinfected with hepatitis delta virus and at high risk of progression, while also highlighting the pitfalls that other researchers have often fallen into.
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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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Llaneras J, Ruiz-Cobo JC, Rando-Segura A, Barreira-Díaz A, Domínguez-Hernández R, Rodríguez-Frías F, Campins M, Colom J, Casado MA, Blanco-Grau A, Bañares J, Monforte A, Falcó-Roget A, Ruíz L, Meza B, Pumarola T, Riveiro-Barciela M, Esteban R, Buti M. Integrating viral hepatitis management into the emergency department: A further step towards viral hepatitis elimination. JHEP Rep 2024; 6:100932. [PMID: 38074506 PMCID: PMC10698271 DOI: 10.1016/j.jhepr.2023.100932] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 09/26/2023] [Accepted: 09/27/2023] [Indexed: 10/16/2024] Open
Abstract
BACKGROUND & AIMS Many people with HCV and HBV infection are unaware of their condition, particularly at-risk and vulnerable populations who face barriers for screening and linkage to care. Emergency departments are often their only point of contact with the health system. METHODS This is a prospective study investigating HBsAg and HCV antibody testing, with reflex testing for HDV antibodies and HCV RNA, in adults attending an emergency department and requiring a blood test. Positive cases were linked to care. A cost-effectiveness analysis was performed. RESULTS From February 2020 to February 2022, a total of 17,560 individuals were screened. HBsAg was detected in 91 (0.5%), HCV RNA in 128 (0.7%), and HDV antibodies in two (0.01%) individuals. Nearly 40% of positive cases were unaware of their condition. Linkage to care was achieved in 42 of 56 HBsAg-positive and 45 of 69 HCV RNA-positive participants who were candidates for referral. HCV and HBV screening vs. no screening yielded 1.06 and 0.42 additional quality-adjusted life-years, respectively, with incremental cost-utility ratios of €7,629 and -€147 per quality-adjusted life-year gained, respectively, and proved even more cost-effective in patients with hepatitis C aged 40-70 years. CONCLUSIONS On emergency department screening for hepatitis B, C, and D in Barcelona, the prevalence of HBsAg was 0.5% and HCV RNA 0.7%, approximately threefold higher than that observed in the general population. This strategy diagnosed patients with active HCV infection and no risk factors, who would not have been screened according to the current recommendations. Screening and linkage to care of viral hepatitis is cost-effective in this setting. IMPACT AND IMPLICATIONS We evaluated the performance and cost-effectiveness of a viral hepatitis screening programme implemented in an emergency department, which aimed to identify and link to care people living with hepatitis B and C. Our findings reveal a threefold higher prevalence of hepatitis B and C than in the general Spanish population, possibly attributable to the role of the emergency department as the main healthcare gateway for vulnerable populations, who have a higher prevalence of viral hepatitis. Risk factors for viral hepatitis could not be identified in most people living with hepatitis B and C attending the emergency department; hence, screening beyond risk factors should be considered in hepatitis detection strategies. Emergency department screening is cost-effective for hepatitis C and is a cost-saving strategy for hepatitis B in our setting. These data should inform future updates to clinical guidelines.
