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Baymakova MP, Konaktchieva M, Kunchev M, Popivanov G, Kundurzhiev T, Tsachev I, Mutafchiyski V. First Insight into the Seroprevalence of Hepatitis E Virus and Associated Risk Factors Among Liver Transplant Recipients from Bulgaria. Vector Borne Zoonotic Dis 2025; 25:303-313. [PMID: 39943906 DOI: 10.1089/vbz.2024.0101] [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] [Indexed: 02/19/2025] Open
Abstract
Introduction: Hepatitis E virus (HEV) infection is caused by viruses belonging to the Hepeviridae family. HEV infection can be self-limiting; however, extrahepatic manifestations may be present. The purpose of the current study was to establish the seroprevalence of HEV among Bulgarian liver transplant recipients (LTRs) and to identify associated risk factors. Materials & Methods: The present study was conducted between April 1, 2023, and October 30, 2023, at the Military Medical Academy, Sofia, Bulgaria. All serum samples were tested for anti-HEV IgG/IgM using HEV IgG/IgM enzyme-linked immunosorbent assay on Dia.Pro (Milan, Italy). Each participating LTR completed a detailed paper-based closed-ended questionnaire regarding the associated risk factors for HEV infection. Results: The study included 73 LTRs with a mean age of 47.0 ± 14.0 years. Anti-HEV IgG antibodies were detected in 25 LTRs (34.2%), including 20 males (37.7%) and 5 females (25%). All participants were HEV-IgM negative. HEV seropositivity rates were higher but not statistically significant in LTRs aged >60 years than in those aged <60 years (40% vs. 32.7%). A significant factor by logistic regression was "high level of education" (odds ratio [OR] = 2.917; p = 0.038). Conclusion: To the best of our knowledge, this is the first seroepidemiological HEV study among LTRs from Bulgaria that found a high seroprevalence (34.2%).
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Affiliation(s)
| | - Marina Konaktchieva
- Department of Gastroenterology and Hepatology, Military Medical Academy, Sofia, Bulgaria
| | - Metodi Kunchev
- Department of Virology, Military Medical Academy, Sofia, Bulgaria
| | - Georgi Popivanov
- Department of Surgery, Military Medical Academy, Sofia, Bulgaria
| | - Todor Kundurzhiev
- Department of Occupational Medicine, Faculty of Public Health, Medical University, Sofia, Bulgaria
| | - Ilia Tsachev
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, Stara Zagora, Bulgaria
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Gan C, Yuan Y, Shen H, Gao J, Kong X, Che Z, Guo Y, Wang H, Dong E, Xiao J. Liver diseases: epidemiology, causes, trends and predictions. Signal Transduct Target Ther 2025; 10:33. [PMID: 39904973 PMCID: PMC11794951 DOI: 10.1038/s41392-024-02072-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 10/06/2024] [Accepted: 11/12/2024] [Indexed: 02/06/2025] Open
Abstract
As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles in metabolism, detoxification, and immune response. Various factors including viruses, alcohol, metabolites, toxins, and other pathogenic agents can compromise liver function, leading to acute or chronic injury that may progress to end-stage liver diseases. While sharing common features, liver diseases exhibit distinct pathophysiological, clinical, and therapeutic profiles. Currently, liver diseases contribute to approximately 2 million deaths globally each year, imposing significant economic and social burdens worldwide. However, there is no cure for many kinds of liver diseases, partly due to a lack of thorough understanding of the development of these liver diseases. Therefore, this review provides a comprehensive examination of the epidemiology and characteristics of liver diseases, covering a spectrum from acute and chronic conditions to end-stage manifestations. We also highlight the multifaceted mechanisms underlying the initiation and progression of liver diseases, spanning molecular and cellular levels to organ networks. Additionally, this review offers updates on innovative diagnostic techniques, current treatments, and potential therapeutic targets presently under clinical evaluation. Recent advances in understanding the pathogenesis of liver diseases hold critical implications and translational value for the development of novel therapeutic strategies.
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Affiliation(s)
- Can Gan
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yuan Yuan
- Aier Institute of Ophthalmology, Central South University, Changsha, China
| | - Haiyuan Shen
- Department of Oncology, the First Affiliated Hospital; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China
| | - Jinhang Gao
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiangxin Kong
- Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, China
| | - Zhaodi Che
- Clinical Medicine Research Institute and Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yangkun Guo
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Hua Wang
- Department of Oncology, the First Affiliated Hospital; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China.
| | - Erdan Dong
- Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital, School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China.
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
| | - Jia Xiao
- Clinical Medicine Research Institute and Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
- Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, China.
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Serricchio M, Gowland P, Widmer N, Stolz M, Niederhauser C. HEV in Blood Donors in Switzerland: The Route to Safe Blood Products. Pathogens 2024; 13:911. [PMID: 39452782 PMCID: PMC11510004 DOI: 10.3390/pathogens13100911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 10/08/2024] [Accepted: 10/16/2024] [Indexed: 10/26/2024] Open
Abstract
The hepatitis E virus (HEV) is an emerging infectious disease with zoonotic potential, causing acute hepatitis in humans. Infections in healthy individuals are often acute, self-limiting and asymptomatic, thus leading to the underdiagnosis of HEV infections. Asymptomatic HEV infections pose a problem for blood transfusion safety by increasing the risk for transfusion-transmitted HEV infections. Here, we describe the journey from determining the HEV seroprevalence among blood donors to the implementation of routine HEV RNA testing of all blood products in Switzerland in 2018 and summarise the HEV cases detected since. In total, 290 HEV-positive blood donations were detected by mini-pool nucleic acid testing (NAT) in Switzerland in the period of October 2018-December 2023, equal to an incidence of 20.7 per 100,000 donations. Thanks to the implemented scheme, no transfusion-transmitted infections occurred in this period. Furthermore, blood donation monitoring has proven to be an effective means of detecting HEV outbreaks in the general population. HEV cases in Swiss blood donors are caused by two major genotypes, the Swiss-endemic subtypes 3h3 and 3c. Interestingly, 11 HEV cases (5%) were of genotype 3ra, a variant found in wild and farmed rabbits. Our results indicate that mini-pool NAT is an efficient method to reduce the risk of transfusion-transmitted HEV infections.
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Affiliation(s)
- Mauro Serricchio
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
| | - Peter Gowland
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
| | - Nadja Widmer
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
| | - Martin Stolz
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
| | - Christoph Niederhauser
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
- Institute for Infectious Diseases, University of Bern, 3012 Bern, Switzerland
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Singson S, Shastry S, Sudheesh N, Chawla K, Madiyal M, Kandasamy D, Mukhopadhyay C. Assessment of Hepatitis E virus transmission risks: a comprehensive review of cases among blood transfusion recipients and blood donors. Infect Ecol Epidemiol 2024; 14:2406834. [PMID: 39421644 PMCID: PMC11486055 DOI: 10.1080/20008686.2024.2406834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 09/17/2024] [Indexed: 10/19/2024] Open
Abstract
Background Hepatitis E Virus is a major cause of acute and fulminant hepatitis, particularly in developing countries. While the virus is commonly spread through the fecal-oral route, numerous cases of transfusion transmitted Hepatitis E Virus (TT-HEV) have been reported, raising concerns about its transmission via blood transfusions, especially in industrialized countries. The high prevalence of antibodies and viremia among asymptomatic blood donors further heightens the risk of transfusion-related transmission. However, there is still debate about the best strategy to minimize TT-HEV. Objective The review was conducted to Summarize the literature on TT-HEV infection cases and the prevalence of HEV among blood donors. Methods The databases PubMed, Scopus, Web of Science, Embase, and CINAHL were searched for relevant studies from 2000 to 2022.Serological and molecular screening data of HEV in blood donors were used to gather prevalence and incidence rates.TT-HEV cases were reviewed by examining evidence of HEV infection before and after transfusion. Results A total of 121 manuscripts reports the prevalence and incidence of HEV among blood donors and cases of TT-HEV. Twenty-six articles reported confirmed cases of TT-HEV and 101 articles reported on HEV prevalence or incidence among blood donors. Conclusion TT-HEV transmission through blood products is a real concern, especially for immunocompromised patients.The risk and severity of infection could vary between immunocompetent and immunosuppressed patients.To increase transfusion safety, the evaluation recommends HEV screening protocols, especially in endemic region.
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Affiliation(s)
- Sangthang Singson
- Department of Immunohematology and Blood Transfusion, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnatka, India
| | - Shamee Shastry
- Department of Immunohematology and Blood Transfusion, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnatka, India
| | - N. Sudheesh
- Department of Microbiology, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Kiran Chawla
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
| | - Mridula Madiyal
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
| | - Dhivya Kandasamy
- Department of Immunohematology and Blood Transfusion, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnatka, India
| | - Chiranjay Mukhopadhyay
- Department of Microbiology, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnataka, India
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
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Abanto J, Sanchez Boluarte AN, Castillo Y, Perez E, Saavedra H, Gonzales I, Bustos JA, Abravanel F, Izopet J, Madden RG, Garcia HH, Dalton HR. Increased Prevalence of Antibodies to Hepatitis E Virus in Patients with Neurocysticercosis. Am J Trop Med Hyg 2024; 110:1210-1213. [PMID: 38653231 PMCID: PMC11154044 DOI: 10.4269/ajtmh.23-0856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 01/24/2024] [Indexed: 04/25/2024] Open
Abstract
We explored the association between serological status for hepatitis E and neurocysticercosis (NCC) in neurologic patients attending a national neurological referral center in Lima, Perú, between the years 2008 and 2012. Anti-hepatitis E antibodies were evaluated in patients with and without NCC, and a control group of rural general population. Anti-hepatitis E IgG was found in 23.8% of patients with NCC, compared with 14.3% in subjects without NCC from a general rural population (P = 0.023) and 14.4% in subjects with neurological complaints without NCC (P = 0.027). Seropositive patients had a median age of 44 years compared with 30 years in seronegative patients (P <0.001). No significant differences in sex, region of residence, or liver enzyme values were found. Seropositivity to hepatitis E was frequent in this Peruvian population and higher in patients with NCC, suggesting shared common routes of infection.
