|
1
|
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: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/27/2024] [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.
Collapse
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)
| |
Collapse
|
|
2
|
Guerrero-Vadillo M, Peñuelas M, Carmona R, León-Gómez I, Varela C. Increasing trends in hepatitis E hospitalisations in Spain, 1997 to 2019. Euro Surveill 2024; 29:2400118. [PMID: 39450516 PMCID: PMC11513759 DOI: 10.2807/1560-7917.es.2024.29.43.2400118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 07/16/2024] [Indexed: 10/26/2024] Open
Abstract
BackgroundHepatitis E, a viral hepatitis caused mainly by the ingestion of raw or undercooked food, is not a notifiable disease in Spain.AimTo analyse the temporal trends, epidemiological characteristics and factors associated with severe disease from hepatitis E hospitalisations in Spain from 1997 to 2019.MethodsHospitalisation records were obtained from the Spanish National Hospital Discharge Database. Temporal trends and seasonality were analysed by Poisson regression in years 1997-2015 and 2016-19, given changes in hospital discharge databases. Multivariate logistic regression was used to identify factors associated with severe disease.ResultsHepatitis E hospitalisation incidence increased from 0.22 cases per 1,000,000 inhabitants in 1997 to a maximum of 2.95 in 2018. Seasonality was observed during 2016-19 period, with more cases in the second and third quarters of the year. The incidence was higher in men vs women, and in the population aged over 40 years. Factors independently associated with death were age ≥ 50 years (adjusted odds ratio (aOR): 2.43), chronic liver disease (aOR: 4.29), HIV infection (aOR: 3.00) and hepatitis B/C (aOR: 2.11).ConclusionsHepatitis E hospitalisations have increased in Spain in recent years, being more severe in cases with older age, chronic hepatic diseases and HIV infection. A greater incidence in men over 40 years and a possible seasonality were observed. Further studies are needed to assess the seasonality, geographical distribution and impact of the disease to guide public health actions for prevention and control.
Collapse
Affiliation(s)
- María Guerrero-Vadillo
- CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III (CIBERESP, ISCIII), Madrid, Spain
- Departamento de Enfermedades Transmisibles, Centro Nacional de Epidemiología (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Programa de Doctorado en Ciencias Biomédicas y Salud Pública, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain
| | - Marina Peñuelas
- CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III (CIBERESP, ISCIII), Madrid, Spain
- Departamento de Enfermedades Transmisibles, Centro Nacional de Epidemiología (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Rocío Carmona
- Departamento de Enfermedades Transmisibles, Centro Nacional de Epidemiología (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Inmaculada León-Gómez
- CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III (CIBERESP, ISCIII), Madrid, Spain
- Departamento de Enfermedades Transmisibles, Centro Nacional de Epidemiología (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Carmen Varela
- CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III (CIBERESP, ISCIII), Madrid, Spain
- Departamento de Enfermedades Transmisibles, Centro Nacional de Epidemiología (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| |
Collapse
|
|
3
|
Zahmanova G, Takova K, Tonova V, Koynarski T, Lukov LL, Minkov I, Pishmisheva M, Kotsev S, Tsachev I, Baymakova M, Andonov AP. The Re-Emergence of Hepatitis E Virus in Europe and Vaccine Development. Viruses 2023; 15:1558. [PMID: 37515244 PMCID: PMC10383931 DOI: 10.3390/v15071558] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/11/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water or food) or by contact with infected animals and their raw meat products. Some animals, such as pigs, wild boars, sheep, goats, rabbits, camels, rats, etc., are natural reservoirs of HEV, which places people in close contact with them at increased risk of HEV disease. Although hepatitis E is a self-limiting infection, it could also lead to severe illness, particularly among pregnant women, or chronic infection in immunocompromised people. A growing number of studies point out that HEV can be classified as a re-emerging virus in developed countries. Preventative efforts are needed to reduce the incidence of acute and chronic hepatitis E in non-endemic and endemic countries. There is a recombinant HEV vaccine, but it is approved for use and commercially available only in China and Pakistan. However, further studies are needed to demonstrate the necessity of applying a preventive vaccine and to create conditions for reducing the spread of HEV. This review emphasizes the hepatitis E virus and its importance for public health in Europe, the methods of virus transmission and treatment, and summarizes the latest studies on HEV vaccine development.
Collapse
Affiliation(s)
- Gergana Zahmanova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
| | - Katerina Takova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Valeria Tonova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Tsvetoslav Koynarski
- Department of Animal Genetics, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Laura L Lukov
- Faculty of Sciences, Brigham Young University-Hawaii, Laie, HI 96762, USA
| | - Ivan Minkov
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
- Institute of Molecular Biology and Biotechnologies, 4108 Markovo, Bulgaria
| | - Maria Pishmisheva
- Department of Infectious Diseases, Pazardzhik Multiprofile Hospital for Active Treatment, 4400 Pazardzhik, Bulgaria
| | - Stanislav Kotsev
- Department of Infectious Diseases, Pazardzhik Multiprofile Hospital for Active Treatment, 4400 Pazardzhik, Bulgaria
| | - Ilia Tsachev
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Magdalena Baymakova
- Department of Infectious Diseases, Military Medical Academy, 1606 Sofia, Bulgaria
| | - Anton P Andonov
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
| |
Collapse
|
|
4
|
Behrendt P, Wedemeyer H. [Vaccines against hepatitis E virus: state of development]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2022; 65:192-201. [PMID: 35099576 PMCID: PMC8802100 DOI: 10.1007/s00103-022-03487-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Accepted: 12/22/2021] [Indexed: 11/30/2022]
Abstract
In Europa ist aktuell kein Impfstoff gegen das Hepatitis-E-Virus (HEV) zugelassen. Demgegenüber steht in China bereits seit 10 Jahren mit HEV-239 (Hecolin®, Xiamen Innovax Biotech Co., Xiamen, China) ein Vakzin gegen den HEV-Genotyp 4 zur Verfügung. Herausforderungen für die Entwicklung von Impfstoffen ergeben sich v. a. aus den Unterschieden zwischen den Genotypen bezüglich Verbreitung, Übertragungswege und Risikogruppen. Weitere Hindernisse sind die Umhüllung von HEV im Blut durch Wirtsmembranen, die Replikation in verschiedenen Organen außerhalb der Leber sowie schwächere Immunantworten in vulnerablen Gruppen. In diesem Artikel wird der aktuelle Stand der verfügbaren und in fortgeschrittener präklinischer Evaluation befindlichen Vakzine gegen HEV mit Fokus auf Strategien der Impfstoffentwicklung dargestellt. Herausforderungen und Limitationen werden beschrieben. Aktuelle Impfkandidaten fokussieren auf proteinbasierte Immunisierungen mit dem Ziel der Induktion von schützenden, neutralisierenden Antikörperantworten. Das Ziel der HEV-239-Zulassungsstudie mit mehr als 100.000 Studienteilnehmern war die Verhinderung von akuten symptomatischen Infektionen. Es ist jedoch unklar, inwieweit asymptomatische Infektionen durch das Vakzin verhindert wurden und ob es in Risikopatienten für einen komplizierten Verlauf, wie Patienten mit Leberzirrhose, Immunsupprimierten und Schwangeren, effektiv genug wirkt. Effiziente In-vitro-Modelle ermöglichen zunehmend die Entwicklung von monoklonalen neutralisierenden Antikörpern zur passiven Immunisierung oder Therapie. Zukünftige Vakzine sollten neben einem sehr guten Sicherheitsprofil eine eindeutige Protektion gegenüber allen Genotypen demonstrieren. Die Entwicklung einer effizienten passiven Immunisierungsstrategie, insbesondere für immunsupprimierte Personen, ist wünschenswert.
