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You S, Zhu B, Xin S. Clinical Manifestations of Hepatitis E. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:185-197. [PMID: 37223867 DOI: 10.1007/978-981-99-1304-6_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
The clinical manifestations of hepatitis E are similar to those of other types of viral hepatitis. While acute hepatitis E is usually self-limited, pregnant women and chronic liver disease patients suffering from acute hepatitis E usually present with severe clinical manifestations that may develop into fulminant hepatic failure. Chronic HEV infection is typically seen in organ transplant patients; most HEV cases are asymptomatic and rarely display jaundice, fatigue, abdominal pain, fever, fatigue, or ascites. The clinical manifestations of HEV infection in neonates are diverse and have varied clinical signs, biochemistry, and virus-biomarkers. Lastly, the extrahepatic manifestations and complications of hepatitis E are in need of further study.
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Affiliation(s)
- Shaoli You
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Bing Zhu
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shaojie Xin
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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2
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PEREIRA JA, MORAIS J, FERREIRA S, GANDARA J, VIZCAÍNO R, MIRANDA HP, DANIEL J, LOPES VD. Acute hepatitis E and liver autoimmunity in a patient with acute liver failure: two separate entities? GAZZETTA MEDICA ITALIANA ARCHIVIO PER LE SCIENZE MEDICHE 2022. [DOI: 10.23736/s0393-3660.20.04332-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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3
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Maslennikov R, Ivashkin V, Efremova I, Shirokova E. Immune disorders and rheumatologic manifestations of viral hepatitis. World J Gastroenterol 2021; 27:2073-2089. [PMID: 34025065 PMCID: PMC8117740 DOI: 10.3748/wjg.v27.i18.2073] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 02/28/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023] Open
Abstract
Infection with hepatotropic viruses is not limited to the liver and can lead to the development of various immunological disorders (the formation of cryoglobulins, rheumatoid factor, antinuclear antibodies, autoantibodies specific for autoimmune hepatitis and primary biliary cholangitis, and others), which can manifest as glomerulonephritis, arthritis, uveitis, vasculitis (cryoglobulinemic vasculitis, polyarteritis nodosa, Henoch-Schonlein purpura, isolated cutaneous necrotizing vasculitis), and other rheumatologic disorders, and be a trigger for the subsequent development of autoimmune hepatitis and primary biliary cholangitis. A further study of the association between autoimmune liver diseases and hepatotropic virus infection would be useful to assess the results of treatment of these associated diseases with antiviral drugs. The relationship of these immune disorders and their manifestations with hepatotropic viruses is best studied for chronic hepatitis B and C. Only isolated cases of these associations are described for hepatitis A. These links are least studied, and are often controversial for hepatitis E, possibly due to their relatively rare diagnoses. Patients with uveitis, glomerulonephritis, arthritis, vasculitis, autoimmune liver diseases should be tested for biomarkers of viral hepatitis, and if present, these patients should be treated with antiviral drugs.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119435, Russia
- Department of Internal Medicine 1, Сonsultative and Diagnostic Center 2 of the Moscow City Health Department, Moscow 107564, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Shirokova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
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4
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Pringle R, van Halsema C. Widespread rash as initial presentation of acute hepatitis E in a woman with well-controlled HIV. Int J STD AIDS 2021; 32:671-673. [PMID: 33530880 DOI: 10.1177/0956462420984697] [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: 11/15/2022]
Abstract
Sporadic, acute hepatitis E is increasingly common in the United Kingdom, associated with travel or locally acquired. A 45-year-old woman with well-controlled HIV presented with a widespread, polymorphic rash and transaminitis. Acute genotype 3 hepatitis E infection was confirmed and resolved without intervention. A review of the literature reveals a number of atypical presentations of acute autochthonous hepatitis E. Clinicians should consider testing for hepatitis E in the presence of nonspecific symptoms and deranged liver function tests.