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Affiliation(s)
- Jesus Abanto
- Centro de Salud Global, Universidad Peruana Cayetano Heredia, Lima, Perú
- Department of Neurology, University of Cincinnati, Cincinnati, Ohio
| | - Arantxa N. Sanchez Boluarte
- Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Perú
- Department of Global Health, University of Washington, Seattle, Washington
| | - Yesenia Castillo
- Centro de Salud Global, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - Erika Perez
- Centro Básico de Investigación en Exámenes Auxiliares en Parasitosis del Sistema Nervioso Central, Instituto Nacional de Ciencias Neurológicas, Lima, Perú
| | - Herbert Saavedra
- Centro Básico de Investigación en Exámenes Auxiliares en Parasitosis del Sistema Nervioso Central, Instituto Nacional de Ciencias Neurológicas, Lima, Perú
| | - Isidro Gonzales
- Centro Básico de Investigación en Exámenes Auxiliares en Parasitosis del Sistema Nervioso Central, Instituto Nacional de Ciencias Neurológicas, Lima, Perú
| | - Javier A. Bustos
- Centro de Salud Global, Universidad Peruana Cayetano Heredia, Lima, Perú
- Centro Básico de Investigación en Exámenes Auxiliares en Parasitosis del Sistema Nervioso Central, Instituto Nacional de Ciencias Neurológicas, Lima, Perú
| | | | | | - Richie G. Madden
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, University of Adelaide, South Australia
- HEV International Direct Action Group (HEViDrAG)
| | - Hector H. Garcia
- Centro de Salud Global, Universidad Peruana Cayetano Heredia, Lima, Perú
- Centro Básico de Investigación en Exámenes Auxiliares en Parasitosis del Sistema Nervioso Central, Instituto Nacional de Ciencias Neurológicas, Lima, Perú
| | - Harry R. Dalton
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, University of Adelaide, South Australia
- HEV International Direct Action Group (HEViDrAG)
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Plümers R, Dreier J, Knabbe C, Gömer A, Steinmann E, Todt D, Vollmer T. Hepatitis E virus infections in German blood donors: results of 8 years of screening, 2015 to 2022. Euro Surveill 2024; 29:2300665. [PMID: 38873797 PMCID: PMC11177570 DOI: 10.2807/1560-7917.es.2024.29.24.2300665] [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: 11/23/2023] [Accepted: 03/29/2024] [Indexed: 06/15/2024] Open
Abstract
BackgroundAwareness of transfusion-transmitted hepatitis E raised in recent years led to the mandatory testing of blood donations in some European countries for hepatitis E virus (HEV) RNA. However, little is known about the epidemiology of HEV infections.AimTo and describe and analyse the epidemiology of HEV infections in blood donors in Germany.MethodsData from routine testing of therapeutic blood products donated between January 2015 and December 2022 at the Uni.Blutspendedienst OWL were analysed at the Institute of Laboratory and Transfusion Medicine, Heart and Diabetes Centre North Rhine-Westphalia. A total of 731,630 allogenic blood donations from 119,610 individual blood donors were tested for HEV RNA in minipools of 96 samples. The HEV RNA-positive donations were analysed for the presence of anti-HEV IgM and IgG. The HEV strains were genotyped and various clinical liver-specific parameters were determined.ResultsA total of 497 HEV-positive blood donations were identified, resulting in a yearly incidence of 1:1,474, from which 78.4% of the donations were RNA-only positive. Increased alanine aminotransferase activity was determined in 26.6% of HEV RNA-positive donors and was associated with the detection of IgG antibodies (1.2% anti-HEV IgM-positive, 11.9% anti-HEV IgM- and IgG-positive and 8.5% anti-HEV IgG-positive). An average incidence of 0.084-0.083% HEV RNA-positive donations in June and July in all years was observed, and a higher proportion of HEV RNA-positive men compared with women. All isolated HEV sequences corresponded to genotype 3.ConclusionOur results underline the necessity of HEV RNA screening in blood donations.
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Affiliation(s)
- Ricarda Plümers
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Bad Oeynhausen, Germany
| | - Jens Dreier
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Bad Oeynhausen, Germany
| | - Cornelius Knabbe
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Bad Oeynhausen, Germany
| | - André Gömer
- Department for Molecular und Medical Medicine, Ruhr University Bochum, Germany
| | - Eike Steinmann
- German Centre for Infection Research (DZIF), External Partner Site, Bochum, Germany
- Department for Molecular und Medical Medicine, Ruhr University Bochum, Germany
| | - Daniel Todt
- European Virus Bioinformatics Center (EVBC), Jena, Germany
- Department for Molecular und Medical Medicine, Ruhr University Bochum, Germany
| | - Tanja Vollmer
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Bad Oeynhausen, Germany
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Ali MM, Gul M, Imran M, Ijaz M, Azeem S, Ullah A, Yaqub HMF. Molecular identification and genotyping of hepatitis E virus from Southern Punjab, Pakistan. Sci Rep 2024; 14:223. [PMID: 38167570 PMCID: PMC10762251 DOI: 10.1038/s41598-023-50514-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 12/20/2023] [Indexed: 01/05/2024] Open
Abstract
Hepatitis E is a global health concern. Hepatitis E virus (HEV) infection is endemic in Pakistan. HEV has four genotypes: HEV-1 through HEV-4. The genotypes HEV-1 and HEV-2 are associated with infection in humans, especially in countries with poor sanitation. The genotypes HEV-3 and HEV-4 are zoonotic and human infection takes place by consuming undercooked meat or being in contact with animals. The present study was designed to ascertain the presence of HEV in the Southern Punjab region of Pakistan. First, blood samples (n = 50) were collected from patients suspected of infection with the hepatitis E virus from the Multan District. The serum was separated and the samples were initially screened using an HEV IgM-ELISA. Second, the ELISA-positive samples were subjected to PCR and were genetically characterized. For PCR, the RNA extraction and complementary DNA synthesis were done using commercial kits. The HEV ORF2 (Open Reading Frame-2, capsid protein) was amplified using nested PCR targeting a 348 bp segment. The PCR amplicons were sequenced and an evolutionary tree was constructed using MEGA X software. A protein model was built employing the SWISS Model after protein translation using ExPASy online tool. The positivity rate of anti-HEV antibodies in serum samples was found as 56% (28/50). All Pakistani HEV showed homology with genotype 1 and shared common evolutionary origin and ancestry with HEV isolates of genotype 1 of London (MH504163), France (MN401238), and Japan (LC314158). Sequence analysis of motif regions assessment and protein structure revealed that the sequences had a similarity with the reference sequence. These data suggest that genotype 1 of HEV is circulating in Pakistan. This finding could be used for the diagnosis and control of HEV in the specific geographic region focusing on its prevalent genotype.
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Affiliation(s)
- Muhammad Muddassir Ali
- Institute of Biochemistry and Biotechnology, Faculty of Biosciences, University of Veterinary and Animal Sciences, Lahore, Pakistan.
| | - Mehek Gul
- Institute of Biochemistry and Biotechnology, Faculty of Biosciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Muhammad Imran
- Institute of Biochemistry and Biotechnology, Faculty of Biosciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Muhammad Ijaz
- Department of Veterinary Medicine, Faculty of Veterinary Science, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Shahan Azeem
- Institute of Microbiology, Faculty of Veterinary Science, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Arif Ullah
- Institute of Biochemistry and Biotechnology, Faculty of Biosciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Hafiz Muhammad Farooq Yaqub
- Institute of Biochemistry and Biotechnology, Faculty of Biosciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
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Lopez-Lopez P, Frias M, Perez-Jimenez AB, Freyre-Carrillo C, Pineda JA, Fuentes A, Alados JC, Ramirez-Arellano E, Viciana I, Corona-Mata D, Caballero-Gomez J, Garcia-Bocanegra I, Risalde MA, Rivero-Juarez A, Rivero A. Temporal changes in the genotypes of Paslahepevirus balayani in southern Spain and their possible link with changes in pig trade imports. One Health 2023; 16:100539. [PMID: 37363253 PMCID: PMC10288091 DOI: 10.1016/j.onehlt.2023.100539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 04/11/2023] [Accepted: 04/11/2023] [Indexed: 06/28/2023] Open
Abstract
Introduction Paslahepevirus balayani (HEV) is an endemic zoonotic disease ranked as a major cause of acute hepatitis in Europe. Most infections occurring in Europe are due to the endemic several subtypes of genotype 3, through the consumption of raw or undercooked pork, observing a genotype geographical distribution pattern among countries Because of global changes in the pig and pork trading markets, subtype distribution might vary. We aimed to evaluate the temporal distribution of HEV genotypes in patients from southern Spain with acute hepatitis to determine whether these changes were related to the pig import trade during the study period between 2018 and 2022. Methods Prospective longitudinal study including patients with acute hepatitis from southern Spain between 2018 and 2022. HEV RNA and antibodies was tested in all patients. In patients with detectable HEV RNA, genotype was obtained. To determine the number of imported pigs and their origins, we checked the official data from the Spanish statistics on international trade of Spanish Minister of Industry during by country of origin during the same study period. Results A total of 659 patients with acute hepatitis were included in the study. Among them, 162 (24.5%) had at least one marker (IgM or RNA) of acute HEV infection. Among the 71 patients with detectable viral RNA, genotypes could be obtained for 58 (81.6%). The most prevalent HEV genotype was 3f (n = 48; 78.6%), showing a decreasing prevalence of over time, from 100% in 2018 to 70.6% in 2022. Since 2021, the emergence of other genotypes has been determined. A significant increase in the number of animals imported was observed since the beginning of the study. Denmark experienced a significant rise, from 0.03% in 2018 of total imports to 10.4% in 2022. Conclusions HEV molecular diversity is changing in Spain, could be linked to changes in fattening pig import origin.
