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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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Kondili LA, Brancaccio G, Tosti ME, Coco B, Quaranta MG, Messina V, Ciancio A, Morisco F, Cossiga V, Claar E, Rosato V, Ciarallo M, Cacciola I, Ponziani FR, Cerrito L, Coppola R, Longobardi F, Biliotti E, Rianda A, Barbaro F, Coppola N, Stanzione M, Barchiesi F, Fagiuoli S, Viganò M, Massari M, Russo FP, Ferrarese A, Laccabue D, Di Marco V, Blanc P, Marrone A, Morsica G, Federico A, Ieluzzi D, Rocco A, Foschi FG, Soria A, Maida I, Chessa L, Milella M, Rosselli Del Turco E, Madonia S, Chemello L, Gentile I, Toniutto P, Bassetti M, Surace L, Baiocchi L, Pellicelli A, De Santis A, Puoti M, Degasperi E, Niro GA, Zignego AL, Craxi A, Raimondo G, Santantonio TA, Brunetto MR, Gaeta GB. A holistic evaluation of patients with chronic Hepatitis D virus (HDV) infection enrolled in the Italian PITER-B and delta cohort. Int J Infect Dis 2024; 146:107115. [PMID: 38801968 DOI: 10.1016/j.ijid.2024.107115] [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: 03/14/2024] [Revised: 05/21/2024] [Accepted: 05/23/2024] [Indexed: 05/29/2024] Open
Abstract
BACKGROUND AND AIMS We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. METHODS This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. RESULTS Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. CONCLUSIONS CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.
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Affiliation(s)
- Loreta A Kondili
- Center for Global Health, Istituto Superiore di Sanità, Rome, Italy; UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy.
| | - Giuseppina Brancaccio
- Department of Molecular Medicine, Infectious Diseases, University of Padua, Padua, Italy
| | | | - Barbara Coco
- Hepatology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | | | - Vincenzo Messina
- Department of Infectious Diseases, Sant'Anna Hospital, Caserta, Italy
| | - Alessia Ciancio
- Gastroenterology Unit, Città della Salute e della Scienza of Turin, University Hospital, Turin, Italy
| | - Filomena Morisco
- Liver and Biliary System Unit, Department of Clinical Medicine and Surgery, University of Naples, Naples, Italy
| | - Valentina Cossiga
- Liver and Biliary System Unit, Department of Clinical Medicine and Surgery, University of Naples, Naples, Italy
| | | | | | | | - Irene Cacciola
- Department of Internal Medicine, University Hospital of Messina, Messina, Italy
| | - Francesca Romana Ponziani
- Liver Unit, Digestive Disease Center, CEMAD Division of Internal Medicine and Gastroenterology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Lucia Cerrito
- Liver Unit, Digestive Disease Center, CEMAD Division of Internal Medicine and Gastroenterology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Roberta Coppola
- Department of Hepatology, Gragnano Hospital, Gragnano (NA), Italy
| | | | - Elisa Biliotti
- National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, Rome, Italy
| | - Alessia Rianda
- National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, Rome, Italy
| | - Francesco Barbaro
- Department of Medicine, Infectious Diseases Unit, University Hospital of Padua, Padua, Italy
| | - Nicola Coppola
- Infectious Diseases Unit, Department of Mental Health and Public Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Maria Stanzione
- Infectious Diseases Unit, Department of Mental Health and Public Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Francesco Barchiesi
- Clinical Infectious Diseases, Polytechnic University of Marche, Ancona, Italy
| | - Stefano Fagiuoli
- Department of Medicine, University of Milan Bicocca & Gastroenterology Hepatology and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Mauro Viganò
- Department of Medicine, University of Milan Bicocca & Gastroenterology Hepatology and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Marco Massari
- Malattie Infettive, Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Francesco Paolo Russo
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padua, Padua, Italy
| | - Alberto Ferrarese
- Gastroenterology Unit, University Hospital Borgo Trento, Verona, Italy
| | - Diletta Laccabue
- Department of Medicine and Surgery, Università degli Studi di Parma, Parma, Italy
| | - Vito Di Marco
- Biomedical Department of Internal and Specialistic Medicine University of Palermo, Unit of Gastroenterology and Hepatology, Palermo, Italy
| | - Pierluigi Blanc
- Infectious Disease Unit, Santa Maria Annunziata Hospital, Florence, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Giulia Morsica
- Unit of Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Alessandro Federico
- Hepato-Gastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | | | - Alba Rocco
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Naples Federico II, Naples, Italy
| | | | - Alessandro Soria
- Clinic of Infectious Diseases, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Ivana Maida
- Infectious and Tropical Diseases Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | - Luchino Chessa
- Liver Unit, University Hospital, Monserrato, Cagliari, Italy
| | - Michele Milella
- Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Bari, Italy
| | - Elena Rosselli Del Turco
- Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Salvatore Madonia
- Department of Internal Medicine Villa Sofia-Cervello Hospital, Palermo, Italy
| | - Liliana Chemello
- Department of Medicine-DIMED, Padua University, University Hospital, Padua, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Pierluigi Toniutto
- Hepatology and Liver Transplant Unit, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy
| | - Matteo Bassetti
- Clinica Malattie Infettive, Università degli Studi di Genova, Policlinico S. Martino IRCCS, Genova, Italy
| | - Lorenzo Surace
- Ambulatorio di Epatologia e Infettivologia, Azienda Sanitaria Provinciale CZ-Distretto del Lametino, Lamezia Terme (CZ), Italy
| | | | | | - Adriano De Santis
- Department of Internal Medicine, Policlinico Umberto I Hospital, Sapienza University of Rome, Rome, Italy
| | - Massimo Puoti
- Infectious Disease Unit, Niguarda Hospital, Milan, Italy
| | | | - Grazia Anna Niro
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy
| | - Anna Linda Zignego
- Department of Experimental and Clinical Medicine, Interdepartmental Centre MASVE, University of Florence, Italy
| | - Antonio Craxi
- Gastroenterology and Hepatology Unit, PROMISE, University of Palermo, Palermo, Italy
| | - Giovanni Raimondo
- Department of Internal Medicine, University Hospital of Messina, Messina, Italy
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Woo Y, Ma M, Okawa M, Saito T. Hepatocyte Intrinsic Innate Antiviral Immunity against Hepatitis Delta Virus Infection: The Voices of Bona Fide Human Hepatocytes. Viruses 2024; 16:740. [PMID: 38793622 PMCID: PMC11126147 DOI: 10.3390/v16050740] [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: 04/04/2024] [Revised: 04/24/2024] [Accepted: 05/05/2024] [Indexed: 05/26/2024] Open
Abstract
The pathogenesis of viral infection is attributed to two folds: intrinsic cell death pathway activation due to the viral cytopathic effect, and immune-mediated extrinsic cellular injuries. The immune system, encompassing both innate and adaptive immunity, therefore acts as a double-edged sword in viral infection. Insufficient potency permits pathogens to establish lifelong persistent infection and its consequences, while excessive activation leads to organ damage beyond its mission to control viral pathogens. The innate immune response serves as the front line of defense against viral infection, which is triggered through the recognition of viral products, referred to as pathogen-associated molecular patterns (PAMPs), by host cell pattern recognition receptors (PRRs). The PRRs-PAMPs interaction results in the induction of interferon-stimulated genes (ISGs) in infected cells, as well as the secretion of interferons (IFNs), to establish a tissue-wide antiviral state in an autocrine and paracrine manner. Cumulative evidence suggests significant variability in the expression patterns of PRRs, the induction potency of ISGs and IFNs, and the IFN response across different cell types and species. Hence, in our understanding of viral hepatitis pathogenesis, insights gained through hepatoma cell lines or murine-based experimental systems are uncertain in precisely recapitulating the innate antiviral response of genuine human hepatocytes. Accordingly, this review article aims to extract and summarize evidence made possible with bona fide human hepatocytes-based study tools, along with their clinical relevance and implications, as well as to identify the remaining gaps in knowledge for future investigations.
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Affiliation(s)
- Yein Woo
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Muyuan Ma
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Masashi Okawa
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
- R&D Department, PhoenixBio USA Corporation, New York, NY 10006, USA
| | - Takeshi Saito
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
- USC Research Center for Liver Diseases, Los Angeles, CA 90033, USA
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
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Demirel A, Uraz S, Deniz Z, Daglilar E, Basar O, Tahan V, Ozaras R. Epidemiology of hepatitis D virus infection in Europe: Is it vanishing? J Viral Hepat 2024; 31:120-128. [PMID: 37964693 DOI: 10.1111/jvh.13899] [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: 06/01/2023] [Revised: 08/13/2023] [Accepted: 11/04/2023] [Indexed: 11/16/2023]
Abstract
Co-infection with hepatitis delta virus (HDV) is a challenging health care problem worldwide, estimated to occur in approximately 5%-10% of patients with chronic hepatitis B virus (HBV) infection. While HBV prevalence is decreasing globally, the prevalence of HDV infection is rising in some parts mainly due to injection drug use, sexual transmission and immigration from high endemicity areas. Eastern Europe and the Mediterranean are among the regions with high rates of endemicity for HDV and the immigration from high endemicity areas to Central and Western Europe has changed the HDV epidemiology. We aimed to review the prevalence of HDV infection in Europe. A paucity of publication appears in many European countries. Prevalence studies from some countries are old dated and some other countries did not report any prevalence studies. The studies are accumulated in few countries. Anti-HDV prevalence is high in Greenland, Norway, Romania, Sweden and Italy. Belgium, France, Germany, Spain, Switzerland, Turkey and United Kingdom reported decreasing prevalences. Among cirrhotic HBV patients, Germany, Italy and Turkey reported higher rates of HDV. The studies including centres across the Europe reported that HIV-HBV coinfected individuals have higher prevalence of HDV infection. The immigrants contribute the HDV infection burden in Greece, Italy, and Spain in an increasing rate. Previous studies revealed extremely high rates of HDV infection in Germany, Greece, Italy and Sweden. The studies report a remarkably high prevalence of hepatitis delta among HIV/HBV-coinfected individuals, individuals who inject drugs, immigrants and severe HBV infected patients across Europe. The HDV infection burden still appears to be significant. In the lack of an effective HDV therapy, prevention strategies and active screening of HBV/HDV appear as the most critical interventions for reducing the burden of liver disease related to HDV infection in Europe.
