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Dudman S, Zerja A, Hasanoğlu İ, Ruta S, van Welzen B, Nicolini LA, Yonga P, Øverbø J, Rawat S, Habibovic S, Kim TB, Rivero-Juarez A. Global vaccination against hepatitis E virus: position paper from the European Society of Clinical Microbiology and Infectious Diseases Viral Hepatitis Study Group. Clin Microbiol Infect 2025; 31:201-210. [PMID: 39550032 DOI: 10.1016/j.cmi.2024.11.016] [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: 09/23/2024] [Revised: 11/05/2024] [Accepted: 11/09/2024] [Indexed: 11/18/2024]
Abstract
SCOPE Hepatitis E virus (HEV) is a significant global health issue, impacting both low- and middle-income countries and industrialized nations. HEV genotypes 1 and 2, primarily transmitted through contaminated water, are endemic in low- and middle-income countries, whereas genotypes 3 and 4 are zoonotically transmitted in industrialized regions. Acute HEV infection poses severe risks, particularly to pregnant women and immunocompromised individuals, whereas chronic HEV infection leads to serious complications in those with pre-existing liver disease and transplant recipients. The development of an HEV vaccine offers new prevention opportunities, though its availability and integration into global immunization programmes remain limited. METHODS This position paper was developed by the European Society of Clinical Microbiology and Infectious Diseases Viral Hepatitis Study Group through an extensive review of clinical data, safety profiles, efficacy, and immunogenicity of HEV vaccines. The study group focused particularly on high-risk and special populations, synthesizing global health insights and incorporating recommendations from the Strategic Advisory Group of Experts to formulate strategies for wider HEV vaccination use. QUESTIONS ADDRESSED IN THE POSITION PAPER The position paper evaluates the efficacy and safety of HEV vaccines in both general and special populations. It identifies key barriers to the integration of HEV vaccines into routine immunization programmes, including infrastructure limitations, costs, and vaccine accessibility. The paper also proposes strategies to overcome these challenges and improve vaccine distribution. Furthermore, it addresses ways to enhance public awareness and international cooperation to promote HEV vaccination efforts globally. IMPLICATIONS European Society of Clinical Microbiology and Infectious Diseases Viral Hepatitis Study Group recommends HEV vaccination for high-risk groups, including women of childbearing age, patients with chronic liver diseases, and immunosuppressed individuals. Prioritizing investments in vaccine logistics, integrating diagnostics, and educational outreach can enhance uptake.
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Affiliation(s)
- Susanne Dudman
- Department of Microbiology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Arjana Zerja
- Department of Infectious Diseases, Hospital University Center "Mother Teresa," Tirana, Albania
| | - İmran Hasanoğlu
- Department of Infectious Disease and Clinical Microbiology, Ankara Yildirim Beyazit University, Ankara City Hospital, Ankara, Turkey
| | - Simona Ruta
- Department of Virology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania; Department of Emerging Viral Diseases, "Stefan S. Nicolau" Institute of Virology, Bucharest, Romania
| | - Berend van Welzen
- Department of Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Laura Ambra Nicolini
- Department of Infectious Diseases, Ospedale Policlinico San Martino-IRCC, Genoa, Italy
| | - Paul Yonga
- Department of Infectious Disease and International Health Clinic, Conenect Afya Medlynks Medical Centre and Laboratory, Nairobi, Kenya
| | - Joakim Øverbø
- Department of Microbiology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Norwegian Institute of Public Health, Oslo, Norway
| | - Sumit Rawat
- Department of Microbiology, Bundelkhand Medical College, Sagar, India; Department of Microbiology, All India Institute of Medical Sciences, Bhopal, India
| | - Selma Habibovic
- Department of Microbiology, Public Health Institute Novi Pazar, Novi Pazar, Serbia
| | - Tan Bou Kim
- Department of Intensive Care, Hospital Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Antonio Rivero-Juarez
- Department of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain; Centro de Investigación Biomédica en Red (CIBER) área de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
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Buti M, Ruiz-Cobo JC, Esteban R, Riveiro-Barciela M. Hepatitis E as a trigger for acute-on-chronic liver failure. Clin Mol Hepatol 2025; 31:S196-S204. [PMID: 39523715 PMCID: PMC11925444 DOI: 10.3350/cmh.2024.0758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 11/07/2024] [Indexed: 11/16/2024] Open
Abstract
Acute hepatitis E virus (HEV) infection is typically self-limiting and has a favourable prognosis. However, certain populations such as patients with pre-existing chronic liver disease may experience severe manifestations, including progression to acute-on-chronic liver failure (ACLF). Among viral hepatitis types, hepatitis A, E, and B are major causes of ACLF. Active screening and early diagnosis of HEV infection in patients with cirrhosis, especially those who develop ACLF, can improve management and enable timely antiviral therapy. Preventive measures, including HEV vaccination for high-risk groups, could reduce the morbidity and mortality associated with hepatitis E.
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Affiliation(s)
- Maria Buti
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Juan Carlos Ruiz-Cobo
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Rafael Esteban
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. S2k-Leitlinie Lebertransplantation der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Luo Q, Chen J, Zhang Y, Xu W, Liu Y, Xie C, Peng L. Viral hepatitis E: Clinical manifestations, treatment, and prevention. LIVER RESEARCH 2024; 8:11-21. [PMID: 39959034 PMCID: PMC11771268 DOI: 10.1016/j.livres.2024.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 11/17/2023] [Accepted: 01/03/2024] [Indexed: 02/18/2025]
Abstract
Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing regions. In the less developed regions of Asia and Africa, a high seropositivity rate has been reported for hepatitis E virus (HEV) antibodies. Although acute hepatitis E is often self-limited and has a favorable prognosis, some populations experience severe manifestations, which may progress to liver failure. Moreover, some immunocompromised patients are at risk of developing chronic HEV infection and cirrhosis. Proactive screening, reducing misdiagnosis, improving patient management, timely antiviral therapy for severe and chronic cases, and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis E. This review focused on the clinical presentation, management, and prevention of hepatitis E.
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Affiliation(s)
- Qiumin Luo
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jia Chen
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yeqiong Zhang
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Wenxiong Xu
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Ying Liu
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chan Xie
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Peng
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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Iqbal H, Mehmood BF, Sohal A, Roytman M. Hepatitis E infection: A review. World J Virol 2023; 12:262-271. [PMID: 38187497 PMCID: PMC10768387 DOI: 10.5501/wjv.v12.i5.262] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/23/2023] [Accepted: 12/05/2023] [Indexed: 12/25/2023] Open
Abstract
Hepatitis E virus (HEV) is a small non-enveloped virus that is transmitted via the fecal-oral route. It is a highly common cause of acute hepatitis, particularly in low to middle income regions of Asia, Africa, and Central America. Most cases are self-limited, and symptomatic patients usually present with acute icteric hepatitis. A subset of patients including pregnant women, older men, those with pre-existing liver disease and immunocompromised patients however, may develop severe disease and hepatic failure. Immunocompromised patients are also at risk for chronic infection, and their immunosuppression should be decreased in order to facilitate viral clearance. HEV can also present with a variety of extra-intestinal manifestations including neurological, renal, hematological, and pancreatic derangements. The gold standard of diagnosis is HEV ribonucleic acid detection via nucleic acid amplification testing. Currently, there are no approved treatments for Hepatitis E, though ribavirin is the most commonly used agent to reduce viral load. Studies assessing the safety and efficacy of other antiviral agents for HEV are currently underway. HEV vaccination has been approved in China, and is currently being investigated in other regions as well. This review article aims to discuss the epidemiology, pathogenesis, presentation, diagnosis, complications, and treatment of Hepatitis E infection.
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Affiliation(s)
- Humzah Iqbal
- Department of Internal Medicine, University of California San Francisco, Fresno, CA 93701, United States
| | - Bilal Fazal Mehmood
- Department of Internal Medicine, University of California San Francisco, Fresno, CA 93701, United States
| | - Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, Seattle, WA 98105, United States
| | - Marina Roytman
- Department of Gastroenterology and Hepatology, University of California San Francisco, Fresno, CA 93701, United States
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Riveiro-Barciela M, Roade L, Martínez-Camprecios J, Vidal-González J, Rodríguez-Diez B, Perelló M, Ortí G, Robles-Alonso V, Berastegui C, Navarro J, Martínez-Valle F, Bilbao I, Castells L, Ventura-Cots M, Llaneras J, Rando-Segura A, Forns X, Lens S, Prieto M, García-Eliz M, Imaz A, Rodríguez-Frías F, Buti M, Esteban R. mTOR inhibitors a potential predisposing factor for chronic hepatitis E: Results from the prospective collaborative CHES study (Chronic Hepatitis EScreening in patients with immune impairment and increased transaminases levels). GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46:764-773. [PMID: 36731726 DOI: 10.1016/j.gastrohep.2023.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 01/03/2023] [Accepted: 01/21/2023] [Indexed: 02/01/2023]
Abstract
BACKGROUND Chronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes. PATIENTS AND METHODS CHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey. RESULTS Three hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model. CONCLUSIONS Despite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E.
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Affiliation(s)
- Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain
| | - Luisa Roade
- Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain
| | - Joan Martínez-Camprecios
- Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain
| | - Judit Vidal-González
- Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain
| | - Basilio Rodríguez-Diez
- Rheumatology Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Manel Perelló
- Nephrology Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Guillermo Ortí
- Department of Hematology, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Virginia Robles-Alonso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Digestive System Research Unit, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Cristina Berastegui
- Pneumology Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Jordi Navarro
- Infectious Diseases Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Fernando Martínez-Valle
- Systemic Autoimmune Diseases Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain
| | - Itxarone Bilbao
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Transplant Unit, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Lluis Castells
- Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain
| | - Meritxell Ventura-Cots
- Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain
| | - Jordi Llaneras
- Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain
| | - Ariadna Rando-Segura
- Microbiology Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Xavier Forns
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Spain
| | - Sabela Lens
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Spain
| | - Martín Prieto
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain
| | - María García-Eliz
- Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain
| | - Arkaitz Imaz
- Infectious Diseases Department, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Francisco Rodríguez-Frías
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Pathology Unit, Departments of Biochemistry and Microbiology, Clinical Laboratories, Vall d'Hebron University Hospital, Spain
| | - Maria Buti
- Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain.
| | - Rafael Esteban
- Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain
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Franz A, Reuken PA, Guliyeva S, Rose M, Boden K, Stallmach A, Bruns T. Early ribavirin for hepatitis E virus infection in patients receiving immunosuppressive therapy: a retrospective, observational study. J Int Med Res 2023; 51:3000605231187941. [PMID: 37523153 PMCID: PMC10392516 DOI: 10.1177/03000605231187941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/01/2023] Open
Abstract
OBJECTIVE Hepatitis E virus (HEV) infections are common, self-limiting causes of acute viral hepatitis. This study aimed to analyze hepatic injury, viremia, and chronicity rates in patients with acute HEV infection receiving immunosuppressive (IS) therapy taking into account ribavirin treatment. METHODS In this retrospective, single-center, observational study, we analyzed the disease course of 25 non-cirrhotic patients receiving IS therapy who were diagnosed with acute HEV viremia. Forty-four patients with acute HEV viremia without IS therapy were controls. RESULTS Demographics, symptoms at presentation, and extrahepatic manifestations were not different between patients with and without IS therapy, but liver injury at presentation was less severe in patients with IS therapy. Among the patients with IS therapy, 18 (72%) received ribavirin for a median of 56 days. Sustained viral clearance was observed in 21 patients with IS therapy, whereas 3 patients relapsed after ribavirin, and 1 patient had viral persistence. Among patients with sustained viral clearance, there was a longer duration of viremia in patients with IS therapy than in those without. CONCLUSIONS In this cohort of non-cirrhotic patient with IS, early treatment with ribavirin for acute HEV infection did not improve viral clearance rates, but may have shortened the duration of viremia.