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Affiliation(s)
- Pedro Lopez-Lopez
- Service of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Mario Frias
- Service of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Ana Belén Perez-Jimenez
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Clinical Microbiology Unit, Hospital Universitario Reina Sofía, Córdoba, Spain
- Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | | | - Juan A. Pineda
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain
| | - Ana Fuentes
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Clinical Microbiology Unit, Hospital Universitario Clínico San Cecilio, Granada, Spain
- Instituto de Investigacion Biosanitaria Ibs. Granada, Granada, Spain
| | - Juan Carlos Alados
- Clinical Microbiology Unit, Hospital Universitario de Jerez, Cádiz, Spain
- Insituto de investigación e innovación biomédica de Cadiz (INIBICA), Spain
| | - Encarnación Ramirez-Arellano
- Infectious Diseases, Microbiology and Preventive Medicine Unit, Virgen Macarena Univ. Hospital, and Department of Medicine, University of Sevilla/Biomedicine Institute of Sevilla, Sevilla, Spain
| | - Isabel Viciana
- Infectious Diseases, Microbiology and Preventive Medicine Unit, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Diana Corona-Mata
- Service of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
| | - Javier Caballero-Gomez
- Service of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14014 Córdoba, Spain
| | - Ignacio Garcia-Bocanegra
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14014 Córdoba, Spain
| | - María A. Risalde
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14014 Córdoba, Spain
| | - Antonio Rivero-Juarez
- Service of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Antonio Rivero
- Service of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
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Higher Risk of HEV Transmission and Exposure among Blood Donors in Europe and Asia in Comparison to North America: A Meta-Analysis. Pathogens 2023; 12:pathogens12030425. [PMID: 36986347 PMCID: PMC10059948 DOI: 10.3390/pathogens12030425] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/01/2023] [Accepted: 03/05/2023] [Indexed: 03/10/2023] Open
Abstract
Background and aims: The increasing number of diagnosed hepatitis E virus (HEV) infections in Europe has led to the implementation of the testing of blood products in various countries. Many nations have not yet implemented such screening. To assess the need for HEV screening in blood products worldwide, we conducted a systematic review and meta-analysis assessing HEV RNA positivity and anti-HEV seroprevalence in blood donors. Methods: Studies reporting anti-HEV IgG/IgM or HEV RNA positivity rates among blood donors worldwide were identified via predefined search terms in PubMed and Scopus. Estimates were calculated by pooling study data with multivariable linear mixed-effects metaregression analysis. Results: A total of 157 (14%) of 1144 studies were included in the final analysis. The estimated HEV PCR positivity rate ranged from 0.01 to 0.14% worldwide, with strikingly higher rates in Asia (0.14%) and Europe (0.10%) in comparison to North America (0.01%). In line with this, anti-HEV IgG seroprevalence in North America (13%) was lower than that in Europe (19%). Conclusions: Our data demonstrate large regional differences regarding the risk of HEV exposure and blood-borne HEV transmission. Considering the cost–benefit ratio, this supports blood product screening in high endemic areas, such as Europe and Asia, in contrast to low endemic regions, such as the U.S.
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10
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Geng Y, Shi T, Wang Y. Transmission of Hepatitis E Virus. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:73-92. [PMID: 37223860 DOI: 10.1007/978-981-99-1304-6_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Transmission of hepatitis E virus (HEV) occurs predominantly by the fecal-oral route. Large epidemics of hepatitis E in the developing countries of Asia and Africa are waterborne and spread through contaminated drinking water. The reservoir of HEV in developed countries is believed to be in animals with zoonotic transmission to humans, possibly through direct contact or the consumption of undercooked contaminated meat. And HEV transmission through blood transfusion, organ transplantation, and vertical transmission has been reported.
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Affiliation(s)
- Yansheng Geng
- Key Laboratory of Public Health Safety of Hebei Province, School of Public Health, Hebei University, Baoding, China
| | - Tengfei Shi
- Key Laboratory of Public Health Safety of Hebei Province, School of Public Health, Hebei University, Baoding, China
| | - Youchun Wang
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, China.
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11
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Low mortality despite temporary liver dysfunction in severe courses of acute hepatitis E. Wien Klin Wochenschr 2023; 135:57-66. [PMID: 36547761 PMCID: PMC9938023 DOI: 10.1007/s00508-022-02126-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 11/10/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) infection can cause severe viral hepatitis and eventually liver failure. We aim to provide novel data on the epidemiology and the course of HEV infections from Q1/2008 to Q3/2018 at the Vienna General Hospital. METHODS Of the 88,945 people tested, we identified HEV-IgM positive (+) or HEV-PCR (+) patients and retrospectively collated information on the course of infection from patient records. RESULTS Among 151 HEV-IgM or PCR (+) (median age 51 years, 45.8% female), 7 (4.6%) had non-severe acute HEV infection (ALT ≥ 2-5-fold upper limit of normal, ULN), 11 (7.3%) had severe HEV infection without liver dysfunction (LD) (ALT > 5-fold ULN), and 9 (6.0%) with LD (ikterus or bilirubin > 5 mg/dL, OR coagulopathy or INR > 1.5, OR encephalopathy or ammonia > 100 µmol/L). HEV-RNA-PCR was performed in 58/190 (30.5%) HEV-IgM (+) patients and was positive in 19 (30.6%). Rates of HEV IgM/PCR positivity remained stable over the observation period. The HEV genotype (GT) was GT‑1 in 71.4% (n = 5) and GT‑3 in 28.6% (n = 2). Travel history was recorded for 9/20 (45.0%) of severe HEV and 12/20 (60.0%) patients with severe HEV infection were hospitalized. One patient with pre-existing liver disease and concomitant EBV infection required intensive care. No patient required transplantation and the 30-day mortality was 3/151 (1.9%). Despite the increased testing rates, the absolute number of diagnosed HEV infections at Vienna General Hospital remained constant between 2008 to 2018. CONCLUSION Although approximately half of the patients with severe acute HEV infection required hospitalization, admissions to the intensive care unit (ICU) and short-term mortality were low.
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12
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Harvala H, Reynolds C, Brailsford S, Davison K. Fulminant Transfusion-Associated Hepatitis E Virus Infection Despite Screening, England, 2016-2020. Emerg Infect Dis 2022; 28:1805-1813. [PMID: 35997399 PMCID: PMC9423923 DOI: 10.3201/eid2809.220487] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
In England, all blood donations are screened in pools of 24 by nucleic acid test (NAT) for hepatitis E virus (HEV) RNA. During 2016-2020, this screening successfully identified and intercepted 1,727 RNA-positive donations. However, review of previous donations from infected platelet donors identified 9 donations in which HEV RNA detection was missed, of which 2 resulted in confirmed transmission: 1 infection resolved with ribavirin treatment, and 1 proceeded to fatal multiorgan failure within a month from infection. Residual risk calculations predict that over the 5-year study period, HEV RNA detection was missed by minipool NAT in 12-23 platelet and 177-354 whole-blood donations, but transmission risk remains undetermined. Although screening has been able to largely eliminate infectious HEV from the blood supply in England, missed detection of low levels of HEV RNA in donated blood can lead to a severe, even fulminant, infection in recipients and could be prevented by more sensitive screening.
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13
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Spada E, Simeoni M, Martina A, Pati I, Villano U, Adriani D, D'Angiò A, Tritarelli E, Taffon S, Bellino S, Boros S, Urciuoli R, Masiello F, Marano G, Bruni R, Pezzotti P, Ciccaglione AR, Pupella S, De Angelis V, Pisani G. Prevalence and risk factors for hepatitis E virus infection in blood donors: a nationwide survey in Italy, 2017 to 2019. EURO SURVEILLANCE : BULLETIN EUROPEEN SUR LES MALADIES TRANSMISSIBLES = EUROPEAN COMMUNICABLE DISEASE BULLETIN 2022; 27. [PMID: 35656832 PMCID: PMC9164674 DOI: 10.2807/1560-7917.es.2022.27.22.2100516] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Background In high-income countries, hepatitis E virus (HEV) infection is mainly a zoonosis. However, it is also transfusion-transmissible and some countries, but not Italy, have introduced HEV screening for blood donations. Aim We assessed HEV infection prevalence and risk factors in a nationwide sample of Italian blood donors. Methods We selected 107 blood establishments (BE) distributed in the 20 Italian regions by a stratified two-stage design and invited them to participate in the study. Donors were tested for anti-HEV IgG and IgM and HEV RNA. Sociodemographic data and risk factors were collected through a questionnaire. Results Overall, 60 BE from 60 provinces in 19 Italian regions joined the study. We assessed HEV markers in 7,172 blood donors, of whom 6,235 completed the questionnaire. Overall crude and adjusted anti-HEV IgG prevalences were 8.3% and 5.5%, respectively. Overall anti-HEV IgM prevalence was 0.5%, while no blood donor was HEV RNA-positive. Anti-HEV IgG prevalence varied widely among regions (range: 1.3%–27.20%) and hyperendemic prevalences (> 40%) were detected in some provinces in two regions. Older age (AOR = 1.81; 95% CI: 1.36–2.41), foreign nationality (AOR = 2.77; 95% CI: 1.06–7.24), eating raw pork liver sausages (AOR = 2.23; 95% CI: 1.55–3.20) and raw homemade sausages (AOR = 3.63; 95% CI: 2.50–5.24) were independent infection predictors. Conclusion Italian blood donors showed a low to moderate HEV seroprevalence. High levels in some regions and/or provinces were mainly attributable to eating habits. Prevention should include avoiding consumption of raw or undercooked meat and safe production of commercial pork products.