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Affiliation(s)
- Aslıhan Demirel
- Department of Infectious Diseases, School of Medicine, Demiroglu Bilim University, Istanbul, Turkey
| | - Suleyman Uraz
- Department of Gastroenterology, School of Medicine, Demiroglu Bilim University, Istanbul, Turkey
| | - Zeynep Deniz
- School of Medicine, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey
| | - Ebubekir Daglilar
- Department of Gastroenterology, West Virginia University-Charleston Area Medical Center, Charleston, West Virginia, USA
| | - Omer Basar
- Division of Gastroenterology, Summa Health System, Akron, Ohio, USA
| | - Veysel Tahan
- Division of Gastroenterology, Summa Health System, Akron, Ohio, USA
- Division of Gastroenterology, Northeast Ohio Medical University, Rootstown, Ohio, USA
| | - Resat Ozaras
- Department of Infectious Diseases, Medilife Hospital, Istanbul, Turkey
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Sandmann L, Berg T, Deterding K, Fischer N, Hinrichsen H, Petersen J, Tacke F, Cornberg M. Addendum „Antivirale Therapie der chronischen Hepatitis-D-Virusinfektion“ zur S3-Leitlinie „Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1635-1653. [PMID: 38081179 DOI: 10.1055/a-2181-3046] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Affiliation(s)
- Lisa Sandmann
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Deutschland
- D-SOLVE Consortium, Horizon Europe Project, partner-site Medizinische Hochschule Hannover, Hannover, Deutschland
| | - Thomas Berg
- Bereich Hepatologie, Medizinische Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Katja Deterding
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Deutschland
| | - Nadine Fischer
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | | | - Jörg Petersen
- IFI Institut für Interdisziplinäre Medizin an der Asklepios Klinik St Georg, Hamburg, Deutschland
| | - Frank Tacke
- Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Markus Cornberg
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Deutschland
- Centre for individualised infection Medicine (CiiM), Hannover, Deutschland
- Deutsches Zentrum für Infektionsforschung (DZIF), partner-site Hannover-Braunschweig, Deutschland
- D-SOLVE Consortium, Horizon Europe Project, partner-site Medizinische Hochschule Hannover, Hannover, Deutschland
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6
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Sandmann L, Berg T, Deterding K, Fischer N, Hinrichsen H, Petersen J, Tacke F, Cornberg M. Antiviral Therapy of Chronic Hepatitis D Virus Infection - Addendum to the S3 Guideline "Prophylaxis, Diagnosis and Therapy of Hepatitis B Virus Infection" of the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:e715-e732. [PMID: 38081178 DOI: 10.1055/a-2181-3345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Affiliation(s)
- Lisa Sandmann
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- D-SOLVE Consortium, Horizon Europe Project, partner-site Hannover Medical School, Germany
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Katja Deterding
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Nadine Fischer
- German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS), Berlin, Germany
| | | | - Jörg Petersen
- IFI Institute for Interdisciplinary Medicine at Asklepios Klinik St Georg, Hamburg, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- Centre for individualised infection Medicine (CiiM), Hannover, Germany
- German Center for Infection Research (DZIF), partner-site Hannover-Braunschweig, Germany
- D-SOLVE Consortium, Horizon Europe Project, partner-site Hannover Medical School, Germany
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Abdul Majeed N, Zehnder B, Koh C, Heller T, Urban S. Hepatitis delta: Epidemiology to recent advances in therapeutic agents. Hepatology 2023; 78:1306-1321. [PMID: 36738087 DOI: 10.1097/hep.0000000000000331] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 12/19/2022] [Indexed: 02/05/2023]
Abstract
Hepatitis D virus (HDV) was first described in 1977 and is dependent on the presence of hepatitis B surface antigen (HBsAg) for its entry into cells and on the human host for replication. Due to the envelopment with the hepatitis B virus (HBV) envelope, early phases of HDV entry resemble HBV infection. Unlike HBV, HDV activates innate immune responses. The global prevalence of HDV is estimated to be about 5% of HBsAg positive individuals. However, recent studies have described a wide range of prevalence between 12 to 72 million individuals. Infection can occur as super-infection or co-infection. The diagnosis of active HDV infection involves screening with anti HDV antibodies followed by quantitative PCR testing for HDV RNA in those who are HBsAg positive. The diagnostic studies have evolved over the years improving the validity and reliability of the tests performed. HDV infection is considered the most severe form of viral hepatitis and the HDV genotype may influence the disease course. There are eight major HDV genotypes with prevalence varying by geographic region. HDV treatment has been challenging as HDV strongly depends on the host cell for replication and provides few, if any viral targets. Better understanding of HDV virology has led to the development of several therapeutic agents currently being studied in different phase II and III clinical trials. There is increasing promise of effective therapies that will ameliorate the course of this devastating disease.
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Affiliation(s)
- Nehna Abdul Majeed
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Benno Zehnder
- Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Stephan Urban
- Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, Germany
- German Center for Infection Research (DZIF) - Heidelberg Partner Site, Heidelberg, Germany
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Schlaak JF. Current Therapy of Chronic Viral Hepatitis B, C and D. J Pers Med 2023; 13:964. [PMID: 37373953 DOI: 10.3390/jpm13060964] [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: 03/25/2023] [Revised: 05/22/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open
Abstract
The majority of chronic viral hepatitis cases are induced via infection with the hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV). These patients are at increased risk for progressive liver disease leading to cirrhosis as well as hepatocellular carcinoma (HCC). HBV infection is well controlled by the currently available nucleosides as well as nucleotides, and the development of cirrhosis can be prevented. Additionally, it has been shown that HBV-induced liver fibrosis can regress during successful antiviral treatment; however, a "functional cure", i.e., loss of HBsAg, is a rare event when these drugs are used. Therefore, novel therapeutic strategies are aiming at the selective suppression of HBsAg levels in combination with immunostimulation. The development of directly acting antivirals (DAAs) has revolutionized HCV therapy, as almost all patients can be cured via this treatment. Additionally, DAA therapy has few, if any, side effects, and is generally well tolerated by patients. HDV remains the most challenging type of chronic viral hepatitis. Although novel therapeutic options have recently been approved, response rates are still less favorable compared to HBV and HCV. This review discusses current and future options for the treatment of chronic HBV, HCV, and HDV infection.
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Affiliation(s)
- Jörg F Schlaak
- Department of Internal Medicine, Ameos Hospital Oberhausen, Wilhelmstr. 34, 46145 Oberhausen, Germany
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Chida T, Ishida Y, Morioka S, Sugahara G, Han C, Lam B, Yamasaki C, Sugahara R, Li M, Tanaka Y, Liang TJ, Tateno C, Saito T. Persistent hepatic IFN system activation in HBV-HDV infection determines viral replication dynamics and therapeutic response. JCI Insight 2023; 8:e162404. [PMID: 37154158 PMCID: PMC10243812 DOI: 10.1172/jci.insight.162404] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 03/22/2023] [Indexed: 05/10/2023] Open
Abstract
Hepatitis delta virus (HDV), a satellite virus of HBV, is regarded as the most severe type of hepatitis virus because of the substantial morbidity and mortality. The IFN system is the first line of defense against viral infections and an essential element of antiviral immunity; however, the role of the hepatic IFN system in controlling HBV-HDV infection remains poorly understood. Herein, we showed that HDV infection of human hepatocytes induced a potent and persistent activation of the IFN system whereas HBV was inert in triggering hepatic antiviral response. Moreover, we demonstrated that HDV-induced constitutive activation of the hepatic IFN system resulted in a potent suppression of HBV while modestly inhibiting HDV. Thus, these pathogens are equipped with distinctive immunogenicity and varying sensitivity to the antiviral effectors of IFN, leading to the establishment of a paradoxical mode of viral interference wherein HDV, the superinfectant, outcompetes HBV, the primary pathogen. Furthermore, our study revealed that HDV-induced constitutive IFN system activation led to a state of IFN refractoriness, rendering therapeutic IFNs ineffective. The present study provides potentially novel insights into the role of the hepatic IFN system in regulating HBV-HDV infection dynamics and its therapeutic implications through elucidating the molecular basis underlying the inefficacy of IFN-based antiviral strategies against HBV-HDV infection.
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Affiliation(s)
- Takeshi Chida
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California (USC), Los Angeles, California, USA
| | - Yuji Ishida
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California (USC), Los Angeles, California, USA
- PhoenixBio, Co., Ltd., Higashi-Hiroshima, Hiroshima, Japan
| | - Sho Morioka
- PhoenixBio, Co., Ltd., Higashi-Hiroshima, Hiroshima, Japan
| | - Go Sugahara
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California (USC), Los Angeles, California, USA
- PhoenixBio, Co., Ltd., Higashi-Hiroshima, Hiroshima, Japan
| | - Christine Han
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California (USC), Los Angeles, California, USA
| | - Bill Lam
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California (USC), Los Angeles, California, USA
| | | | - Remi Sugahara
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California (USC), Los Angeles, California, USA
| | - Meng Li
- Bioinformatics Service, Norris Medical Library, USC, Los Angeles, California, USA
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
| | - T. Jake Liang
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Chise Tateno
- PhoenixBio, Co., Ltd., Higashi-Hiroshima, Hiroshima, Japan
| | - Takeshi Saito
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California (USC), Los Angeles, California, USA
- Department of Molecular Microbiology & Immunology
- Department of Pathology, and
- USC Research Center for Liver Diseases, Keck School of Medicine, USC, Los Angeles, California, USA
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10
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Tsaneva-Damyanova DT, Georgieva LH. Epidemiology Pattern, Prevalent Genotype Distribution, Fighting Stigma and Control Options for Hepatitis D in Bulgaria and Other European Countries. Life (Basel) 2023; 13:1115. [PMID: 37240760 PMCID: PMC10222293 DOI: 10.3390/life13051115] [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: 04/04/2023] [Revised: 04/24/2023] [Accepted: 04/28/2023] [Indexed: 05/28/2023] Open
Abstract
Hepatitis D virus (HDV) is a satellite virus that causes the most aggressive form of all viral hepatitis in individuals already infected with HBV (hepatitis B virus). In recent years, there has been a negative trend towards an increase in the prevalence of chronic hepatitis D in Europe, especially among immigrant populations coming from regions endemic for the virus. The aim of this review is to analyse the current epidemiology of chronic HDV, routes of transmission, prevalent genotype, its management, prevention, fighting stigma and options for viral control in European countries, such as Bulgaria.
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Affiliation(s)
| | - Lora Hristova Georgieva
- Department of Social Medicine and Healthcare Organization, Medical University, 9000 Varna, Bulgaria
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11
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Bahoussi AN, Wang PH, Guo YY, Rabbani N, Wu C, Xing L. Global Distribution and Natural Recombination of Hepatitis D Virus: Implication of Kyrgyzstan Emerging HDVs in the Clinical Outcomes. Viruses 2022; 14:v14071467. [PMID: 35891448 PMCID: PMC9323457 DOI: 10.3390/v14071467] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 06/28/2022] [Accepted: 06/30/2022] [Indexed: 02/05/2023] Open
Abstract
Discrepancies in human hepatitis delta virus (HDV) genotypes impact the virus’ biological behavior, clinical manifestation, and treatment response. Herein, this report aims to explore the role of recombination in the worldwide genotypic distribution and genetic diversity of HDV. Three-hundred-forty-eight human HDV full-length genomic sequences of ~1678 nt in length, isolated in twenty-eight countries worldwide between 1986 and 2018, were analysed. Similarity analysis and recombination mapping were performed, and forty-eight recombination events were identified, twenty-nine of which were isolated from Kyrgyzstan and determined to be involved in the diversity and extension of HDV sub-genotypes. HDV recombination occurred only between the genetically close genotypes (genotype 5 and genotype 2) or mainly within genotype 1, suggesting the complex replicative molecular mechanisms of HDV-RNA. The global distribution and classification of HDV genotypes have been updated, indicating that HDV recombination is one of the driving forces behind the biodiversity and the evolution of human HDV genomes. The outcome analysis suggests that the expansion of HDV sub-genotypes and the complex recombination networks might be related to the genomic character of Kyrgyzstan circulating strains and extensive mobility within countries and across borders. These findings will be of great importance in formulating more effective public health HDV surveillance strategies and guiding future molecular and epidemiological research to achieve better clinical outcomes.
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Affiliation(s)
- Amina Nawal Bahoussi
- Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan 030006, China; (A.N.B.); (P.-H.W.); (Y.-Y.G.); (N.R.); (C.W.)
| | - Pei-Hua Wang
- Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan 030006, China; (A.N.B.); (P.-H.W.); (Y.-Y.G.); (N.R.); (C.W.)
| | - Yan-Yan Guo
- Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan 030006, China; (A.N.B.); (P.-H.W.); (Y.-Y.G.); (N.R.); (C.W.)
| | - Nighat Rabbani
- Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan 030006, China; (A.N.B.); (P.-H.W.); (Y.-Y.G.); (N.R.); (C.W.)
| | - Changxin Wu
- Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan 030006, China; (A.N.B.); (P.-H.W.); (Y.-Y.G.); (N.R.); (C.W.)
- The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Shanxi University, 92 Wucheng Road, Taiyuan 030006, China
- Shanxi Provincial Key Laboratory for Prevention and Treatment of Major Infectious Diseases, 92 Wucheng Road, Taiyuan 030006, China
| | - Li Xing
- Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan 030006, China; (A.N.B.); (P.-H.W.); (Y.-Y.G.); (N.R.); (C.W.)