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Affiliation(s)
- Rachel Pringle
- Department of Infectious Diseases and Tropical Medicine, 156778North Manchester General Hospital, Manchester, UK
| | - Clare van Halsema
- Department of Infectious Diseases and Tropical Medicine, 156778North Manchester General Hospital, Manchester, UK
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5
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Fernandes B, Dias E, Mascarenhas-Saraiva M, Bernardes M, Costa L, Cardoso H, Macedo G. Rheumatologic manifestations of hepatic diseases. Ann Gastroenterol 2019; 32:352-360. [PMID: 31263357 PMCID: PMC6595923 DOI: 10.20524/aog.2019.0386] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Accepted: 04/01/2019] [Indexed: 02/06/2023] Open
Abstract
The course of hepatic diseases may be complicated by a multitude of rheumatologic manifestations, which can complicate the diagnostic approach and alter the natural history of primary liver disease, sometimes worsening prognosis due to associated multiple organ dysfunction. These manifestations can occur in association with a multitude of liver diseases, including viral hepatitis, autoimmune hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, hemochromatosis, or Wilson’s disease. It is necessary not only for rheumatologists, but also for other clinicians, to be aware that these atypical manifestations may reflect an undiagnosed hepatic disease. On the other hand, it is crucial that, in a patient with known hepatic disease presenting with rheumatologic symptoms, an accurate distinction be made between the rheumatologic manifestations of hepatic disease and primary rheumatologic disease, since the treatment is often different. This review aims to summarize the current evidence regarding rheumatologic manifestations of hepatic diseases, how to distinguish them from primary rheumatologic disorders, and how to provide adequate management.
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Affiliation(s)
- Bruno Fernandes
- Rheumatology Department (Bruno Fernandes, Miguel Bernardes, Lúcia Costa)
| | - Emanuel Dias
- Gastrenterology Department (Emanuel Dias, Miguel Mascarenhas-Saraiva, Hélder Cardoso, Guilherme Macedo), Centro Hospitalar de São João, Porto, Portugal
| | - Miguel Mascarenhas-Saraiva
- Gastrenterology Department (Emanuel Dias, Miguel Mascarenhas-Saraiva, Hélder Cardoso, Guilherme Macedo), Centro Hospitalar de São João, Porto, Portugal
| | - Miguel Bernardes
- Rheumatology Department (Bruno Fernandes, Miguel Bernardes, Lúcia Costa)
| | - Lúcia Costa
- Rheumatology Department (Bruno Fernandes, Miguel Bernardes, Lúcia Costa)
| | - Hélder Cardoso
- Gastrenterology Department (Emanuel Dias, Miguel Mascarenhas-Saraiva, Hélder Cardoso, Guilherme Macedo), Centro Hospitalar de São João, Porto, Portugal
| | - Guilherme Macedo
- Gastrenterology Department (Emanuel Dias, Miguel Mascarenhas-Saraiva, Hélder Cardoso, Guilherme Macedo), Centro Hospitalar de São João, Porto, Portugal
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Anang S, Kaushik N, Surjit M. Recent Advances Towards the Development of a Potent Antiviral Against the Hepatitis E Virus. J Clin Transl Hepatol 2018; 6:310-316. [PMID: 30271744 PMCID: PMC6160310 DOI: 10.14218/jcth.2018.00005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 02/19/2018] [Accepted: 03/23/2018] [Indexed: 12/18/2022] Open
Abstract
Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. It also causes acute liver failure and acute-on-chronic liver failure in many patients, such as those suffering from other infections/liver injuries or organ transplant/chemotherapy recipients. Despite widespread sporadic and epidemic incidents, there is no specific treatment against HEV, justifying an urgent need for developing a potent antiviral against it. This review summarizes the known antiviral candidates and provides an overview of the potential targets for the development of specific antivirals against HEV.