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Affiliation(s)
- Enea Spada
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Matteo Simeoni
- National Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
| | - Antonio Martina
- National Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
| | - Ilaria Pati
- Italian National Blood Centre, Istituto Superiore di Sanità, Rome, Italy
| | - Umbertina Villano
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Daniela Adriani
- National Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
| | - Agnese D'Angiò
- National Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
| | - Elena Tritarelli
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Stefania Taffon
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Stefania Bellino
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Stefano Boros
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Roberta Urciuoli
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Francesca Masiello
- Italian National Blood Centre, Istituto Superiore di Sanità, Rome, Italy
| | - Giuseppe Marano
- Italian National Blood Centre, Istituto Superiore di Sanità, Rome, Italy
| | - Roberto Bruni
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Patrizio Pezzotti
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | | | - Simonetta Pupella
- Italian National Blood Centre, Istituto Superiore di Sanità, Rome, Italy
| | | | - Giulio Pisani
- National Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
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14
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Filipe R, Prista-Leão B, Silva-Pinto A, Abreu I, Serrão R, Costa R, Guedes E, Sobrinho-Simões J, Sarmento A, Koch C, Santos L. Hepatitis E in a Portuguese cohort of human immunodeficiency virus positive patients: High seroprevalence but no chronic infections. Health Sci Rep 2022; 5:e624. [PMID: 35601036 PMCID: PMC9121181 DOI: 10.1002/hsr2.624] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/31/2022] [Accepted: 03/21/2022] [Indexed: 12/03/2022] Open
Abstract
Introduction Hepatitis E virus (HEV) infection causes zoonotic hepatitis in Europe, with a higher risk of complications in immunocompromised hosts. HEV natural history in human immunodeficiency virus (HIV) positive patients is not fully understood, and its prevalence is unknown. Objectives To study the seroprevalence of HEV and prevalence of chronic HEV in HIV‐positive patients from Porto, Portugal. Methods We randomly selected patients from the cohort of HIV‐positive patients followed in our hospital. We performed an enzyme‐linked immunosorbent assay to search for immunoglobulin G for HEV. When the absorbance/cut‐off was inferior to 3.5, the test was repeated, and a confirmatory test executed in that sample. For reactive tests and for immunosuppressed patients (CD4 count < 200/mm3) with nonreactive test, a polymerase chain reaction (PCR) test was also performed. Results We included 299 patients. The mean age was 48 and 75.3% were men. Regarding HIV infection, the median follow‐up time was 10 years, the acquisition was mainly heterosexual contact, and 94% were on antiretroviral therapy. Seventy‐six patients (25.4%) had reactive immunoglobulin G (IgG) hepatitis E serology. Patients with a reactive test were older (statistically significant difference). Otherwise, there was no difference between groups concerning birthplace, rural residence, chronic viral hepatitis coinfection, or cirrhosis. Nadir and actual TCD4+ lymphocyte counts did not differ significantly from patients with HEV reactive and nonreactive serology. Gamma‐glutamyl‐transferase (GGT) was higher in patients with reactive IgG HEV. All serum HEV PCR tests were negative. Conclusions Seroprevalence of HEV was 25.4% in HIV‐positive patients. Older age and higher GGT correlated to HEV reactive IgG test. No cases of current hepatitis E were found.
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Affiliation(s)
- Rita Filipe
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal.,Faculty of Medicine University of Porto Porto Portugal
| | - Beatriz Prista-Leão
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal.,Faculty of Medicine University of Porto Porto Portugal
| | - André Silva-Pinto
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal.,Faculty of Medicine University of Porto Porto Portugal.,ESCMID Study Group for Immunocompromised Hosts-ESGICH Porto Portugal
| | - Isabel Abreu
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal.,Faculty of Medicine University of Porto Porto Portugal
| | - Rosário Serrão
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal
| | - Rosário Costa
- Clinical Pathology Department Centro Hospitalar Universitário de São João Porto Portugal
| | - Edite Guedes
- Imunohemotherapy Department Centro Hospitalar Universitário São João Porto Portugal
| | - Joana Sobrinho-Simões
- Clinical Pathology Department Centro Hospitalar Universitário de São João Porto Portugal
| | - António Sarmento
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal.,Faculty of Medicine University of Porto Porto Portugal
| | - Carmo Koch
- Imunohemotherapy Department Centro Hospitalar Universitário São João Porto Portugal
| | - Lurdes Santos
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal.,Faculty of Medicine University of Porto Porto Portugal.,ESCMID Study Group for Immunocompromised Hosts-ESGICH Porto Portugal
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15
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Villalba R, Mirabet V. Risk assessment of hepatitis E transmission through tissue allografts. World J Gastrointest Pathophysiol 2022; 13:50-58. [PMID: 35433096 PMCID: PMC8976234 DOI: 10.4291/wjgp.v13.i2.50] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/06/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is a small non-enveloped single stranded RNA virus whose genotypes 3 and 4 have been associated with zoonotic transmission in industrialized countries. HEV infection is considered the main cause of acute hepatitis worldwide. In some cases, transfusion of blood components or organ transplantation have been reported as the source of infection. We have conducted a literature review on the risk of transmission through cell and tissue allografts. Although no case was found, measures to control this risk should be taken when donor profile (based upon geographical and behavioural data) recommended it. Issues to be considered in donor screening and tissue processing to assess and to reduce the risk of HEV transmission are approached.
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Affiliation(s)
- Rafael Villalba
- Center for Blood Transfusion, Tissues and Cells, Córdoba 14004, Spain
| | - Vicente Mirabet
- Cell and Tissue Bank, Centro de Transfusión de Valencia, Valencia 46014, Spain
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16
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Cheung CKM, Wong SH, Law AWH, Law MF. Transfusion-transmitted hepatitis E: What we know so far? World J Gastroenterol 2022; 28:47-75. [PMID: 35125819 PMCID: PMC8793017 DOI: 10.3748/wjg.v28.i1.47] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 07/16/2021] [Accepted: 12/22/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. There is growing concern about transfusion-transmitted HEV (TT-HEV) as an emerging global health problem. HEV can potentially result in chronic infection in immunocompromised patients, leading to a higher risk of liver cirrhosis and even death. Between 0.0013% and 0.281% of asymptomatic blood donors around the world have HEV viremia, and 0.27% to 60.5% have anti-HEV immunoglobulin G. HEV is infectious even at very low blood concentrations of the virus. Immunosuppressed patients who develop persistent hepatitis E infection should have their immunosuppressant regimen reduced; ribavirin may be considered as treatment. Pegylated interferon can be considered in those who are refractory or intolerant to ribavirin. Sofosbuvir, a nucleotide analog, showed modest antiviral activity in some clinical studies but sustained viral response was not achieved. Therefore, rescue treatment remains an unmet need. The need for HEV screening of all blood donations remains controversial. Universal screening has been adopted in some countries after consideration of risk and resource availability. Various pathogen reduction methods have also been proposed to reduce the risk of TT-HEV. Future studies are needed to define the incidence of transmission through transfusion, their clinical features, outcomes and prognosis.
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Affiliation(s)
| | - Sunny Hei Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong 852, China
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore
| | | | - Man Fai Law
- Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
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17
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Kamani L, Padhani ZA, Das JK. Hepatitis E: Genotypes, strategies to prevent and manage, and the existing knowledge gaps. JGH Open 2021; 5:1127-1134. [PMID: 34621997 PMCID: PMC8485408 DOI: 10.1002/jgh3.12646] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 08/02/2021] [Accepted: 08/14/2021] [Indexed: 12/23/2022]
Abstract
Hepatitis E virus (HEV) is considered an emergent source of viral hepatitis worldwide, with an increasing burden of jaundice, liver failure, extrahepatic illnesses, and deaths in developed countries. With the scarcity of data from efficient animal models, there are still open-ended questions about designing new models to study pathogenesis, types, virology, and evolution of these viruses. With an emphasis on available data and updates, there is still enough information to understand the HEV life cycle, pathogen interaction with the host, and the valuation of the role of vaccine and new anti-HEV therapies. However, the World Health Organization (WHO) and the European Association for the Study of the Liver (EASL) preferred to stress prevention and control measures of HEV infections in animals, zoonotic transmission, and foodborne transmission. It is being reviewed that with current knowledge on HEV and existing prevention tools, there is an excellent room for in-depth information about the virus strains, their replication, pathogenicity, and virulence. The current knowledge set also has gaps regarding standardized and validated diagnostic tools, efficacy and safety of the vaccine, and extrahepatic manifestations specifically in pregnant females, immunocompromised patients, and others. This review highlights the areas for more research exploration, focusing on enlisted research questions based on HEV infection to endorse the need for significant improvement in the current set of knowledge for this public health problem.
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Affiliation(s)
- Lubna Kamani
- Associate Professor & Director, GI Residency Program, Department of GastroenterologyLiaquat National Hospital and Medical CollegeKarachiPakistan
- ConsultantAga Khan University HospitalKarachiPakistan
| | - Zahra Ali Padhani
- Health Policy and Management, Manager (Research)Aga Khan University HospitalKarachiPakistan
| | - Jai K Das
- Assistant Professor and Head, Section of Public Health and EpidemiologyAga Khan University HospitalKarachiPakistan
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18
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Casares-Jimenez M, Lopez-Lopez P, Caballero-Gomez J, Frias M, Perez-Hernando B, Oluremi AS, Risalde MA, Ruiz-Caceres I, Opaleye OO, Garcia-Bocanegra I, Rivero-Juarez A, Rivero A. Global molecular diversity of Hepatitis E virus in wild boar and domestic pig. One Health 2021; 13:100304. [PMID: 34466650 PMCID: PMC8385159 DOI: 10.1016/j.onehlt.2021.100304] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 08/06/2021] [Accepted: 08/06/2021] [Indexed: 01/05/2023] Open
Abstract
Our study aim was to describe and characterize the global Hepatitis E virus (HEV) molecular and genotype geographical distribution in domestic pig and wild boar, which could facilitate the traceability of human cases. We performed a systematic sequence search for HEVs identified in domestic pig and wild boar from the available data in GenBank. Only sequences with lengths greater than 300 nt were included. For all sequences, the sequence length, host (i.e., domestic pig or wild boar), country of origin, and HEV genotype/subtype were recorded. Genotypes were assigned by the HEVnet typing tool. The genotype distributions were described by country and host. In countries with sequences available for both species, the genotype coincidences between both animal populations were analyzed. A total of 1404 viral sequences were included: 32.6% from wild boar and 67.4% from domestic pig. Most sequences were consistent with HEV genotype 3 (n = 1165). Genotype 4 was represented by 193 sequences, while genotypes 5 and 6 were represented by only 6 sequences. Sequences were identified in 39 countries, which included all continents except Antarctica. The genotypes with a wide distribution were 3a and 3f. Twenty-five countries had sequences that were found only in domestic pig, three countries only in wild boar, and 11 countries had sequences in both populations. In all countries with available sequences in both populations, the same viral genotype was identified. Our study shows that the number of swine HEV sequences is small, which limits direct comparisons with the sequences identified in humans. The global distribution of genotype 3, together with the wide distribution of genotype 4 in Asia, strongly limits the interpretation of the molecular analysis in the absence of an epidemiological survey of the cases. Increased HEV sequencing in swine should be a priority.