Collapse
Affiliation(s)
- Patrick Behrendt
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland
| | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland.
| |
Collapse
|
|
5
|
Withenshaw SM, Grierson SS, Smith RP. Study of Animal Mixing and the Dynamics of Hepatitis E Virus Infection on a Farrow-to-Finish Pig Farm. Animals (Basel) 2022; 12:ani12030272. [PMID: 35158596 PMCID: PMC8833537 DOI: 10.3390/ani12030272] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 12/17/2021] [Accepted: 12/22/2021] [Indexed: 02/05/2023] Open
Abstract
In Europe, swine are a livestock reservoir for Hepatitis E virus genotype 3 (HEV-3). Consumption of food containing HEV-3 can cause zoonotic human infection, though risk is reduced by heat treatment. Implementing controls that limit infection in slaughter pigs may further reduce foodborne transmission risk but knowledge of infection dynamics on commercial farms is limited. This study addressed this knowledge gap and in particular investigated the influence of group mixing. Faeces were collected from grower (n = 212) and fattener (n = 262) pigs on a farrow-to-finish farm on four occasions. HEV RNA was detected on all occasions, and prevalence was higher in growers (85.8%) than fatteners (26.0%; p < 0.001). HEV-positive samples were also collected from the wider farm environment (n = 67; 64.7% prevalence), indicating potential sources for HEV re-circulation within the herd. Timing of infection in a cohort was also investigated. HEV was absent from all piglet faeces (n = 98) and first detected at weaner stage (25.7% prevalence), but only in groups weaned earlier or comprising pigs from many different litters. Farrowing sow faeces (n = 75) were HEV-negative but antibodies were detected in blood from two sows. Results suggest that multiple factors influence HEV infection dynamics on pig farms, and potential foci for further study into practical control solutions are highlighted.
Collapse
Affiliation(s)
- Susan M. Withenshaw
- Department of Epidemiological Sciences, Animal and Plant Health Agency, Weybridge KT15 3NB, UK;
- Correspondence:
| | - Sylvia S. Grierson
- Department of Virology, Animal and Plant Health Agency, Weybridge KT15 3NB, UK;
| | - Richard P. Smith
- Department of Epidemiological Sciences, Animal and Plant Health Agency, Weybridge KT15 3NB, UK;
| |
Collapse
|
|
6
|
Choi JW, Son HJ, Lee SS, Jeon H, Cho JK, Kim HJ, Cha RR, Lee JM, Kim HJ, Jung WT, Lee OJ. Acute hepatitis E virus superinfection increases mortality in patients with cirrhosis. BMC Infect Dis 2022; 22:62. [PMID: 35042464 PMCID: PMC8767750 DOI: 10.1186/s12879-022-07050-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 01/12/2022] [Indexed: 12/20/2022] Open
Abstract
Background Although acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases the mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD).
Methods This study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed.
Results Among the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately eightfold increase in the 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate. Conclusions Our findings suggest that the acute hepatitis E mortality rate was low in healthy individuals but higher in patients with cirrhosis, and especially high in those with ACLF. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-022-07050-w.
Collapse
|
|
7
|
Fantilli A, López Villa SD, Zerega A, Di Cola G, López L, Wassaf Martínez M, Pisano MB, Ré VE. Hepatitis E virus infection in a patient with alcohol related chronic liver disease: a case report of acute-on-chronic liver failure. Virol J 2021; 18:245. [PMID: 34886883 PMCID: PMC8662871 DOI: 10.1186/s12985-021-01714-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 11/26/2021] [Indexed: 02/07/2023] Open
Abstract
Background The hepatitis E virus (HEV) infection has been described as a causing factor for acute-on-chronic-liver-failure (ACLF) in patients with underlying chronic liver disease (CLD), such as chronic hepatitis or cirrhosis, which could end in the failure of one or more organs and high short-term mortality. There are scarce data about the association of HEV in patients with chronic liver disorders in South America. Case presentation A 56-year-old hypertensive male with a history of type 2 diabetes was diagnosed with alcohol-related-liver cirrhosis in February 2019. A year later, the patient was admitted to hospital due to fatigue, jaundice and acholia. No evidence of hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein–Barr virus, herpes zoster virus and cytomegalovirus infections were found. Nevertheless, in February and March, 2020 the patient was positive for HEV-IgM and HEV-IgG, and HEV genotype 3 RNA was detected in sera. Afterwards, he presented grade I hepatic encephalopathy and, therefore, was diagnosed with acute hepatitis E-on-chronic liver disease. The patient reported a recent travel to the Argentine coast, where he consumed seafood. Besides, he reveled to have consumed pork meat and had no history of blood transfusion. Conclusion This report describes a unique case of hepatitis E virus infection in a patient with alcohol-related cirrhosis. This is the first report of a patient with HEV-related ACLF in Argentina and it invokes the importance of HEV surveillance and treatment among patients with CLD, such as alcohol-related cirrhosis.
Collapse
Affiliation(s)
- Anabella Fantilli
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina.
| | | | | | - Guadalupe Di Cola
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina
| | - Luis López
- Instituto Modelo de Cardiología, Córdoba, Argentina
| | | | - María Belén Pisano
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina
| | - Viviana Elizabeth Ré
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina
| |
Collapse
|
|
8
|
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: 31] [Impact Index Per Article: 7.8] [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: 04/21/2021] [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.
Collapse
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
| |
Collapse
|
|
9
|
Wang Y, Liu H, Jiang Y, Pan Q, Zhao J. Poor Outcomes of Acute Hepatitis E in Patients With Cirrhotic Liver Diseases Regardless of Etiology. Open Forum Infect Dis 2020; 7:ofaa107. [PMID: 32355864 PMCID: PMC7186119 DOI: 10.1093/ofid/ofaa107] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 03/24/2020] [Indexed: 02/06/2023] Open
Abstract
Background: Chronic liver diseases (CLDs) have been documented to exacerbate clinical outcomes of acute hepatitis E (AHE). This study aimed to uncover the role of etiology and status of CLD in the adverse outcomes of AHE. We found that superinfection with hepatitis E virus (HEV) in patients with cirrhotic CLD can cause a worsen outcome, leading to exacerbation of AHE, compared with HEV-infected patients without CLD or with noncirrhotic CLD. Additional analysis revealed that the etiology of CLD is not associated with outcomes of AHE patients. These finding suggests that the overall liver status plays a predominant role in determining the outcomes of AHE.
Collapse
Affiliation(s)
- Yijin Wang
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Hongyang Liu
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, Beijing, China.,Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Yiyun Jiang
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, Beijing, China.,Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Jingmin Zhao
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, Beijing, China
| |
Collapse
|
|
10
|
He B, Zhang Z, Zhang X, Tang Z, Liu C, Zheng Z, Li S, Zhang J, Xia N, Zhao Q. Functional epitopes on hepatitis E virions and recombinant capsids are highly conformation-dependent. Hum Vaccin Immunother 2020; 16:1554-1564. [PMID: 31995442 DOI: 10.1080/21645515.2019.1703454] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Hepatitis E virus (HEV) is responsible for epidemic and sporadic acute hepatitis cases, especially in developing countries. Hepatitis E has become a vaccine-preventable disease in recent years with the development of a licensed vaccine. Most functional and neutralizing monoclonal antibodies (mAbs) are known to be highly sensitive to antigen conformation. In this study, a similar approach was used to characterize the conformational sensitivity of antibodies in human or mouse serum samples. Interestingly, comparative binding analysis using different antigen forms showed that the antibodies in the sera of naturally infected individuals, of human vaccinees and from mice immunized with the HEV p239 vaccine all exhibited a strong preference to particulate antigens over the monomeric form of the truncated capsid protein. The degree of discriminating the two test antigens is similar for serum samples to that for the well-characterized murine mAbs. A functional assay for assessing the inhibition of subviral particle cell entry by antibodies was used to determine the functional titers of anti-HEV antibodies in mouse sera. A good correlation was observed between the functional and binding titers in mouse sera determined using two different methods. This result supports the continued use of the enzyme-linked immunosorbent assay as the primary serological assay assuming that the coating antigen contains conformational and native-like epitopes, as in the case for HEV p239.
Collapse
Affiliation(s)
- Bin He
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University , Xiamen, Fujian, PR China
| | - Zhigang Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University , Xiamen, Fujian, PR China
| | - Xinyuan Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University , Xiamen, Fujian, PR China
| | - Zimin Tang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University , Xiamen, Fujian, PR China
| | - Chang Liu
- School of Life Science, Xiamen University , Xiamen, Fujian, PR China
| | - Zizheng Zheng
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University , Xiamen, Fujian, PR China
| | - Shaowei Li
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University , Xiamen, Fujian, PR China.,School of Life Science, Xiamen University , Xiamen, Fujian, PR China
| | - Jun Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University , Xiamen, Fujian, PR China
| | - Ningshao Xia
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University , Xiamen, Fujian, PR China.,School of Life Science, Xiamen University , Xiamen, Fujian, PR China
| | - Qinjian Zhao
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University , Xiamen, Fujian, PR China
| |
Collapse
|
|
11
|
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: 85] [Impact Index Per Article: 17.0] [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.