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Affiliation(s)
- Saumya Anang
- Virology Laboratory, Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad, Haryana, India
| | - Nidhi Kaushik
- Virology Laboratory, Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad, Haryana, India
| | - Milan Surjit
- Virology Laboratory, Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad, Haryana, India
- *Correspondence to: Milan Surjit, Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, PO Box No. 04, Faridabad-121001, Haryana, India. Tel: +91-129-2876-318, Fax: +91-129-2876400, E-mail:
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Potent Inhibition of Hepatitis E Virus Release by a Cyclic Peptide Inhibitor of the Interaction between Viral Open Reading Frame 3 Protein and Host Tumor Susceptibility Gene 101. J Virol 2018; 92:JVI.00684-18. [PMID: 30068652 DOI: 10.1128/jvi.00684-18] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 07/25/2018] [Indexed: 12/15/2022] Open
Abstract
Hepatitis E virus (HEV) generally causes self-limiting acute viral hepatitis in normal individuals. It causes a more severe disease in immunocompromised persons and pregnant women. Due to the lack of an efficient cell culture system or animal model, the life cycle of the virus is understudied, few antiviral targets are known, and very few antiviral candidates against HEV infection have been identified. Inhibition of virus release is one possible antiviral development strategy, which limits the spread of the virus. Previous studies have demonstrated the essential role of the interaction between the PSAP motif of the viral open reading frame 3 protein (ORF3-PSAP) and the UEV domain of the host tumor susceptibility gene 101 (TSG101) protein (UEV-TSG101) in mediating the release of genotype 3 HEV. Cyclic peptide (CP) inhibitors of the interaction between the human immunodeficiency virus (HIV) gag-PTAP motif and UEV-TSG101 are known to block the release of HIV. Using a molecular dynamic simulation, we observed that both gag-PTAP and ORF3-PSAP motifs bind to the same site in UEV-TSG101 by hydrogen bonding. HIV-released inhibitory CPs also displayed binding to the same site in UEV-TSG101, indicating that they may compete with ORF3-PSAP or gag-PTAP for binding to UEV-TSG101. Two independent assays confirmed the ability of a cyclic peptide (CP11) to inhibit the ORF3-TSG101 interaction. CP11 treatment also reduced the release of both genotype 1 and genotype 3 HEV by approximately 90%, with a 50% inhibitory concentration (IC50) of 2 μM. Thus, CP11 appears to be an attractive candidate for further validation of its anti-HEV properties.IMPORTANCE There is no specific therapy against hepatitis E virus (HEV)-induced hepatic and nonhepatic health problems. Prevention of the release of the progeny viruses from infected cells is an attractive strategy to limit the spread of the virus. Interactions between the viral open reading frame 3 and the host tumor susceptibility gene 101 proteins have been shown to be essential for the release of genotype 3 HEV from infected cells. In this study, we have identified a cyclic peptide inhibitor of the above-mentioned interaction and demonstrate the efficiency of the inhibitor in preventing virus release from infected cells. Thus, our findings uncover the possibility of developing a specific antiviral agent against HEV by blocking its release from infected cells.
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Weigand K, Weigand K, Schemmerer M, Müller M, Wenzel JJ. Hepatitis E Seroprevalence and Genotyping in a Cohort of Wild Boars in Southern Germany and Eastern Alsace. FOOD AND ENVIRONMENTAL VIROLOGY 2018; 10:167-175. [PMID: 29214558 DOI: 10.1007/s12560-017-9329-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2017] [Accepted: 12/01/2017] [Indexed: 06/07/2023]
Abstract
In the last few years it has been realized that the hepatitis E virus (HEV) is endemic in most industrialized countries and that it is a zoonotic disease. Potential reservoirs for HEV have been identified to be wild boars and deers, but HEV has also been found in domestic pigs and other animals. Due to the probable spread of the virus via contaminated food or contact to infected animals, HEV antibodies are present in more than 16% of the German adult population and rates are increasing with age. We collected blood from 104 wild boars in southern Germany and the border region of Alsace. We found an anti-HEV seroprevalence of 11.5% in our cohort, using ELISA. Furthermore, we observed active infection in 3.85% of the animals by positive HEV PCR in the sera of the boars. In our cohort, no regional differences of seroprevalence or active infection were seen. Sequencing revealed rather close homology of some detected HEV sequences to genotypes isolated from patients in Germany. Hence wild boars are a potential source of HEV infection in Middle Europe and the rate of infectious animals is quite high.
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Affiliation(s)
- Kilian Weigand
- Department of Gastroenterology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
| | - Kurt Weigand
- Department of Internal Medicine, Stauferklinikum Schwaebisch Gmuend, Mutlangen, Germany
| | - Mathias Schemmerer
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany
| | - Martina Müller
- Department of Gastroenterology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | - Juergen J Wenzel
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany
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Xin S, Xiao L. Clinical Manifestations of Hepatitis E. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 948:175-189. [PMID: 27738985 DOI: 10.1007/978-94-024-0942-0_10] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The clinical manifestations of hepatitis E are similar to those of other types of viral hepatitis. While acute hepatitis E is usually self-limited, pregnant women and chronic liver disease patients suffering from acute hepatitis E usually present with severe clinical manifestations that may develop into fulminant hepatic failure. Chronic HEV infection is typically only seen in organ transplant patients; most HEV cases are asymptomatic and rarely display jaundice, fatigue, abdominal pain, fever, fatigue, or ascites. The clinical manifestations of HEV infection in neonates are diverse and have varied clinical signs, biochemistry, and virus biomarkers. Lastly, the extrahepatic manifestations and complications of hepatitis E are in need of further study.