Our study shows that the number of swine HEV sequences is small. The global distribution of genotype 3 strongly limits the interpretation of the molecular analysis. Increased HEV sequencing in swine should be a priority.
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Affiliation(s)
- Maria Casares-Jimenez
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Pedro Lopez-Lopez
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Javier Caballero-Gomez
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain.,Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Mario Frias
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Belen Perez-Hernando
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Adeolu Sunday Oluremi
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain.,Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - Maria A Risalde
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain.,Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, Facultad de Veterinaria, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Inmaculada Ruiz-Caceres
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Oluyinka Oladele Opaleye
- Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - Ignacio Garcia-Bocanegra
- Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Antonio Rivero-Juarez
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Antonio Rivero
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
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19
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Al Dossary RA, Alnafie AN, Aljaroodi SA, Rahman JU, Hunasemarada BC, Alkharsah KR. Prevalence of Hepatitis E Virus Infection Among Blood Donors in the Eastern Province of Saudi Arabia. J Multidiscip Healthc 2021; 14:2381-2390. [PMID: 34475765 PMCID: PMC8407670 DOI: 10.2147/jmdh.s328029] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 08/16/2021] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Hepatitis E virus (HEV) causes acute hepatitis in humans and constitutes a major problem for immunocompromised patients, patients with hematological diseases, and pregnant women. It is transmitted mainly through fecal oral route; however, transmission through blood and blood products is reported globally and becoming a health concern. We sought to determine the prevalence of HEV among blood donors in the Eastern Province of Saudi Arabia using molecular as well as serological assays to assess the safety of blood transfusion and the need for HEV screening among blood donors. PATIENTS AND METHODS A total of 806 whole blood samples were collected from blood donors between May and November 2020 and tested for anti-HEV IgG and IgM antibodies by ELISA and for HEV RNA by RT-PCR. RESULTS The overall seroprevalence of HEV IgG antibodies was 3.2% with no statistically significant difference between the non-Saudis (3.28%) and Saudis (3.17%) (p value 0.929) or between males (3.14%) and females (4.88%) (p value 0.527). None of the IgG positive individuals had IgM antibodies. HEV RNA was not detected in any of the blood donors. CONCLUSION HEV seroprevalence is low among blood donors in the Eastern Province of Saudi Arabia and may constitute minimal risk for transfusion associated infections.
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Affiliation(s)
- Reem A Al Dossary
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Awatif N Alnafie
- Department of Pathology, College of Medicine, King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Salma Ali Aljaroodi
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Jawad Ur Rahman
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Basavaraj C Hunasemarada
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Khaled R Alkharsah
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
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20
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Mishra KK, Patel K, Trivedi A, Patel P, Ghosh K, Bharadva S. Risk of hepatitis-E virus infections among blood donors in a regional blood transfusion centre in western India. Transfus Med 2021; 31:193-199. [PMID: 33738857 DOI: 10.1111/tme.12760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 01/02/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Hepatitis-E virus (HEV) is an emerging infectious threat to blood safety. The enormity of the transmission of HEV and its clinical consequence are issues currently under debate. This study aimed to evaluate the prevalence of HEV-RNA in blood donors in western India. MATERIALS AND METHODS We screened 13 050 blood donors for HEV using HEV-RNA screening of 10 mini-pools using RealStar HEV RT-PCR Kit (95% limit of detection (LOD): 4.7 IU/ml). Furthermore, all HEV-RNA-positive donors were investigated for the presence of IgM/IgG antibody along with liver function tests. RESULTS Of the 13 050 blood donations, 7 (0.53%) were found to be HEV-RNA positive, and the prevalence of HEV nucleic acid testing yield cases among blood donors was 1 in 1864. All seven HEV-RNA-positive samples were tested with anti-HEV IgM and anti-HEV IgG antibodies; this resulted in two (28.5%) positive anti-HEV IgM and two (28.5%) positive anti-HEV IgG antibodies. Hepatic activity was measured, with two of seven HEV-RNA-positive donors demonstrating abnormal serum glutamic oxaloacetic transaminase (SGOT) andserum glutamic pyruvic transaminase (SGPT). Two HEV-RNA-positive blood donors who had abnormal SGOT and SGPT were found to have a high HEV viral load. Furthermore, we were able to follow up two HEV-RNA donors, and both were HEV-RNA positive and had anti-HEV IgM and anti-HEV IgG antibodies; moreover, their liver function tests were also abnormal. One of the HEV-RNA donors with high viral load did show hepatitis-E-like virus on electron microscopy. CONCLUSION Our studies indicate that there is a significant risk of blood-borne transmission of HEV. This finding may help to provide a direction towards the safety of blood transfusions in clinical settings in countries like India, which fall under the endemic category for HEV infection.
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Affiliation(s)
- Kanchan K Mishra
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Krima Patel
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Apeksha Trivedi
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Parizad Patel
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Kanjaksha Ghosh
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Sumit Bharadva
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
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21
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O’Keefe J, Tracy L, Yuen L, Bonanzinga S, Li X, Chong B, Nicholson S, Jackson K. Autochthonous and Travel Acquired Hepatitis E Virus in Australia. Front Microbiol 2021; 12:640325. [PMID: 33633719 PMCID: PMC7901960 DOI: 10.3389/fmicb.2021.640325] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 01/18/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) is a common cause of acute viral hepatitis with significant morbidity and mortality, particularly in pregnant women. There are four major genotypes which can cause disease in humans. Genotypes 1 and 2 are usually associated with outbreaks and spread via facal/oral route or contaminated water. Genotypes 3 and 4 are zoonotic and usually associated with handling of pigs or consumption of contaminated pork. The strains circulating in Australia have never been characterized. RATIONALE/AIMS The aims for this project are to identify the HEV genotypes found in Australia and link them to possible sources of transmission by phylogenetic analysis. MATERIALS AND METHODS Between 2015 and 2020, 91 HEV isolates were sequenced and genotyped using an in-house PCR. Sixty-six of these were also sequenced by using the international HEVnet primers. Genotypes were determined using the BLASTn program. Relatedness to other strains in Australia was determined by phylogenetic analyses of the HEVnet sequences. Isolates were also stratified by state of origin, gender, age, predisposing factors and travel history (if known). RESULTS Of the 91 HEV isolates sequenced, 55 (60.4%) were genotype 1. There were 34 (37.4%) genotype 3 strains and two genotype 4 (2.2%). At least 20 of the genotype 1 strains have been linked to travel in India, and another three with Pakistan. Five of the "Indian" strains were closely related and are suspected to have originated in Gujarat. Phylogenetic analysis also showed that 12 genotype 3 strains were genetically related and potentially acquired in/from New South Wales, Australia. The two genotype 4 strains may have originated in China. DISCUSSION This is the first study to describe the HEV isolates identified in Australia. The results infer that HEV may be acquired during overseas travel as well as locally, presumably from consumption of pork or pork-related products. The phylogenetic analyses also reveal clusters of infection originating from India and Pakistan. This study provides some insight into the source and epidemiology of HEV infection in Australia which may be used to guide public health procedure and enable the implementation of measures to deal with potential outbreaks of infection.
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Affiliation(s)
| | | | | | | | | | | | | | - Kathy Jackson
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
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Jing W, Liu J, Liu M. The global trends and regional differences in incidence of HEV infection from 1990 to 2017 and implications for HEV prevention. Liver Int 2021; 41:58-69. [PMID: 33025620 DOI: 10.1111/liv.14686] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 09/14/2020] [Accepted: 09/29/2020] [Indexed: 02/13/2023]
Abstract
BACKGROUND/AIMS Hepatitis E virus (HEV) infection is an important cause of acute viral hepatitis worldwide, but it is long-neglected. We aimed to understand the global trends and regional differences in the incidence of HEV infection, thereby making global tailored prevention strategies. METHODS This study is a post-hoc analysis of the data from Global Burden of Disease Study 2017. Annual HEV incident cases and incidence rates from 1990 to 2017 were collected. Changes in incident cases and estimated annual percentage changes (EAPCs) of age-standardized incidence rates (ASRs) were calculated to quantify the temporal trends of HEV infection. RESULTS Globally, HEV ASRs decreased by an average 0.16% (95% CI: 0.14%-0.17%) per year from 279.79 per 100 000 in 1990 to 269.70 per 100 000 in 2017; however, the number of HEV incident cases increased by 17.63% from 16.53 million in 1990 to 19.44 million in 2017. Against the global trend of ASR falling, an increasing trend was reported in Oceania (EAPC = 0.03; 95% CI: 0.03-0.04) and Western Europe (EAPC = 0.02; 95% CI: 0.01-0.03). The number of HEV incident cases increased remarkably in low (63.07%) and low-middle (37.46%) Socio-Demographic Index (SDI) regions between 1990 and 2017. Additionally, the number of HEV incident cases increased by 4.63% in high SDI regions, mainly in 40 plus age group. Surprisingly, more than 40% of HEV incident cases in Western Europe in 2017 were over 40 years old. CONCLUSIONS HEV is still pending in hyperendemic regions, and it is emerging in low endemic regions, suggesting more efforts should be done to make targeted prevention strategies.