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Affiliation(s)
- Anika Franz
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Philipp A Reuken
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Sura Guliyeva
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Michael Rose
- Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany
| | - Katharina Boden
- Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany
- Dianovis GmbH, Greiz, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
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8
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Gabrielli F, Alberti F, Russo C, Cursaro C, Seferi H, Margotti M, Andreone P. Treatment Options for Hepatitis A and E: A Non-Systematic Review. Viruses 2023; 15:v15051080. [PMID: 37243166 DOI: 10.3390/v15051080] [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: 03/02/2023] [Revised: 04/27/2023] [Accepted: 04/27/2023] [Indexed: 05/28/2023] Open
Abstract
Hepatitis A and hepatitis E are relatively common causes of liver disease. Both viruses are mainly transmitted through the faecal-oral route and, consequently, most outbreaks occur in countries with poor sanitation. An important role of the immune response as the driver of liver injury is also shared by the two pathogens. For both the hepatitis A (HAV) and hepatitis E (HEV) viruses, the clinical manifestations of infection mainly consist of an acute disease with mild liver injury, which results in clinical and laboratory alterations that are self-limiting in most cases. However, severe acute disease or chronic, long-lasting manifestations may occur in vulnerable patients, such as pregnant women, immunocompromised individuals or those with pre-existing liver disease. Specifically, HAV infection rarely results in fulminant hepatitis, prolonged cholestasis, relapsing hepatitis and possibly autoimmune hepatitis triggered by the viral infection. Less common manifestations of HEV include extrahepatic disease, acute liver failure and chronic HEV infection with persistent viraemia. In this paper, we conduct a non-systematic review of the available literature to provide a comprehensive understanding of the state of the art. Treatment mainly consists of supportive measures, while the available evidence for aetiological treatment and additional agents in severe disease is limited in quantity and quality. However, several therapeutic approaches have been attempted: for HAV infection, corticosteroid therapy has shown outcome improvement, and molecules, such as AZD 1480, zinc chloride and heme oxygenase-1, have demonstrated a reduction in viral replication in vitro. As for HEV infection, therapeutic options mainly rely on the use of ribavirin, and some studies utilising pegylated interferon-alpha have shown conflicting results. While a vaccine for HAV is already available and has led to a significant reduction in the prevalence of the disease, several vaccines for HEV are currently being developed, with some already available in China, showing promising results.
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Affiliation(s)
- Filippo Gabrielli
- Postgraduate School of Internal Medicine, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Department of Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Francesco Alberti
- Postgraduate School of Internal Medicine, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Cristina Russo
- Postgraduate School of Internal Medicine, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Carmela Cursaro
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Hajrie Seferi
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Marzia Margotti
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Pietro Andreone
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Postgraduate School of Allergology and Clinical Immunology, University of Modena and Reggio Emilia, 41126 Modena, Italy
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9
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Hui W, Wei L. Treatment of Hepatitis E. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:215-226. [PMID: 37223869 DOI: 10.1007/978-981-99-1304-6_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Hepatitis E virus (HEV) infections are the most common cause of acute hepatitis, but they can also take a chronic course. There is no specific therapy for acute hepatitis, and current treatment is supportive. Choosing ribavirin as the first-line therapy for chronic HEV is advisable, especially immunosuppressed individuals. Moreover, ribavirin therapy in the acute phase of infection provides major benefits for those at high risk of acute liver failure (ALF)/acute-on-chronic liver failure (ACLF). Pegylated interferon α has been used successfully for treatment of hepatitis E but is associated with major side effects. Cholestasis is one of the most common, but devastating, manifestations in hepatitis E. Current therapy for HEV aims to treat symptoms. Therapy generally involves several measures, such as vitamins, albumin, and plasma for supporting treatment, symptomatic treatment for cutaneous pruritus, ursodeoxycholic acid, Obeticholic acid, S-adenosylmethionine, etc. for removing jaundice. HEV infection during pregnancy and patients with underlying liver disease may develop liver failure. For these patients, active monitoring, standard care, and supportive treatment are the foundations. Ribavirin has successfully been used to prevent liver transplantation (LT). Prevention and treatment of complications are important for treatment of liver failure. Liver support devices are intended to support liver function until such time as native liver function recovers, or until LT. LT is widely considered as irreplaceable and definitive treatment for liver failure, particularly for patients who do not improve with supportive measures to sustain life.
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Affiliation(s)
- Wei Hui
- Chronic Disease Management Center, Youan Hospital, Capital Medical University, Beijing, China
| | - Linlin Wei
- The Second Department of Liver Disease Center, Youan Hospital, Capital Medical University, Beijing, China.
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10
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MADUREIRA S, SOARES N, LINO R, ALMEIDA C, CEIA F, SILVA-PINTO A, ALBUQUERQUE I, ALMEIDA J. Ribavirin for severe acute hepatitis E virus infection. GAZZETTA MEDICA ITALIANA ARCHIVIO PER LE SCIENZE MEDICHE 2022. [DOI: 10.23736/s0393-3660.21.04605-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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11
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Nagra N, Kozarek RA, Burman BE. Therapeutic Advances in Viral Hepatitis A-E. Adv Ther 2022; 39:1524-1552. [PMID: 35220557 DOI: 10.1007/s12325-022-02070-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 01/31/2022] [Indexed: 11/25/2022]
Abstract
Viral hepatitis remains a significant global health problem. All forms of viral hepatitis A through E (A-E) can lead to acute symptomatic infection, while hepatitis B and C can lead to chronic infection associated with significant morbidity and mortality related to progression to cirrhosis, end-stage-liver disease, and liver cancer. Viral hepatitis occurs worldwide, though certain regions are disproportionately affected. We now, remarkably, have highly effective curative regimens for hepatitis C, and safe and tolerable medications to suppress hepatitis B activity, and to prevent liver damage and slow disease progression. We have effective vaccines for hepatitis A and B which provide long-lasting immunity, while improved sanitation and awareness can curb outbreaks of hepatitis A and E. However, more effective and available preventive and curative strategies are needed to achieve global eradication of viral hepatitis. This review provides an overview of the epidemiology, transmission, diagnosis, and clinical features of each viral hepatitis with a primary focus on current and future therapeutic and curative options.
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Affiliation(s)
- Navroop Nagra
- Department of Gastroenterology, University of Louisville, Louisville, KY, 40202, USA
| | - Richard A Kozarek
- Center for Digestive Health, Virginia Mason Franciscan Health, 1100 9th Ave., Seattle, WA, 98101, USA
| | - Blaire E Burman
- Center for Digestive Health, Virginia Mason Franciscan Health, 1100 9th Ave., Seattle, WA, 98101, USA.
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12
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Liang Z, Shu J, He Q, Zhang F, Dai L, Wang L, Lu F, Wang L. High dose sofosbuvir and sofosbuvir-plus-ribavirin therapy inhibit Hepatitis E Virus (HEV) replication in a rabbit model for acute HEV infection. Antiviral Res 2022; 199:105274. [PMID: 35247472 DOI: 10.1016/j.antiviral.2022.105274] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 02/23/2022] [Accepted: 02/28/2022] [Indexed: 12/14/2022]
Abstract
Hepatitis E virus (HEV) is an important cause of viral hepatitis worldwide and there is currently no FDA-approved anti-HEV drug. The commonly used drug ribavirin (RBV) could not achieve viral clearance in all patients and can induce drug resistance. Recent studies showed sofosbuvir (SOF) can inhibit HEV replication in vitro and has add-on effect when combined with RBV, but the effect of SOF against HEV infection remains controversial and the dosage of SOF warrants further exploration. In this study, a rabbit model for acute HEV infection was used to evaluate the effect of SOF at different doses against HEV genotype 3 and 4, and to compare the antiviral effect of SOF-plus-RBV therapy with RBV monotherapy. Virological parameters on fecal, serological and intrahepatic level were tested by real-time PCR and ELISA. Liver function tests and histopathological assays were performed. Both 200 mg/d and 300 mg/d SOF treatment inhibits HEV replication with relieved liver inflammation and declined levels of fecal HEV RNA, viremia and antigenemia. 300 mg/d SOF eliminated HEV replication while a short viral rebound was observed after 200 mg/d SOF treatment. The SOF-plus-RBV therapy also showed stronger anti-HEV effect than RBV monotherapy. Our study suggests that high dose of SOF showed better anti-HEV effect in the rabbit model. Moreover, the de novo SOF-plus-RBV therapy which eliminated acute HEV infection more efficiently than RBV monotherapy may serve as an alternative treatment strategy.
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Affiliation(s)
- Zhaochao Liang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Jingyi Shu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Qiyu He
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Fan Zhang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Lizhong Dai
- Peking University-Sansure Biotech Joint Laboratory of Molecular Medicine, Peking University, Beijing, China
| | - Ling Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
| | - Fengmin Lu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Peking University-Sansure Biotech Joint Laboratory of Molecular Medicine, Peking University, Beijing, China.
| | - Lin Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Peking University-Sansure Biotech Joint Laboratory of Molecular Medicine, Peking University, Beijing, China.