- The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Shanxi University, 92 Wucheng Road, Taiyuan 030006, China
- Shanxi Provincial Key Laboratory for Prevention and Treatment of Major Infectious Diseases, 92 Wucheng Road, Taiyuan 030006, China
- Correspondence: ; Tel.: +86-351-701-025
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12
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Wu S, Yi W, Gao Y, Deng W, Bi X, Lin Y, Yang L, Lu Y, Liu R, Chang M, Shen G, Hu L, Zhang L, Li M, Xie Y. Immune Mechanisms Underlying Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B Patients With Viral Coinfection. Front Immunol 2022; 13:893512. [PMID: 35634301 PMCID: PMC9130599 DOI: 10.3389/fimmu.2022.893512] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 04/11/2022] [Indexed: 12/28/2022] Open
Abstract
It is considered that chronic hepatitis B patients have obtained functional cure if they get hepatitis B surface antigen (HBsAg) seroclearance after treatment. Serum HBsAg is produced by cccDNA that is extremely difficult to clear and dslDNA that is integrated with host chromosome. High HBsAg serum level leads to failure of host immune system, which makes it unable to produce effective antiviral response required for HBsAg seroclerance. Therefore, it is very difficult to achieve functional cure, and fewer than 1% of chronic hepatitis B patients are cured with antiviral treatment annually. Some chronic hepatitis B patients are coinfected with other chronic viral infections, such as HIV, HCV and HDV, which makes more difficult to cure. However, it is found that the probability of obtaining HBsAg seroclearance in patients with coinfection is higher than that in patients with HBV monoinfection, especially in patients with HBV/HIV coinfection who have an up to 36% of HBsAg 5-year-seroclerance rate. The mechanism of this interesting phenomenon is related to the functional reconstruction of immune system after antiretroviral therapy (ART). The quantity increase and function recovery of HBV specific T cells and B cells, and the higher level of cytokines and chemokines such as IP-10, GM-CSF, promote HBsAg seroclearance. This review summarizes recent studies on the immune factors that have influence on HBsAg seroconversion in the chronic hepatitis B patients with viral coinfection, which might provide new insights for the development of therapeutic approaches to partially restore the specific immune response to HBV and other viruses.
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Affiliation(s)
- Shuling Wu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Yi
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lin
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ruyu Liu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Min Chang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ge Shen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Leiping Hu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
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13
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Sagnelli C, Pisaturo M, Curatolo C, Codella AV, Coppola N, Sagnelli E. Hepatitis B virus/hepatitis D virus epidemiology: Changes over time and possible future influence of the SARS-CoV-2 pandemic. World J Gastroenterol 2021; 27:7271-7284. [PMID: 34876788 PMCID: PMC8611207 DOI: 10.3748/wjg.v27.i42.7271] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 06/20/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis D virus (HDV) is a defective liver-tropic virus that needs the helper function of hepatitis B virus (HBV) to infect humans and replicate. HDV is transmitted sexually or by a parenteral route, in co-infection with HBV or by super-infection in HBV chronic carriers. HDV infection causes acute hepatitis that may progress to a fulminant form (7%-14% by super-infection and 2%-3% by HBV/HDV co-infection) or to chronic hepatitis (90% by HDV super-infection and 2%-5% by HBV/HDV co-infection), frequently and rapidly progressing to cirrhosis or hepatocellular carcinoma (HCC). Peg-interferon alfa the only recommended therapy, clears HDV in only 10%-20% of cases and, consequently, new treatment strategies are being explored. HDV endemicity progressively decreased over the 50 years from the identification of the virus, due to improved population lifestyles and economic levels, to the use of HBV nuclei(t)side analogues to suppress HBV replication and to the application of universal HBV vaccination programs. Further changes are expected during the severe acute respiratory syndrome coronavirus-2 pandemic, unfortunately towards increased endemicity due to the focus of healthcare towards coronavirus disease 2019 and the consequently lower possibility of screening and access to treatments, lower care for patients with severe liver diseases and a reduced impulse to the HBV vaccination policy.
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Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80131, Italy
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, University of Campania, Naples 80135, Italy
| | - Caterina Curatolo
- Department of Mental Health and Public Medicine, University of Campania, Naples 80135, Italy
| | - Alessio Vinicio Codella
- Department of Mental Health and Public Medicine, University of Campania, Naples 80135, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, University of Campania, Naples 80135, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80131, Italy
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14
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Cornberg M, Sandmann L, Protzer U, Niederau C, Tacke F, Berg T, Glebe D, Jilg W, Wedemeyer H, Wirth S, Höner Zu Siederdissen C, Lynen-Jansen P, van Leeuwen P, Petersen J. S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion – (AWMF-Register-Nr. 021-11). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:691-776. [PMID: 34255317 DOI: 10.1055/a-1498-2512] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Markus Cornberg
- Deutsches Zentrum für Infektionsforschung (DZIF), Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover; Centre for individualised infection Medicine (CiiM), Hannover.,Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Lisa Sandmann
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Ulrike Protzer
- Institut für Virologie, Technische Universität München/Helmholtz Zentrum München, München
| | | | - Frank Tacke
- Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité Universitätsmedizin Berlin, Berlin
| | - Thomas Berg
- Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig
| | - Dieter Glebe
- Institut für Medizinische Virologie, Nationales Referenzzentrum für Hepatitis-B-Viren und Hepatitis-D-Viren, Justus-Liebig-Universität Gießen, Gießen
| | - Wolfgang Jilg
- Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensberg, Regensburg
| | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Stefan Wirth
- Zentrum für Kinder- und Jugendmedizin, Helios Universitätsklinikum Wuppertal, Wuppertal
| | | | - Petra Lynen-Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin
| | - Pia van Leeuwen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin
| | - Jörg Petersen
- IFI Institut für Interdisziplinäre Medizin an der Asklepios Klinik St. Georg, Hamburg
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15
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Rizzetto M, Hamid S, Negro F. The changing context of hepatitis D. J Hepatol 2021; 74:1200-1211. [PMID: 33484770 DOI: 10.1016/j.jhep.2021.01.014] [Citation(s) in RCA: 115] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 01/04/2021] [Accepted: 01/09/2021] [Indexed: 12/18/2022]
Abstract
The global epidemiology of hepatitis D is changing with the widespread implementation of vaccination against hepatitis B. In high-income countries that achieved optimal control of HBV, the epidemiology of hepatitis D is dual, consisting of an ageing cohort of domestic patients with advanced liver fibrosis who represent the end stage of the natural history of HDV, and of a younger generation of immigrants from endemic countries who account for the majority of new infections. As observed in Europe in the 1980s, the distinctive clinical characteristic of chronic hepatitis D in endemic countries is the accelerated progression to cirrhosis and hepatocellular carcinoma. Despite some recent progress, the therapeutic management of HDV remains unsatisfactory, as most patients are not cured of HDV with currently available medicines. This review article describes the current epidemiology and clinical features of chronic hepatitis D, based on the literature published in the last 10 years.
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Affiliation(s)
- Mario Rizzetto
- Department of Medical Sciences, University of Turin, Turin, Italy.
| | - Saeed Hamid
- Department of Medicine, The Aga Khan University, Karachi, Pakistan
| | - Franco Negro
- Division of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva, Switzerland; Division of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland
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16
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Ajayi BB, Latbone S, Igwegbe IU, Kida IM, Goni BW, Samuel OO, Dawurung JS, Ibrahim HM, Danue BA, Abdullahi IN, Oderinde BS. Serological detection of hepatitis B and D virus co-infection among patients attending a tertiary health facility at Maiduguri, Nigeria. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2021. [DOI: 10.1186/s43162-021-00036-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Hepatitis D virus (HDV) is highly pathogenic, and clinical studies revealed that HDV infection aggravates the natural history of the underlying hepatitis B virus (HBV) infection by progression to cirrhosis that leads to early decompensation of liver function compared with HBV mono-infection. To determine the seroprevalence of HDV among HBsAg-seropositive patients and associated biochemical profiles at Maiduguri, Nigeria, a hospital-based cross-sectional study on 180 sera of patients positive for HBsAg by ELISA were evaluated for anti-HDV, hepatitis B envelop antigen, anti-HBs antibodies and liver enzyme profiles.
Results
HDV seroprevalence of 3.3% among 180 HBsAg-positive patients. Relatively higher seroprevalence of HDV was observed in males (4.3%) than in females (2.3%). The highest infection rate (20%) was obtained in patients ≥ 56 years. However, no significant association between positive anti-HDV seroprevalence and gender (p > 0.05). Of the 6 (3.3%) anti-HDV-positive patients, only 1 (16.7%) was positive for HBeAg while all were negative for anti-HBs antibodies. The mean level of liver enzyme level of AST and ALT of the anti-HDV-positive patients significantly differ from that of HBsAg mono-infected patients (p ˂ 0.05). However, no significant difference (p < 0.05) between the mean levels of liver enzymes of ALP in anti-HDV-positive and HBsAg mono-infected patients (p ˃ 0.05) was found.
Conclusion
This study revealed a relatively low presence of HDV in HBsAg-positive patients. Furthermore, HDV-HBV co-infected patients had somewhat worse liver enzyme upregulation. This underscores the need for rapid HDV testing and treatment in HBV-infected patients.
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17
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Kumar P, Freeland C, Bodor S, Farrell S, Cohen C, Frasso R. Needs of Individuals Living With Hepatitis Delta Virus and Their Caregivers, 2016-2019. Prev Chronic Dis 2020; 17:E159. [PMID: 33337297 PMCID: PMC7769086 DOI: 10.5888/pcd17.200324] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Introduction Hepatitis delta virus (HDV) is a serious coinfection of the hepatitis B virus (HBV) that is estimated to affect between 48 to 72 million people worldwide. Data are limited on the informational needs of people living with HDV. The Hepatitis B Foundation, a US-based nonprofit organization that provides support to people living with HBV and HDV, receives emails (queries) as part of a helpline, a service to provide information, resources, and support to people affected by HBV and HDV. Methods Query content was analyzed to assess the impact of HDV at the individual level. A total of 65 HDV-related queries from 17 countries were received from October 2016 to January 2019, and all were analyzed for this study. Results Thematic analysis of queries indicated 4 dominant themes. Three were related to a need for information about 1) the disease and prevention of it, 2) disease symptoms and outcomes, and 3) treatment options. The fourth theme was related to barriers and quality of life. Individuals requested information on treatment options, medication access, diagnostic test interpretation, and clinical trials. Conclusion Our study highlights the needs and lived experience of patients with HDV and summarizes critical information gaps. Findings can inform health care providers, public health professionals, and the pharmaceutical and biotechnology industries about the informational needs and lived experiences of individuals living with HDV and help create future HDV-related educational resources, care, and clinical trials.