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Affiliation(s)
- Wenzhan Jing
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Jue Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Min Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
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Capai L, Hozé N, Chiaroni J, Gross S, Djoudi R, Charrel R, Izopet J, Bosseur F, Priet S, Cauchemez S, de Lamballerie X, Falchi A, Gallian P. Seroprevalence of hepatitis E virus among blood donors on Corsica, France, 2017. ACTA ACUST UNITED AC 2020; 25. [PMID: 32046820 PMCID: PMC7014670 DOI: 10.2807/1560-7917.es.2020.25.5.1900336] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Background Hepatitis E virus (HEV) is an emerging zoonotic pathogen and an important cause of acute viral hepatitis in European countries. Corsica Island has been previously identified as a hyperendemic area for HEV. Aim Our aim was to characterise the prevalence and titres of IgG antibodies to HEV among blood donors on Corsica and establish a model of the annual force of infection. Methods Between September 2017 and January 2018, 2,705 blood donations were tested for anti-HEV IgG using the Wantai HEV IgG enzyme immunoassay. Results The overall seroprevalence was 56.1%. In multivariate analysis, seroprevalence was higher in men than in women (60.0% vs 52.2%; p < 0.01), increased with age and was significantly higher among donors born on Corsica (60.6% vs 53.2%; p < 0.01). No significant difference was observed between the five districts of the island. IgG anti-HEV titres were mostly low (70% of positive donors had titres < 3 IU/mL). In Corsican natives, increasing seroprevalence by age could be explained by models capturing a loss of immunity (annual probability of infection: 4.5%; duration of immunity: 55 years) or by age-specific probabilities of infection (3.8% for children, 1.3% for adults). Conclusion We confirmed the high HEV seroprevalence on Corsica and identified three aspects that should be further explored: (i) the epidemiology in those younger than 18 years, (ii) common sources of contamination, in particular drinking water, that may explain the wide exposure of the population, and (iii) the actual protection afforded by the low IgG titres observed and the potential susceptibility to secondary HEV infection.
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Affiliation(s)
- Lisandru Capai
- EA 7310, Laboratoire de Virologie, Université de Corse, Corte, France
| | - Nathanaël Hozé
- Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, UMR2000, CNRS, Paris, France
| | - Jacques Chiaroni
- Etablissement Français du Sang Provence alpes Côte d'Azur et Corse, Marseille, France
| | - Sylvie Gross
- Etablissement Français du Sang, 93210, La Plaine-Saint-Denis, France
| | - Rachid Djoudi
- Etablissement Français du Sang, 93210, La Plaine-Saint-Denis, France
| | - Rémi Charrel
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France
| | - Jacques Izopet
- Institut National de la Santé et de la Recherche Médicale Unité 1043, Université Toulouse III, Toulouse, France.,Laboratoire de Virologie, Institut Fédératif de Biologie, Centre Hospitalier et Universitaire, Toulouse, France
| | - Frédéric Bosseur
- Sciences Pour l'Environnement - UMR CNRS 6134 Université de Corse, Corte, France
| | - Stéphane Priet
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France
| | - Simon Cauchemez
- Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, UMR2000, CNRS, Paris, France
| | - Xavier de Lamballerie
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France
| | - Alessandra Falchi
- EA 7310, Laboratoire de Virologie, Université de Corse, Corte, France
| | - Pierre Gallian
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.,Etablissement Français du Sang, 93210, La Plaine-Saint-Denis, France.,Etablissement Français du Sang Provence alpes Côte d'Azur et Corse, Marseille, France
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24
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Webb GW, Kelly S, Dalton HR. Hepatitis A and Hepatitis E: Clinical and Epidemiological Features, Diagnosis, Treatment, and Prevention. CLINICAL MICROBIOLOGY NEWSLETTER 2020; 42:171-179. [PMID: 33110280 PMCID: PMC7581387 DOI: 10.1016/j.clinmicnews.2020.10.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Hepatitis A and E are both ancient diseases but have only been properly recognized as being caused by distinct pathogens in modern times. Despite significantly different genomic structures, both viruses employ remarkably similar strategies to avoid host detection and increase environmental transmission. There are millions of cases of acute viral hepatitis due to hepatitis A virus (HAV) and hepatitis E virus (HEV) each year, resulting in tens of thousands of deaths. The presentations can be clinically indistinguishable, but each virus also has a range of less common but more specific phenotypes. The epidemiology of HAV is complex, and is shifting in countries that are making improvements to public health and sanitation. HEV presents a significant public health challenge in resource-limited settings but has historically been incorrectly regarded as having little clinical relevance in industrialized countries.
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Affiliation(s)
- Glynn W Webb
- Royal Liverpool University Hospital, Liverpool, United Kingdom
- University of Liverpool, Liverpool, United Kingdom
- University of Manchester, Manchester, United Kingdom
| | - Sophie Kelly
- Royal Liverpool University Hospital, Liverpool, United Kingdom
- University of Liverpool, Liverpool, United Kingdom
| | - Harry R Dalton
- University of Manchester, Manchester, United Kingdom
- Retired Consultant, Department of Gastroenterology, Royal Cornwall Hospital, Truro, Cornwall, United Kingdom
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25
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Hepatitis E: an expanding epidemic with a range of complications. Clin Microbiol Infect 2020; 26:828-832. [PMID: 32251845 DOI: 10.1016/j.cmi.2020.03.039] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 03/30/2020] [Accepted: 03/31/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) is a common cause of viral hepatitis worldwide. Previously considered a disease of the developing world, it is increasingly recognized that locally acquired HEV infection is common in industrialized countries. OBJECTIVES The aim was to highlight the changing epidemiology of HEV infection, particularly in the developed world, and inform clinicians of the diverse clinical presentations and extra-hepatic complications associated with the virus. SOURCES References for this review were identified through searches of MEDLINE/PubMed, and Google Scholar, up to January 2020. Searches were restricted to articles published in English. CONTENT Hepatitis E virus is an under-recognized, emerging pathogen with important implications for public health in both the developing and developed world. The number of cases reported in resource-rich settings is increasing, in part due to improved case ascertainment but also as a result of increased incidence in some countries. The reasons behind these epidemiological shifts are not currently known. Chronic HEV infection has been reported in immunocompromised patients. A range of extra-hepatic manifestations have also been reported, most notably neurological and renal complications. There is evidence to suggest a causal link with Guillain-Barré syndrome, neuralgic amyotrophy and encephalitis/myelitis. Glomerular disease has been reported in the context of both acute and chronic infection. IMPLICATIONS HEV should be included in non-invasive liver screens and considered in the differentials for patients presenting with alanine aminotransferase elevation, suspected drug-induced liver injury or decompensated liver disease. Any patients with acute neurological injury and deranged liver function should be tested for hepatitis E, and all patients presenting with Guillain-Barré syndrome or neuralgic amyotrophy should be tested regardless of liver enzymes. Immunocompromised patients with persistently raised liver enzymes should be tested with molecular techniques and offered annual routine screening.
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26
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Goel A, Vijay HJ, Katiyar H, Aggarwal R. Prevalence of hepatitis E viraemia among blood donors: a systematic review. Vox Sang 2020; 115:120-132. [PMID: 32030767 DOI: 10.1111/vox.12887] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 12/18/2019] [Accepted: 12/19/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) is usually transmitted by faecal-oral route. Recent reports have documented HEV viraemia in donated blood units and HEV transmission through blood transfusion. This systematic review summarizes the available data on prevalence of HEV viraemia in blood donors. METHODS Electronic databases were searched on 17 December 2018 to identify full-text English papers reporting original data on prevalence of HEV RNA in donated blood units. Two authors independently extracted the relevant data, which were pooled using simple aggregation as well as a random-effects meta-analysis; heterogeneity was assessed using the I2 method. RESULTS In all, 59 data sets from 28 countries were identified. The available data showed marked heterogeneity. Of a total of 2 127 832 units studied, 561 (263·6 [95% confidence intervals = 242·7-286·4] per million units) tested positive for HEV RNA. On random-effects meta-analysis, the pooled prevalence was 60·9 [6·7-155·4] per million units. In the viraemic units, HEV RNA titre varied by nearly one million-fold, and most had genotype 3 HEV. The prevalence was higher in blood units with anti-HEV antibodies or elevated alanine aminotransferase. Only nearly one-fourth of viraemic units had anti-HEV antibodies. CONCLUSIONS The prevalence of HEV viraemia among healthy blood donors is low, though the available data had limited geographical representation and marked heterogeneity. There is a need for further data on HEV viraemia in blood donors from areas with non-3 HEV genotype preponderance.
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Affiliation(s)
- Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | | | - Harshita Katiyar
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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27
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Seroprevalence of hepatitis E virus in dromedary camels, Bedouins, Muslim Arabs and Jews in Israel, 2009-2017. Epidemiol Infect 2020; 147:e92. [PMID: 30869027 PMCID: PMC6518832 DOI: 10.1017/s0950268819000062] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Hepatitis E virus (HEV) is an emerging cause of viral hepatitis worldwide. Recently, HEV-7 has been shown to infect camels and humans. We studied HEV seroprevalence in dromedary camels and among Bedouins, Arabs (Muslims, none-Bedouins) and Jews and assessed factors associated with anti-HEV seropositivity. Serum samples from dromedary camels (n = 86) were used to determine camel anti-HEV IgG and HEV RNA positivity. Human samples collected between 2009 and 2016 from >20 years old Bedouins (n = 305), non-Bedouin Arabs (n = 320) and Jews (n = 195), were randomly selected using an age-stratified sampling design. Human HEV IgG levels were determined using Wantai IgG ELISA assay. Of the samples obtained from camels, 68.6% were anti-HEV positive. Among the human populations, Bedouins and non-Bedouin Arabs had a significantly higher prevalence of HEV antibodies (21.6% and 15.0%, respectively) compared with the Jewish population (3.1%). Seropositivity increased significantly with age in all human populations, reaching 47.6% and 34.8% among ⩾40 years old, in Bedouins and non-Bedouin Arabs, respectively. The high seropositivity in camels and in ⩾40 years old Bedouins and non-Bedouin Arabs suggests that HEV is endemic in Israel. The low HEV seroprevalence in Jews could be attributed to higher socio-economic status.