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13
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Raji YE, Toung OP, Taib NM, Sekawi ZB. Hepatitis E Virus: An emerging enigmatic and underestimated pathogen. Saudi J Biol Sci 2022; 29:499-512. [PMID: 35002446 PMCID: PMC8716866 DOI: 10.1016/j.sjbs.2021.09.003] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 08/31/2021] [Accepted: 09/05/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is an RNA virus causing hepatitis E disease. The virus is of one serotype but has diverse genotypes infecting both humans and animals. Based on evidence from seroprevalence studies, about 2 billion people are estimated to have been infected with HEV globally. HEV, therefore, poses a significant public health and economic challenge worldwide. HEV was discovered in the 1980s and was traced back to the 1955 - 1956 outbreak of hepatitis that occurred in India. Subsequently, several HEV epidemics involving thousands of individuals have occurred nearly annually in different countries in Asia and Africa. Initially, the virus was thought to be only enterically transmitted, and endemic in developing countries. Due to the environmental hygiene and sanitation challenges in those parts of the world. However, recent studies have suggested otherwise with the report of autochthonous cases in industrialised countries with no history of travel to the so-called endemic countries. Thus, suggesting that HEV has a global distribution with endemicity in both developing and industrialised nations. Studies have also revealed that HEV has multiple risk factors, and modes of transmission as well as zoonotic potentials. Additionally, recent findings have shown that HEV leads to severe disease, particularly among pregnant women. In contrast to the previous narration of a strictly mild and self-limiting infection. Studies have likewise demonstrated chronic HEV infection among immunocompromised persons. Consequent to these recent discoveries, this pathogen is considered a re - emerging virus, particularly in the developed nations. However, despite the growing public health challenges of this pathogen, the burden is still underestimated. The underestimation is often attributed to poor awareness among clinicians and a lack of routine checks for the disease in the hospitals. Thus, leading to misdiagnosis and underdiagnosis. Hence, this review provides a concise overview of epidemiology, diagnosis, and prevention of hepatitis E.
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Affiliation(s)
- Yakubu Egigogo Raji
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 1, Malaysia
- Faculty of Natural and Applied Sciences Ibrahim Badamasi Babangida University, Lapai, Nigeria
| | - Ooi Peck Toung
- Department of Veterinary Clinical Studies Faculty of Veterinary Medicine, Universiti Putra Malaysia 2, Malaysia
| | - Niazlin Mohd Taib
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 1, Malaysia
| | - Zamberi Bin Sekawi
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 1, Malaysia
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14
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Lhomme S, Abravanel F, Cintas P, Izopet J. Hepatitis E Virus Infection: Neurological Manifestations and Pathophysiology. Pathogens 2021; 10:pathogens10121582. [PMID: 34959537 PMCID: PMC8705630 DOI: 10.3390/pathogens10121582] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 11/30/2021] [Accepted: 12/01/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is the first cause of viral hepatitis in the world. While the water-borne HEV genotypes 1 and 2 are found in developing countries, HEV genotypes 3 and 4 are endemic in developed countries due to the existence of animal reservoirs, especially swine. An HEV infection produces many extra-hepatic manifestations in addition to liver symptoms, especially neurological disorders. The most common are neuralgic amyotrophy or Parsonage–Turner syndrome, Guillain–Barré syndrome, myelitis, and encephalitis. The pathophysiology of the neurological injuries due to HEV remains uncertain. The immune response to the virus probably plays a role, but direct virus neurotropism could also contribute to the pathophysiology. This review describes the main neurological manifestations and their possible pathogenic mechanisms.
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Affiliation(s)
- Sébastien Lhomme
- Infinity, Université Toulouse, CNRS, INSERM, UPS, 31300 Toulouse, France; (F.A.); (J.I.)
- Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, 31300 Toulouse, France
- Correspondence: ; Tel.: +33-(0)-5-67-69-04-24
| | - Florence Abravanel
- Infinity, Université Toulouse, CNRS, INSERM, UPS, 31300 Toulouse, France; (F.A.); (J.I.)
- Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, 31300 Toulouse, France
| | - Pascal Cintas
- Service de Neurologie, Hôpital Purpan, CHU Toulouse, 31300 Toulouse, France;
| | - Jacques Izopet
- Infinity, Université Toulouse, CNRS, INSERM, UPS, 31300 Toulouse, France; (F.A.); (J.I.)
- Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, 31300 Toulouse, France
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15
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García-Cortés M, Ortega-Alonso A, Andrade RJ. Safety of treating acute liver injury and failure. Expert Opin Drug Saf 2021; 21:191-203. [PMID: 34254839 DOI: 10.1080/14740338.2021.1955854] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Acute liver injury and progression to acute liver failure can be life-threatening conditions that require prompt careful clinical assessment and therapeutic management. AREAS COVERED The aim of this article is to review the safety and side effect profile of pharmacological therapies used in the treatment of acute liver injury with specific focus on hepatic toxicity. We performed an extensive literature search with the terms 'acute liver injury,' 'acute liver failure,' 'therapy,' 'safety,' 'adverse reactions' and 'drug induced liver injury.' A thorough discussion of the main drugs and devices used in patients with acute liver injury and acute liver failure, its safety profile and the management of complications associated to therapy of these conditions is presented. EXPERT OPINION Several pharmacological approaches are used in acute liver injury and acute liver failure in an empirical basis. Whilst steroids are frequently tried in serious drug-induced liver injury there is concern on a potential harmful effect of these agents because of the higher mortality in patients receiving the drug; hence, statistical approaches such as propensity score matching might help resolve this clinical dilemma. Likewise, properly designed clinical trials using old and new drugs for subjects with serious drug-induced liver injury are clearly needed.
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Affiliation(s)
- Miren García-Cortés
- Servicio De Aparato Digestivo, Instituto De Investigación Biomédica De Málaga-IBIMA. Hospital Universitario Virgen De La Victoria, Universidad De Málaga, Centro De Investigación Biomédica En Red De Enfermedades Hepáticas Y Digestivas CIBERehd, Málaga, Spain
| | - Aida Ortega-Alonso
- Servicio De Aparato Digestivo, Instituto De Investigación Biomédica De Málaga-IBIMA. Hospital Universitario Virgen De La Victoria, Universidad De Málaga, Centro De Investigación Biomédica En Red De Enfermedades Hepáticas Y Digestivas CIBERehd, Málaga, Spain
| | - Raúl J Andrade
- Servicio De Aparato Digestivo, Instituto De Investigación Biomédica De Málaga-IBIMA. Hospital Universitario Virgen De La Victoria, Universidad De Málaga, Centro De Investigación Biomédica En Red De Enfermedades Hepáticas Y Digestivas CIBERehd, Málaga, Spain
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16
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Effective treatment of acute hepatitis E by ribavirin in a patient complicated with renal impairment: a case report. JOURNAL OF PHARMACY PRACTICE AND RESEARCH 2021. [DOI: 10.1002/jppr.1719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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17
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Almeida PH, Matielo CEL, Curvelo LA, Rocco RA, Felga G, Della Guardia B, Boteon YL. Update on the management and treatment of viral hepatitis. World J Gastroenterol 2021; 27:3249-3261. [PMID: 34163109 PMCID: PMC8218370 DOI: 10.3748/wjg.v27.i23.3249] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/11/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023] Open
Abstract
This review aims to summarize the current evidence on the treatment of viral hepatitis, focusing on its clinical management. Also, future treatment options and areas of potential research interest are detailed. PubMed and Scopus databases were searched for primary studies published within the last ten years. Keywords included hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus, hepatitis D virus (HDV), hepatitis E virus, and treatment. Outcomes reported in the studies were summarized, tabulated, and synthesized. Significant advances in viral hepatitis treatment were accomplished, such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A, hepatitis B, and hepatitis E vaccination. Drugs that cure hepatitis B, going beyond viral suppression, are so far unavailable; however, targeted antiviral drugs against HBV (immunomodulatory therapies and gene silencing technologies) are promising approaches to eradicating the virus. Ultimately, high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health systems. The development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B, albeit further investigation is required. Novel therapeutic options targeting HDV life cycle are currently under clinical investigation.
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Affiliation(s)
| | - Celso E L Matielo
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Lilian A Curvelo
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Rodrigo A Rocco
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Guilherme Felga
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | | | - Yuri L Boteon
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
- Instituto Israelita de Ensino e Pesquisa Albert Einstein, Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo 05652-900, Brazil
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18
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Jha AK, Kumar G, Dayal VM, Ranjan A, Suchismita A. Neurological manifestations of hepatitis E virus infection: An overview. World J Gastroenterol 2021; 27:2090-2104. [PMID: 34025066 PMCID: PMC8117739 DOI: 10.3748/wjg.v27.i18.2090] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 02/27/2021] [Accepted: 04/05/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is an important cause of repeated waterborne outbreaks of acute hepatitis. Recently, several extrahepatic manifestations (EHMs) have been described in patients with HEV infection. Of these, neurological disorders are the most common EHM associated with HEV. The involvement of both the peripheral nervous system and central nervous system can occur together or in isolation. Patients can present with normal liver function tests, which can often be misleading for physicians. There is a paucity of data on HEV-related neurological manifestations; and these data are mostly described as case reports and case series. In this review, we analyzed data of 163 reported cases of HEV-related neurological disorders. The mechanisms of pathogenesis, clinico-demographic profile, and outcomes of the HEV-related neurological disorders are described in this article. Nerve root and plexus disorder were found to be the most commonly reported disease, followed by meningoencephalitis.
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Affiliation(s)
- Ashish Kumar Jha
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Patna 800014, India
| | - Gaurav Kumar
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Patna 800014, India
| | - Vishwa Mohan Dayal
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Patna 800014, India
| | - Abhay Ranjan
- Department of Neurology, Indira Gandhi Institute of Medical Sciences, Patna 800014, India
| | - Arya Suchismita
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, Basant Kunj 110070, New Delhi, India
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19
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Belei O, Ancusa O, Mara A, Olariu L, Amaricai E, Folescu R, Zamfir CL, Gurgus D, Motoc AG, Stânga LC, Strat L, Marginean O. Current Paradigm of Hepatitis E Virus Among Pediatric and Adult Patients. Front Pediatr 2021; 9:721918. [PMID: 34660485 PMCID: PMC8515027 DOI: 10.3389/fped.2021.721918] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 08/31/2021] [Indexed: 12/26/2022] Open
Abstract
Hepatitis E virus (HEV) infection is a polymorphic condition, present throughout the world and involving children and adults. Multiple studies over the last decade have contributed to a better understanding of the natural evolution of this infection in various population groups, several reservoirs and transmission routes being identified. To date, acute or chronic HEV-induced hepatitis has in some cases remained underdiagnosed due to the lower accuracy of serological tests and due to the evolutionary possibility with extrahepatic manifestations. Implementation of diagnostic tests based on nucleic acid analysis has increased the detection rate of this disease. The epidemiological and clinical features of HEV hepatitis differ depending on the geographical areas studied. HEV infection is usually a self-limiting condition in immunocompetent patients, but in certain categories of vulnerable patients it can induce a sudden evolution toward acute liver failure (pregnant women) or chronicity (immunosuppressed patients, post-transplant, hematological, or malignant diseases). In acute HEV infections in most cases supportive treatment is sufficient. In patients who develop chronic hepatitis with HEV, dose reduction of immunosuppressive medication should be the first therapeutic step, especially in patients with transplant. In case of unfavorable response, the initiation of antiviral therapy is recommended. In this review, the authors summarized the essential published data related to the epidemiological, clinical, paraclinical, and therapeutic aspects of HEV infection in adult and pediatric patients.