Collapse
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
| |
Collapse
|
|
12
|
Rossotti R, Puoti M. Sexually Transmitted Hepatitis. Sex Transm Infect 2020. [DOI: 10.1007/978-3-030-02200-6_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
|
|
13
|
Hepatitis E virus infections in Europe. J Clin Virol 2019; 120:20-26. [PMID: 31536936 DOI: 10.1016/j.jcv.2019.09.004] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 09/06/2019] [Indexed: 12/11/2022]
|
|
14
|
Tulen AD, Vennema H, van Pelt W, Franz E, Hofhuis A. A case-control study into risk factors for acute hepatitis E in the Netherlands, 2015–2017. J Infect 2019; 78:373-381. [PMID: 30738918 DOI: 10.1016/j.jinf.2019.02.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 02/03/2019] [Indexed: 11/28/2022]
|
|
15
|
Kmush BL, Yu H, Huang S, Zhang X, Wu T, Nelson KE, Labrique AB. Long-term Antibody Persistence After Hepatitis E Virus Infection and Vaccination in Dongtai, China. Open Forum Infect Dis 2019; 6:ofz144. [PMID: 31024978 PMCID: PMC6475590 DOI: 10.1093/ofid/ofz144] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Accepted: 03/25/2019] [Indexed: 01/25/2023] Open
Abstract
Background Hepatitis E virus (HEV) is of global significance. HEV is a common cause of acute hepatitis in China. One of the major unanswered questions about HEV is the persistence of antibodies after infection and vaccination. Methods We examined antibody persistence 6.5 years after HEV exposures through natural infection and vaccination. Ninety-seven vaccine recipients and 70 individuals asymptomatically infected with HEV enrolled in the phase III HEV239 vaccine trial in Dongtai, China, were revisited. Results Antibody loss was 23.4% (95% confidence interval [CI], 17.1%-30.5%), with a nonsignificantly higher percentage of loss among those naturally infected (30.0%; 95% CI, 19.6%-42.1%) than those vaccinated (18.6%; 95% CI, 11.4%-27.7%; P = .085). Age and gender were not associated with antibody persistence. Only 2 people (1.2%) self-reported medically diagnosed jaundice or hepatitis-like illness in the last 10 years, both of whom had persistent antibodies. Contact with a jaundice patient and injectable contraceptive use were marginally associated with loss of detectable anti-HEV antibodies (P = .047 and .082, respectively), whereas transfusion was marginally associated with antibody persistence (P = .075). Conclusions Antibody loss was more common among those naturally infected compared with those vaccinated. However, none of the characteristics examined were strongly associated with antibody loss, suggesting that factors not yet identified may play a more important role in antibody loss. Long-term postvaccination antibody persistence is currently unknown and will be an important consideration in the development of policies for the use of the highly efficacious HEV vaccine. ClinicalTrials.gov registration. NCT01014845.
Collapse
Affiliation(s)
- Brittany L Kmush
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Huan Yu
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China
| | - Shoujie Huang
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China
| | - Xuefang Zhang
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China
| | - Ting Wu
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China
| | - Kenrad E Nelson
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Alain B Labrique
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| |
Collapse
|
|
16
|
Pathogenic mechanisms and current epidemiological status of HEV infection in asymptomatic blood donors and patients with chronic diseases. Eur J Clin Microbiol Infect Dis 2019; 38:1203-1209. [PMID: 30888550 DOI: 10.1007/s10096-019-03534-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 03/08/2019] [Indexed: 12/15/2022]
|
|
17
|
Meta-Analysis of Human IgG anti-HEV Seroprevalence in Industrialized Countries and a Review of Literature. Viruses 2019; 11:v11010084. [PMID: 30669517 PMCID: PMC6357031 DOI: 10.3390/v11010084] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 01/16/2019] [Accepted: 01/18/2019] [Indexed: 12/11/2022] Open
Abstract
Although Hepatitis E is increasingly described as a major cause of liver disease in industrialized countries, the epidemiology is far from being fully elucidated. We provide here a comprehensive review of documented clusters of cases, and of serological studies conducted in populations with distinct types of exposure. Seroprevalence rates range from <5% to >50% depending on the countries and the groups of population. Such discrepancies can be attributed to the type of serological assay used, but this solves only a part of the problem. We performed a meta-analysis of studies performed with the broadly used Wantai HEV-IgG ELISA and found striking differences that remain difficult to understand with the current knowledge of transmission pathways.
Collapse
|
|
18
|
Tripathy AS, Puranik S, Sharma M, Chakraborty S, Devakate UR. Hepatitis E virus seroprevalence among blood donors in Pune, India. J Med Virol 2018; 91:813-819. [PMID: 30489644 DOI: 10.1002/jmv.25370] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 11/24/2018] [Indexed: 01/17/2023]
Abstract
BACKGROUND Blood transfusion is a recently reported route of hepatitis E virus (HEV) transmission. It is a bigger concern in regions where large-scale HEV genotype 1 infections occur causing more severe disease. The present study aims to assess the prevalence and rate of HEV infection in the blood donors of Pune, India. MATERIALS AND METHODS A total of 2447 healthy blood donors were screened for anti-HEV IgG and IgM antibodies. Anti-HEV IgM antibody positives were further subjected to alanine aminotransferase measurement, HEV RNA detection, viral load quantification and phylogenetic analysis. RESULTS Anti-HEV seroprevalence rate was 17.70%, while IgM prevalence rate was 0.20%. An age dependent increase in IgG seropositive rate was observed. Two of five IgM-positives tested positive for HEV RNA. The viral load ranged from 3.5 × 104 to 4.6 × 105 copies/mL and belonged to HEV genotype 1. CONCLUSIONS HEV prevalence rate of 17.70% in the blood donors of Pune, India, a developing country, goes at par with the developed countries. Current data of 0.20% (5 of 2447) blood donors positive for anti-HEV IgM and two of them being HEV RNA positive suggest a need for consideration of cost-effective evaluation towards pooled HEV RNA testing in blood banks.
Collapse
Affiliation(s)
| | - Shaila Puranik
- Department of Pathology, B.J. Medical College and Sassoon General Hospitals, Pune, India
| | - Meenal Sharma
- Hepatitis Group, National Institute of Virology, Pune, Maharashtra, India
| | | | - Ujwal R Devakate
- Department of Pathology, B.J. Medical College and Sassoon General Hospitals, Pune, India
| |
Collapse
|
|
19
|
Abstract
Soon after the 1991 molecular cloning of hepatitis E virus (HEV), recombinant viral capsid antigens were expressed and tested in nonhuman primates for protection against liver disease and infection. Two genotype 1 subunit vaccine candidates entered clinical development: a 56 kDA vaccine expressed in insect cells and HEV 239 vaccine expressed in Escherichia coli Both were highly protective against hepatitis E and acceptably safe. The HEV 239 vaccine was approved in China in 2011, but it is not yet prequalified by the World Health Organization, a necessary step for introduction into those low- and middle-income countries where the disease burden is highest. Nevertheless, the stage is set for the final act in the hepatitis E vaccine story-policymaking, advocacy, and pilot introduction of vaccine in at-risk populations, in which it is expected to be cost-effective.
Collapse
Affiliation(s)
- Bruce L Innis
- Center for Vaccine Innovation and Access, PATH, Washington, D.C. 20001
| | - Julia A Lynch
- International Vaccine Institute, SNU Research Park, Gwanak-gu, Seoul 08826, Korea
| |
Collapse
|
|
20
|
Summary of the British Transplantation Society UK Guidelines for Hepatitis E and Solid Organ Transplantation. Transplantation 2018; 102:15-20. [PMID: 28795981 DOI: 10.1097/tp.0000000000001908] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The incidence and prevalence of hepatitis E virus (HEV) infection has increased in many developed countries over the last decade, predominantly due to infection with genotype 3 (G3) HEV. Infection with HEV G3 is important in transplant recipients because it can persist in immunosuppressed individuals, leading, if untreated, to the development of chronic hepatitis and significant liver fibrosis. The British Transplantation Society (BTS) has developed Guidelines for "Hepatitis E and Solid Organ Transplantation" to inform clinical teams and patients about hepatitis E, to help increase the recognition of persistent hepatitis E infection, and to provide clear guidance on its management. This guideline was published on the BTS website in June 2017 and aims to review the evidence relating to the diagnosis and management of persistent hepatitis E in solid organ transplant recipients and the methods of prevention of HEV infection. In line with previous guidelines published by the BTS, the guideline has used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system to rate the strength of evidence and recommendations. This article includes a summary overview of hepatitis E and transplantation with key references, and the statements of recommendation contained within the guideline. It is recommended that the full guideline document is consulted for complete details of the relevant references and evidence base. This may be accessed at https://bts.org.uk/guidelines-standards/.