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Affiliation(s)
- Priyanka Kumar
- Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania.,Jefferson College of Population Health, Philadelphia, Pennsylvania.,101 The City Drive S, Suite 400, Orange, CA 92868.
| | - Catherine Freeland
- Jefferson College of Population Health, Philadelphia, Pennsylvania.,Hepatitis B Foundation, Doylestown, Pennsylvania
| | - Sierra Bodor
- Hepatitis B Foundation, Doylestown, Pennsylvania
| | - Sean Farrell
- Jefferson College of Population Health, Philadelphia, Pennsylvania.,Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania
| | - Chari Cohen
- Hepatitis B Foundation, Doylestown, Pennsylvania
| | - Rosemary Frasso
- Jefferson College of Population Health, Philadelphia, Pennsylvania
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18
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Spaan M, Carey I, Bruce M, Shang D, Horner M, Dusheiko G, Agarwal K. Hepatitis delta genotype 5 is associated with favourable disease outcome and better response to treatment compared to genotype 1. J Hepatol 2020; 72:1097-1104. [PMID: 31981726 DOI: 10.1016/j.jhep.2019.12.028] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 12/29/2019] [Accepted: 12/31/2019] [Indexed: 02/02/2023]
Abstract
BACKGROUND & AIMS Coinfection with HDV causes rapid progression to liver cirrhosis and hepatic decompensation in patients with chronic hepatitis B. Factors that are associated with disease progression are poorly understood. In this study we aim to identify risk factors associated with disease progression and better characterise clinical differences and treatment response between HDV genotype 1 and 5. METHODS In this retrospective study, all patients under our care between 2005 and 2016 with HBV/HDV coinfection (HBsAg+, anti-HDV antibodies positive) were analysed. Patients were excluded if follow-up was less than 6 months, if they had HCV and/or HIV coinfection or an acute HDV infection. Demographic data, stage of liver disease, development of liver complications and treatment response were recorded. RESULTS One-hundred seven patients (mean age 36.0 years, 57% male) were followed for a median period of 4.4 years (range 0.6-28.1 years); 64% were of African origin and 17% were of European origin, with 28% of patients being cirrhotic at first visit; 43% patients had actively replicating HDV virus (anti-HDV-IgG+, anti-HDV-IgM+ or HDV RNA+) and 57% of patients were HDV exposed (anti-HDV-IgG+, HDV RNA-). Patients with actively replicating HDV more often developed liver complications than HDV-exposed patients (p = 0.002), but no differences in baseline characteristics were observed. Patients with HDV genotype 5 less often developed cirrhosis or hepatic decompensation compared to patients with HDV genotype 1. Twenty-four patients were treated with peg-IFN and post-treatment response was significantly better in patients infected with genotype 5 (10% GT1 vs. 64% GT5, p = 0.013). CONCLUSION Patients infected with HDV genotype 5 appear to have a better prognosis with fewer episodes of hepatic decompensation and better response to peg-IFN treatment than patients infected with HDV genotype 1. LAY SUMMARY Hepatitis delta is a virus that affects the liver. The virus is known to have different subtypes, called genotypes. With this research we discovered that hepatitis delta virus genotype 1 behaves differently than genotype 5 and causes faster development of liver disease. This is important for education of our patients and to determine how often we need to check our patients.
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Affiliation(s)
- Michelle Spaan
- Institute of Liver Studies, King's College Hospital, London, United Kingdom; Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, the Netherlands.
| | - Ivana Carey
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Matthew Bruce
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Dazhuang Shang
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Mary Horner
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Geoff Dusheiko
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Kosh Agarwal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
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19
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Akande KO, Fowotade A, Adekanmbi O. The effect of Hepatitis D co-infection on the immunologic and molecular profile of Hepatitis B in asymptomatic Chronic Hepatitis B patients in southwest Nigeria. J Immunoassay Immunochem 2020; 41:272-280. [PMID: 32096684 DOI: 10.1080/15321819.2020.1728542] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Introduction: Hepatitis D infection causes severe form of viral hepatitis in humans and only affects those with hepatitis B either as a co-infection or superinfection. The aim of this study was to determine the prevalence of Hepatitis D and its effect on the immunologic and molecular profile of Hepatitis B among asymptomatic Chronic Hepatitis B patients in Abeokuta.Methodology: A cross-sectional study of 99 chronic HBV patient who met the inclusion criteria. All the patients were tested for HBsAg, anti HCV, HDV antigen, anti HDV, HBsAg quantification, and HBV DNA quantification. Associations were tested for and P value less than 0.05 was considered significant.Results: The participants included 53 (58%) male and 38 (42%) females with ages ranging from 18 to 69 (means 39 ± 11) years. Ten (11%) participants were positive for HDV-Ag while 1 (1.1%) was positive for anti-HDV. Five (5.5%) were positive for HIV 1 &2 while 1 (1.1%) was positive for anti HCV. HBV DNA quantification ranged from 15 to 17,000,000 IU/ml while HBsAg quantification ranged from 0.25 to45,520 IU/ml. There was no statistically significant relationship between HDV-Ag and age (p = .51), sex (p = .73), HBV DNA (p = .8) and HBsAg quantification (p = 1).Conclusion: The prevalence of HDV-Ag among asymptomatic treatment naïve chronic hepatitis B patients in Abeokuta was 11% and there was no significant difference in the levels of HBV DNA and HBsAg among those with or without hepatitis D.
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Affiliation(s)
| | - Adeola Fowotade
- Medical Microbiology and Parasitology, University of Ibadan College of Medicine, Ibadan, Nigeria
- Medical Microbiology and Parasitology, University College Hospital, Ibadan, Nigeria
| | - Olukemi Adekanmbi
- Medical Microbiology, University of Ibadan College of Medicine, Ibadan, Nigeria
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20
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Coppola N, Alessio L, Onorato L, Sagnelli C, Sagnelli E, Pisaturo M. HDV infection in immigrant populations. J Med Virol 2019; 91:2049-2058. [PMID: 31429940 DOI: 10.1002/jmv.25570] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 08/10/2019] [Indexed: 12/16/2022]
Abstract
AIMS Little data have been published so far on the epidemiological aspects of hepatitis D virus (HDV) infection in immigrant populations and even poorer is the information on the virological, phylogenetic, and clinical aspects of this infection in these populations. This review article, aimed primarily at physicians caring for immigrants, summarizes the information available on HDV infection and analyzes data on this topic concerning the immigrant populations. METHODS AND RESULTS The prevalence of HDV infection in HBsAg-positive immigrants varies according to the country of origin. For example, in immigrants from sub-Saharan Africa, this prevalence is higher in those born in Equatorial Guinea (24.4%) than those from other African countries (10.3%). The epidemiological impact of HDV infection linked to migratory flows is a function of the different endemicity between countries of origin and countries in which a new existence has been established. This impact is high when immigrants from areas endemic to HDV infection (eg, Equatorial Guinea) settle in areas of low endemicity (eg, Germany or England, with a prevalence of around 4%), while the impact is lesser or nonexistent if the migratory flows are directed toward countries with intermediate endemicity (eg, Italy and Greece, with a prevalence of around 10%). CONCLUSION This impact of immigration on HDV epidemiology can be strong when HDV endemicity is high in the country of origin and low in the host country and slight when immigrants move to high or medium endemic countries.
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Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
- Infectious Disease Unit, AORN Caserta, Caserta, Italy
| | | | - Lorenzo Onorato
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
- Infectious Disease Unit, AORN Caserta, Caserta, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
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21
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Da BL, Heller T, Koh C. Hepatitis D infection: from initial discovery to current investigational therapies. Gastroenterol Rep (Oxf) 2019; 7:231-245. [PMID: 32477569 DOI: 10.1093/gastro/goz023] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 03/15/2019] [Accepted: 05/09/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis D is the most severe form of viral hepatitis associated with a more rapid progression to cirrhosis and an increased risk of hepatocellular carcinoma and mortality compared with hepatitis B mono-infection. Although once thought of as a disappearing disease, hepatitis D is now becoming recognized as a serious worldwide issue due to improvement in diagnostic testing and immigration from endemic countries. Despite these concerns, there is currently only one accepted medical therapy (pegylated-interferon-α) for the treatment of hepatitis D with less than desirable efficacy and significant side effects. Due to these reasons, many patients never undergo treatment. However, increasing knowledge about the virus and its life cycle has led to the clinical development of multiple promising new therapies that hope to alter the natural history of this disease and improve patient outcome. In this article, we will review the literature from discovery to the current investigational therapies.
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Affiliation(s)
- Ben L Da
- Digestive Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
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22
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Turcanu A, Pitel E, Dumbrava VT, Tcaciuc E, Donscaia A, Peltec A, Pineau P. Profile of hepatocellular carcinoma in the Republic of Moldova: first-hand information on the presentation, distribution and etiologies. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2019; 57:37-46. [PMID: 30375353 DOI: 10.2478/rjim-2018-0026] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Moldova is the European country with the highest incidence of hepatocellular carcinoma (HCC) in both sexes. There is, however, no data comprehensively describing the presentation and the risk factors of HCC in the country. We decided to analyze cases of HCC recently received in a tertiary healthcare Institution from Chisinau, the Moldovian capital. METHODS A series of 148 primary liver tumors including 139 cases of HCC were retrospectively analyzed for demographic features, serological and biochemical data, and clinical presentation. RESULTS The mean age of patients was 59 ± 10 years (range: 19-66) with a M:F sex ratio of 1.9. Tumors appeared on full-blown liver cirrhosis in 83% of cases and were composed of multiple nodules at diagnosis in 36% of patients. Serum Alpha-fetoprotein was exceeding 10ng/mL in 76% of cases. Liver tumor and hepatitis were co-discovered in 34% of cases. More than 81% of hepatocellular carcinomas were associated with at least one hepatitis virus. Carriers of anti-hepatitis C virus were predominating (55% of cases) over patients seropositive for hepatitis B virus surface antigen (36%). Half of the latter were also infected with hepatitis Delta virus. In total, dual or triple infections were present in 24% and 7% of cases. CONCLUSIONS The burden of infections with hepatitis viruses is particularly important in Moldova and corresponds to a situation commonly observed in countries of the Southern hemisphere. A pro-active policy of screening for persistent liver infection targeting population at risk of HCC (> 50 years) and coupled with the distribution of antivirals in positive cases should be rapidly implemented in Moldova to reduce incidence or primary liver cancer.
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Affiliation(s)
- Adela Turcanu
- Department of Gastroenterology, Nicolae Testemitanu State University of Medicine and Pharmacy, Bd. Stefan cel Mare 165,Chisinau, Republic of Moldova
| | - Ecaterina Pitel
- Department of Gastroenterology, Nicolae Testemitanu State University of Medicine and Pharmacy, Bd. Stefan cel Mare 165,Chisinau, Republic of Moldova
| | - Vlada-Tatiana Dumbrava
- Department of Gastroenterology, Nicolae Testemitanu State University of Medicine and Pharmacy, Bd. Stefan cel Mare 165,Chisinau, Republic of Moldova
| | - Eugen Tcaciuc
- Department of Gastroenterology, Nicolae Testemitanu State University of Medicine and Pharmacy, Bd. Stefan cel Mare 165,Chisinau, Republic of Moldova
| | - Ana Donscaia
- Institute of Oncology of the Republic of Moldova, str. Testemitanu 30,Chisinau
| | - Angela Peltec
- Department of Gastroenterology, Nicolae Testemitanu State University of Medicine and Pharmacy, Bd. Stefan cel Mare 165,Chisinau, Republic of Moldova
| | - Pascal Pineau
- Unité "Organisation nucléaire et Oncogenèse", INSERM U993, Institut Pasteur, 28, rue du Docteur Roux,75015 Paris, France
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23
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White SL, Rawlinson W, Boan P, Sheppeard V, Wong G, Waller K, Opdam H, Kaldor J, Fink M, Verran D, Webster A, Wyburn K, Grayson L, Glanville A, Cross N, Irish A, Coates T, Griffin A, Snell G, Alexander SI, Campbell S, Chadban S, Macdonald P, Manley P, Mehakovic E, Ramachandran V, Mitchell A, Ison M. Infectious Disease Transmission in Solid Organ Transplantation: Donor Evaluation, Recipient Risk, and Outcomes of Transmission. Transplant Direct 2019; 5:e416. [PMID: 30656214 PMCID: PMC6324914 DOI: 10.1097/txd.0000000000000852] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 08/15/2018] [Indexed: 12/11/2022] Open
Abstract
In 2016, the Transplantation Society of Australia and New Zealand, with the support of the Australian Government Organ and Tissue authority, commissioned a literature review on the topic of infectious disease transmission from deceased donors to recipients of solid organ transplants. The purpose of this review was to synthesize evidence on transmission risks, diagnostic test characteristics, and recipient management to inform best-practice clinical guidelines. The final review, presented as a special supplement in Transplantation Direct, collates case reports of transmission events and other peer-reviewed literature, and summarizes current (as of June 2017) international guidelines on donor screening and recipient management. Of particular interest at the time of writing was how to maximize utilization of donors at increased risk for transmission of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus, given the recent developments, including the availability of direct-acting antivirals for hepatitis C virus and improvements in donor screening technologies. The review also covers emerging risks associated with recent epidemics (eg, Zika virus) and the risk of transmission of nonendemic pathogens related to donor travel history or country of origin. Lastly, the implications for recipient consent of expanded utilization of donors at increased risk of blood-borne viral disease transmission are considered.