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28
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Swartling L, Nordén R, Samuelsson E, Boriskina K, Valentini D, Westin J, Norder H, Sparrelid E, Ljungman P. Hepatitis E virus is an infrequent but potentially serious infection in allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant 2020; 55:1255-1263. [PMID: 32071417 DOI: 10.1038/s41409-020-0823-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 01/27/2020] [Accepted: 01/30/2020] [Indexed: 01/05/2023]
Abstract
Hepatitis E virus (HEV) can cause chronic infection and liver cirrhosis in immunocompromised individuals. The frequency and clinical importance of HEV was studied retrospectively in a cohort of 236 Swedish allogeneic hematopoietic stem cell transplantation (HSCT) recipients. In blood samples collected at 6 months after HSCT, HEV RNA was identified in 8/236 (3.4%) patients, and 11/236 (4.7%) patients had detectable anti-HEV IgG and/or IgM, eight of whom were HEV RNA negative. Two of the patients with positive HEV RNA died with ongoing signs of hepatitis: one of acute liver and multiple organ failure, the other of unrelated causes. The remaining six patients with HEV RNA had cleared the infection at 7-24 (median 8.5) months after HSCT. HEV infection was associated with elevated alanine aminotransferase at 6 months after HSCT (OR 15, 1.3-174, p = 0.03). Active graft-versus-host disease of the liver at 6 months after HSCT was present in 3/8 (38%) patients with HEV RNA, but was not significantly associated with HEV infection. In conclusion, HEV infection is an important differential diagnosis in patients with elevated liver enzymes after HSCT. Although spontaneous clearance was common, the clinical course may be severe.
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Affiliation(s)
- Lisa Swartling
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden. .,Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
| | - Rickard Nordén
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.,Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ebba Samuelsson
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.,Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ksenia Boriskina
- Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Davide Valentini
- Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Johan Westin
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Infectious Diseases, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
| | - Heléne Norder
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.,Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Elda Sparrelid
- Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Per Ljungman
- Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden.,Division of Hematology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
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29
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Wallace SJ, Crossan C, Hussaini SH, Dalton HR. Hepatitis E: a largely underestimated, emerging threat. Br J Hosp Med (Lond) 2020; 80:399-404. [PMID: 31283400 DOI: 10.12968/hmed.2019.80.7.399] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Hepatitis E virus has two distinct clinical and epidemiological patterns based on the varying genotypes. Genotypes 3 and 4 cause widespread, sporadic infection in high-income countries and are emerging as the most common type of viral hepatitis in much of Europe. These infections carry significant morbidity and mortality in the growing numbers of immunosuppressed patients or in patients with established liver disease. Furthermore the growing extra-hepatic associations of the virus, including neurological and kidney injury, suggest that it may have been misnamed as a 'hepatitis' virus. This review explores current understanding of the epidemiology, virology and clinical presentations of hepatitis E infection and identifies vulnerable patient groups, who are at serious risk from infection. Guidance is offered regarding the diagnosis, treatment and prevention of this growing public health hazard.
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Affiliation(s)
- S J Wallace
- Speciality Registrar, Department of Gastroenterology, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN
| | - C Crossan
- Research Fellow, Department of Life Sciences, Glasgow Caledonian University, Glasgow
| | - S H Hussaini
- Consultant, Department of Gastroenterology, Royal Cornwall Hospital, Truro, Cornwall
| | - H R Dalton
- Retired Consultant, Department of Gastroenterology, Royal Cornwall Hospital, Truro, Cornwall
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30
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Kilonzo SB, Gunda D, Ning Q, Han M. Where Hepatitis B and Hepatitis E Meet: Epidemiological and Clinical Aspects. HEPATITIS MONTHLY 2019; 19. [DOI: 10.5812/hepatmon.93840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 07/09/2019] [Indexed: 08/30/2023]
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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: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 09/06/2019] [Indexed: 12/11/2022]
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Liu Z, Behloul N, Baha S, Wei W, Shi R, Meng J. Design and immunogenicity analysis of the combined vaccine against zoonotic hepatitis E and foot-and-mouth disease. Vaccine 2019; 37:6922-6930. [PMID: 31604580 DOI: 10.1016/j.vaccine.2019.09.036] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 08/30/2019] [Accepted: 09/02/2019] [Indexed: 02/06/2023]
Abstract
AIM Design and immunogenicity assessment of the combined vaccine candidate against zoonotic hepatitis E virus (HEV) and foot-and-mouth disease virus (FMDV). METHODS Using the molecular cloning technology, we produced and purified 9 HEV ORF2-truncated proteins (HEV genotype 4). Then, we compared their thermal stability, antigenicity, and immunogenicity to select the best HEV immunogen. Next, we used the adjuvant Montanide ISA-206 to prepare different formulations of HEV vaccine alone, FMDV vaccine alone and HEV-FMDV combined vaccine. The formulations were injected into mice and the induced humoral immune responses were monitored up 12 weeks post-immunization. RESULTS The HEV p222 protein could self-assemble into VLPs (∼34 nm) and showed higher stability and better antigenicity/immunogenicity than the other HEV antigens, thus it was selected as the best HEV immunogen. Mice immunization with the FMDV vaccine alone induced high FMDV-specific antibody titers in a dose-dependent manner; the HEV p222 protein also induced high levels of anti-HEV antibodies but in a dose-independent manner. The HEV-FMDV combination induced anti-FMDV antibody titers 7-16-fold higher than the titers induced by the FMDV vaccine alone, and HEV-specific antibody titers 2.4-fold higher than those induced by the HEV p222 antigen alone. CONCLUSION Herein, we proposed a new approach for the control of zoonotic HEV infection through its control in its main host (pig). We also designed the first HEV-FMDV combined vaccine and the preliminary analyses revealed a synergistic effect on the immunogenicity of both HEV and FMDV antigens.
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Affiliation(s)
- Zhenzhen Liu
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China
| | - Nouredine Behloul
- College of Basic Medicine, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Sarra Baha
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China
| | - Wenjuan Wei
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China
| | - Ruihua Shi
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China.
| | - Jihong Meng
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China; College of Basic Medicine, Shanghai University of Medicine & Health Sciences, Shanghai, China.
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33
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Denner J, Pischke S, Steinmann E, Blümel J, Glebe D. Why all blood donations should be tested for hepatitis E virus (HEV). BMC Infect Dis 2019; 19:541. [PMID: 31221098 PMCID: PMC6585104 DOI: 10.1186/s12879-019-4190-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 06/13/2019] [Indexed: 02/06/2023] Open
Abstract
Background Hepatitis E is a liver disease caused by a small RNA virus known as hepatitis E virus (HEV). Four major genotypes infect humans, of which genotype 1 and 2 (HEV-1, HEV-2) are endemic mainly in Asia and responsible for waterborne epidemics. HEV-3 and HEV-4 are widely distributed in pigs and can be transmitted to humans mainly by undercooked meat, and contact with pigs. HEV-3 is the main genotype in industrialised countries with moderate climate conditions and object of this debate. Main text Whereas an HEV-3 infection in healthy humans is mostly asymptomatic, HEV-3 can induce chronic infection in immunocompromised individuals and acute-on-chronic liver failure (ACLF) in patients with underlying liver diseases. The number of reported cases of HEV-infections in industrialised nations increased significantly in the last years. Since HEV-3 has been transmitted by blood transfusion to other humans, testing of blood donors has been introduced or introduction is being discussed in some industrialised countries. In this article we summarise the arguments in favour of testing all blood donations for HEV-3. Conclusion The number of HEV infection in the population and the possibility of HEV transmission by blood transfusion are increasing. Transmission by blood transfusion can be dangerous for the recipients considering their immunosuppressive status, underlying disease or other circumstances requiring blood transfusion. This argues in favour of testing all blood donations for HEV-3 to prevent transmission.
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Affiliation(s)
- Joachim Denner
- Robert Koch Institute, Nordufer 20, 13353, Berlin, Germany.
| | - Sven Pischke
- 1. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany
| | - Eike Steinmann
- Ruhr-Universität Bochum, Universitätsstraße 150, 44801, Bochum, Germany
| | - Johannes Blümel
- Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany
| | - Dieter Glebe
- Institute of Medical Virology, National Reference Centre for Hepatitis B and D Viruses, German Center for Infection Research (DZIF), Schubertstr. 81, Justus-Liebig-Universität Giessen, 35392, Giessen, Germany
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34
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Lhomme S, Legrand-Abravanel F, Kamar N, Izopet J. Screening, diagnosis and risks associated with Hepatitis E virus infection. Expert Rev Anti Infect Ther 2019; 17:403-418. [DOI: 10.1080/14787210.2019.1613889] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Sébastien Lhomme
- Department of Virology, National reference center for Hepatitis E Virus, CHU Purpan, Toulouse, France
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
| | - Florence Legrand-Abravanel
- Department of Virology, National reference center for Hepatitis E Virus, CHU Purpan, Toulouse, France
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
| | - Nassim Kamar
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
- Department of Nephrology and Organs Transplantation, CHU Rangueil, Toulouse, France
| | - Jacques Izopet
- Department of Virology, National reference center for Hepatitis E Virus, CHU Purpan, Toulouse, France
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
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35
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Rivero-Juarez A, Jarilla-Fernandez M, Frias M, Madrigal-Sanchez E, López-López P, Andújar-Troncoso G, Machuca I, Camacho A, Muñoz-Valbuena P, Rivero A. Hepatitis E virus in Spanish donors and the necessity for screening. J Viral Hepat 2019; 26:603-608. [PMID: 30661278 DOI: 10.1111/jvh.13064] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Revised: 10/31/2018] [Accepted: 12/18/2018] [Indexed: 12/27/2022]
Abstract
Hepatitis E virus (HEV) represents a major health problem worldwide. As the course of HEV cases is often subclinical, asymptomatic infections could represent an important source of viral spread and infection via routes such as blood donations. Before universal screening for HEV in blood donations can be implemented, studies evaluating the incidence of infection are needed to establish the potential risk of viral transmission. This is a prospective longitudinal study that included blood donors recruited at the Hospital de Ciudad Real Transfusion Service between October 2017 and January 2018. Pools of eight donations were tested for HEV viremia by PCR. Positive pools were individually evaluated following the same procedure. Positive samples were tested for anti-HEV IgG and IgM. Recipients of blood transfusions obtained from HEV-positive donors were retrospectively evaluated. The prevalence of HEV was calculated. A total of 11 313 healthy donors were analysed during the study period. Four blood donations from four different donors were HEV RNA-reactive. The prevalence of HEV infection was 0.035% (95% CI: 0.01%-0.09%), which meant a ratio of one positive donation per 2828 donations. All donors were negative for anti-HEV IgM at the time of the donation. Five patients received transfusions from HEV-positive blood donations, none of them showed an increase in alanine aminotransferase levels after transfusion. In conclusion, our study found a high prevalence of HEV infection in blood donors from south-central Spain. In view of the prevalence, Spanish blood banks should carefully consider including screening for HEV.