Collapse
|
|
21
|
|
|
22
|
Frias M, López-López P, Rivero A, Rivero-Juarez A. Role of Hepatitis E Virus Infection in Acute-on-Chronic Liver Failure. BIOMED RESEARCH INTERNATIONAL 2018; 2018:9098535. [PMID: 30050945 PMCID: PMC6046156 DOI: 10.1155/2018/9098535] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 06/06/2018] [Indexed: 12/11/2022]
Abstract
Chronic liver disease (CLD) with a variety of causes is currently reported to be one of the main causes of death worldwide. Patients with CLD experience deteriorating liver function and fibrosis, progressing to cirrhosis, chronic hepatic decompensation (CHD), end-stage liver disease (ESLD), and death. Patients may develop acute-on-chronic liver failure (ACLF), typically related to a precipitating event and associated with increased mortality. The objective of this review was to analyze the role of acute hepatitis E virus (HEV) infection in patients with CLD, focusing on the impact of this infection on patient survival and prognosis in several world regions.
Collapse
Affiliation(s)
- Mario Frias
- Clinical Virology and Zooneses, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Spain
| | - Pedro López-López
- Clinical Virology and Zooneses, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Spain
| | - Antonio Rivero
- Clinical Virology and Zooneses, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Spain
| | - Antonio Rivero-Juarez
- Clinical Virology and Zooneses, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Spain
| |
Collapse
|
|
23
|
Hepatitis E in High-Income Countries: What Do We Know? And What Are the Knowledge Gaps? Viruses 2018; 10:v10060285. [PMID: 29799485 PMCID: PMC6024799 DOI: 10.3390/v10060285] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 05/16/2018] [Accepted: 05/23/2018] [Indexed: 12/11/2022] Open
Abstract
Hepatitis E virus (HEV) is a positive-strand RNA virus transmitted by the fecal–oral route. HEV genotypes 1 and 2 infect only humans and cause mainly waterborne outbreaks. HEV genotypes 3 and 4 are widely represented in the animal kingdom, and are mainly transmitted as a zoonosis. For the past 20 years, HEV infection has been considered an imported disease in developed countries, but now there is evidence that HEV is an underrecognized pathogen in high-income countries, and that the incidence of confirmed cases has been steadily increasing over the last decade. In this review, we describe current knowledge about the molecular biology of HEV, its clinical features, its main routes of transmission, and possible therapeutic strategies in developed countries.
Collapse
|
|
24
|
Liu L, Xiao D, Yu JH, Shen R, Wang M, Li Q. Clinical course of sporadic acute hepatitis E in a hepatitis B virus endemic region. Int J Infect Dis 2018; 70:107-114. [PMID: 29551632 DOI: 10.1016/j.ijid.2018.03.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 03/03/2018] [Accepted: 03/09/2018] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES In China, the epidemic pattern of acute hepatitis E virus (HEV) infection has changed from waterborne outbreaks to foodborne sporadic cases. However, the clinical course of sporadic acute hepatitis E (AHE) has not been well defined. METHODS Consecutive patients with AHE who were admitted to the Jinan Infectious Disease Hospital, Jinan, Shandong Province between January 2003 and December 2014 were evaluated and followed. Demographic data, clinical manifestations, results of laboratory tests, and outcomes were recorded. Risk factors for liver failure and death were analyzed. RESULTS A total of 680 patients with AHE were identified during the study period. The incidence was highest in February, March, and April, accounting for about 41% of the cases. The male to female ratio was 5.1:1 (574/106). The average age was 50.9±12.8years. The prevalence rates of prodromal fever, fatigue, loss of appetite, and jaundice were 25.6%, 85.6%, 83.8%, and 92.8%, respectively. The median (range) serum alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, and platelet levels were 727 (8-6270) U/l, 300 (17-6226) U/l, 196.8 (8.0-1083) μmol/l, 33.0 (15.2-45.8) g/l, and 162 (10-589)×109/l, respectively. The prevalence of hepatitis B surface antigen (HBsAg) was 18.5% (126/680) and of liver cirrhosis was 9.4% (64/680). Thirteen percent (89/680) of the cases progressed to liver failure, including 4.1% (28/680) with acute liver failure (ALF) and 9.0% (61/680) with acute-on-chronic liver failure (ACLF). Among patients with HBsAg positivity or cirrhosis, 28.6% (36/126) and 36.0% (23/64), respectively, progressed to ACLF. Multiple logistic regression analysis indicated that age >53years, prodromal fever, HBsAg positivity, cirrhosis, and thrombocytopenia (platelet count <150×109/l) were independently associated with the development of liver failure, with an odds ratio (95% confidence interval) of 2.5 (1.5-4.3), 1.9 (1.1-3.2), 3.7 (2.0-6.7), 2.1 (1.1-4.2), and 5.9 (3.3-10.4), respectively. The overall mortality was 5.6% (38/680), and the mortality rates in patients with and without underlying liver disease were 9.3% (22/237) and 3.6% (16/443), respectively. Multiple logistic regression analysis indicated that hepatic encephalopathy, bilirubin >500μmol/l, international normalized ratio (INR)>2, and severe thrombocytopenia (platelet count <100×109/l) were independently associated with death, with an odds ratio (95% confidence interval) of 7.2 (2.4-21.8), 5.8 (1.9-17.2), 24.1 (7.9-73.3), and 10.8 (3.6-32.9), respectively. CONCLUSIONS In areas that are dual endemic for hepatitis B virus and HEV, the HEV vaccine for patients with obvious liver diseases is of significance. Thrombocytopenia is an important predictor of liver failure and mortality in sporadic AHE.
Collapse
Affiliation(s)
- Li Liu
- Division of Liver Diseases, Jinan Infectious Disease Hospital, Shandong University, Jinan, China
| | - Di Xiao
- Division of Liver Diseases, Jinan Infectious Disease Hospital, Shandong University, Jinan, China
| | - Jin-Hong Yu
- Division of Liver Diseases, Jinan Infectious Disease Hospital, Shandong University, Jinan, China
| | - Rui Shen
- Division of Liver Diseases, Jinan Infectious Disease Hospital, Shandong University, Jinan, China
| | - Meng Wang
- Division of Liver Diseases, Jinan Infectious Disease Hospital, Shandong University, Jinan, China; Division of Infectious Diseases, Jinan Central Hospital, Shandong University, Jinan, China
| | - Qiang Li
- Division of Liver Diseases, Jinan Infectious Disease Hospital, Shandong University, Jinan, China.
| |
Collapse
|
|
25
|
Grabarczyk P, Sulkowska E, Gdowska J, Kopacz A, Liszewski G, Kubicka-Russel D, Baylis SA, Corman VM, Noceń E, Piotrowski D, Antoniewicz-Papis J, Łętowska M. Molecular and serological infection marker screening in blood donors indicates high endemicity of hepatitis E virus in Poland. Transfusion 2018; 58:1245-1253. [PMID: 29492976 DOI: 10.1111/trf.14531] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 12/11/2017] [Accepted: 01/04/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND Until now, markers of hepatitis E virus (HEV) infection have not been studied in blood donors throughout Poland, and no acute case of HEV infection has been closely documented or confirmed by HEV RNA detection. The prevalence of HEV infection markers, including HEV RNA in Polish blood donors and virus genotypes was investigated. STUDY DESIGN AND METHODS In total, 12,664 individual donations from 22 Polish blood transfusion centers were tested for HEV RNA by transcription-mediated amplification. In addition, 3079 first-time donors sampled throughout Poland also were screened for antibodies to HEV. HEV RNA and immunoglobulin M-positive donations were confirmed using real-time reverse transcription-polymerase chain reaction and Western blotting, respectively. RESULTS Ten donors were identified as RNA initial reactive (one of 1266 donors), and six (one of 2109) were identified as repeat reactive and confirmed by real-time reverse transcription-polymerase chain reaction or seroconversion. Sequence analysis identified HEV Genotype 3c in one donor and Genotype 3i in two others. On average, 43.5% of donors were immunoglobulin G-positive. Immunoglobulin G seroprevalence ranged from 22.7% to 60.8% in group ages 18 to 27 years and 48 to 57 years, respectively and differed between administrative regions from 28.9% in Podlasie to 61.3% in Wielkopolska. Thirty-nine of the donors were immunoglobulin M-positive, and seven donors were IgM positive only (0.2%). Of 37 immunoglobulin M-reactive samples tested by Western blot, 24 (64.9%) were confirmed. CONCLUSIONS The current results indicate a high level of HEV endemicity throughout Poland compared with other countries. There is an urgent need to consider the protection of recipients of blood components against transfusion-transmitted HEV infection.