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Affiliation(s)
- Shaojie Xin
- Liver Failure Treatment and Research Center, 302 Hospital, No.100 West 4th middle Road, Fengtai District, Beijing, 100039, China.
| | - Long Xiao
- Liver Failure Treatment and Research Center, 302 Hospital, No.100 West 4th middle Road, Fengtai District, Beijing, 100039, China
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10
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Prost S, Crossan CL, Dalton HR, De Man RA, Kamar N, Selves J, Dhaliwal C, Scobie L, Bellamy COC. Detection of viral hepatitis E in clinical liver biopsies. Histopathology 2017; 71:580-590. [DOI: 10.1111/his.13266] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Revised: 05/11/2017] [Accepted: 05/20/2017] [Indexed: 12/20/2022]
Affiliation(s)
- Sandrine Prost
- Department of Pathology; Royal Infirmary of Edinburgh; Edinburgh UK
| | - Claire L Crossan
- Department of Biological and Biomedical Sciences; Glasgow Caledonian University; Glasgow UK
| | - Harry R Dalton
- European Centre for Environment and Human Health; University of Exeter; Exeter UK
| | - Robert A De Man
- Department of Gastroenterology and Hepatology; Erasmus Medical Center; Rotterdam the Netherlands
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation; Université Paul Sabatier; Toulouse France
| | - Janick Selves
- Centre de Recherche en Cancérologie de Toulouse; Department of Pathology; Centre Hospitalier Universitaire de Toulouse; Toulouse France
| | | | - Linda Scobie
- Department of Biological and Biomedical Sciences; Glasgow Caledonian University; Glasgow UK
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Goel A, Aggarwal R. Advances in hepatitis E - II: Epidemiology, clinical manifestations, treatment and prevention. Expert Rev Gastroenterol Hepatol 2016; 10:1065-1074. [PMID: 27148907 DOI: 10.1080/17474124.2016.1185365] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Infection with hepatitis E virus (HEV) is the commonest cause of acute hepatitis worldwide. This infection, with fecal-oral transmission, was previously thought to be limited to humans residing in developing countries with poor sanitation, spreading via contaminated drinking water. In recent years, our understanding of epidemiology and clinical spectrum of this infection have changed markedly. AREAS COVERED This article reviews the epidemiology, including routes of transmission, and clinical manifestations of HEV infection around the world. In addition, recent findings on transmission-associated HEV infection, extrahepatic manifestations of hepatitis E and chronic infection with HEV, and treatment and prevention of this infection are discussed. Expert commentary: HEV infection has two distinct epidemiologic forms and clinical patterns of disease: (i) acute epidemic or sporadic hepatitis caused by fecal-oral (usually water-borne) transmission of genotype 1 and 2 HEV from a human reservoir in areas with poor hygiene and frequent water contamination, and (ii) infrequent sporadic hepatitis E caused by zoonotic infection, possibly from an animal source through ingestion of undercooked animal meal, of genotype 3 or 4 virus. In disease-endemic areas, pregnant women are at a particular risk of serious disease and high mortality. In less-endemic areas, chronic infection with HEV among immunosuppressed persons is observed. HEV can also be transmitted through Transfusion of blood and blood products. Ribivirin treatment is effective in chronic hepatitis E. Two efficacious vaccines have been tried in humans; one of these has received marketing approval in its country of origin.
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Affiliation(s)
- Amit Goel
- a Department of Gastroenterology , Sanjay Gandhi Postgraduate Institute of Medical Sciences , Lucknow , India
| | - Rakesh Aggarwal
- a Department of Gastroenterology , Sanjay Gandhi Postgraduate Institute of Medical Sciences , Lucknow , India
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12
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Kamar N, Marion O, Abravanel F, Izopet J, Dalton HR. Extrahepatic manifestations of hepatitis E virus. Liver Int 2016; 36:467-72. [PMID: 27005692 DOI: 10.1111/liv.13037] [Citation(s) in RCA: 79] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 11/25/2015] [Indexed: 02/06/2023]
Abstract
Hepatitis E virus can cause acute, fulminant and chronic hepatitis and has been associated with a range of extrahepatic manifestations. Guillain-Barré syndrome, neuralgic amyotrophy and encephalitis are the main neurological manifestations associated with acute and chronic hepatitis E virus infection. Renal injuries have been also reported, including membranoproliferative glomerulonephritis with or without cryoglobulinemia and membranous glomerulonephritis. Acute pancreatitis, haematological disorders and other autoimmune extrahepatic manifestations of hepatitis E virus, such as myocarditis and thyroiditis, have been also reported. In this comprehensive article, we review all published reports describing hepatitis E virus-associated extrahepatic manifestations.