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Affiliation(s)
- Sarah L White
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
| | - William Rawlinson
- Serology and Virology Division, NSW Health Pathology Prince of Wales Hospital, Sydney, Australia
- Women's and Children's Health and Biotechnology and Biomolecular Sciences, University of New South Wales Schools of Medicine, Sydney, Australia
| | - Peter Boan
- Departments of Infectious Diseases and Microbiology, Fiona Stanley Hospital, Perth, Australia
- PathWest Laboratory Medicine, Perth, Australia
| | - Vicky Sheppeard
- Communicable Diseases Network Australia, New South Wales Health, Sydney, Australia
| | - Germaine Wong
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Karen Waller
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
| | - Helen Opdam
- Austin Health, Melbourne, Australia
- The Organ and Tissue Authority, Australian Government, Canberra, Australia
| | - John Kaldor
- Kirby Institute, University of New South Wales, Sydney, Australia
| | - Michael Fink
- Austin Health, Melbourne, Australia
- Department of Surgery, Melbourne Medical School, The University of Melbourne, Melbourne, Australia
| | - Deborah Verran
- Transplantation Services, Royal Prince Alfred Hospital, Sydney, Australia
| | - Angela Webster
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, Australia
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Kate Wyburn
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
- Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia
| | - Lindsay Grayson
- Austin Health, Melbourne, Australia
- Department of Surgery, Melbourne Medical School, The University of Melbourne, Melbourne, Australia
| | - Allan Glanville
- Department of Thoracic Medicine and Lung Transplantation, St Vincent's Hospital, Sydney, Australia
| | - Nick Cross
- Department of Nephrology, Canterbury District Health Board, Christchurch Hospital, Christchurch, New Zealand
| | - Ashley Irish
- Department of Nephrology, Fiona Stanley Hospital, Perth, Australia
- Faculty of Health and Medical Sciences, UWA Medical School, The University of Western Australia, Crawley, Australia
| | - Toby Coates
- Renal and Transplantation, Royal Adelaide Hospital, Adelaide, Australia
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
| | - Anthony Griffin
- Renal Transplantation, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
| | - Greg Snell
- Lung Transplant, Alfred Health, Melbourne, Victoria, Australia
| | - Stephen I Alexander
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
| | - Scott Campbell
- Department of Renal Medicine, University of Queensland at Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
| | - Steven Chadban
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
- Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia
| | - Peter Macdonald
- Department of Cardiology, St Vincent's Hospital, Sydney, Australia
- St Vincent's Hospital Victor Chang Cardiac Research Institute, University of New South Wales, Sydney, Australia
| | - Paul Manley
- Kidney Disorders, Auckland District Health Board, Auckland City Hospital, Auckland, New Zealand
| | - Eva Mehakovic
- The Organ and Tissue Authority, Australian Government, Canberra, Australia
| | - Vidya Ramachandran
- Serology and Virology Division, NSW Health Pathology Prince of Wales Hospital, Sydney, Australia
| | - Alicia Mitchell
- Department of Thoracic Medicine and Lung Transplantation, St Vincent's Hospital, Sydney, Australia
- Woolcock Institute of Medical Research, Sydney, Australia
- School of Medical and Molecular Biosciences, University of Technology, Sydney, Australia
| | - Michael Ison
- Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL
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24
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25
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Abstract
Hepatitis D virus (HDV) infection leads to the most severe form of chronic viral hepatitis and requires the attention of a liver specialist. In this review, I will recapitulate recent advances in the management of HDV, present background information on HDV infection as well as current chronic hepatitis D treatment, briefly examine the HDV life cycle and discuss new management strategies.
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Affiliation(s)
- Cihan Yurdaydin
- Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.,Hepatology Institute, University of Ankara, Ankara, Turkey
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26
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Unsolved Puzzles Surrounding HCV Immunity: Heterologous Immunity Adds Another Dimension. Int J Mol Sci 2017; 18:ijms18081626. [PMID: 28749434 PMCID: PMC5578017 DOI: 10.3390/ijms18081626] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Revised: 07/19/2017] [Accepted: 07/20/2017] [Indexed: 12/21/2022] Open
Abstract
Chronic infection with hepatitis C virus (HCV) afflicts 3% of the world’s population and can lead to serious and late-stage liver diseases. Developing a vaccine for HCV is challenging because the correlates of protection are uncertain and traditional vaccine approaches do not work. Studies of natural immunity to HCV in humans have resulted in many enigmas. Human beings are not immunologically naïve because they are continually exposed to various environmental microbes and antigens, creating large populations of memory T cells. Heterologous immunity occurs when this pool of memory T cells cross-react against a new pathogen in an individual. Such heterologous immunity could influence the outcome when an individual is infected by a pathogen. We have recently made an unexpected finding that adenoviruses, a common environmental pathogen and an experimental vaccine vector, can induce robust cross-reactive immune responses against multiple antigens of HCV. Our unique finding of previously uncharacterized heterologous immunity against HCV opens new avenues to understand HCV pathogenesis and develop effective vaccines.
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27
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Lempp FA, Urban S. Hepatitis Delta Virus: Replication Strategy and Upcoming Therapeutic Options for a Neglected Human Pathogen. Viruses 2017; 9:E172. [PMID: 28677645 PMCID: PMC5537664 DOI: 10.3390/v9070172] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 06/28/2017] [Accepted: 06/29/2017] [Indexed: 12/15/2022] Open
Abstract
The human Hepatitis Delta Virus (HDV) is unique among all viral pathogens. Encoding only one protein (Hepatitis Delta Antigen; HDAg) within its viroid-like self-complementary RNA, HDV constitutes the smallest known virus in the animal kingdom. To disseminate in its host, HDV depends on a helper virus, the human Hepatitis B virus (HBV), which provides the envelope proteins required for HDV assembly. HDV affects an estimated 15-20 million out of the 240 million chronic HBV-carriers and disperses unequally in disparate geographical regions of the world. The disease it causes (chronic Hepatitis D) presents as the most severe form of viral hepatitis, leading to accelerated progression of liver dysfunction including cirrhosis and hepatocellular carcinoma and a high mortality rate. The lack of approved drugs interfering with specific steps of HDV replication poses a high burden for gaining insights into the molecular biology of the virus and, consequently, the development of specific novel medications that resiliently control HDV replication or, in the best case, functionally cure HDV infection or HBV/HDV co-infection. This review summarizes our current knowledge of HBV molecular biology, presents an update on novel cell culture and animal models to study the virus and provides updates on the clinical development of the three developmental drugs Lonafarnib, REP2139-Ca and Myrcludex B.
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Affiliation(s)
- Florian A Lempp
- Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
- German Centre for Infection Research (DZIF), Partner Site Heidelberg, 69120 Heidelberg, Germany.
| | - Stephan Urban
- Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
- German Centre for Infection Research (DZIF), Partner Site Heidelberg, 69120 Heidelberg, Germany.
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28
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Wranke A, Serrano BC, Heidrich B, Kirschner J, Bremer B, Lehmann P, Hardtke S, Deterding K, Port K, Westphal M, Manns MP, Cornberg M, Wedemeyer H. Antiviral treatment and liver-related complications in hepatitis delta. Hepatology 2017; 65:414-425. [PMID: 27770553 DOI: 10.1002/hep.28876] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Accepted: 09/22/2016] [Indexed: 12/14/2022]
Abstract
UNLABELLED Hepatitis delta virus (HDV) is the most severe form of viral hepatitis. Pegylated interferon alfa (PEG-IFNα) is effective in only 25%-30% of patients and is associated with frequent side effects. The aim of this study was to analyze the clinical long-term outcome of hepatitis delta in relation to different antiviral treatment strategies. We studied 136 anti-HDV-positive patients who were followed for at least 6 months in a retrospective single-center cohort (mean time of follow-up, 5.2 years; range, 0.6-18.8). Liver cirrhosis was already present in 62 patients at first presentation. Twenty-nine percent of patients did not receive any antiviral treatment, 38% were treated with interferon alfa (IFNα)-based therapies, and 33% received nucleos(t)ide analogues (NAs) only. Clinical endpoints defined as hepatic decompensation (ascites, encephalopathy, and variceal bleeding), hepatocellular carcinoma, liver transplantation, and liver-related death developed in 55 patients (40%). Patients who received IFNα-based therapies developed clinical endpoints less frequently than those treated with NA (P = 0.02; HR, 4.0) or untreated patients (P = 0.05; HR, 2.2; 17%, 64%, and 44%), respectively, which was significant in both chi-square and Kaplan-Meier analysis. In addition, considering various clinical and virological parameters, IFNα therapy was independently associated with a more benign clinical long-term outcome in multivariate logistic regression analysis (P = 0.04; odds ratio, 0.25; 95% confidence interval, 0.07-0.9). Loss of HDV RNA during follow-up was more frequent in IFNα-treated patients and strongly linked with a lower likelihood to experience liver-related complications. CONCLUSION IFNα-based antiviral therapy of hepatitis delta was independently associated with a lower likelihood for clinical disease progression. Durable undetectability of HDV RNA is a valid surrogate endpoint in the treatment of hepatitis delta. (Hepatology 2017;65:414-425).
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Affiliation(s)
- Anika Wranke
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Beatriz Calle Serrano
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Benjamin Heidrich
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner Side Hannover Medical School, Hannover, Germany
| | - Janina Kirschner
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Birgit Bremer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Patrick Lehmann
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Svenja Hardtke
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner Side Hannover Medical School, Hannover, Germany
| | - Katja Deterding
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Kerstin Port
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Max Westphal
- Institute for Biometry, Hannover Medical School, Germany
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner Side Hannover Medical School, Hannover, Germany.,Integrated Research and Treatment Center Transplantation, Hannover Medical School, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner Side Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner Side Hannover Medical School, Hannover, Germany.,Integrated Research and Treatment Center Transplantation, Hannover Medical School, Germany
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29
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Cornberg M, Wong VWS, Locarnini S, Brunetto M, Janssen HLA, Chan HLY. The role of quantitative hepatitis B surface antigen revisited. J Hepatol 2017; 66:398-411. [PMID: 27575311 DOI: 10.1016/j.jhep.2016.08.009] [Citation(s) in RCA: 259] [Impact Index Per Article: 32.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Revised: 08/09/2016] [Accepted: 08/16/2016] [Indexed: 02/06/2023]
Abstract
In the past 10years, there has been a lot of enthusiasm surrounding the use of serum hepatitis B surface antigen (HBsAg) quantification to predict disease activity and monitor treatment response in chronic hepatitis B. The measurement of HBsAg levels have been standardized in IU/ml, and nowadays it is almost a mandatory measurement due to the development of new antiviral treatments aiming at HBsAg seroclearance, i.e., functional cure of hepatitis B. Recently, there has been an improved understanding of the molecular virology of HBsAg, and particularly the relative roles of covalently closed circular DNA and integrated hepatitis B virus (HBV) DNA. This has shed new light on the interpretation of HBsAg levels in different phases of chronic hepatitis B. HBsAg level can assist the differentiation of immune tolerance and immune clearance in hepatitis B e antigen (HBeAg)-positive patients, and it can predict inactive disease and spontaneous HBsAg seroclearance in HBeAg-negative patients. The determination of HBsAg level is pivotal to individualize pegylated interferon (PegIFN) treatment; it is the key investigation to decide early termination of PegIFN among non-responders. Among patients treated by nucleos(t)ide analogues, responders tend to have dramatic reduction of HBsAg to low levels, which may be followed by HBsAg seroclearance. With newer data on combination treatment of PegIFN and nucleos(t)ide analogues as well as emerging new antiviral agents, HBsAg quantification is expected to become increasingly important to monitor and guide antiviral therapy for chronic hepatitis B.