Collapse
Affiliation(s)
| | | | | | - Aneta Kopacz
- Institute of Haematology and Transfusion Medicine
| | | | | | - Sally A Baylis
- Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institut, Langen, Germany
| | - Victor M Corman
- Institute of Virology, Charité-Universitätsmedizin Berlin.,German Centre for Infection Research (DZIF), Berlin, Germany
| | - Ewa Noceń
- Institute of Haematology and Transfusion Medicine
| | | | | | | |
Collapse
|
|
26
|
Melgaço JG, Gardinali NR, de Mello VDM, Leal M, Lewis-Ximenez LL, Pinto MA. Hepatitis E: Update on Prevention and Control. BIOMED RESEARCH INTERNATIONAL 2018; 2018:5769201. [PMID: 29546064 PMCID: PMC5818934 DOI: 10.1155/2018/5769201] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 11/28/2017] [Accepted: 12/13/2017] [Indexed: 12/20/2022]
Abstract
Hepatitis E virus (HEV) is a common etiology of acute viral hepatitis worldwide. Recombinant HEV vaccines have been developed, but only one is commercially available and licensed in China since 2011. Epidemiological studies have identified genotype 3 as the major cause of chronic infection in immunocompromised individuals. Ribavirin has been shown to be effective as a monotherapy to induce HEV clearance in chronic patients who have undergone solid organ transplant (SOT) under immunosuppressive therapy. Efforts and improvements in prevention and control have been made to reduce the instances of acute and chronic hepatitis E in endemic and nonendemic countries. However, this review shows that further studies are required to demonstrate the importance of preventive vaccination and treatment worldwide, with emphasis on hepatitis E infection in the public health system.
Collapse
Affiliation(s)
- Juliana Gil Melgaço
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Noemi Rovaris Gardinali
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Vinicius da Motta de Mello
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Mariana Leal
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Lia Laura Lewis-Ximenez
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Marcelo Alves Pinto
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| |
Collapse
|
|
27
|
Pondé RADA. The serological markers of acute infection with hepatitis A, B, C, D, E and G viruses revisited. Arch Virol 2017; 162:3587-3602. [PMID: 28884240 DOI: 10.1007/s00705-017-3538-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2016] [Accepted: 12/20/2016] [Indexed: 12/19/2022]
Abstract
Viral hepatitis is a liver infection caused by one of the six hepatitis viruses: hepatitis A, B, C, D, E, and G virus (HAV to HEV and HGV). These agents differ in their biological, immunological, pathological and epidemiological characteristics. They cause infections that, when symptomatic, lead to clinical manifestations and laboratory findings that are not specific to a particular virus, often making differential diagnosis difficult, especially when no knowledge is available regarding the patient's medical history or the epidemiological background. A number of acute-phase serological markers, such as anti-HAV, anti-HBc, anti-HDV and anti-HEV IgM antibodies, are able to provide a clear indication of an infection caused by HAV, HBV, HDV or HEV. Anti-HCV antibodies and HGV/RNA are used for the diagnosis of HCV and HGV infections. The importance of each of these markers will be reviewed, and different factors that can interfere with the diagnosis of acute infections caused by these viruses will be described.
Collapse
Affiliation(s)
- Robério Amorim de Almeida Pondé
- Laboratory of Human Virology, Institute of Tropical Pathology and Public Health, Federal University of Goias, Goiânia, Goiás, Brazil. .,Secretaria Estadual de Saúde -SES/Superintendência de Vigilância em Saúde-SUVISA/GO, Gerência de Vigilância em Saúde-GVE/Coordenação de Análises e Pesquisas-CAP, Goiânia, Goiás, Brazil. .,Faculdade União de Goyazes-FUG (College Union of Goyazes), Department of Hematology and Clinical Microbiology, Trindade, Goiás, Brazil. .,, Rua 136 Qd F44 Lt 22/24 Ed. César Sebba - Setor Sul, Goiânia, Goiás, 74-093-250, Brazil.
| |
Collapse
|
|
28
|
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
| | | |
Collapse
|
|
29
|
Grabarczyk P, Kopacz A, Sulkowska E, Kalińska A. [Risk of transmission of blood-derived pathogens by transfusion in Poland]. ACTA HAEMATOLOGICA POLONICA 2017; 48:174-182. [PMID: 32226060 PMCID: PMC7094117 DOI: 10.1016/j.achaem.2017.07.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 07/18/2017] [Indexed: 06/10/2023]
Abstract
Blood transfusion in Poland is the safest in history. High virological level of safety has been achieved mainly by improving not only the qualification of donors and methods used for donor screening, but also applying leukoreduction, pathogen reduction technology and grace period for serum.In this article, we discuss the improvement of the epidemic situation among blood donors for hepatitis B virus (HBV) and hepatitis C virus (HCV) and the increasing trend for HIV. Preliminary results of residual risk calculation for these pathogens are presented.Hepatitis E virus (HEV) and Babesia microti were considered as new factors potentially relevant for the safety of blood transfusion in our country. Due to evidence of West Nile virus (WNV) circulation in the ecosystem in Poland, it is also necessary to monitor the infections with this pathogen.In this article, it was emphasized that the reporting of all possible complications associated with transfusion and meticulous implementation of the look-back procedure play a key role for monitoring the risk of transmission of infectious agents by blood. It is especially important in view of the increasing epidemiological problems associated with emerging infectious agents.
Collapse
Affiliation(s)
- Piotr Grabarczyk
- Zakład Wirusologii, Instytut Hematologii i Transfuzjologii w Warszawie, Polska
| | - Aneta Kopacz
- Zakład Wirusologii, Instytut Hematologii i Transfuzjologii w Warszawie, Polska
| | - Ewa Sulkowska
- Zakład Wirusologii, Instytut Hematologii i Transfuzjologii w Warszawie, Polska
| | - Aleksandra Kalińska
- Zakład Wirusologii, Instytut Hematologii i Transfuzjologii w Warszawie, Polska
| |
Collapse
|
|
30
|
Amanya G, Kizito S, Nabukenya I, Kalyango J, Atuheire C, Nansumba H, Abwoye SA, Opio DN, Kibuuka E, Karamagi C. Risk factors, person, place and time characteristics associated with Hepatitis E Virus outbreak in Napak District, Uganda. BMC Infect Dis 2017; 17:451. [PMID: 28651629 PMCID: PMC5485539 DOI: 10.1186/s12879-017-2542-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 06/09/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Hepatitis E is self-limiting, but can cause death in most at risk groups like pregnant women and those with preexisting acute liver disease. In developing countries it presents as epidemic, in 2014 Hepatitis E Virus (HEV) outbreak was reported in Napak district Uganda. The role of factors in this setting that might have propagated this HEV epidemic, including host, agent, and environmental characteristics, were still not clear. This study was therefore conducted to investigate the risk factors, person, place and time characteristics, associated with the hepatitis E virus (HEV) epidemic in Napak district. METHODS Review of line lists data for epidemiological description and matched case control study on neighborhood and age in the ratio of 1:2 were used to assess risk factors for HEV outbreak in Napak. Cluster and random sampling were used to obtain a sample size of 332, (111 cases, 221 controls). Possible interaction and confounding was assessed using conditional logistic regression. RESULTS Over 1359 cases and 30 deaths were reported during 2013/2014 HEV outbreak. The mean age of patients was 29 ± years, 57.9% of cases were females. Overall case Fatality Ratio was 2.2% in general population but 65.2% in pregnant women. More than 94% of the cases were reported in the sub counties of Napak, 5.7% of cases were reported in the outside neighboring districts. The epidemic peaked in January 2014 and gradually subsided by December 2014. Risk factors found to be associated with HEV included drinking untreated water (OR 6.69, 95% CI 3.15-14.16), eating roadside food (OR 6.11, 95% CI 2.85-13.09), reported not cleaning utensils (OR 3.24, 95% CI 1.55-1.76), and being a hunter (OR 1.14, 95% CI 1.03-12.66). CONCLUSION The results of this study suggest that the virus is transmitted by the feco-oral route through contaminated water. They also suggest that active surveillance and appropriate measures targeting community and routine individual health actions are important to prevent transmission and decrease the deaths.