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Affiliation(s)
- Nassim Kamar
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.,INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.,Université Paul Sabatier, Toulouse, France
| | - Olivier Marion
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - Florence Abravanel
- INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.,Université Paul Sabatier, Toulouse, France.,Department of Virology, CHU Purpan, Toulouse, France
| | - Jacques Izopet
- INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.,Université Paul Sabatier, Toulouse, France.,Department of Virology, CHU Purpan, Toulouse, France
| | - Harry R Dalton
- Cornwall Gastrointestinal Unit, Royal Cornwall Hospital and European Centre for the Environment and Human Health, University of Exeter Medical School, Truro, UK
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Kokki I, Smith D, Simmonds P, Ramalingam S, Wellington L, Willocks L, Johannessen I, Harvala H. Hepatitis E virus is the leading cause of acute viral hepatitis in Lothian, Scotland. New Microbes New Infect 2015; 10:6-12. [PMID: 26904201 PMCID: PMC4726789 DOI: 10.1016/j.nmni.2015.12.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Revised: 12/01/2015] [Accepted: 12/03/2015] [Indexed: 12/12/2022] Open
Abstract
Acute viral hepatitis affects all ages worldwide. Hepatitis E virus (HEV) is increasingly recognized as a major cause of acute hepatitis in Europe. Because knowledge of its characteristics is limited, we conducted a retrospective study to outline demographic and clinical features of acute HEV in comparison to hepatitis A, B and C in Lothian over 28 months (January 2012 to April 2014). A total of 3204 blood samples from patients with suspected acute hepatitis were screened for hepatitis A, B and C virus; 913 of these samples were also screened for HEV. Demographic and clinical information on patients with positive samples was gathered from electronic patient records. Confirmed HEV samples were genotyped. Of 82 patients with confirmed viral hepatitis, 48 (59%) had acute HEV. These patients were older than those infected by hepatitis A, B or C viruses, were more often male and typically presented with jaundice, nausea, vomiting and/or malaise. Most HEV cases (70%) had eaten pork or game meat in the few months before infection, and 14 HEV patients (29%) had a recent history of foreign travel. The majority of samples were HEV genotype 3 (27/30, 90%); three were genotype 1. Acute HEV infection is currently the predominant cause of acute viral hepatitis in Lothian and presents clinically in older men. Most of these infections are autochthonous, and further studies confirming the sources of infection (i.e. food or blood transfusion) are required.
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Affiliation(s)
- I Kokki
- Specialist Virology Laboratory, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - D Smith
- CIIE, University of Edinburgh, King's Buildings, Edinburgh, UK
| | - P Simmonds
- Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh, UK
| | - S Ramalingam
- Specialist Virology Laboratory, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - L Wellington
- Public Health and Health Policy and NHS Lothian, Edinburgh, UK
| | - L Willocks
- Public Health and Health Policy and NHS Lothian, Edinburgh, UK
| | - I Johannessen
- Specialist Virology Laboratory, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - H Harvala
- Specialist Virology Laboratory, Royal Infirmary of Edinburgh, Edinburgh, UK; Public Health Agency of Sweden, Solna, Sweden; European Programme for Public Health Microbiology Training (EUPHEM), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
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14
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Sayed IM, Vercouter AS, Abdelwahab SF, Vercauteren K, Meuleman P. Is hepatitis E virus an emerging problem in industrialized countries? Hepatology 2015; 62:1883-1892. [PMID: 26175182 DOI: 10.1002/hep.27990] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Accepted: 07/13/2015] [Indexed: 02/05/2023]
Abstract
Hepatitis E virus (HEV) is yearly responsible for approximately 20 million infections worldwide. Although most infections occur in developing countries, HEV appears to be an emerging problem in several industrialized countries, where it is mostly associated with either traveling to an HEV endemic area or contact with pigs, which represent a major reservoir of HEV. The major risk groups for HEV infection and its ensuing complications are elderly men, pregnant women, young children, immunocompromised patients, patients with preexisting liver disease, and workers that come into close contact with HEV-infected animals. Whereas HEV mainly causes acute self-limiting infections, chronic infections may occur among immunocompromised patients (e.g., transplant recipients and human immunodeficiency virus [HIV]-infected patients). Accordingly, HEV-HIV coinfection leads to accelerated liver cirrhosis and increased mortality rates compared to HEV infection alone, which is, except during pregnancy, usually associated with only low mortality. In the Western world, the most common genotype (gt) causing HEV infection is gt 3. Ribavirin (RBV) and interferon have been used successfully for treatment of HEV, but this treatment is contraindicated in certain patient groups. Therefore, novel antiviral compounds are highly needed, especially given that viral isolates with RBV resistance have been recently identified. Moreover, eradication of HEV is hampered by long-term environmental persistence of the virus, which represents a continuous source of the virus. In 2011, the first prophylactic HEV vaccine, Hecolin, was approved in China, but it is not yet globally available. In this review, we will discuss the molecular virology of HEV, mode of transmission in industrialized countries, and potential implications for different specific patient populations.