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Affiliation(s)
- Oana Belei
- First Pediatric Clinic, Disturbance of Growth and Development on Children Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Oana Ancusa
- Fifth Department of Internal Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Adelina Mara
- Department of Internal Medicine, Emergency City Hospital, Timisoara, Romania
| | - Laura Olariu
- First Pediatric Clinic, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Elena Amaricai
- Department of Rehabilitation Physical Medicine and Rheumatology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Roxana Folescu
- Department of Balneology, Medical Recovery and Rheumatology, Family Discipline, Center for Preventive Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Carmen Lacramioara Zamfir
- Department of Morpho-Functional Sciences I, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Daniela Gurgus
- Department of Balneology, Medical Recovery and Rheumatology, Family Discipline, Center for Preventive Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Andrei G Motoc
- Department of Anatomy and Embriology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Livia Claudia Stânga
- Department of Microbiology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Liliana Strat
- Department of Mother and Child Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Otilia Marginean
- First Pediatric Clinic, Disturbance of Growth and Development on Children Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
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20
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Aslan AT, Balaban HY. Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment. World J Gastroenterol 2020; 26:5543-5560. [PMID: 33071523 PMCID: PMC7545399 DOI: 10.3748/wjg.v26.i37.5543] [Citation(s) in RCA: 105] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 08/11/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023] Open
Abstract
The hepatitis E virus (HEV) is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s. Globally, it is one of the most frequent causes of acute viral hepatitis. The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus. Among the eight different genotypes identified to date, HEV genotype 1 (HEV1), HEV2, HEV3, and HEV4 are the most frequent genotypes causing infections in humans. HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies. They are also responsible for severe hepatitis in pregnant patients and infants. In contrast, HEV3 and HEV4 are zoonotic, and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals. Their main reservoir is the pig, and they are mostly encountered in developed countries. The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women, infants, older people, immunocompromised individuals, patients with underlying chronic liver diseases, and workers that come into close contact with HEV-infected animals. In the clinical perspective, HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis, acute-on-chronic liver disease, chronic hepatitis, cirrhosis, and liver failure. Although HEV mainly results in acute self-limiting infection, chronic HEV infection may occur among immunocompromised patients (e.g., solid-organ transplant recipients). Additionally, HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade, although the causal link for many of them still needs to be proven. Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success. However, ribavirin is contraindicated in pregnant patients, and interferon-alpha cannot be used in most transplant recipients. Therefore, there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirin-resistant HEV. In this review article, a literature search using PubMed and MEDLINE databases was performed, up to March 2020. Only the articles published in English were reviewed.
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Affiliation(s)
| | - Hatice Yasemin Balaban
- Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey
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Nasir M, Wu GY. HEV and HBV Dual Infection: A Review. J Clin Transl Hepatol 2020; 8:313-321. [PMID: 33083255 PMCID: PMC7562801 DOI: 10.14218/jcth.2020.00030] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 05/29/2020] [Accepted: 06/07/2020] [Indexed: 12/17/2022] Open
Abstract
Hepatitis E virus (HEV) is a global health problem, affecting about 20 million people worldwide. There is significant overlap of hepatitis B virus (HBV) and HEV endemicity in many Asian countries where dual infections with HEV and HBV can occur. Though the clinical course of HEV is largely self-limited, HEV superinfection in patients with chronic hepatitis B (CHB) can result in acute exacerbation of underlying CHB. HEV superinfection in patients with CHB-related cirrhosis has been identified as a risk factor for decompensated cirrhosis and an independent predictor of mortality. Whereas acute HEV infection in pregnancy can cause fulminant liver failure, the few studies on pregnant patients with dual HBV and HEV infection have shown a subclinical course. Immunosuppression is a risk factor for the development of chronic HEV infection, which can be managed by decreasing the dose of immune-suppressants and administering ribavirin. Vaccination for HEV has been developed and is in use in China but its efficacy in patients with CHB has yet to be established in the USA. In this review, we appraise studies on dual infection with HEV and HBV, including the effect of HEV superinfection and coinfection in CHB, management strategies used and the role of active vaccination in the prevention of HEV.
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Affiliation(s)
- Myra Nasir
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- Correspondence to: Myra Nasir, Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA. Tel: +1-860-470-6616, E-mail:
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
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Abstract
A 21-year-old man from India presented with acute hepatitis associated with a 1-week history of abdominal pain, pruritus, and dark urine. Over a 7-day admission, the patient's acute hepatitis evolved into acute liver failure with low-grade encephalopathy, markedly elevated transaminases, bilirubin, and impaired hepatic synthetic function. He was eventually diagnosed with acute hepatitis E virus (HEV) and was transitioned to supportive management. Acute HEV is a rare cause of acute liver failure. Hence, this case highlights the importance of early consideration of HEV in all patients with acute hepatitis who have originated from endemic regions.
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Affiliation(s)
- Timothy Phan
- Department of Gastroenterology, Monash Health, Clayton, Melbourne, Victoria, Australia
| | - Christopher Desmond
- Department of Gastroenterology, Monash Health, Clayton, Melbourne, Victoria, Australia
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Istrate A, Rădulescu AL. A comparison of hepatitis E and A in a teaching hospital in Northwestern Romania. Acute hepatitis E - a mild disease? Med Pharm Rep 2020; 93:30-38. [PMID: 32133444 PMCID: PMC7051815 DOI: 10.15386/mpr-1487] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 11/20/2019] [Accepted: 12/09/2019] [Indexed: 12/13/2022] Open
Abstract
Background and aims The incidence of locally acquired hepatitis E has increased in recent years across Europe. There are only few data on hepatitis E in Romania. The purpose of our research was to describe and compare hepatitis E and hepatitis A in adult patients. Methods We included all consecutive adult patients with hepatitis E and hepatitis A admitted to the Teaching Hospital of Infectious Diseases, Cluj-Napoca, Romania between January 2017 and August 2019. Results Hepatitis E incidence increased in 2018–2019 compared to 2017. The average age in hepatitis E (n=48) patients was 50.6 versus 39.1 years in hepatitis A (n=152, not including 262 minors) and two-thirds of the patients in both groups were men. Compared to hepatitis A, patients with hepatitis E presented significantly less modified AST and ALT, bilirubin, prothrombin index and INR levels. We found more comorbidities in hepatitis E patients adjusted for age and gender. Severe forms were found in 5 (3.3%) hepatitis A patients, compared to 12 (25%) of hepatitis E patients, of which 3 died. Ribavirin treatment was considered in 9 patients with acute-on-chronic hepatitis E, immunosuppression, cancers or neurological manifestations, showing good results. Conclusions We observed an increased number of hepatitis E cases. Although laboratory results were less modified compared to hepatitis A, we found a higher number of severe hepatitis E cases. Ribavirin treatment seems to be beneficial in patients with preexisting conditions.
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Affiliation(s)
- Alexandru Istrate
- Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.,Department of Epidemiology, Clinical Hospital of Infectious Diseases, Cluj-Napoca, Romania
| | - Amanda Lelia Rădulescu
- Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.,Department of Epidemiology, Clinical Hospital of Infectious Diseases, Cluj-Napoca, Romania
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Lhomme S, Marion O, Abravanel F, Izopet J, Kamar N. Clinical Manifestations, Pathogenesis and Treatment of Hepatitis E Virus Infections. J Clin Med 2020; 9:E331. [PMID: 31991629 PMCID: PMC7073673 DOI: 10.3390/jcm9020331] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 01/14/2020] [Accepted: 01/22/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis throughout the world. Most infections are acute but they can become chronic in immunocompromised patients, such as solid organ transplant patients, patients with hematologic malignancy undergoing chemotherapy and those with a human immunodeficiency virus (HIV) infection. Extra-hepatic manifestations, especially neurological and renal diseases, have also been described. To date, four main genotypes of HEV (HEV1-4) were described. HEV1 and HEV2 only infect humans, while HEV3 and HEV4 can infect both humans and animals, like pigs, wild boar, deer and rabbits. The real epidemiology of HEV has been underestimated because most infections are asymptomatic. This review focuses on the recent advances in our understanding of the pathophysiology of acute HEV infections, including severe hepatitis in patients with pre-existing liver disease and pregnant women. It also examines the mechanisms leading to chronic infection in immunocompromised patients and extra-hepatic manifestations. Acute infections are usually self-limiting and do not require antiviral treatment. Conversely, a chronic HEV infection can be cleared by decreasing the dose of immunosuppressive drugs or by treating with ribavirin for 3 months. Nevertheless, new drugs are needed for those cases in which ribavirin treatment fails.
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Affiliation(s)
- Sébastien Lhomme
- Virology Laboratory, National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France; (F.A.); (J.I.)
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
| | - Olivier Marion
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
- Department of Nephrology and Organs Transplantation, Toulouse Rangueil University Hospital, 31400 Toulouse, France
| | - Florence Abravanel
- Virology Laboratory, National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France; (F.A.); (J.I.)
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
| | - Jacques Izopet
- Virology Laboratory, National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France; (F.A.); (J.I.)
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
| | - Nassim Kamar
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
- Department of Nephrology and Organs Transplantation, Toulouse Rangueil University Hospital, 31400 Toulouse, France
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Wenter C, Borena W, Oberhuber G, Graziadei I. Acute liver failure in immunocompetent patients infected with hepatitis E. Wien Klin Wochenschr 2019; 131:442-445. [PMID: 31493102 PMCID: PMC6748887 DOI: 10.1007/s00508-019-01547-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 08/17/2019] [Indexed: 01/10/2023]
Abstract
In almost all immunocompetent patients an acute hepatitis E virus (HEV) infection is clinically silent with spontaneous viral clearance. So far, only a very small number of severe acute HEV infections have been described. This article reports the case of a 78-year-old immunocompetent, diabetic patient, who presented with a symptomatic acute HEV genotype (GT) 3 infection and that progressed to acute liver failure. After starting with an antiviral therapy with ribavirin, the HEV viral load rapidly decreased with a significant improvement of the laboratory parameters as well as a clinical amelioration of the patient. The treatment was continued for 3 months and led to a complete resolution of this acute fulminant hepatitis E. Although the risk is almost negligible this article clearly demonstrates that an acute liver failure due to HEV should also be considered in immunocompetent patients, especially in older male individuals with diabetes mellitus.