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Affiliation(s)
- Jordi Llaneras
- Emergency Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | | | - Ariadna Rando-Segura
- Microbiology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain
- CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain
| | | | | | - Francisco Rodríguez-Frías
- CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain
- Biochemistry Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | - Magda Campins
- Epidemiology Service, Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | - Joan Colom
- Public Health Agency of Catalonia, Health Department, General Subdirection on Prevention, Control and Care on Addictions, HIV, STI and Viral Hepatitis, Barcelona, Spain
| | - Miguel Angel Casado
- CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain
- Pharmacoeconomics & Outcomes Research Iberia (PORIB), Madrid, Spain
| | - Albert Blanco-Grau
- Biochemistry Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | - Juan Bañares
- Liver Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - Arnau Monforte
- Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | - Anna Falcó-Roget
- Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | - Lourdes Ruíz
- Liver Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - Beatriz Meza
- Emergency Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | - Tomàs Pumarola
- Microbiology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - Mar Riveiro-Barciela
- Liver Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain
- CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain
| | - Rafael Esteban
- Liver Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain
- CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain
| | - María Buti
- Liver Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain
- CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain
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Salpini R, Piermatteo L, Torre G, D'Anna S, Khan S, Duca L, Bertoli A, La Frazia S, Malagnino V, Teti E, Iannetta M, Paba P, Ciotti M, Lenci I, Francioso S, Paquazzi C, Lichtner M, Mastroianni C, Santopaolo F, De Sanctis G, Pellicelli A, Galati G, Moretti A, Casinelli K, Caterini L, Iapadre N, Parruti G, Vecchiet I, Paoloni M, Marignani M, Ceccherini-Silberstein F, Baiocchi L, Grelli S, Sarmati L, Svicher V. Prevalence of hepatitis D virus infection in Central Italy has remained stable across the last 2 decades with dominance of subgenotypes 1 and characterized by elevated viral replication. Int J Infect Dis 2024; 138:1-9. [PMID: 37944585 DOI: 10.1016/j.ijid.2023.11.005] [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: 11/02/2023] [Accepted: 11/02/2023] [Indexed: 11/12/2023] Open
Abstract
OBJECTIVES Here we investigate Hepatitis D virus (HDV)-prevalence in Italy and its fluctuations over time and we provide an extensive characterization of HDV-infected patients. METHODS The rate of HDV seroprevalence and HDV chronicity was assessed in 1579 hepatitis B surface antigen (HBsAg)+ patients collected from 2005 to 2022 in Central Italy. RESULTS In total, 45.3% of HBsAg+ patients received HDV screening with an increasing temporal trend: 15.6% (2005-2010), 45.0% (2011-2014), 49.4% (2015-2018), 71.8% (2019-2022). By multivariable model, factors correlated with the lack of HDV screening were alanine-aminotransferase (ALT) less than two times of upper limit of normality (<2ULN) and previous time windows (P <0.002). Furthermore, 13.4% of HDV-screened patients resulted anti-HDV+ with a stable temporal trend. Among them, 80.8% had detectable HDV-ribonucleic acid (RNA) (median [IQR]:4.6 [3.6-5.6] log copies/ml) with altered ALT in 89.3% (median [IQR]:92 [62-177] U/L). Anti-HDV+ patients from Eastern/South-eastern Europe were younger than Italians (44 [37-54] vs 53 [47-62] years, P <0.0001), less frequently nucleos(t)ide analogs (NUC)-treated (58.5% vs 80%, P = 0.026) with higher HDV-RNA (4.8 [3.6-5.8] vs 3.9 [1.4-4.9] log copies/ml, P = 0.016) and HBsAg (9461 [4159-24,532] vs 4447 [737-13,336] IU/ml, P = 0.032). Phylogenetic analysis revealed the circulation of HDV subgenotype 1e (47.4%) and -1c (52.6%). Notably, subgenotype 1e correlated with higher ALT than 1c (168 [89-190] vs 58 [54-88] U/l, P = 0.015) despite comparable HDV-RNA. CONCLUSIONS HDV-screening awareness is increasing over time even if some gaps persist to achieve HDV screening in all HBsAg+ patients. HDV prevalence in tertiary care centers tend to scarcely decline in native/non-native patients. Detection of subgenotypes, triggering variable inflammatory stimuli, supports the need to expand HDV molecular characterization.