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Affiliation(s)
- Ibrahim M Sayed
- Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Gent, Belgium
- Microbiology and Immunology Department, Faculty of Medicine, Assuit University, Assuit, Egypt
| | - Ann-Sofie Vercouter
- Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Gent, Belgium
| | - Sayed F Abdelwahab
- Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia, Egypt
- Microbiology Department, College of Pharmacy, Taif University, Taif, Saudi Arabia
| | - Koen Vercauteren
- Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Gent, Belgium
| | - Philip Meuleman
- Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Gent, Belgium
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15
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Bazerbachi F, Haffar S, Garg SK, Lake JR. Extra-hepatic manifestations associated with hepatitis E virus infection: a comprehensive review of the literature. Gastroenterol Rep (Oxf) 2015; 4:1-15. [PMID: 26358655 PMCID: PMC4760069 DOI: 10.1093/gastro/gov042] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2015] [Accepted: 07/09/2015] [Indexed: 02/07/2023] Open
Abstract
Background and aims: Hepatitis E virus (HEV) infection is a significant public health problem that afflicts almost 20 million individuals annually and causes acute liver injury in 3.5 million, with approximately 56 000 deaths. As with other viral hepatitides, extra-hepatic manifestations could represent an important aspect of this infection. The spectrum of these manifestations is still emerging. Acute pancreatitis and neurological, musculoskeletal, hematological, renal, and other immune-mediated manifestations have been described. The aim of this article is to comprehensively review the published literature of extra-hepatic manifestations associated with HEV infection. Data sources: We searched the PubMed database using the MeSH term “hepatitis E” and each of the extra-hepatic manifestations associated with HEV infection. No language or date restrictions were set in these searches. Searches retrieving articles with non-A, non-B hepatitis were excluded. Additional articles were identified through the reference lists of included articles. Results: Several extra-hepatic manifestations associated with HEV infection have been published. The temporal association between some extra-hepatic manifestations and HEV infection and the exclusion of other possible etiologies suggests that HEV infection could have caused some of them. According to the available data, HEV infection appears to be strongly associated with acute pancreatitis, neurological disorders (with primarily dominant peripheral nerve involvement, most commonly manifested as Guillain-Barré syndrome, followed by neuralgic amyotrophy), hematological diseases (hemolytic anemia due to glucose phosphate dehydrogenase deficiency, and severe thrombocytopenia), glomerulonephritis, and mixed cryoglobulinemia. More data are needed to clarify whether an association exists with musculoskeletal or other immune-mediated manifestations. Conclusions: HEV infection should be considered in patients with acute pancreatitis, Guillain-Barré syndrome, neuralgic amyotrophy, hemolytic anemia due to glucose phosphate dehydrogenase deficiency, severe thrombocytopenia, glomerulonephritis, and mixed cryoglobulinemia. Alternatively, signs and symptoms of these conditions should be sought in patients with acute or chronic HEV infection. More data are needed to confirm the role of HEV in other extra-hepatic disorders.