Collapse
Affiliation(s)
- Geofrey Amanya
- Clinical Epidemiology Unit, School of Medicine, P.O Box 7072, Kampala, Uganda
| | - Samuel Kizito
- Clinical Epidemiology Unit, School of Medicine, P.O Box 7072, Kampala, Uganda
- Makerere University College of Health Sciences, P.O Box 7072, Kampala, Uganda
| | - Immaculate Nabukenya
- Epidemiology and surveillance Division, Ministry Of Health, P.O Box 7076, Kampala, Uganda
| | - Joan Kalyango
- Clinical Epidemiology Unit, School of Medicine, P.O Box 7072, Kampala, Uganda
- Makerere University College of Health Sciences, P.O Box 7072, Kampala, Uganda
| | - Collins Atuheire
- Clinical Epidemiology Unit, School of Medicine, P.O Box 7072, Kampala, Uganda
| | - Hellen Nansumba
- Clinical Epidemiology Unit, School of Medicine, P.O Box 7072, Kampala, Uganda
| | | | - Denis Nixon Opio
- Clinical Epidemiology Unit, School of Medicine, P.O Box 7072, Kampala, Uganda
| | - Edrisa Kibuuka
- Clinical Epidemiology Unit, School of Medicine, P.O Box 7072, Kampala, Uganda
| | - Charles Karamagi
- Clinical Epidemiology Unit, School of Medicine, P.O Box 7072, Kampala, Uganda
- Makerere University College of Health Sciences, P.O Box 7072, Kampala, Uganda
| |
Collapse
|
|
31
|
Vollmer T, Diekmann J, Eberhardt M, Knabbe C, Dreier J. Hepatitis E in blood donors: investigation of the natural course of asymptomatic infection, Germany, 2011. ACTA ACUST UNITED AC 2017; 21:30332. [PMID: 27608433 PMCID: PMC5015460 DOI: 10.2807/1560-7917.es.2016.21.35.30332] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 02/16/2016] [Indexed: 12/16/2022]
Abstract
Asymptomatic hepatitis E virus (HEV) infections have been found in blood donors from various European countries, but the natural course is rarely specified. Here, we compared the progression of HEV viraemia, serostatus and liver-specific enzymes in 10 blood donors with clinically asymptomatic genotype 3 HEV infection, measuring HEV RNA concentrations, plasma concentrations of alanine/aspartate aminotransferase, glutamate dehydrogenase and bilirubin and anti-HEV IgA, IgM and IgG antibodies. RNA concentrations ranged from 77.2 to 2.19×105 IU/mL, with viraemia lasting from less than 10 to 52 days. Donors showed a typical progression of a recent HEV infection but differed in the first detection of anti-HEV IgA, IgM and IgG and seropositivity of the antibody classes. The diagnostic window between HEV RNA detection and first occurrence of anti-HEV antibodies ranged from eight to 48 days, depending on the serological assay used. The progression of laboratory parameters of asymptomatic HEV infection was largely comparable to the progression of symptomatic HEV infection, but only four of 10 donors showed elevated liver-specific parameters. Our results help elucidate the risk of transfusion-associated HEV infection and provide a basis for development of screening strategies. The diagnostic window illustrates that infectious blood donors can be efficiently identified only by RNA screening.
Collapse
Affiliation(s)
- Tanja Vollmer
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | | | | | | | | |
Collapse
|
|
32
|
Molecular Epidemiology and Strain Comparison between Hepatitis E Viruses in Human Sera and Pig Livers during 2014 to 2016 in Hong Kong. J Clin Microbiol 2017; 55:1408-1415. [PMID: 28202801 DOI: 10.1128/jcm.02020-16] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Accepted: 02/08/2017] [Indexed: 12/21/2022] Open
Abstract
Hepatitis E virus (HEV) causes substantial morbidity and mortality in developing countries and is considered an emerging foodborne pathogen in developed countries in which it was previously not endemic. To investigate genetic association between human HEV infection and HEV-contaminated high-risk food in Hong Kong, we compared local virus strains obtained from hepatitis E patient sera with those surveyed from high-risk food items during 2014 to 2016. Twenty-four cases of laboratory-confirmed human HEV infections were identified from January 2014 to March 2016 in our hospitals. Five types of food items at risk of HEV contamination were purchased on a biweekly basis from April 2014 to March 2016 in two local market settings: supermarkets (lamb, oyster, and pig liver) and wet markets (oyster, pig blood curd, pig large intestine, and pig liver). HEV RNA detection was performed by a real-time reverse transcription-PCR assay. HEV RNA was detected in pig liver, pig intestine, and oyster samples with prevalences of 1.5%, 0.4%, and 0.2%, respectively. Neighbor-joining phylogenetic inference showed that all human and swine HEV strains belonged to genotype 4. HEV subtype distributions in humans and swine were highly comparable: subtype 4b predominated, while subtype 4d was the minority. Local human and swine HEV genotype 4 strains shared over 95% nucleotide identity and were genetically very similar, implicating swine as an important foodborne source of autochthonous human HEV infections in Hong Kong. Action should be taken to raise the awareness among public and health care professionals of hepatitis E as an emerging foodborne disease.
Collapse
|
|
33
|
Müller A, Collineau L, Stephan R, Müller A, Stärk KD. Assessment of the risk of foodborne transmission and burden of hepatitis E in Switzerland. Int J Food Microbiol 2017; 242:107-115. [DOI: 10.1016/j.ijfoodmicro.2016.11.018] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 10/11/2016] [Accepted: 11/19/2016] [Indexed: 01/16/2023]
|
|
34
|
Wallace SJ, Webb GW, Madden RG, Dalton HC, Palmer J, Dalton RT, Pollard A, Martin R, Panayi V, Bennett G, Bendall RP, Dalton HR. Investigation of liver dysfunction: who should we test for hepatitis E? Eur J Gastroenterol Hepatol 2017; 29:215-220. [PMID: 27832041 DOI: 10.1097/meg.0000000000000781] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
AIM Hepatitis E virus (HEV) is endemic in developed countries, but unrecognized infection is common. Many national guidelines now recommend HEV testing in patients with acute hepatitis irrespective of travel history. The biochemical definition of 'hepatitis' that best predicts HEV infection has not been established. This study aimed to determine parameters of liver biochemistry that should prompt testing for acute HEV. METHODS This was a retrospective study of serial liver function tests (LFTs) in cases of acute HEV (n=74) and three comparator groups: common bile duct stones (CBD, n=87), drug-induced liver injury (DILI, n=69) and patients testing negative for HEV (n=530). To identify the most discriminating parameters, LFTs from HEV cases, CBD and DILI were compared. Optimal LFT cutoffs for HEV testing were determined from HEV true positives and HEV true negatives using receiver operating characteristic curve analysis. RESULTS Compared with CBD and DILI, HEV cases had a significantly higher maximum alanine aminotransferase (ALT) (P<0.001) and ALT/alkaline phosphatase (ALKP) ratio (P<0.001). For HEV cases/patients testing negative for HEV, area under receiver operating characteristic curve was 0.805 for ALT (P<0.001) and 0.749 for the ALT/ALKP ratio (P<0.001). Using an ALT of at least 300 IU/l to prompt HEV testing has a sensitivity of 98.6% and a specificity of 30.3% compared with an ALT/ALKP ratio higher than or equal to 2 (sensitivity 100%, specificity 9.4%). CONCLUSION Patients with ALT higher than or equal to 300 IU/l should be tested for HEV. This is simple, detects nearly all cases and requires fewer samples to be tested than an ALT/ALKP ratio higher than or equal to 2. Where clinically indicated, patients with an ALT less than 300 IU/l should also be tested, particularly if HEV-associated neurological injury is suspected.