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Affiliation(s)
- Christian Wenter
- Department of Internal Medicine, Academic Teaching Hospital Hall in Tirol, Milserstraße 10, 6060, Hall in Tirol, Austria
| | - Wegene Borena
- Division of Virology, Medical University Innsbruck, Innsbruck, Austria
| | - Georg Oberhuber
- INNPATH, Institute of Pathology, Tirol Kliniken Innsbruck, Innsbruck, Austria
| | - Ivo Graziadei
- Department of Internal Medicine, Academic Teaching Hospital Hall in Tirol, Milserstraße 10, 6060, Hall in Tirol, Austria. .,Medical University Innsbruck, Innsbruck, Austria.
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Horvatits T, Schulze Zur Wiesch J, Lütgehetmann M, Lohse AW, Pischke S. The Clinical Perspective on Hepatitis E. Viruses 2019; 11:E617. [PMID: 31284447 PMCID: PMC6669652 DOI: 10.3390/v11070617] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 06/26/2019] [Accepted: 07/03/2019] [Indexed: 12/17/2022] Open
Abstract
Every year, there are an estimated 20 million hepatitis E virus (HEV) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. HEV is largely circulating in the west and is associated with several hepatic and extrahepatic diseases. HEV Genotype 1 and 2 infections are waterborne and causative for epidemics in the tropics, while genotype 3 and 4 infections are zoonotic diseases and are mainly transmitted by ingestion of undercooked pork in industrialized nations. The clinical course of these infections differs: genotype 1 and 2 infection can cause acute illness and can lead to acute liver failure (ALF) or acute on chronic liver failure (ACLF) with a high mortality rate of 20% in pregnant women. In contrast, the majority of HEV GT-3 and -4 infections have a clinically asymptomatic course and only rarely lead to acute on chronic liver failure in elderly or patients with underlying liver disease. Immunosuppressed individuals infected with genotype 3 or 4 may develop chronic hepatitis E, which then can lead to life-threatening cirrhosis. Furthermore, several extra-hepatic manifestations affecting various organs have been associated with ongoing or previous HEV infections but the causal link for many of them still needs to be proven. There is no approved specific therapy for the treatment of acute or chronic HEV GT-3 or -4 infections but off-label use of ribavirin has been demonstrated to be safe and effective in the majority of patients. However, in approximately 15% of chronically HEV infected patients, cure is not possible.
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Affiliation(s)
- Thomas Horvatits
- Department of Medicine, University Medical Center Hamburg-Eppendorf, 22527 Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, 22527 Hamburg, Germany
| | - Julian Schulze Zur Wiesch
- Department of Medicine, University Medical Center Hamburg-Eppendorf, 22527 Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, 22527 Hamburg, Germany
| | - Marc Lütgehetmann
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, 22527 Hamburg, Germany
- Institute of Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, 22527 Hamburg, Germany
| | - Ansgar W Lohse
- Department of Medicine, University Medical Center Hamburg-Eppendorf, 22527 Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, 22527 Hamburg, Germany
| | - Sven Pischke
- Department of Medicine, University Medical Center Hamburg-Eppendorf, 22527 Hamburg, Germany.
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, 22527 Hamburg, Germany.
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Kamar N, Pischke S. Acute and Persistent Hepatitis E Virus Genotype 3 and 4 Infection: Clinical Features, Pathogenesis, and Treatment. Cold Spring Harb Perspect Med 2019; 9:cshperspect.a031872. [PMID: 29735575 DOI: 10.1101/cshperspect.a031872] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hepatitis E virus (HEV) genotype (gt)3 and 4 infections are prevalent in industrialized and high-income countries. Although most HEV gt3 and gt4 infections are clinically silent, acute infection may be symptomatic in some patients. In persons with underlying liver disease and in elderly men, HEV infections may present as acute or acute-on-chronic liver failure. Chronic hepatitis may develop in immunosuppressed individuals, including transplant recipients, human immunodeficiency virus (HIV)-infected patients, and persons with hematologic malignancy undergoing chemotherapy, and may progress to life-threatening liver cirrhosis. Extrahepatic manifestations of infection may include neurological and renal disease. Although there is no approved specific therapy for the treatment of acute or chronic HEV gt3 or gt4 infection, off-label use of ribavirin appears to be capable of eliminating chronic HEV infection, and may reduce disease severity in patients suffering from acute liver failure.
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Affiliation(s)
- Nassim Kamar
- Department of Nephrology and Organ Transplantation, Université Paul Sabatier, Toulouse 31059, France
| | - Sven Pischke
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany
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Althof N, Trojnar E, Böhm T, Burkhardt S, Carl A, Contzen M, Kilwinski J, Mergemeier S, Moor D, Mäde D, Johne R. Interlaboratory Validation of a Method for Hepatitis E Virus RNA Detection in Meat and Meat Products. FOOD AND ENVIRONMENTAL VIROLOGY 2019; 11:1-8. [PMID: 30465253 DOI: 10.1007/s12560-018-9360-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 11/12/2018] [Indexed: 05/25/2023]
Abstract
Increasing numbers of hepatitis E cases are currently recognized in many European countries. The zoonotic hepatitis E virus (HEV) genotype 3 mainly circulates in domestic pigs and wild boars, and can be transmitted to humans via consumption of insufficiently heated meat or meat products produced from those animals. Here, a detailed protocol for detection of HEV RNA in meat products is provided, which is based on the method originally described by Szabo et al. (Intl J Food Microbiol 215:149-156, 2015). It consists of a TRI Reagent®/chloroform-based food matrix homogenization, a silica bead-based RNA extraction and a real-time RT-PCR-based RNA detection. The method was further validated in a ring trial with nine independent laboratories using pork liver sausage samples artificially contaminated with different amounts of HEV. The results indicate sufficient sensitivity, specificity, and accuracy of the method for its broad future use in survey studies, routine food control or outbreak investigations.
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Affiliation(s)
- Nadine Althof
- German Federal Institute for Risk Assessment, Berlin, Germany
| | - Eva Trojnar
- German Federal Institute for Risk Assessment, Berlin, Germany
| | - Thomas Böhm
- Landesbetrieb Hessisches Landeslabor, Kassel, Germany
| | | | - Anja Carl
- Bayrisches Landesamt für Gesundheit und Lebensmittelsicherheit, Erlangen, Germany
| | - Matthias Contzen
- Chemisches und Veterinäruntersuchungsamt Stuttgart, Fellbach, Germany
| | - Jochen Kilwinski
- Chemisches und Veterinäruntersuchungsamt Westfalen, Arnsberg, Germany
| | | | - Dominik Moor
- Bundesamt für Lebensmittelsicherheit und Veterinärwesen, Bern, Switzerland
| | - Dietrich Mäde
- Landesamt für Verbraucherschutz Sachsen-Anhalt, Halle (Saale), Germany
| | - Reimar Johne
- German Federal Institute for Risk Assessment, Berlin, Germany.
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Dalton HR, Kamar N, Baylis SA, Moradpour D, Wedemeyer H, Negro F. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018; 68:1256-1271. [PMID: 29609832 DOI: 10.1016/j.jhep.2018.03.005] [Citation(s) in RCA: 415] [Impact Index Per Article: 59.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 03/09/2018] [Indexed: 02/08/2023]
Abstract
Infection with hepatitis E virus (HEV) is a significant cause of morbidity and mortality, representing an important global health problem. Our understanding of HEV has changed completely over the past decade. Previously, HEV was thought to be limited to certain developing countries. We now know that HEV is endemic in most high-income countries and is largely a zoonotic infection. Given the paradigm shift in our understanding of zoonotic HEV and that locally acquired HEV is now the commonest cause of acute viral hepatitis in many European countries, the focus of these Clinical Practice Guidelines will be on HEV genotype 3 (and 4).
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von Wulffen M, Westhölter D, Lütgehetmann M, Pischke S. Hepatitis E: Still Waters Run Deep. J Clin Transl Hepatol 2018; 6:40-47. [PMID: 29577031 PMCID: PMC5862998 DOI: 10.14218/jcth.2017.00030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Accepted: 08/19/2017] [Indexed: 12/11/2022] Open
Abstract
Hepatitis E is an infectious inflammatory disease of the liver caused by the hepatitis E virus (HEV), a single-stranded RNA virus. Today, it is estimated that there are more than 20 million HEV infections every year, leading to 3.3 million symptomatic cases and more than 56,000 deaths. For a long time it was believed that HEV was a travel-associated disease, endemic in developing countries with poor hygienic standards and unsafe water supply. However, over the past years, publications have demonstrated that autochthonous HEV infections in industrialized countries are far more common than previously thought. Awareness for HEV amongst health care practitioners in industrialized countries is still limited. This relatively rare disease is of great importance, especially in immunocompromised patients where it can cause chronic liver disease. This article comprehensively reviews current literature to give an overview on clinically important topics. It will focus on epidemiological aspects, acute and chronic HEV infection as well as extra-hepatic manifestations, diagnostic approach and treatment options. Furthermore, the article is concluded with a brief outlook on perspectives and urgent problems to be addressed in the future.
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Affiliation(s)
- Moritz von Wulffen
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Dirk Westhölter
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marc Lütgehetmann
- Institute for Medical Microbiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sven Pischke
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Shrestha A, P Gupta B, K Lama T. Current Treatment of Acute and Chronic Hepatitis E Virus Infection: Role of Antivirals. Euroasian J Hepatogastroenterol 2017; 7:73-77. [PMID: 29201777 PMCID: PMC5663779 DOI: 10.5005/jp-journals-10018-1216] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 11/25/2016] [Indexed: 12/16/2022] Open
Abstract
Hepatitis E virus (HEV) infection results in nearly 20 million new infections, resulting in 70,000 deaths globally each year. Previously thought as a disease limited to developing nations with poor sanitation and hygiene, it is increasingly recognized that even the most developed nations are not spared. A clear dichotomy in epidemiology of HEV is noted between developing and industrialized nations. The HEV genotypes 1 and 2 are common in Asia and Africa and are transmitted mainly by contaminated drinking water. Sporadic as well as large-scale epidemics of acute hepatitis have been noted with HEV genotype 1 infection in developing countries of Asia and Africa. On the contrary, HEV genotypes 3 and 4 are common in industrialized nations and unlike genotypes 1 and 2, they are transmitted by consumption of raw meat products, fruits, and blood transfusion. Large epidemics have not been reported with HEV genotypes 3 and 4 and manifestation is usually indolent, though severe acute hepatitis has been reported. How to cite this article: Shrestha A, Gupta BP, Lama TK. Current Treatment of Acute and Chronic Hepatitis E Virus Infection: Role of Antivirals. Euroasian J Hepato-Gastroenterol 2017;7(1):73-77.