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Affiliation(s)
- Fateh Bazerbachi
- Division of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Samir Haffar
- Department of Gastroenterology and Hepatology, University of Damascus, Damascus, Syrian Arab Republic
| | - Sushil K Garg
- Division of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA
| | - John R Lake
- Division of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA
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Mystery of hepatitis e virus: recent advances in its diagnosis and management. Int J Hepatol 2015; 2015:872431. [PMID: 25692043 PMCID: PMC4322671 DOI: 10.1155/2015/872431] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2014] [Accepted: 12/27/2014] [Indexed: 02/06/2023] Open
Abstract
Mysterious aspects of the long presumed to be well-known hepatitis E virus (HEV) have recently surfaced that distinguish it from other hepatotropic viruses. It is a cause of chronic hepatitis in immunosuppressed patients. It has human to human transmission through blood and mantains high seroprevalence in blood donors. HEV has also been found to occur more frequently in the West in those without a history of travel to endemic countries. It has varied extrahepatic manifestations and has multiple non-human reservoirs including pigs and rats. Considering these recent discoveries, it appears odd that HEV is not sought more frequently when working up acute and chronic hepatitis patients. The disease is particularly severe among pregnant women and has a high attack rate in young adults. What adds to its ambiguity is the absence of a well-established diagnostic criteria for its detection and that there is no specific antiviral drug for hepatitis E, except for isolated cases where ribavirin or pegylated interferon alpha has been used with occasional success. This review paper discusses the recent advances in the knowledge of the virus itself, its epidemiology, diagnostic approach and prevention, and the treatment options available.
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Pischke S, Behrendt P, Manns MP, Wedemeyer H. HEV-associated cryoglobulinaemia and extrahepatic manifestations of hepatitis E. THE LANCET. INFECTIOUS DISEASES 2014; 14:678-679. [PMID: 25056019 DOI: 10.1016/s1473-3099(14)70823-0] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Sven Pischke
- Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Outpatient Clinic for Liver Transplant Recipients, University Hospital Hamburg Eppendorf, Hamburg, Germany
| | - Patrick Behrendt
- Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; German Center for Infection Research, Hannover, Germany; Twincore, Centre for Experimental and Clinical Infection Research, A Joint Venture Between Medical School Hannover and Helmholtz Centre for Infection Research, Hannover, Germany
| | - Michael P Manns
- Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; German Center for Infection Research, Hannover, Germany.
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Hepatitis E: an old infection with new implications. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2014; 13:6-17. [PMID: 25369613 DOI: 10.2450/2014.0063-14] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Accepted: 06/18/2014] [Indexed: 12/24/2022]
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Pischke S, Behrendt P, Bock CT, Jilg W, Manns MP, Wedemeyer H. Hepatitis E in Germany--an under-reported infectious disease. DEUTSCHES ARZTEBLATT INTERNATIONAL 2014; 111:577-583. [PMID: 25249359 PMCID: PMC4174681 DOI: 10.3238/arztebl.2014.0577] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Revised: 06/05/2014] [Accepted: 06/05/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND At least 17% of the population in Germany has been infected with the hepatitis E virus (HEV); thus, HEV infections are more frequent than was previously assumed. However, fewer than 500 HEV infections were reported to the Robert Koch Institute in 2013. METHOD Review of pertinent literature retrieved by a selective search in PubMed. RESULTS Persons living in Germany generally acquire hepatitis E infection within the country by consuming infected and undercooked pork; in rare cases, hepatitis E infections are imported from the tropics. HEV can be transmitted via blood products, blood transfusions, and organ transplantation. More than 99% of HEV infections are asymptomatic and self-limiting, but there are also severe cases with acute liver failure. Immunosuppressed persons can develop chronic HEV infection, potentially leading, within a few years, to liver cirrhosis with life-threatening sequelae. Moreover, HEV infection may be associated with extrahepatic manifestations such as Guillain-Barré syndrome. In two retrospectively evaluated case series, ribavirin was found to be active against HEV and can be used to treat either acute or chronic HEV infection. CONCLUSION Hepatitis E must be considered in the differential diagnosis of elevated hepatic enzyme levels and of systemic and neurological conditions of uncertain origin. The infection is usually self-limiting but can take a severe course in immunosuppressed persons. In such cases, ribavirin can be used as an antiviral treatment.
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Affiliation(s)
- Sven Pischke
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover
- Health Care Center at the University Medical Center Hamburg-Eppendorf
| | - Patrick Behrendt
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover
- TWINCORE Institute for Experimental Infection Research, Hanover
| | | | - Wolfgang Jilg
- Consiliary Laboratory for Hepatitis A and Hepatitis E, Institute for Medical Microbiology and Hygiene, University Hospital Regensburg, Regensburg
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover
- German Centre for Infection Research, Hanover
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover
- German Centre for Infection Research, Hanover
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