Collapse
Affiliation(s)
- Sebastian J Wallace
- Royal Cornwall Hospital Trust and European Centre for Environment and Human Health, University of Exeter, Truro, UK
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Pelosi E, Clarke I. Hepatitis E: a complex and global disease. EMERGING HEALTH THREATS JOURNAL 2017. [DOI: 10.3402/ehtj.v1i0.7069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- E Pelosi
- Department of Microbiology and Virology, Health Protection Agency, Southeast Regional Laboratory, Southampton General Hospital, Southampton, UK; and
| | - I Clarke
- Department of Molecular Microbiology, Southampton Medical School, Southampton General Hospital, Southampton, UK
| |
Collapse
|
|
36
|
Vollmer T, Knabbe C, Dreier J. Knowledge Is Safety: The Time Is Ripe for Hepatitis E Virus Blood Donor Screening. Transfus Med Hemother 2016; 43:425-427. [PMID: 27994530 DOI: 10.1159/000450794] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Accepted: 09/06/2016] [Indexed: 01/22/2023] Open
Affiliation(s)
- Tanja Vollmer
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - Cornelius Knabbe
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - Jens Dreier
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| |
Collapse
|
|
37
|
van Tong H, Hoan NX, Wang B, Wedemeyer H, Bock CT, Velavan TP. Hepatitis E Virus Mutations: Functional and Clinical Relevance. EBioMedicine 2016; 11:31-42. [PMID: 27528267 PMCID: PMC5049923 DOI: 10.1016/j.ebiom.2016.07.039] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 07/29/2016] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) infection is a major cause of acute hepatitis and affects more than 20 million individuals, with three million symptomatic cases and 56,000 recognized HEV-related deaths worldwide. HEV is endemic in developing countries and is gaining importance in developed countries, due to increased number of autochthone cases. Although HEV replication is controlled by the host immune system, viral factors (especially specific viral genotypes and mutants) can modulate HEV replication, infection and pathogenesis. Limited knowledge exists on the contribution of HEV genome variants towards pathogenesis, susceptibility and to therapeutic response. Nonsynonymous substitutions can modulate viral proteins structurally and thus dysregulate virus-host interactions. This review aims to compile knowledge and discuss recent advances on the casual role of HEV heterogeneity and its variants on viral morphogenesis, pathogenesis, clinical outcome and antiviral resistance.
Collapse
Affiliation(s)
- Hoang van Tong
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
| | - Nghiem Xuan Hoan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Bo Wang
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - C-Thomas Bock
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany.
| | | |
Collapse
|
|
38
|
O'Riordan J, Boland F, Williams P, Donnellan J, Hogema BM, Ijaz S, Murphy WG. Hepatitis E virus infection in the Irish blood donor population. Transfusion 2016; 56:2868-2876. [DOI: 10.1111/trf.13757] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 06/23/2016] [Accepted: 06/23/2016] [Indexed: 12/17/2022]
Affiliation(s)
- Joan O'Riordan
- Irish Blood Transfusion Service, National Blood Centre; Dublin Ireland
| | - Fiona Boland
- Irish Blood Transfusion Service, National Blood Centre; Dublin Ireland
| | - Padraig Williams
- Irish Blood Transfusion Service, National Blood Centre; Dublin Ireland
| | - Joe Donnellan
- Irish Blood Transfusion Service, National Blood Centre; Dublin Ireland
| | - Boris M. Hogema
- Departments of Blood-borne Infections and Virology; Sanquin Research and Diagnostic Services; Amsterdam the Netherlands
| | - Samreen Ijaz
- Blood Borne Virus Unit, Virus Reference Department; National Infection Service, Public Health England; London UK
| | - William G. Murphy
- Irish Blood Transfusion Service, National Blood Centre; Dublin Ireland
| |
Collapse
|
|
39
|
Lhomme S, Marion O, Abravanel F, Chapuy-Regaud S, Kamar N, Izopet J. Hepatitis E Pathogenesis. Viruses 2016; 8:E212. [PMID: 27527210 PMCID: PMC4997574 DOI: 10.3390/v8080212] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 07/22/2016] [Accepted: 07/27/2016] [Indexed: 02/08/2023] Open
Abstract
Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years.
Collapse
Affiliation(s)
- Sébastien Lhomme
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
| | - Olivier Marion
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
- INSERM, UMR1043, Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Université Paul Sabatier, 31000 Toulouse, France.
| | - Florence Abravanel
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
| | - Sabine Chapuy-Regaud
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
| | - Nassim Kamar
- INSERM, UMR1043, Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Université Paul Sabatier, 31000 Toulouse, France.
| | - Jacques Izopet
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
| |
Collapse
|
|
40
|
Erez-Granat O, Lachish T, Daudi N, Shouval D, Schwartz E. Hepatitis E in Israel: A nation-wide retrospective study. World J Gastroenterol 2016; 22:5568-5577. [PMID: 27350735 PMCID: PMC4917617 DOI: 10.3748/wjg.v22.i24.5568] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Revised: 05/11/2016] [Accepted: 05/23/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the epidemiology, risk factors and clinical course of acute hepatitis E virus (HEV) infection in Israel, an industrialized country.
METHODS: A retrospective analysis of acute HEV cases diagnosed in Israel from 1993 to 2013. Acute HEV was defined by ALT/AST elevation and a positive HEV PCR test or positive anti-HEV-IgM serology. HEV RNA was tested by quantitative reverse transcription PCR. Antibodies to HEV were tested retrospectively using an ELISA assay. HEV-RNA was sequenced using RT-PCR of ORF1 and ORF2 regions to diagnose genotype of the virus. Epidemiologic and clinical data were collected by reviewing the clinical files and through a telephone interview according to a structured questionnaire.
RESULTS: Acute HEV was diagnosed in 68 patients. Among the 59 patients who gave an informed consent and were interviewed, 41% of infections were autochthonous (acquired in Israel), 44% travel-related and 15% imported by foreign workers. Autochthonous patients were mainly females (62.5%), more than half of them pregnant, 26% recalled consuming food or water in areas with poor sanitation, 44% ate non-kosher meat. Fulminant hepatitis developed in 3 patients (5%), all of them were females, two of them with post-partum infection, all acquired the disease in Israel (autochthonous). Israeli travelers with imported infection were predominantly males (73%), acquired the disease in the Indian subcontinent (81%), with 100% reporting having consumed fresh vegetables and drinks with ice cubes abroad. Six patients’ sera were tested for genotype and revealed HEV genotype 1 (all cases acquired in the Indian subcontinent).
CONCLUSION: This is the first report which highlights the existence of hepatitis E as an autochthonous infection in Israel. Imported HEV originates mostly from the Indian subcontinent.
Collapse
|
|
41
|
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.
Collapse
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
| |
Collapse
|
|
42
|
Wang X, Li M, Li S, Wu T, Zhang J, Xia N, Zhao Q. Prophylaxis against hepatitis E: at risk populations and human vaccines. Expert Rev Vaccines 2016; 15:815-27. [PMID: 26775537 DOI: 10.1586/14760584.2016.1143365] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatitis E is an emerging global disease caused by hepatitis E virus (HEV) infection. While in developing countries the infection was primarily due to poor sanitary conditions through intake of contaminated water or undercooked meats of infected animals, increasing cases of chronic hepatitis E resulting in rapidly progressive liver cirrhosis and end-stage liver disease have been reported in organ transplant patients or in immune compromised patients in developed countries. Fortunately, hepatitis E is now a vaccine preventable disease with a HEV239 based vaccine licensed for human use. Much work is needed to enable its use outside China. This review recounted the development process of the vaccine, outlined the critical quality attributes of the vaccine antigen and, most importantly, listed the populations at risk for HEV infection and the subsequent disease. These at risk populations could benefit the most from the vaccination if the vaccine is widely adopted.