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Affiliation(s)
| | - Birendra P Gupta
- Central Department of Biotechnology, Tribhuvan University, Kathmandu, Nepal
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van der Eijk AA, Pas SD, de Man RA. Hepatitis E virus: A potential threat for patients with liver disease and liver transplantation. Best Pract Res Clin Gastroenterol 2017. [PMID: 28624102 DOI: 10.1016/j.bpg.2017.03.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Immunocompromised patients are at risk of acquiring acute hepatitis E virus infection (HEV), leading to chronicity. Chronic HEV infection is associated with persistent viraemia, raised transaminase activity, histological features associated with chronic hepatitis and evidence of rapid development of cirrhosis. Extrahepatic manifestations have been associated with HEV. Most frequently reported are neurological disorders with predominantly involvement of the peripheral nervous system. In patients using immunosuppressive drugs antibody production is often delayed and HEV RNA detection is superior to serology to detect infection. Therapeutic options for chronic HEV includes tapering immunosuppressive and secondly ribavirin, pegylated interferon alpha (PEG-IFN). Present recommendation is to treat chronic HEV patients for 3 months, asses serum HEV RNA and stool HEV RNA and stop therapy if both are undetectable. Studies are required to determine which other antiviral agents than ribavirin and (PEG-)IFN are of clinical utility in treating HEV in the minority of patients who do not respond to ribavirin.
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Affiliation(s)
- Annemiek A van der Eijk
- Department of Viroscience, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
| | - Suzan D Pas
- Department of Viroscience, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
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Thodou V, Buechter M, Canbay A, Baba HA, Kalsch J, Gerken G, Kahraman A. De-Novo Autoimmune Hepatitis with Consecutive Acute Liver Failure Induced by Hepatitis E Infection: A Case Report. HEPATITIS MONTHLY 2017; 17. [DOI: 10.5812/hepatmon.40744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Brown A, Halliday JS, Swadling L, Madden RG, Bendall R, Hunter JG, Maggs J, Simmonds P, Smith DB, Vine L, McLaughlin C, Collier J, Bonsall D, Jeffery K, Dunachie S, Klenerman P, Izopet J, Kamar N, Dalton HR, Barnes E. Characterization of the Specificity, Functionality, and Durability of Host T-Cell Responses Against the Full-Length Hepatitis E Virus. Hepatology 2016; 64:1934-1950. [PMID: 27631819 PMCID: PMC5132006 DOI: 10.1002/hep.28819] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Revised: 07/13/2016] [Accepted: 08/17/2016] [Indexed: 12/19/2022]
Abstract
UNLABELLED The interplay between host antiviral immunity and immunopathology during hepatitis E virus (HEV) infection determines important clinical outcomes. We characterized the specificity, functionality, and durability of host T-cell responses against the full-length HEV virus and assessed a novel "Quantiferon" assay for the rapid diagnosis of HEV infection. Eighty-nine volunteers were recruited from Oxford, Truro (UK), and Toulouse (France), including 44 immune-competent patients with acute HEV infection, 18 HEV-exposed immunosuppressed organ-transplant recipients (8 with chronic HEV), and 27 healthy volunteers. A genotype 3a peptide library (616 overlapping peptides spanning open reading frames [ORFs] 1-3) was used in interferon-gamma (IFN-γ) T-cell ELISpot assays. CD4+ /CD8+ T-cell subsets and polyfunctionality were defined using ICCS and SPICE analysis. Quantification of IFN-γ used whole-blood stimulation with recombinant HEV-capsid protein in the QuantiFERON kit. HEV-specific T-cell responses were detected in 41/44 immune-competent HEV exposed volunteers (median magnitude: 397 spot-forming units/106 peripheral blood mononuclear cells), most frequently targeting ORF2. High-magnitude, polyfunctional CD4 and CD8+ T cells were detected during acute disease and maintained to 12 years, but these declined over time, with CD8+ responses becoming more monofunctional. Low-level responses were detectable in immunosuppressed patients. Twenty-three novel HEV CD4+ and CD8+ T-cell targets were mapped predominantly to conserved genomic regions. QuantiFERON testing demonstrated an inverse correlation between IFN-γ production and the time from clinical presentation, providing 100% specificity, and 71% sensitivity (area under the receiver operator characteristic curve of 0.86) for HEV exposure at 0.3 IU/mL. CONCLUSION Robust HEV-specific T-cell responses generated during acute disease predominantly target ORF2, but decline in magnitude and polyfunctionality over time. Defining HEV T-cell targets will be important for the investigation of HEV-associated autoimmune disease. (Hepatology 2016;64:1934-1950).
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Affiliation(s)
- Anthony Brown
- Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUnited Kingdom
| | - John S. Halliday
- Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUnited Kingdom,The Royal Melbourne HospitalMelbourneVictoriaAustralia
| | - Leo Swadling
- Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUnited Kingdom
| | | | | | | | - James Maggs
- Oxford University Hospitals NHS Foundation TrustOxfordUnited Kingdom
| | - Peter Simmonds
- Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUnited Kingdom,Centre for Immunity, Infection and Evolution, University of EdinburghUnited Kingdom
| | - Donald B. Smith
- Centre for Immunity, Infection and Evolution, University of EdinburghUnited Kingdom
| | - Louisa Vine
- The Royal Cornwall HospitalTruroUnited Kingdom
| | | | - Jane Collier
- Oxford University Hospitals NHS Foundation TrustOxfordUnited Kingdom
| | - David Bonsall
- Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUnited Kingdom
| | - Katie Jeffery
- Oxford University Hospitals NHS Foundation TrustOxfordUnited Kingdom
| | - Susanna Dunachie
- Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUnited Kingdom,Centre for Tropical Medicine & Global HealthUniversity of OxfordOxfordUnited Kingdom
| | - Paul Klenerman
- Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUnited Kingdom,Oxford University Hospitals NHS Foundation TrustOxfordUnited Kingdom,National Institute for Health Research (NIHR)Oxford Biomedical Research CentreOxfordUnited Kingdom
| | | | | | | | - Eleanor Barnes
- Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUnited Kingdom,Oxford University Hospitals NHS Foundation TrustOxfordUnited Kingdom,National Institute for Health Research (NIHR)Oxford Biomedical Research CentreOxfordUnited Kingdom
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Hartl J, Wehmeyer MH, Pischke S. Acute Hepatitis E: Two Sides of the Same Coin. Viruses 2016; 8:E299. [PMID: 27827877 PMCID: PMC5127013 DOI: 10.3390/v8110299] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Revised: 10/04/2016] [Accepted: 10/17/2016] [Indexed: 12/12/2022] Open
Abstract
The relevance of acute hepatitis E virus (HEV) infections has been underestimated for a long time. In the past, HEV infection had been interpreted falsely as a disease limited to the tropics until the relevance of autochthonous HEV infections in the Western world became overt. Due to increased awareness, the incidence of diagnosed autochthonous HEV infections (predominantly genotype 3) in industrialized countries has risen within the last decade. The main source of infections in industrialized countries seems to be infected swine meat, while infections with the tropical HEV genotypes 1 and 2 usually are mainly transmitted fecal-orally by contaminated drinking water. In the vast majority of healthy individuals, acute HEV infection is either clinically silent or takes a benign self-limited course. In patients who develop a symptomatic HEV infection, a short prodromal phase with unspecific symptoms is followed by liver specific symptoms like jaundice, itching, uncoloured stool and darkened urine. Importantly, tropical HEV infections may lead to acute liver failure, especially in pregnant women, while autochthonous HEV infections may lead to acute-on-chronic liver failure in patients with underlying liver diseases. Immunosuppressed individuals, such as transplant recipients or human immunodeficiency virus (HIV)-infected patients, are at risk for developing chronic hepatitis E, which may lead to liver fibrosis and cirrhosis in the long term. Importantly, specific treatment options for hepatitis E are not approved by the regulation authorities, but off-label ribavirin treatment seems to be effective in the treatment of chronic HEV-infection and may reduce the disease severity in patients suffering from acute liver failure.
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Affiliation(s)
- Johannes Hartl
- First Medical Department, University Medical Center Hamburg-Eppendorf, University Hospital Hamburg Eppendorf (UKE), 20246 Hamburg, Germany.
| | - Malte H Wehmeyer
- First Medical Department, University Medical Center Hamburg-Eppendorf, University Hospital Hamburg Eppendorf (UKE), 20246 Hamburg, Germany.
| | - Sven Pischke
- First Medical Department, University Medical Center Hamburg-Eppendorf, University Hospital Hamburg Eppendorf (UKE), 20246 Hamburg, Germany.
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Ji SB, Lee SS, Jung HC, Kim HJ, Kim HJ, Kim TH, Jung WT, Lee OJ, Song DH. A Korean patient with Guillain-Barré syndrome following acute hepatitis E whose cholestasis resolved with steroid therapy. Clin Mol Hepatol 2016; 22:396-399. [PMID: 27572076 PMCID: PMC5066380 DOI: 10.3350/cmh.2015.0039] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2015] [Revised: 12/10/2015] [Accepted: 12/16/2015] [Indexed: 01/12/2023] Open
Abstract
Autochthonous hepatitis E virus (HEV) is an emerging pathogen in developed countries, and several cases of acute HEV infection have been reported in South Korea. However, there have been no reports on HEV-associated Guillain-Barré syndrome (GBS) in Korea. We recently experienced the case of a 58-year-old Korean male with acute HEV infection after ingesting raw deer meat. Persistent cholestasis was resolved by the administration of prednisolone. At 2.5 months after the clinical presentation of HEV infection, the patient developed weakness of the lower limbs, and was diagnosed with GBS associated with acute hepatitis E. To our knowledge, this is the second report on supportive steroid therapy for persistent cholestasis due to hepatitis E, and the first report of GBS in a Korean patient with acute HEV infection.
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Affiliation(s)
- Sung Bok Ji
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Sang Soo Lee
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Hee Cheul Jung
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Hong Jun Kim
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Hyun Jin Kim
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Tae Hyo Kim
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Woon Tae Jung
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Ok Jae Lee
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Dae Hyun Song
- Department of Pathology, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
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Treatment of HEV Infection in Patients with a Solid-Organ Transplant and Chronic Hepatitis. Viruses 2016; 8:v8080222. [PMID: 27537905 PMCID: PMC4997584 DOI: 10.3390/v8080222] [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: 06/28/2016] [Revised: 07/30/2016] [Accepted: 08/09/2016] [Indexed: 12/19/2022] Open
Abstract
Hepatitis E virus (HEV) infection can cause hepatic and extra-hepatic manifestations. Treatment of HEV infection has been thoroughly studied in solid-organ-transplant patients who have developed a chronic HEV infection. In this review, we report on our current knowledge regarding treatment of HEV infection.