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Affiliation(s)
- Romina Salpini
- Tor Vergata University, Department of Biology, Rome, Italy
| | | | - Giulia Torre
- Tor Vergata University, Department of Biology, Rome, Italy
| | - Stefano D'Anna
- Tor Vergata University, Department of Experimental Medicine, Rome, Italy
| | - Sohaib Khan
- Tor Vergata University, Department of Experimental Medicine, Rome, Italy
| | - Leonardo Duca
- Tor Vergata University, Department of Experimental Medicine, Rome, Italy
| | - Ada Bertoli
- Tor Vergata University, Department of Experimental Medicine, Rome, Italy; Tor Vergata University Hospital, Virology Unit, Rome, Italy
| | | | | | - Elisabetta Teti
- Tor Vergata University Hospital, Infectious Diseases Unit, Rome, Italy
| | - Marco Iannetta
- Tor Vergata University Hospital, Infectious Diseases Unit, Rome, Italy
| | - Pierpaolo Paba
- Tor Vergata University Hospital, Virology Unit, Rome, Italy
| | - Marco Ciotti
- Tor Vergata University Hospital, Virology Unit, Rome, Italy
| | - Ilaria Lenci
- Tor Vergata University Hospital, Hepatology Unit, Rome, Italy
| | | | | | - Miriam Lichtner
- La Sapienza University, Department of Public Health and Infectious Disease, Rome, Italy
| | - Claudio Mastroianni
- La Sapienza University, Department of Public Health and Infectious Disease, Rome, Italy
| | - Francesco Santopaolo
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Internal Medicine and Gastroenterology-Hepatology Unit, Rome, Italy
| | | | | | - Giovanni Galati
- University Campus Bio-Medico, Internal Medicine and Hepatology Unit, Rome, Italy
| | | | - Katia Casinelli
- Spaziani Hospital, Infectious Disease Unit, Frosinone, Italy
| | | | - Nerio Iapadre
- San Salvatore Hospital, Infectious Diseases Unit, L'Aquila, Italy
| | - Giustino Parruti
- Pescara General Hospital, Infectious Disesases Unit, Pescara, Italy
| | - Iacopo Vecchiet
- University "G. d'Annunzio" Chieti-Pescara, Clinic of Infectious Diseases, Department of Medicine and Science of Aging, Chieti, Italy
| | - Maurizio Paoloni
- Avezzano General Hospital, Infectious Diseases Unit, Avezzano, Italy
| | - Massimo Marignani
- Regina Apostolorum Hospital, Department of Gastroenterology and Hepatology, Albano Laziale, Italy
| | | | | | - Sandro Grelli
- Tor Vergata University Hospital, Virology Unit, Rome, Italy
| | - Loredana Sarmati
- Tor Vergata University Hospital, Infectious Diseases Unit, Rome, Italy
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Abstract
Importance Hepatitis D virus (HDV) infection occurs in association with hepatitis B virus (HBV) infection and affects approximately 12 million to 72 million people worldwide. HDV causes more rapid progression to cirrhosis and higher rates of hepatocellular carcinoma than HBV alone or hepatitis C virus. Observations HDV requires HBV to enter hepatocytes and to assemble and secrete new virions. Acute HDV-HBV coinfection is followed by clearance of both viruses in approximately 95% of people, whereas HDV superinfection in an HBV-infected person results in chronic HDV-HBV infection in more than 90% of infected patients. Chronic hepatitis D causes more rapidly progressive liver disease than HBV alone. Approximately 30% to 70% of patients with chronic hepatitis D have cirrhosis at diagnosis and more than 50% die of liver disease within 10 years of diagnosis. However, recent studies suggested that progression is variable and that more than 50% of people may have an indolent course. Only approximately 20% to 50% of people infected by hepatitis D have been diagnosed due to lack of awareness and limited access to reliable diagnostic tests for the HDV antibody and HDV RNA. The HBV vaccine prevents HDV infection by preventing HBV infection, but no vaccines are available to protect those with established HBV infection against HDV. Interferon alfa inhibits HDV replication and reduces the incidence of liver-related events such as liver decompensation, hepatocellular carcinoma, liver transplant, or mortality from 8.5% per year to 3.3% per year. Adverse effects from interferon alfa such as fatigue, depression, and bone marrow suppression are common. HBV nucleos(t)ide analogues, such as entecavir or tenofovir, are ineffective against HDV. Phase 3 randomized clinical trials of bulevirtide, which blocks entry of HDV into hepatocytes, and lonafarnib, which interferes with HDV assembly, showed that compared with placebo or observation, these therapies attained virological and biochemical response in up to 56% of patients after 96 weeks of bulevirtide monotherapy and 19% after 48 weeks of lonafarnib, ritonavir, and pegylated interferon alfa treatment. Conclusions and Relevance HDV infection affects approximately 12 million to 72 million people worldwide and is associated with more rapid progression to cirrhosis and liver failure and higher rates of hepatocellular carcinoma than infection with HBV alone. Bulevirtide was recently approved for HDV in Europe, whereas pegylated interferon alfa is the only treatment available in most countries.