Collapse
Affiliation(s)
- Xin Wang
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China
| | - Min Li
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China
| | - Shaowei Li
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China.,c School of Life Science , Xiamen University , Xiamen , PR China
| | - Ting Wu
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China.,c School of Life Science , Xiamen University , Xiamen , PR China
| | - Jun Zhang
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China.,c School of Life Science , Xiamen University , Xiamen , PR China
| | - Ningshao Xia
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China.,c School of Life Science , Xiamen University , Xiamen , PR China
| | - Qinjian Zhao
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China
| |
Collapse
|
|
43
|
Marion O, Abravanel F, Lhomme S, Izopet J, Kamar N. Hepatitis E in Transplantation. Curr Infect Dis Rep 2016; 18:8. [DOI: 10.1007/s11908-016-0515-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
|
|
44
|
Nijskens CM, Pas SD, Cornelissen J, Caliskan K, Hoek RA, Hesselink DA, van der Eijk AA, de Man RA. Hepatitis E virus genotype 3 infection in a tertiary referral center in the Netherlands: Clinical relevance and impact on patient morbidity. J Clin Virol 2016; 74:82-7. [DOI: 10.1016/j.jcv.2015.11.038] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Revised: 11/27/2015] [Accepted: 11/29/2015] [Indexed: 01/05/2023]
|
|
45
|
De Keukeleire S, Reynders M. Hepatitis E: An Underdiagnosed, Emerging Infection in Nonendemic Regions. J Clin Transl Hepatol 2015; 3:288-91. [PMID: 26807386 PMCID: PMC4721898 DOI: 10.14218/jcth.2015.00039] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Revised: 11/24/2015] [Accepted: 11/26/2015] [Indexed: 02/07/2023] Open
Abstract
Although hepatitis E virus (HEV) is the primary cause of enterically transmitted acute hepatitis and jaundice in developing countries, locally acquired HEV infections are increasing in nonendemic countries. As such, HEV is emerging as an underdiagnosed cause of infection. This report describes three clinically variable cases of HEV infection with unusual clinical presentations. These cases highlight the fact that HEV should be considered in the differential diagnosis of patients with unexplained hepatitis (acute or chronic) with or without extrahepatic manifestations. HEV should also be considered in patients with persistently elevated liver enzymes who have not travelled to known HEV-endemic regions. Lack of knowledge among physicians and an absence of standardized diagnostic tests may result in increased morbidity and mortality from HEV infection.
Collapse
Affiliation(s)
| | - Marijke Reynders
- Correspondence to: Marijke Reynders, Department of Laboratory Medicine, Clinical Microbiology, AZ Sint-Jan Bruges-Ostend, Ruddershove 10, Bruges 8000, Belgium. Tel: +32-5045-2603, Fax: +32-5045-2619, E-mail:
| |
Collapse
|
|
46
|
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; 42:574-581. [PMID: 26174470 DOI: 10.1111/apt.13309] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [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.
Collapse
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
| |
Collapse
|
|
47
|
Dalton HR, Kamar N, Izopet J. Hepatitis E in developed countries: current status and future perspectives. Future Microbiol 2015; 9:1361-72. [PMID: 25517900 DOI: 10.2217/fmb.14.89] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Hepatitis E virus (HEV) was for many years thought to be found almost exclusively in developing countries, where it is a major health issue. Recent studies have shown that HEV causes acute and chronic infection in developed countries. In these geographical settings, HEV is primarily a porcine zoonosis caused by genotypes 3 (HEV3) and 4 (HEV4). The clinical phenotype of hepatitis E continues to emerge, and recent data show that HEV is associated with a range of neurological syndromes including Guillain-Barré syndrome and neuralgic amytrophy.
Collapse
Affiliation(s)
- Harry R Dalton
- Cornwall Gastrointestinal Unit, Royal Cornwall Hospital & European Centre for the Environment & Human Health, University of Exeter Medical School, Truro TR1 3LJ, UK
| | | | | |
Collapse
|
|
48
|
Colson P, Saint-Jacques P, Ferretti A, Davoust B. Hepatitis E Virus of Subtype 3a in a Pig Farm, South-Eastern France. Zoonoses Public Health 2015; 62:593-8. [PMID: 26102074 DOI: 10.1111/zph.12211] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Indexed: 12/16/2022]
Abstract
Hepatitis E virus (HEV) has emerged during the past decade as a causative agent of autochthonous hepatitis and is a clinical concern in Western developed countries. It has been increasingly recognized that pigs are a major reservoir of HEV of genotypes 3 and 4 worldwide and pig-derived food items represent a potential source of infections by these viruses in humans. Hepatitis E virus RNA testing was performed here on faeces from rectal swabs sampled in 2012 from 50 3-month-old farm pigs from the same farm located in south-eastern France than in a previous work conducted in 2007. Pig HEV sequences corresponding to genomic fragments of ORF2 and ORF1 genes were obtained after RT-PCR amplification with in-house protocols. Hepatitis E virus genotype was determined by phylogenetic analysis. Prevalence was similar to that determined 5 years earlier (68% versus 62%). Two robust phylogenetic clusters of HEV subtypes 3a and 3f were identified, and these sequences obtained in 2012 largely differ compared with those obtained in 2007. Notably, HEV sequences obtained in 2012 from a majority (62%) of the infected pigs belonged to subtype 3a, which was not previously described in France, including not being found in any of humans, pigs or wild boars. Further studies are needed to assess the circulation of HEV-3a in pigs and humans in this country. In addition, along with previous findings, this study supports the need for increased information to the public on the risk of HEV infection through contacts with pigs or consumption of pig-derived products in France.
Collapse
Affiliation(s)
- P Colson
- Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE) UM 63 CNRS 7278 IRD 198 INSERM U1095, Aix-Marseille Université, Marseille, France.,Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France
| | - P Saint-Jacques
- Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France
| | - A Ferretti
- Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France
| | - B Davoust
- Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE) UM 63 CNRS 7278 IRD 198 INSERM U1095, Aix-Marseille Université, Marseille, France
| |
Collapse
|
|
49
|
Wu J, Si F, Jiang C, Li T, Jin M. Molecular detection of hepatitis E virus in sheep from southern Xinjiang, China. Virus Genes 2015; 50:410-7. [PMID: 25833205 PMCID: PMC4445917 DOI: 10.1007/s11262-015-1194-9] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Accepted: 03/27/2015] [Indexed: 12/16/2022]
Abstract
Hepatitis E virus (HEV) is a causative agent of infectious hepatitis in animals and humans both in developing and developed countries. Here, we collected 500 sheep sera and 75 raw sheep liver samples from a slaughterhouse in the southern part of the Xinjiang region, China, along with 26 sera of butchers from the same slaughterhouse. All serum samples were tested for anti-HEV antibody by enzyme-linked immunosorbent assay. Both serum and liver samples were evaluated for the presence of HEV RNA by nested polymerase chain reaction targeting partial nucleotide sequences of open reading frame 2 (ORF2). The results indicate that sheep seroprevalence was 35.20 % (176/500) and that four of the 75 (5.3 %) sheep livers showed detectable amounts of HEV RNA. The seroprevalence of the butchers was 57.7 % (15/26). The four amplicons shared 97.8-100 % nucleotide sequence identity and had pairwise sequence identities of 81.6-85.3 %, 84.2-85.3 %, 82.1-85.3 % and 84.7-97.9 % with the corresponding regions of genotypes 1, 2, 3 and 4 of HEV, respectively. A phylogenetic tree was constructed based on alignments of an amplified 186-bp ORF2 sequence and corresponding reference strains. The analysis showed that the four sheep strains detected in our study formed a lineage within a genotype 4 cluster that contains hb-3, bjsw1, T1, swCH189 and swCH25, all of which belong to genotype 4, subtype 4d. The results indicated a high level of seroconversion in sheep and suggested that sheep liver may be a source of foodborne HEV infection in humans.
Collapse
Affiliation(s)
- Junyuan Wu
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China,
| | | | | | | | | |
Collapse
|
|
50
|
Sayed IM, Vercauteren K, Abdelwahab SF, Meuleman P. The Emergence of Hepatitis E Virus in Europe. Future Virol 2015; 10:763-778. [DOI: 10.2217/fvl.15.29] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Ibrahim M Sayed
- Center for Vaccinology, Ghent University, Ghent University Hospital, B-9000Gent, Belgium
- Microbiology & Immunology Department, Faculty of Medicine, Assuit University, Assuit71515, Egypt
| | - Koen Vercauteren
- Center for Vaccinology, Ghent University, Ghent University Hospital, B-9000Gent, Belgium
| | - Sayed F Abdelwahab
- Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia61511, Egypt
| | - Philip Meuleman
- Center for Vaccinology, Ghent University, Ghent University Hospital, B-9000Gent, Belgium
| |
Collapse
|