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Abstract
BACKGROUND Hepatitis E virus (HEV) is endemic in large parts of the developing world. Waterborne transmission of genotypes 1 or 2 commonly causes acute hepatitis, which is usually self-limited in healthy individuals. In addition, acute HEV infections also occur outside endemic areas, mostly related to foodborne transmission of HEV genotype 3. A growing number of publications in the last decade have reported chronic infection progressing to cirrhosis in immunosuppressed patients. It has also been suggested that HEV transmission may occur via contaminated blood products. This publication aims to provide recommendations for diagnosis, prevention, and treatment of HEV infection, particularly in children after solid organ transplantation. METHODS A systematic PubMed literature search on HEV infection from 1990 to January 2016 was performed focusing on pediatric studies. The existing body of evidence was reviewed and recommendations were agreed upon following discussion and unanimous agreement by all members of the ESPGHAN Hepatology Committee during a consensus meeting in January 2016. In the absence of randomized controlled studies these recommendations were considered to be expert opinions. KEY RECOMMENDATIONS Immunocompetent children with increased transaminases and/or extrahepatic manifestations should be considered for testing for evidence of HEV infection. Immunocompromised children with increased aminotransferases should be repeatedly tested for HEV and may require therapeutic intervention.
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40
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Pérez-Gracia MT, Suay-García B, García M, Mateos-Lindemann ML. Hepatitis E: latest developments in knowledge. Future Microbiol 2016; 11:789-808. [PMID: 27203841 DOI: 10.2217/fmb-2016-0012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Hepatitis E, caused by Hepatitis E virus (HEV), is a highly prevalent disease in developing countries. In developed nations, autochthonous HEV infections seem to be an emergent disease. Its clinical manifestations and epidemiology are well known for endemic countries. It has been confirmed that hepatitis E is a zoonosis and that parenteral transmission can also occur. The molecular mechanisms of HEV replication are not fully understood, mostly because there are no efficient cell culture systems. HEV can cause chronic hepatitis in organ transplant recipients and immunocompetent patients. Cases with fulminant hepatitis and other extrahepatic manifestations have also been reported. The diagnosis is based on serological studies and detection of HEV RNA in blood and feces. Treatment with ribavirin and/or pegylated-IFN-α have proven to be successful in some cases. The recently approved/marketed vaccine is a good option in order to prevent this infection.
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Affiliation(s)
- M Teresa Pérez-Gracia
- Área de Microbiología, Departamento de Farmacia, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avenida Seminario s/n 46113, Moncada, Valencia, Spain
| | - Beatriz Suay-García
- Área de Microbiología, Departamento de Farmacia, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avenida Seminario s/n 46113, Moncada, Valencia, Spain
| | - Mario García
- Área de Microbiología, Departamento de Farmacia, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avenida Seminario s/n 46113, Moncada, Valencia, Spain
| | - M Luisa Mateos-Lindemann
- Unidad de Virología, Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Ctra. Colmenar Km 9,1, Madrid 28034, Spain
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41
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Perrin HB, Cintas P, Abravanel F, Gérolami R, d'Alteroche L, Raynal JN, Alric L, Dupuis E, Prudhomme L, Vaucher E, Couzigou P, Liversain JM, Bureau C, Vinel JP, Kamar N, Izopet J, Peron JM. Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E. Emerg Infect Dis 2016; 21:1928-34. [PMID: 26490255 PMCID: PMC4622229 DOI: 10.3201/eid2111.141789] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Neurologic disorders, mainly Guillain-Barré syndrome and Parsonage–Turner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barré syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection.
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Péron JM, Abravanel F, Guillaume M, Gérolami R, Nana J, Anty R, Pariente A, Renou C, Bureau C, Robic MA, Alric L, Vinel JP, Izopet J, Kamar N. Treatment of autochthonous acute hepatitis E with short-term ribavirin: a multicenter retrospective study. Liver Int 2016; 36:328-33. [PMID: 26179015 DOI: 10.1111/liv.12911] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 07/02/2015] [Indexed: 12/24/2022]
Abstract
BACKGROUND & AIMS Hepatitis E virus (HEV) genotypes 3 and 4 cause sporadic cases of infection in developed countries. Being elderly and having an underlying liver disease are the main risk factors for death in this population. Chronic infection has been described in immunocompromised patients. Ribavirin is now the antiviral treatment of choice in solid-organ-transplant recipients with chronic HEV infection. We hypothesized that early short-term treatment of acute HEV infection may be useful for patients with risk factors or undergoing chemotherapy. METHODS Between July 2010 and January 2014, 21 patients diagnosed with acute HEV infection were treated with ribavirin, at 600-800 mg/day for up to 3 months. All serum samples were positive for HEV RNA. RESULTS Nine patients were treated for severe hepatitis. Six patients were aged >70 years. Four patients were receiving an immunosuppressive therapy for an autoimmune disease and two patients were undergoing chemotherapy for a malignancy. Two patients received a fixed-dose regimen. For all other patients, ribavirin was stopped when HEV became undetectable in the serum. The median duration of ribavirin treatment was 26 days. Two patients developed severe anaemia. Two patients with encephalopathy died. One patient relapsed transiently. All patients were cleared of HEV and regained normalized liver-enzyme levels. Immunosuppressive treatment and chemotherapy could be resumed. CONCLUSIONS Treatment of acute HEV infection using ribavirin seems safe and effective. Short-term treatment tailored to viraemia may be the best regimen for this indication.
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Affiliation(s)
- Jean Marie Péron
- Service d'Hépato-gastroentérologie, Hôpital Purpan, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier Toulouse III, Toulouse, France
| | - Florence Abravanel
- Laboratoire de Virologie, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier Toulouse III, INSERM, UMR 1043, Centre de Physiopathologie de Toulouse, Toulouse, France
| | - Maeva Guillaume
- Service d'Hépato-gastroentérologie, Hôpital Purpan, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier Toulouse III, Toulouse, France.,INSERM U1048, Institute of Metabolic and Cardiovascular Diseases I2MC, Université Paul Sabatier Toulouse III, Toulouse, France
| | - René Gérolami
- Service d'Hépato-gastroentérologie, Hôpital de la Conception, Centre Hospitalier Universitaire de Marseille, Université de Marseille, Marseille, France
| | - Jean Nana
- Service d'Hépato-gastroentérologie, Hôpital Purpan, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier Toulouse III, Toulouse, France
| | - Rodolphe Anty
- Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nice, Université de Nice-Sophia-Antipolis, INSERM U1065, Nice, France
| | - Alexandre Pariente
- Service d'Hépato-gastroentérologie, Centre Hospitalier de Pau, Pau, France
| | - Christophe Renou
- Service d'Hépato-gastroentérologie, Hôpital de Hyères, Hyères, France
| | - Christophe Bureau
- Service d'Hépato-gastroentérologie, Hôpital Purpan, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier Toulouse III, Toulouse, France
| | - Marie-Angèle Robic
- Service d'Hépato-gastroentérologie, Hôpital Purpan, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier Toulouse III, Toulouse, France
| | - Laurent Alric
- Service de Médecine Interne, Hôpital Purpan, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier Toulouse III, Toulouse, France
| | - Jean Pierre Vinel
- Service d'Hépato-gastroentérologie, Hôpital Purpan, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier Toulouse III, Toulouse, France
| | - Jacques Izopet
- Laboratoire de Virologie, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier Toulouse III, INSERM, UMR 1043, Centre de Physiopathologie de Toulouse, Toulouse, France
| | - Nassim Kamar
- Service de Néphrologie et transplantation d'organes, Hôpital Rangueil, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier Toulouse III, INSERM, UMR 1043, Toulouse, France
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Hui W, Wei L, Li Z, Guo X. Treatment of Hepatitis E. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 948:211-221. [PMID: 27738987 DOI: 10.1007/978-94-024-0942-0_12] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Hepatitis E virus (HEV) infections are the most common cause of acute hepatitis, but they can also take a chronic course. There is no specific therapy for acute hepatitis, and current treatment is supportive. Choosing ribavirin as the first-line therapy for chronic HEV is advisable, especially in solid organ transplant patients. Pegylated interferon-α has been used successfully for treatment of hepatitis E but is associated with major side effects. Cholestasis is one of the most common, but devastating, manifestations in hepatitis E. Current therapy for HEV aims to treat symptoms. Therapy generally involves several measures, such as vitamins for adequate nutrition, albumin and plasma for supporting treatment, symptomatic treatment for cutaneous pruritus, and ursodeoxycholic acid and S-adenosylmethionine, and Traditional Chinese medicine for removing jaundice. Patients with underlying liver disease may develop liver failure. For these patients, supportive treatment is the foundation. Ribavirin has successfully been used to prevent liver transplantation. Prevention and treatment of complications are important for treatment of liver failure. Liver support devices are intended to support liver function until such time as native liver function recovers or until liver transplantation. Liver transplantation is widely considered as irreplaceable and definitive treatment for acute-on-chronic liver failure, particularly for patients who do not improve with supportive measures to sustain life.
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Affiliation(s)
- Wei Hui
- Department of Liver Diseases Endocrine, Youan Hospital, Capital Medical University, No. 8 XitoutiaoYouanmenWai, Fengtai District, Beijing, 100069, China.
| | - Linlin Wei
- Department of Liver Diseases Endocrine, Youan Hospital, Capital Medical University, No. 8 XitoutiaoYouanmenWai, Fengtai District, Beijing, 100069, China
| | - Zhuo Li
- Beijing Institute of Liver Disease, No.8 Xitoutiao Youanmen Wai, Fengtai District, Beijing, 100069, China
| | - Xinhui Guo
- Department of Liver Diseases Endocrine, Youan Hospital, Capital Medical University, No. 8 XitoutiaoYouanmenWai, Fengtai District, Beijing, 100069, China
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Ramsay I, Snell L, Sharma V, O'Beirne J, Patch D, Marshall A, Imber C, Ijaz S, Dianne Irish, Westbrook RH. Liver transplantation for acute liver failure because of genotype 3 hepatitis E virus infection. Liver Transpl 2015; 21:1557-9. [PMID: 26178234 DOI: 10.1002/lt.24213] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Revised: 07/01/2015] [Accepted: 07/02/2015] [Indexed: 02/07/2023]
Affiliation(s)
- Isobel Ramsay
- Department of Virology, Royal Free London, NHS Foundation Trust, London, UK
| | - Luke Snell
- Department of Hepatology, Royal Free London, NHS Foundation Trust, London, UK
| | - Vikram Sharma
- Department of Hepatology, Royal Free London, NHS Foundation Trust, London, UK
| | - James O'Beirne
- Department of Hepatology, Royal Free London, NHS Foundation Trust, London, UK
| | - David Patch
- Department of Hepatology, Royal Free London, NHS Foundation Trust, London, UK
| | - Aileen Marshall
- Department of Hepatology, Royal Free London, NHS Foundation Trust, London, UK
| | - Charles Imber
- Department of Virology, Royal Free London, NHS Foundation Trust, London, UK
| | - Samreen Ijaz
- Infectious Diseases, Gastroenterology, Hepatology, Public Health England, London, UK
| | - Dianne Irish
- Department of Virology, Royal Free London, NHS Foundation Trust, London, UK
| | - Rachel H Westbrook
- Department of Hepatology, Royal Free London, NHS Foundation Trust, London, UK
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Szabo K, Trojnar E, Anheyer-Behmenburg H, Binder A, Schotte U, Ellerbroek L, Klein G, Johne R. Detection of hepatitis E virus RNA in raw sausages and liver sausages from retail in Germany using an optimized method. Int J Food Microbiol 2015; 215:149-56. [DOI: 10.1016/j.ijfoodmicro.2015.09.013] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Revised: 09/18/2015] [Accepted: 09/19/2015] [Indexed: 01/22/2023]
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Mengel AM, Stenzel W, Meisel A, Büning C. Hepatitis E-induced severe myositis. Muscle Nerve 2015; 53:317-20. [PMID: 26514272 DOI: 10.1002/mus.24959] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/28/2015] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Hepatitis E virus (HEV) is endemic in Asian and African countries but is rarely reported in Western countries. Although there are some prominent neurological manifestations, HEV is rarely recognized by neurologists. METHODS This is a case report of myositis induced by HEV. RESULTS We report the life-threatening case of a 57-year-old man with flaccid tetraparesis due to myositis, acute hepatitis, and renal failure caused by HEV infection. Muscle biopsy revealed scattered myofiber necrosis with a diffuse, mild lymphomonocytic infiltrate in the endomysium and perimysium. Because the patient suffered from an acute HEV infection with a rapidly progressive course of severe myopathy, we started ribavirin treatment. He recovered partially within 3 weeks and recovered fully within 6 months. CONCLUSION This case highlights a neurological manifestation of endemic HEV infection with severe myositis in a patient with alcoholic chronic liver disease. Ribavirin treatment is effective in severe HEV infection and may also lead to rapid neurological recovery.