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Affiliation(s)
- Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Institute of Digestive Disease and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Stephen Locarnini
- Victorian Infectious Diseases Reference Laboratory (VIDRL), Doherty Institute for Infection and Immunity, Melbourne, Australia
| | - Maurizia Brunetto
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Italy
| | - Harry L A Janssen
- Toronto Center for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, Institute of Digestive Disease and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
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30
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Performance Characteristics of a New Consensus Commercial Kit for Hepatitis D Virus RNA Viral Load Quantification. J Clin Microbiol 2016; 55:431-441. [PMID: 27881614 DOI: 10.1128/jcm.02027-16] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Accepted: 11/07/2016] [Indexed: 12/16/2022] Open
Abstract
Hepatitis D virus (HDV) is responsible for fulminant hepatitis and liver failure and accelerates evolution toward cirrhosis and hepatocellular carcinoma in hepatitis B virus (HBV)-infected patients. To date, treatment relies upon long-term administration of pegylated alpha-interferon with a sustained virological response in 30% of the patients. Very recently, new, promising anti-HDV therapies have been developed and are already being used in clinical trials. HDV RNA viral load (HDVL) monitoring must be an integral part of the management of the infected patients. However, HDV genus is characterized by a high genetic variability into eight genotypes (HDV-1 to -8), and most available in-house or commercial assays are useful for only a limited subset of genotypes. Results of a comparison of the performance of a new kit for HDVL quantification with the consensus in-house assay of the French National Reference Laboratory for HDV developed in 2005 are reported here. A total of 611 clinical samples of all HDV genotypes with various HDVL values, including several consecutive samples over several years from 36 patients, were studied. A specificity, sensitivity, and reproducibility evaluation was conducted using HDV-positive clinical samples, hepatitis A, B, C and E (HAV, HBV, HCV, and HEV, respectively) and HIV mono-infected samples, and the WHO HDV RNA international standard. Overall results were strictly comparable between the two assays (median difference, 0.07 log IU/ml), with high diagnosis precision and capacity. In summary, this new kit showed high performance in detection/quantification of HDVL, regardless of the genotype of the infecting strain used, and seems to be a suitable tool for patient management.
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Amougou MA, Noah DN, Moundipa PF, Pineau P, Njouom R. A prominent role of Hepatitis D Virus in liver cancers documented in Central Africa. BMC Infect Dis 2016; 16:647. [PMID: 27821080 PMCID: PMC5100184 DOI: 10.1186/s12879-016-1992-2] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Accepted: 10/29/2016] [Indexed: 02/06/2023] Open
Abstract
Background Hepatocellular Carcinoma (HCC) is one of the commonest cancers in Central Africa, a region with the unusual peculiarity to be hyperendemic for infections with Hepatitis B, C and D viruses. However, data estimating the respective proportions of HCC cases attributable to these viruses are still limited in this area. The current study was undertaken to determine the role of these viruses in HCC compared to non-HCC Cameroonian patients. Methods A case–control study was conducted in the Gastroenterology Unit of Central Hospital of Yaounde in collaboration with Centre Pasteur of Cameroon. Blood samples of all HCC cases (n = 88) and matched control individuals without known liver disease (n = 85) were tested for serological markers of Hepatitis B, C and D viral infections using commercially available enzyme immune-assay kits. Hepatitis B and C viral loads were quantified for positive patients by real-time PCR using commercial kits. Results The mean age was 46.0 ± 18 and 42.1 ± 16 years old for HCC-patients and controls, respectively for a 2.3 Male/Female sex ratio. The prevalence of hepatitis B surface antigen, antibody to HCV and antibody to HDV were significantly higher in HCC patients (65.90, 20.26 and 26 % respectively) than in control patients (9.23, 4.62 and 1 %) (P < 2.5 10−5). The risk factors analysis showed that both HBV and HCV infections were strongly associated with HCC development in Cameroon with crude odds ratios of 15.98 (95 % CI 6.19-41.25) and 7.33 (95 % CI 2.09-25.77), respectively. Furthermore, the risk of developing HCC increased even more significantly in case of HBV and HDV co-infections with the odd ratio of 29.3 (95 % CI, 4.1-1231). HBV-DNA level was significantly higher in HBsAg-positive HCC-patients than in HBsAg-positive controls with (6.3 Log IU/mL and 5.7 Log IU/mL) respectively (P < 0.05). Conclusion HBV and HCV infections are the mains factors of HCC development in Cameroon. Our results show that patients co-infected with HDV are at very high risk to develop HCC. An active surveillance program of patients and, foremost, an easier access to antivirals and primary prevention measures are crucial steps to reduce the incidence of HCC in this country. Due to the lack of truly efficient antiviral therapy, the fate of HDV-infected patients remains, however, particularly worrying.
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Affiliation(s)
| | | | - Paul Fewou Moundipa
- Laboratory of Pharmacology and Toxicology of University of Yaounde I, Yaounde, Cameroon
| | - Pascal Pineau
- Unité « Organisation nucléaire et Oncogenèse », INSERM U993, Institut Pasteur, Paris, France
| | - Richard Njouom
- Virology Unit, Centre Pasteur of Cameroon, BP 1274, Yaounde, Cameroon.
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Lempp FA, Ni Y, Urban S. Hepatitis delta virus: insights into a peculiar pathogen and novel treatment options. Nat Rev Gastroenterol Hepatol 2016; 13:580-9. [PMID: 27534692 DOI: 10.1038/nrgastro.2016.126] [Citation(s) in RCA: 121] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Chronic hepatitis D is the most severe form of viral hepatitis, affecting ∼20 million HBV-infected people worldwide. The causative agent, hepatitis delta virus (HDV), is a unique human pathogen: it is the smallest known virus; it depends on HBV to disseminate its viroid-like RNA; it encodes only one protein (HDAg), which has both structural and regulatory functions; and it replicates using predominantly host proteins. The failure of HBV-specific nucleoside analogues to suppress the HBV helper function, and the limitations of experimental systems to study the HDV life cycle, have impeded the development of HDV-specific drugs. Thus, the only clinical regimen for HDV is IFNα, which shows some efficacy but long-term virological responses are rare. Insights into the receptor-mediated entry of HDV, and the observation that HDV assembly requires farnesyltransferase, have enabled novel therapeutic strategies to be developed. Interference with entry, for example through blockade of the HBV-HDV-specific receptor sodium/taurocholate cotransporting polypeptide NTCP by Myrcludex B, and inhibition of assembly by blockade of farnesyltransferase using lonafarnib or nucleic acid polymers such as REP 2139-Ca, have shown promising results in phase II studies. In this Review, we summarize our knowledge of HDV epidemiology, pathogenesis and molecular biology, with a particular emphasis on possible future developments.
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Affiliation(s)
- Florian A Lempp
- Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany
| | - Yi Ni
- Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.,German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
| | - Stephan Urban
- Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.,German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
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Rizzetto M, Smedile A, Ciancio A. Hepatitis D. CLINICAL VIROLOGY 2016:1409-1423. [DOI: 10.1128/9781555819439.ch58] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Hepatitis C virus infection from the perspective of heterologous immunity. Curr Opin Virol 2016; 16:41-48. [DOI: 10.1016/j.coviro.2016.01.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2015] [Accepted: 01/08/2016] [Indexed: 01/14/2023]
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Mhalla S, Kadri Y, Alibi S, Letaief A, Boukadida J, Hannachi N. Hepatitis D Virus Infection Among Hepatitis B Surface Antigen Carriers and in "Isolated anti-HBc" Antibodies Profile in Central Tunisia. HEPATITIS MONTHLY 2016; 16:e32354. [PMID: 27110257 PMCID: PMC4834381 DOI: 10.5812/hepatmon.32354] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 10/31/2015] [Accepted: 12/04/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatitis D Virus (HDV) causes accelerated liver diseases in patients with Hepatitis B Virus (HBV) infection. There is lack of data about its prevalence, related risk factors and interaction with HBV carriers in our country. OBJECTIVES The aim of this study was to estimate the prevalence of hepatitis delta and associated risk factors among Hepatitis B surface antigen (HBsAg) and "isolated anti-HBc" profile carriers in central Tunisia. PATIENTS AND METHODS In this cross-sectional study, 540 patients with positive HBsAg and 109 "isolated anti-HBc" profile receiving care in a teaching hospital were tested for the presence of HDV serum-markers using commercially available enzyme immunoassay kit. HBV-DNA was detected by nested PCR in "isolated anti-HBc" profile group. RESULTS Prevalence of HDV was 8.1% in HBsAg carriers group, but it was significantly higher in active than inactive hepatitis (30.2% and 4.5%, respectively, OR = 9, 95% CI: [4.48-18.58]). There was no significant association between studied risk factors and HDV infection. In the "isolated anti-HBc" profile group, prevalence of HDV was 4.6% and HBV-DNA had negative result in all patients with positive results for HDV. CONCLUSIONS Although HDV had low prevalence in our area, it is vital to plan preventive strategies for HDV spread as well as HBV prevention. It is particularly important to suspect HDV infection in active HBV carriers to manage a particularly severe dual infection. HDV infection should be suspected even in negative HBsAg patients having "isolated anti-HBc" profile.
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Affiliation(s)
- Salma Mhalla
- Laboratory of Microbiology and Immunology, F. Hached Teaching Hospital, (UR12SP34) University of Sousse, Sousse, Tunisia
- Department of Microbiology, Fattouma Bourguiba Teaching Hospital, University of Monastir, Monastir, Tunisia
- Corresponding Author: Salma Mhalla, Department of Microbiology, Fattouma Bourguiba Teaching Hospital, University of Monastir, Monastir, Tunisia. E-mail:
| | - Yosr Kadri
- Department of Microbiology, Fattouma Bourguiba Teaching Hospital, University of Monastir, Monastir, Tunisia
| | - Sana Alibi
- Laboratory of Microbiology and Immunology, F. Hached Teaching Hospital, (UR12SP34) University of Sousse, Sousse, Tunisia
| | - Amel Letaief
- Department of Infectious Disease, F. Hached Teaching Hospital, University of Sousse, Sousse, Tunisia
| | - Jalel Boukadida
- Laboratory of Microbiology and Immunology, F. Hached Teaching Hospital, (UR12SP34) University of Sousse, Sousse, Tunisia
| | - Naila Hannachi
- Laboratory of Microbiology and Immunology, F. Hached Teaching Hospital, (UR12SP34) University of Sousse, Sousse, Tunisia
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Wranke A, Heidrich B, Hardtke S, Wedemeyer H. Current Management of HBV/HDV Coinfection and Future Perspectives. ACTA ACUST UNITED AC 2015. [DOI: 10.1007/s11901-015-0280-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Giersch K, Dandri M. Hepatitis B and Delta Virus: Advances on Studies about Interactions between the Two Viruses and the Infected Hepatocyte. J Clin Transl Hepatol 2015; 3:220-9. [PMID: 26623269 PMCID: PMC4663204 DOI: 10.14218/jcth.2015.00018] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Revised: 07/11/2015] [Accepted: 07/12/2015] [Indexed: 12/14/2022] Open
Abstract
The mechanisms determining persistence of hepatitis B virus (HBV) infection and long-term pathogenesis of HBV-associated liver disease appear to be multifactorial. Although viral replication can be efficiently suppressed by the antiviral treatments currently available, viral clearance is generally not achieved since HBV has developed unique replication strategies, enabling persistence of its genome within the infected hepatocytes. Moreover, no direct antiviral therapy exists for the more than 15 million people worldwide that are also coinfected with the hepatitis delta virus (HDV), a defective virus that needs the HBV envelope proteins for propagation. The limited availability of robust HBV and HDV infection systems has hindered the understanding of the complex network of virus-virus and virus-host interactions that are established in the course of infection and slowed down progress in drug development. Since chronic HBV/HDV coinfection leads to the most severe form of chronic viral hepatitis, elucidation of the molecular mechanisms regulating virus-host interplay and pathogenesis are urgently needed. This article summarizes the current knowledge regarding the interactions among HBV, HDV, and the infected target cell and discusses the dependence of HDV on HBV activity and possible future therapeutic approaches.