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Affiliation(s)
- Francesco Negro
- Division of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva, Switzerland
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor
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Rizzetto M. Hepatitis D Virus Infection. Reply. N Engl J Med 2023; 389:1441-1442. [PMID: 37819969 DOI: 10.1056/nejmc2309735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/13/2023]
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Deng X, Liu D, Delcourt MP, Gao H, Zhou L, Candotti D. No Hepatitis Delta Virus Seropositivity among Blood Donors with Overt and Occult Hepatitis B Infection in Dalian, Liaoning Province, China. Viruses 2023; 15:1509. [PMID: 37515195 PMCID: PMC10384194 DOI: 10.3390/v15071509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 06/28/2023] [Accepted: 07/04/2023] [Indexed: 07/30/2023] Open
Abstract
Hepatitis delta virus (HDV) is an obligate satellite of hepatitis B virus (HBV). Dual HDV/HBV infection is associated with down-regulated HBV replication and fast progression to severe liver disease. Although HDV is transmissible through exposure to infected blood, data about HDV infection in blood donors remain scarce. Between 2011 and 2021, 869,633 donations were collected from prequalified donors in Dalian, China. In total, 1060 (0.12%) were confirmed HBsAg and/or HBV DNA-reactive. Subsequently, anti-HDV IgG was tested in 2175 donations, including 65 that tested HBsAg+ pre donation, 1017 confirmed HBV-positive (507 HBsAg+/HBV DNA+, 33 HBsAg+/DNA-, 477 HBsAg-/DNA+ (451 occult (OBI) and 26 acute infections)), 327 viral DNA non-repeated-reactive, 397 anti-HBc-only, and 369 anti-HBs-only. Two (0.09%) samples tested anti-HDV IgG weakly reactive but were unconfirmed by IgM and IgG repeat testing with alternative assays, suggesting an initial false reactivity. In addition, HDV testing in a subgroup of confirmed OBI donors, comprising 451 donors from Dalian and 126 archived samples of OBI donors from around the world, showed only one non-Chinese donor to be repeatedly anti-HDV-reactive, suggesting that HDV/HBV coinfection does not play a significant role in the genesis of OBI. The overall data suggested an extremely low prevalence of HDV infection among blood donors in Liaoning province, Northeast China.
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Affiliation(s)
- Xuelian Deng
- Dalian Blood Center, No. 90 Yan'an Road, Zhongshan District, Dalian 116001, China
| | - Dan Liu
- Dalian Blood Center, No. 90 Yan'an Road, Zhongshan District, Dalian 116001, China
| | - Maelenn Pailine Delcourt
- Department of Virology, Henri Mondor Hospital, Paris-Est University, Inserm U955-IMRB-Team 18, 94010 Creteil, France
| | - Huihui Gao
- Dalian Blood Center, No. 90 Yan'an Road, Zhongshan District, Dalian 116001, China
| | - Lu Zhou
- Dalian Blood Center, No. 90 Yan'an Road, Zhongshan District, Dalian 116001, China
| | - Daniel Candotti
- Department of Virology, Henri Mondor Hospital, Paris-Est University, Inserm U955-IMRB-Team 18, 94010 Creteil, France
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