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Affiliation(s)
| | | | - Andreas Meisel
- Department of Neurology, Charité, Berlin, Charitéplatz 1, Germany
| | - Carsten Büning
- Department of Gastroenterology and Hepatology, Kr. Waldfriede, Berlin, Germany
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47
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Lee GY, Poovorawan K, Intharasongkroh D, Sa-nguanmoo P, Vongpunsawad S, Chirathaworn C, Poovorawan Y. Hepatitis E virus infection: Epidemiology and treatment implications. World J Virol 2015; 4:343-355. [PMID: 26568916 PMCID: PMC4641226 DOI: 10.5501/wjv.v4.i4.343] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Revised: 08/06/2015] [Accepted: 09/18/2015] [Indexed: 02/05/2023] Open
Abstract
Hepatitis E virus (HEV) infection is now established as an emerging enteric viral hepatitis. Standard treatments in acute and chronic hepatitis E remain to be established. This study undertakes a review of the epidemiology, treatment implication and vaccine prevention from published literature. HEV infection is a worldwide public health problem and can cause acute and chronic hepatitis E. HEV genotypes 1 and 2 are primarily found in developing countries due to waterborne transmission, while the zoonotic potential of genotypes 3 and 4 affects mostly industrialized countries. An awareness of HEV transmission through blood donation, especially in the immunocompromised and solid organ transplant patients, merits an effective anti-viral therapy. There are currently no clear indications for the treatment of acute hepatitis E. Despite concerns for side effects, ribavirin monotherapy or in combination with pegylated interferon alpha for at least 3 mo appeared to show significant efficacy in the treatment of chronic hepatitis E. However, there are no available treatment options for specific patient population groups, such as women who are pregnant. Vaccination and screening of HEV in blood donors are currently a global priority in managing infection. New strategies for the treatment and control of hepatitis E are required for both acute and chronic infections, such as prophylactic use of medications, controlling large outbreaks, and finding acceptable antiviral therapy for pregnant women and other patient groups for whom the current options of treatment are not viable.
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Blasco-Perrin H, Madden RG, Stanley A, Crossan C, Hunter JG, Vine L, Lane K, Devooght-Johnson N, Mclaughlin C, Petrik J, Stableforth B, Hussaini H, Phillips M, Mansuy JM, Forrest E, Izopet J, Blatchford O, Scobie L, Peron JM, Dalton HR. Hepatitis E virus in patients with decompensated chronic liver disease: a prospective UK/French study. Aliment Pharmacol Ther 2015; 42:574-81. [PMID: 26174470 DOI: 10.1111/apt.13309] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 06/05/2015] [Accepted: 06/16/2015] [Indexed: 12/24/2022]
Abstract
BACKGROUND In developed countries, hepatitis E is a porcine zoonosis caused by hepatitis E virus (HEV) genotype 3. In developing countries, hepatitis E is mainly caused by genotype 1, and causes increased mortality in patients with pre-existing chronic liver disease (CLD). AIM To determine the role of HEV in patients with decompensated CLD. METHODS Prospective HEV testing of 343 patients with decompensated CLD at three UK centres and Toulouse France, with follow-up for 6 months or death. IgG seroprevalence was compared with 911 controls. RESULTS 11/343 patients (3.2%) had acute hepatitis E infection, and three died. There were no differences in mortality (27% vs. 26%, OR 1.1, 95% CI 0.28-4.1), age (P = 0.9), bilirubin (P = 0.5), alanine aminotransferase (P = 0.06) albumin (P = 0.5) or international normalised ratio (P = 0.6) in patients with and without hepatitis E infection. Five cases were polymerase chain reaction (PCR) positive (genotype 3). Hepatitis E was more common in Toulouse (7.9%) compared to the UK cohort (1.2%, P = 0.003). HEV IgG seroprevalence was higher in Toulouse (OR 17, 95% CI 9.2-30) and Truro (OR 2.5, 95% CI 1.4-4.6) than in Glasgow, but lower in cases, compared to controls (OR 0.59, 95% CI 0.41-0.86). CONCLUSIONS Hepatitis E occurs in a minority of patients with decompensated chronic liver disease. The mortality is no different to the mortality in patients without hepatitis E infection. The diagnosis can only be established by a combination of serology and PCR, the yield and utility of which vary by geographical location.
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Affiliation(s)
- H Blasco-Perrin
- Service d'Hépato-Gastro-Entérologie, Hôpital Purpan, Université Paul Sabatier III, Toulouse, France
| | - R G Madden
- Royal Cornwall Hospital Trust, Truro, UK
| | - A Stanley
- Glasgow Royal Infirmary, Glasgow, UK
| | - C Crossan
- Glasgow Caledonian University, Glasgow, UK
| | - J G Hunter
- Royal Cornwall Hospital Trust, Truro, UK
| | - L Vine
- Royal Cornwall Hospital Trust, Truro, UK
| | - K Lane
- Royal Cornwall Hospital Trust, Truro, UK
| | | | | | - J Petrik
- Scottish National Blood Transfusion Service, Edinburgh, UK
| | | | - H Hussaini
- Royal Cornwall Hospital Trust, Truro, UK
| | - M Phillips
- Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
| | - J M Mansuy
- Laboratoire de virologie, Hôpital Purpan, CHU de Toulouse, Toulouse, France
| | - E Forrest
- Glasgow Royal Infirmary, Glasgow, UK
| | - J Izopet
- Laboratoire de virologie, Hôpital Purpan, CHU de Toulouse, Toulouse, France.,INSERM, U1043, Toulouse, France.,Université Toulouse III Paul Sabatier, Toulouse, France
| | | | - L Scobie
- Glasgow Caledonian University, Glasgow, UK
| | - J M Peron
- Service d'Hépato-Gastro-Entérologie, Hôpital Purpan, Université Paul Sabatier III, Toulouse, France
| | - H R Dalton
- Royal Cornwall Hospital Trust, Truro, UK
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Mallet V. [The emergence of the universal hepatitis E virus]. Presse Med 2015; 44:326-7. [PMID: 25662036 DOI: 10.1016/j.lpm.2014.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2014] [Accepted: 10/08/2014] [Indexed: 11/28/2022] Open
Affiliation(s)
- Vincent Mallet
- Institut Cochin, université Paris-Descartes, Sorbonne Paris Cité (UMR-S1016), CNRS (UMR 8104), 75015 Paris, France; Inserm UMS 020, centre d'immunologie humaine (CIH), Institut Pasteur, 75015 Paris, France; AP-HP, groupe hospitalier Cochin-Saint-Vincent-de-Paul, unité d'hépatologie, 75014 Paris, France.
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Kamar N, Abravanel F, Lhomme S, Rostaing L, Izopet J. Hepatitis E virus: chronic infection, extra-hepatic manifestations, and treatment. Clin Res Hepatol Gastroenterol 2015; 39:20-7. [PMID: 25150374 DOI: 10.1016/j.clinre.2014.07.005] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Accepted: 07/07/2014] [Indexed: 02/04/2023]
Abstract
Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. It is an underdiagnosed disease because of the use of low-sensitivity serological assays; however, diagnostics tools, including nucleic-acid tests, have improved. HEV infection is usually an acute self-limiting disease, but causes chronic infection with rapidly progressive cirrhosis in adult and pediatric organ-transplant-patients. HEV infection evolves to chronic hepatitis in nearly 60% of HEV-infection solid-organ-transplant patients. HEV can also cause extra-hepatic manifestations, such as neurological symptoms and kidney injury. Reducing immunosuppression in transplant patients can lead to HEV clearance in one-third of patients with chronic hepatitis. The use of anti-viral therapies, such as pegylated-interferon and ribavirin, has been found to efficaciously treat HEV infection.
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Affiliation(s)
- Nassim Kamar
- Department of Nephrology and Organ Transplantation, CHU Rangueil, TSA 50032, 31059 Toulouse cedex 9, France; Inserm U1043, IFR-BMT, CHU Purpan, Toulouse, France; Université Paul-Sabatier, Toulouse, France.
| | - Florence Abravanel
- Inserm U1043, IFR-BMT, CHU Purpan, Toulouse, France; Université Paul-Sabatier, Toulouse, France; Laboratory of Virology, CHU Purpan, Toulouse, France
| | - Sebastien Lhomme
- Inserm U1043, IFR-BMT, CHU Purpan, Toulouse, France; Université Paul-Sabatier, Toulouse, France; Laboratory of Virology, CHU Purpan, Toulouse, France
| | - Lionel Rostaing
- Department of Nephrology and Organ Transplantation, CHU Rangueil, TSA 50032, 31059 Toulouse cedex 9, France; Inserm U1043, IFR-BMT, CHU Purpan, Toulouse, France; Université Paul-Sabatier, Toulouse, France
| | - Jacques Izopet
- Inserm U1043, IFR-BMT, CHU Purpan, Toulouse, France; Université Paul-Sabatier, Toulouse, France; Laboratory of Virology, CHU Purpan, Toulouse, France
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