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Affiliation(s)
- Katja Giersch
- Department of Internal Medicine, Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Maura Dandri
- Department of Internal Medicine, Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel site, Germany
- Correspondence to: Maura Dandri, Department of Internal Medicine, Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany. Tel: +49-40741052949, Fax: +49-40741057232, E-mail:
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Abstract
Hepatitis D virus (HDV) is an uncommon, defective, single-stranded circular RNA virus that is dependent on the hepatitis B virus' surface antigen envelope proteins for transmission. It is highly pathogenic and associated with high rates of progression to cirrhosis and associated complications. HDV continues to ravage endemic parts of Asia and Europe, and its prevalence in the United States, although low, has not decreased in frequency, despite universal hepatitis B virus vaccination, because of lack of testing and underrecognition. There are few reports on the prevalence and characteristics of HDV infection in the pediatric population. We present 2 patients with HDV infection at our institution; both were from eastern Europe and were treated with pegylated interferon-α. The present standard of care treatment for HDV yields suboptimal results, but insights into the virology of hepatitis D are stimulating the search for novel therapeutic approaches, particularly the development of prenylation inhibitors and viral entry inhibitors.
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Lin HH, Lee SSJ, Yu ML, Chang TT, Su CW, Hu BS, Chen YS, Huang CK, Lai CH, Lin JN, Wu JC. Changing hepatitis D virus epidemiology in a hepatitis B virus endemic area with a national vaccination program. Hepatology 2015; 61:1870-1879. [PMID: 25677884 DOI: 10.1002/hep.27742] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2014] [Revised: 01/27/2015] [Accepted: 02/03/2015] [Indexed: 12/13/2022]
Abstract
UNLABELLED The emergence of hepatitis D virus (HDV) infection in the era of widespread HBV vaccination has not been described before. We aimed to investigate the changing epidemiology of HDV infection among high- and low-risk populations after an outbreak of human immunodeficiency virus (HIV) infection among injection drug users (IDUs) in Taiwan. A prospective, multicenter, cohort study of 2,562 hepatitis B surface antigen (HBsAg)-positive individuals was conducted to determine the prevalence, genotype, and risk factors of HDV infection from 2001 through 2012. The prevalence rates of HDV infection were 74.9%, 43.9%, 11.4%, 11.1%, and 4.4% among HIV-infected IDUs, HIV-uninfected IDUs, HIV-infected men who have sex with men, HIV-infected heterosexuals, and the general population of HBsAg-positive subjects, respectively. A significant increase in the trend of HDV prevalence from 38.5% to 89.8% was observed in HIV-infected IDUs (odds ratio = 3.06; 95% confidence interval: 1.68-5.56; P = 0.0002). In multivariate analysis, injection drug use, hepatitis C virus infection, HIV infection, serum HBsAg level ≧250 IU/mL, duration of drug use, and older age were significant factors associated with HDV infection. HDV genotype IV (72.2%) was the prevalent genotype circulating among IDUs, whereas genotype II was predominant in the non-IDU populations (73.3%). In the HIV cohort born after 1987 who were HBsAg negative, over half (52.9%) had antibody to hepatitis B surface antigen antibody levels of <10 mIU/mL and there was a significantly higher HBsAg seroprevalence in the HIV cohort, compared to the control group (8.1% vs. 0.0%; P = 0.02). CONCLUSION In the era of HBV vaccination, IDUs and HIV-infected individuals have emerged as high-risk groups and a reservoir for HDV infection. Effective strategies are needed to curb the reemerging epidemic of HDV infection in these high-risk groups.
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Affiliation(s)
- Hsi-Hsun Lin
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
- Department of Medicine and Infection Control, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Susan Shin-Jung Lee
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
- Department of Medicine, Medical College of National Cheng Kung University, Tainan, Taiwan
| | - Chien-Wei Su
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Bor-Shen Hu
- Section of Infectious Diseases, Taipei City Hospital, Taipei City Government, Taipei, Taiwan
| | - Yaw-Sen Chen
- Department of General Surgery, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Chun-Kai Huang
- Department of Medicine and Infection Control, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Chung-Hsu Lai
- Department of Medicine and Infection Control, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Jiun-Nong Lin
- Department of Medicine and Infection Control, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Jaw-Ching Wu
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
- Translational Research Division, Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan
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Aldabe R, Suárez-Amarán L, Usai C, González-Aseguinolaza G. Animal models of chronic hepatitis delta virus infection host-virus immunologic interactions. Pathogens 2015; 4:46-65. [PMID: 25686091 PMCID: PMC4384072 DOI: 10.3390/pathogens4010046] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Accepted: 02/05/2015] [Indexed: 02/08/2023] Open
Abstract
Hepatitis delta virus (HDV) is a defective RNA virus that has an absolute requirement for a virus belonging to the hepadnaviridae family like hepatitis B virus (HBV) for its replication and formation of new virions. HDV infection is usually associated with a worsening of HBV-induced liver pathogenesis, which leads to more frequent cirrhosis, increased risk of hepatocellular carcinoma (HCC), and fulminant hepatitis. Importantly, no selective therapies are available for HDV infection. The mainstay of treatment for HDV infection is pegylated interferon alpha; however, response rates to this therapy are poor. A better knowledge of HDV–host cell interaction will help with the identification of novel therapeutic targets, which are urgently needed. Animal models like hepadnavirus-infected chimpanzees or the eastern woodchuck have been of great value for the characterization of HDV chronic infection. Recently, more practical animal models in which to perform a deeper study of host virus interactions and to evaluate new therapeutic strategies have been developed. Therefore, the main focus of this review is to discuss the current knowledge about HDV host interactions obtained from cell culture and animal models.
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Affiliation(s)
- Rafael Aldabe
- Gene Therapy and Regulation of Gene Expression Program, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra (UNAV), Pamplona 31008, Spain.
| | - Lester Suárez-Amarán
- Gene Therapy and Regulation of Gene Expression Program, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra (UNAV), Pamplona 31008, Spain
| | - Carla Usai
- Gene Therapy and Regulation of Gene Expression Program, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra (UNAV), Pamplona 31008, Spain.
| | - Gloria González-Aseguinolaza
- Gene Therapy and Regulation of Gene Expression Program, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra (UNAV), Pamplona 31008, Spain.
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41
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Galimova SF. Chronic hepatitis D. DOKAZATEL'NAYA GASTROENTEROLOGIYA 2015; 4:32. [DOI: 10.17116/dokgastro201543-432-42] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Liao B, Zhang F, Lin S, He H, Liu Y, Zhang J, Xu Y, Yi J, Chen Y, Liu H, Wang Z, Cai W. Epidemiological, clinical and histological characteristics of HBV/HDV co-infection: a retrospective cross-sectional study in Guangdong, China. PLoS One 2014; 9:e115888. [PMID: 25532128 PMCID: PMC4274124 DOI: 10.1371/journal.pone.0115888] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Accepted: 11/27/2014] [Indexed: 12/13/2022] Open
Abstract
Background The epidemiology of hepatitis D virus (HDV) in China is fairly unknown. The mechanisms whereby HDV leads to accelerated liver disease in hepatitis B virus (HBV)/HDV co-infected patients and the histological characteristics of chronic hepatitis D (CHD) patients need further investigation. Methods The prevalence of HDV was retrospectively evaluated in all consecutive hospitalized patients with chronic HBV infection from May 2005 to October 2011. HBV/HDV co-infected patients and HBV mono-infected patients were compared clinically and histologically. Significant histological abnormality was defined as significant necroinflammation (grade ≥A2) and/or significant fibrosis (stage ≥ F2). Results 6.5% of patients (426/6604) tested positive for IgM anti-HDV. HDV was more common in patients over 50 years old than those under 50 (11.7% vs. 5.1%, P<0.001). HBV/HDV co-infected patients had higher frequencies of end-stage liver disease (ESLD) than HBV mono-infected patients, and HDV co-infection was an independent risk factor for ESLD (OR: 1.428, 95%CI: 1.116–1.827; P = 0.005). The HBV DNA levels in the HBV/HDV group were significantly lower than the HBV group in chronic hepatitis patients (median: 6.50 log10copies/mL vs 6.80 log10copies/mL, P = 0.003), but higher than the HBV group in ESLD patients (median: 5.73 log10copies/mL vs 5.16 log10copies/mL, P<0.001). When stratified by alanine aminotransferase (ALT) level, 46.7%, 56.5% and 80.5% of CHD patients had significant necroinflammation and 86.7%, 87.0% and 90.3% had significant fibrosis with ALT 1–2×upper limit normal (ULN), 2–5×ULN and>5×ULN respectively. Conclusion The prevalence of HDV is not low in patients with chronic HBV infection. HDV may contribute to progression to ESLD through late-phase HBV DNA reactivation.
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Affiliation(s)
- Baolin Liao
- Department of Infectious Disease, Guangzhou No. 8 People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Fuchun Zhang
- Department of Infectious Disease, Guangzhou No. 8 People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Siwei Lin
- Department of Third Internal Medicine, Yuexiu District Traditional Chinese Medicine Hospital, Guangzhou, China
| | - Haolan He
- Department of Infectious Disease, Guangzhou No. 8 People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Yu Liu
- Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jiansheng Zhang
- Department of Infectious Disease, Guangzhou No. 8 People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Ying Xu
- Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Junqing Yi
- Department of Infectious Disease, Guangzhou No. 8 People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Yunqing Chen
- Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Huiyuan Liu
- Department of Infectious Disease, Guangzhou No. 8 People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Zhanhui Wang
- Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Weiping Cai
- Department of Infectious Disease, Guangzhou No. 8 People's Hospital, Guangzhou Medical University, Guangzhou, China
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Braga WSM, de Oliveira CMC, de Araújo JR, Castilho MDC, Rocha JM, Gimaque JBDL, Silva MLCR, Vasconcelos HL, Ramasawmy R, Paraná R. Chronic HDV/HBV co-infection: predictors of disease stage---a case series of HDV-3 patients. J Hepatol 2014; 61:1205-11. [PMID: 24905491 DOI: 10.1016/j.jhep.2014.05.041] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Revised: 05/26/2014] [Accepted: 05/27/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Chronic HDV/HBV co-infection is perhaps the most intriguing amongst all viral hepatitis. Only few studies focus deeply on this topic, particularly with patients infected with HDV-3. This study aimed to identify predictors of advanced disease, examining a cross-sectional data of 64 patients. METHODS Histological grading was used to characterize the disease stages and viral loads were tested as predictors of necroinflammatory activity and fibrosis. RESULTS We identified three HDV/HBV co-infection patterns: patients with predominant HDV replication (56.3%), patients with similar viral loads of both viruses (40.6%), and patients with predominant HBV replication (3.1%). Mean HDV-RNA showed a positive trend regarding inflammatory activity and grade of fibrosis. HDV viral load correlated positively with serum levels of liver enzymes and inversely with platelets count. HBV viral load showed no correlation with any of the above parameters. Advanced fibrosis was associated with age, splenomegaly, and HDV viral load of more than 2 log10. Multiple logistic regression confirmed the independent effect of HDV viral predominance. Advanced necroinflammatory activity was independently associated with HDV viral load and splenomegaly. CONCLUSIONS HDV may possibly play an important and direct role in the establishment of necroinflammatory activity and fibrosis. Data show an indigenous HDV genotype, HDV-3, similar to those described in the Amazon region.
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Affiliation(s)
| | - Cintia Mara Costa de Oliveira
- Virology Department, Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil; Multidisciplinar Center, Federal University of Amazonas, Manaus, Amazonas, Brazil
| | - José Ribamar de Araújo
- Anatomopatology Department, Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil
| | - Marcia da Costa Castilho
- Virology Department, Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil
| | - Joelma Martins Rocha
- Virology Department, Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil
| | | | | | - Heline Lira Vasconcelos
- Virology Department, Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil
| | - Rajendranath Ramasawmy
- Virology Department, Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil; Nilton Lins University, Manaus, Amazonas, Brazil
| | - Raymundo Paraná
- Gastroenterology Unit, Federal University of Bahia, Salvador, Bahia, Brazil
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Calle Serrano B, Großhennig A, Homs M, Heidrich B, Erhardt A, Deterding K, Jaroszewicz J, Bremer B, Koch A, Cornberg M, Manns MP, Buti M, Wedemeyer H. Development and evaluation of a baseline-event-anticipation score for hepatitis delta. J Viral Hepat 2014; 21:e154-63. [PMID: 24673975 PMCID: PMC4263246 DOI: 10.1111/jvh.12251] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2013] [Accepted: 01/02/2014] [Indexed: 12/13/2022]
Abstract
Hepatitis delta is considered the most severe form of viral hepatitis, but variables associated with disease progression are poorly defined. This study aimed to identify risk factors associated with worse clinical outcome in patients with hepatitis delta and to develop a clinical score to determine their risk of experiencing liver-related morbidity or mortality. We followed 75 HBsAg-anti-HDV-positive patients with hepatitis delta for up to 16 years (median 5 years). The baseline-event-anticipation score (BEA score) was developed based on variables associated with the development of liver-related clinical complications. Age, region of origin, presence of cirrhosis, albumin, INR, hyperbilirubinemia and thrombocytopenia were all associated with the development of an event in the training cohort. The BEA score included age, sex, region of origin, bilirubin, platelets and INR. Points were allocated according to hazard ratios, and three risk groups were defined: BEA-A mild risk, BEA-B moderate risk and BEA-C high risk. Hazard ratios of BEA-B and BEA-C patients for liver-related clinical endpoints were 9.01 and 25.27 vs BEA-A with an area under curve of the receiving operating characteristic curve of 0.88. The accuracy of the BEA score was confirmed in two independent validation cohorts followed in Barcelona (n = 77) and Düsseldorf (n = 62). Delta hepatitis is associated with a very severe long-term outcome. The BEA score is easy to apply and predicts with a very high accuracy the development of liver-related complications in patients with hepatitis delta.
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Affiliation(s)
- B Calle Serrano
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical SchoolHannover, Germany,German Center for Infection Research (DZIF), Partner Side HepNet Study-HouseHannover, Germany
| | - A Großhennig
- Institute for Biostatistics Hannover Medical SchoolHannover, Germany
| | - M Homs
- Liver Unit, Hospital General Universitario Vall d'Hebron and CIBERehd of Instituto Carlos IIIBarcelona, Spain
| | - B Heidrich
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical SchoolHannover, Germany,Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical SchoolHannover, Germany
| | - A Erhardt
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-UniversityDusseldorf, Germany
| | - K Deterding
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical SchoolHannover, Germany
| | - J Jaroszewicz
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical SchoolHannover, Germany,Department of Infectious Diseases and Hepatology, Medical University of BialystokBialystok, Poland
| | - B Bremer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical SchoolHannover, Germany
| | - A Koch
- Institute for Biostatistics Hannover Medical SchoolHannover, Germany
| | - M Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical SchoolHannover, Germany
| | - M P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical SchoolHannover, Germany,Liver Unit, Hospital General Universitario Vall d'Hebron and CIBERehd of Instituto Carlos IIIBarcelona, Spain
| | - M Buti
- Institute for Biostatistics Hannover Medical SchoolHannover, Germany
| | - H Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical SchoolHannover, Germany,German Center for Infection Research (DZIF), Partner Side HepNet Study-HouseHannover, Germany,Liver Unit, Hospital General Universitario Vall d'Hebron and CIBERehd of Instituto Carlos IIIBarcelona, Spain
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45
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Heidrich B, Yurdaydın C, Kabaçam G, Ratsch BA, Zachou K, Bremer B, Dalekos GN, Erhardt A, Tabak F, Yalcin K, Gürel S, Zeuzem S, Cornberg M, Bock CT, Manns MP, Wedemeyer H. Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta. Hepatology 2014; 60:87-97. [PMID: 24585488 DOI: 10.1002/hep.27102] [Citation(s) in RCA: 217] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Accepted: 02/24/2014] [Indexed: 12/12/2022]
Abstract
UNLABELLED Interferon alpha is the only treatment option for hepatitis delta virus (HDV). Trials investigating the efficacy of pegylated interferon alpha (PEG-IFNa) showed HDV RNA negativity rates of 25-30% 24 weeks after therapy. However, the clinical and virological long-term outcome of HDV-infected patients treated with PEG-IFNa is unknown. We performed a retrospective-prospective follow-up of 77 patients treated for 48 weeks with either PEG-alfa-2a and adefovir (ADV) or either drug alone in the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-1) trial. Long-term follow-up data were available for 58 out of 77 patients (75%) with a median time of follow-up of 4.5 (0.5-5.5) years and a median 3 visits per patient. Patients treated with ADV alone received retreatment with PEG-IFNa (48% versus 19%; P = 0.02) more often. Hepatitis B virus surface antigen (HBsAg) became negative in six PEG-IFNa-treated patients until the end of long-term follow-up (10%). Sixteen patients tested HDV RNA-negative 6 months after PEG-IFNa treatment who were entered in the long-term follow-up study. Out of these, nine individuals tested HDV RNA-positive at least once during further long-term follow-up, with seven patients being HDV RNA-positive at the most recent visit. Clinical endpoints (liver-related death, liver transplantation, hepatic decompensation, hepatocellular carcinoma) were observed in three PEG-IFNa-treated (8%) and three ADV-treated (14%) patients during posttreatment long-term follow-up with an overall annual event rate of 2.5% (4.9% in cirrhosis). Sequencing confirmed the reappearance of pretreatment virus strains in all cases. CONCLUSION Late HDV RNA relapses may occur after PEG-IFNa therapy of hepatitis delta and thus the term sustained virological response should be avoided in HDV infection. The annual posttreatment rate of clinical events in hepatitis delta patients eligible for PEG-IFNa therapy is about 2.5% and 4.9% in patients with cirrhosis.
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Affiliation(s)
- Benjamin Heidrich
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), partner site, Hannover-Braunschweig, Germany
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46
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Hønge B, Jespersen S, Medina C, Té D, da Silva Z, Ostergaard L, Laursen A, Wejse C, Krarup H, Erikstrup C. Hepatitis B virus surface antigen and anti-hepatitis C virus rapid tests underestimate hepatitis prevalence among HIV-infected patients. HIV Med 2014; 15:571-6. [PMID: 24717010 DOI: 10.1111/hiv.12158] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2014] [Indexed: 11/28/2022]
Abstract
OBJECTIVES In the case of coinfection with HIV and hepatitis B virus (HBV) and/or hepatitis C virus (HCV), hepatic disease progression is often accelerated, with higher rates of liver cirrhosis and liver-related mortality. We aimed to evaluate the performance of the rapid tests used routinely to detect HBV surface antigen (HBsAg) and anti-HCV among HIV-infected patients in Guinea-Bissau. METHODS Blood samples from HIV-infected patients in Guinea-Bissau were stored after testing for HBsAg and anti-HCV with rapid tests. Samples were subsequently re-tested for HBsAg and anti-HCV in Denmark. RESULTS Two rapid tests were used in Guinea-Bissau: HBsAg Strip Ref 2034 (VEDA.LAB, Alençon, France; sensitivity 62.3%; specificity 99.2%) and HEPA-SCAN (Bhat Bio-Tech, Bangalore, India; sensitivity 57.1%; specificity 99.7%). In the two tests the ability to obtain the correct outcome depended on the antigen and antibody concentrations, respectively. Sex, age, CD4 cell count and antiretroviral therapy status did not differ between false negative and true positive samples in either of the tests. The study is limited by a low number of anti-HCV positive samples. CONCLUSIONS New diagnostic rapid tests should always be evaluated in the setting in which they will be used before implementation.
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Affiliation(s)
- Bl Hønge
- The Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
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47
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Serological and molecular diagnosis of hepatitis delta virus infection: results of a French national quality control study. J Clin Microbiol 2014; 52:1694-7. [PMID: 24523467 DOI: 10.1128/jcm.03521-13] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
A French national quality control study for the serological and molecular diagnosis of hepatitis delta virus (HDV) was organized. Total HDV antibodies were properly detected by all laboratories; 8/14 laboratories failed to detect low titers of IgM, and 6/11 failed to quantify and/or underestimated the RNA viral load in several samples. These discrepancies are likely related to the molecular diversity of HDV.
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48
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Ho E, Deltenre P, Nkuize M, Delwaide J, Colle I, Michielsen P. Coinfection of hepatitis B and hepatitis delta virus in Belgium: a multicenter BASL study. Prospective epidemiology and comparison with HBV mono-infection. J Med Virol 2014; 85:1513-7. [PMID: 23852675 DOI: 10.1002/jmv.23653] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2013] [Indexed: 12/17/2022]
Abstract
Epidemiological data on hepatitis delta virus (HDV) infection in Belgium are lacking. A multicenter questionnaire-based registry on HDV infection was collated between March 1, 2008 and February 28, 2009. It consisted of patients coinfected with hepatitis B virus (HBV) and HDV. The data samples were compared to those of a concurrent registry on HBV infection. Prospective data of patients with HBV-HDV coinfection were collected. Active HBV replication is defined as HBeAg positivity or HBV DNA > 2,000 IU/ml. Forty-four patients from 15 centers were registered. A comparison of 29 patients infected with HDV (registered in the concurrent HBV registry) was made against 785 HBV mono-infected patients. The seroprevalence of patients coinfected with HBV and HDV in Belgium is reported to be 3.7% (29/785), consisting solely of the HBV-HDV coinfected patients in the HBV registry. This rises to 5.5% (44/800) if all patients infected with HDV from the two registries combined are included. The patients coinfected with HBV and HDV had higher (P < 0.05) ALT values and more advanced liver disease (Metavir score ≥F2), but had less active HBV replication and lower HBV DNA titers when compared with the patients infected only with HBV. Additionally, the majority of HBV-HDV coinfected patient was male, and 13.6% (6/44) of the patients that were coinfected HBV and HDV were also infected with HCV. In conclusion, this study provided much needed epidemiological data on the current state of HDV infection in Belgium.
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Affiliation(s)
- E Ho
- Faculty of Medicine and Health Sciences, Laboratory Medicine/Microbiology, Antwerp University Hospital, Antwerp, Edegem, Belgium.
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49
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Abstract
Immigration is fuelling a new reservoir of hepatitis D virus (HDV) in Europe, and hepatitis D still represents an important medical problem in the USA. The disease continues to be a major medical scourge in the developing world, in particular in countries such as Pakistan, Mongolia and Mauritania. New therapeutic strategies are being developed to disrupt interactions between HDV and its viral partner HBV, or with the host. Blocking or modifying the hepatitis B surface antigen (HBsAg) might interfere with the uptake or release of the hepatitis D virion; interference with host-mediated post-translational changes of proteins that are crucial to the HDV life cycle, such as prenylation, is another potential therapeutic option. At present, however, the only realistic option is to optimize IFN-α therapy. As eradication of HBsAg is the ultimate end point of therapy, long-term interferon administration might be required, raising an issue of tolerance in patients. Treatment with IFN-λ is a potential alternative approach to IFN-α; treatment of hepatitis C with this cytokine seems to cause fewer adverse effects than IFN-α and, therefore, might be more suitable for long-term treatment of HDV.
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50
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Lunemann S, Grabowski J, Wedemeyer H. Immunopathogenesis of Hepatitis D. LIVER IMMUNOLOGY 2014:231-241. [DOI: 10.1007/978-3-319-02096-9_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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