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Affiliation(s)
- Antonio Rivero-Juarez
- Infectious Diseases Unit, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía de Córdoba, Universidad de Córdoba, Cordoba, Spain
| | | | - Mario Frias
- Infectious Diseases Unit, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía de Córdoba, Universidad de Córdoba, Cordoba, Spain
| | | | - Pedro López-López
- Infectious Diseases Unit, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía de Córdoba, Universidad de Córdoba, Cordoba, Spain
| | | | - Isabel Machuca
- Infectious Diseases Unit, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía de Córdoba, Universidad de Córdoba, Cordoba, Spain
| | - Angela Camacho
- Infectious Diseases Unit, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía de Córdoba, Universidad de Córdoba, Cordoba, Spain
| | | | - Antonio Rivero
- Infectious Diseases Unit, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía de Córdoba, Universidad de Córdoba, Cordoba, Spain
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36
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Boland F, Martinez A, Pomeroy L, O'Flaherty N. Blood Donor Screening for Hepatitis E Virus in the European Union. Transfus Med Hemother 2019; 46:95-103. [PMID: 31191195 PMCID: PMC6514502 DOI: 10.1159/000499121] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 02/25/2019] [Indexed: 12/11/2022] Open
Abstract
This review article summarises hepatitis E virus (HEV) blood donation screening strategies in effect in the European Union (EU). Since 2012, eight EU countries have implemented HEV screening. Local rates of seroprevalence, RNA incidence, and molecular epidemiology are variable and not usually directly comparable. We report a range of HEV-RNA reactivity rates from 1 in 744 donations (France) to 1 in 8,636 donations (Wales) with an overall EU rate of 1 in 3,109 donations (3.2 million donations screened). HEV genotypes 3c, 3e, and 3f are the most frequently reported subtypes. In these 8 countries, both universal (n = 5) and selective (n = 3) screening policies have been introduced utilising either individual donation (ID; n = 1) or mini-pool (MP; n = 7; MP-6, -16, -24, and -96) testing. We also describe the Irish experience of HEV screening utilising an ID-NAT-based donor screening algorithm which intercepts donations even from those with low-level viraemia; 21 of 56 donors (37.5%) had a viral load (VL) < 100 IU/mL. We performed a MP-24 experiment which may prove useful to colleagues in relation to donor screening and associated blood component transmissibility. Irish results indicate that 59% of donors with a HEV-VL < 450 IU/mL may have screened negative in a MP-24.
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Affiliation(s)
- Fiona Boland
- Irish Blood Transfusion Service (IBTS), NAT Laboratory, Dublin, Ireland
| | | | - Louise Pomeroy
- Irish Blood Transfusion Service (IBTS), NAT Laboratory, Dublin, Ireland
| | - Niamh O'Flaherty
- Irish Blood Transfusion Service (IBTS), NAT Laboratory, Dublin, Ireland
- National Virus Reference Laboratory, University College Dublin (UCD), Dublin, Ireland
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37
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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.
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38
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Webb GW, Dalton HR. Hepatitis E: an underestimated emerging threat. Ther Adv Infect Dis 2019; 6:2049936119837162. [PMID: 30984394 PMCID: PMC6448100 DOI: 10.1177/2049936119837162] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 02/08/2019] [Indexed: 12/22/2022] Open
Abstract
Hepatitis E virus (HEV) is the most common cause of viral hepatitis in the world. It is estimated that millions of people are infected every year, resulting in tens of thousands of deaths. However, these estimates do not include industrialized regions and are based on studies which employ assays now known to have inferior sensitivity. As such, this is likely to represent a massive underestimate of the true global burden of disease. In the developing world, HEV causes large outbreaks and presents a significant public-health problem. Until recently HEV was thought to be uncommon in industrialized countries, and of little relevance to clinicians in these settings. We now know that this is incorrect, and that HEV is actually very common in developed regions. HEV has proved difficult to study in vitro, with reliable models only recently becoming available. Our understanding of the lifecycle of HEV is therefore incomplete. Routes of transmission vary by genotype and location: endemic regions experience large waterborne epidemics, while sporadic cases in industrialized regions are zoonotic infections likely spread via the food chain. Both acute and chronic infection has been observed, and a wide range of extrahepatic manifestations have been reported. This includes neurological, haematological and renal conditions. As the complete clinical phenotype of HEV infection is yet to be characterized, a large proportion of cases go unrecognized or misdiagnosed. In many cases HEV infection does not feature in the differential diagnosis due to a lack of knowledge and awareness of the disease amongst clinicians. In combination, these factors have contributed to an underestimation of the threat posed by HEV. Improvements are required in terms of recognition and diagnosis of HEV infection if we are to understand the natural history of the disease, improve management and reduce the burden of disease around the world.
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Affiliation(s)
- Glynn W. Webb
- University of Manchester NHS Foundation Trust, 7 Radnor Rd London NW6 6TT Manchester, UK
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39
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Vollmer T, Diekmann J, Knabbe C, Dreier J. Hepatitis E virus blood donor NAT screening: as much as possible or as much as needed? Transfusion 2018; 59:612-622. [PMID: 30548866 DOI: 10.1111/trf.15058] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 09/16/2018] [Accepted: 10/18/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND The cost-benefit question of general screening of blood products for the hepatitis E virus (HEV) is currently being discussed. One central question is the need for individual nucleic acid amplification techniques (NAT) screening (ID-NAT) versus minipool NAT screening (MP-NAT) approaches to identify all relevant viremias in blood donors. Here, the findings of ID-NAT versus MP-NAT in pools of 96 samples were compared. STUDY DESIGN AND METHODS From November 2017 to January 2018, a total of 10,141 allogenic blood donations from 7650 individual German blood donors were screened for the presence of HEV RNA using MP-NAT (96 samples) (RealStar HEV RT-PCR Kit) compared to ID-NAT (cobas HEV assay) on the fully automated cobas 6800 platform. RESULTS Parallel screening of MP (n = 122, 96 samples/MP) using both methods detected seven reactive pools. After pool resolution, 8 HEV RNA-positive donations were identified by the in-house detection method, whereas 17 HEV RNA-positive donations were identified by ID-NAT with the cobas HEV assay. This resulted in an incidence of 1:1268 donations (0.079%) for MP-NAT screening and 1:597 donations (0.168%) for ID-NAT screening. CONCLUSIONS The detection frequency of HEV RNA was approximately 50% higher if ID-NAT was used compared to MP-NAT. However, viral loads of ID-NAT-only samples were below 25 IU/mL and will often not result in transfusion-transmitted HEV (TT-HEV) infection, taking into account the currently known infectious dose of 5.0E + 04 IU inevitably resulting in TT-HEV infection. The clinical relevance and need for identification of these low-level HEV-positive donors still require further investigation.
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Affiliation(s)
- T Vollmer
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - J Diekmann
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - C Knabbe
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - J Dreier
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
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40
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Dalton HR, Izopet J. Transmission and Epidemiology of Hepatitis E Virus Genotype 3 and 4 Infections. Cold Spring Harb Perspect Med 2018. [PMID: 29530946 DOI: 10.1101/cshperspect.a032144] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Following the introduction of robust serological and molecular tools, our understanding of the epidemiology of zoonotic hepatitis E virus (HEV) has improved considerably in recent years. Current thinking suggests that consumption of pork meat products is the key route of infection in humans, but it is certainly not the only one. Other routes of infection include environmental spread, contaminated water, and via the human blood supply. The epidemiology of HEV genotype (gt)3 and gt4 is complex, as there are several sources and routes of infection, and it is likely that these vary between and within countries and over time.
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Affiliation(s)
- Harry R Dalton
- Royal Cornwall Hospital, Truro TR1 3LJ, United Kingdom.,European Centre for Environment and Human Health, University of Exeter, Truro TR1 3LJ, United Kingdom
| | - Jacques Izopet
- Department of Virology, Hepatitis E Virus National Reference Centre, Toulouse University Hospital, 31059 Toulouse, France.,Toulouse-Purpan Centre for Pathophysiology, INSERM UMR1043/CNRS UMR 5282, CPTP, Toulouse University Paul Sabatier, 31024 Toulouse, France
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41
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Mesquita JR, Istrate C, Santos-Ferreira NL, Ferreira AS, Abreu-Silva J, Veiga J, van der Poel WHM, Nascimento MSJ. Short communication: detection and molecular characterization of hepatitis E virus in domestic animals of São Tomé and Príncipe. Trop Anim Health Prod 2018; 51:481-485. [PMID: 30178438 DOI: 10.1007/s11250-018-1700-x] [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: 05/23/2018] [Accepted: 08/27/2018] [Indexed: 12/15/2022]
Abstract
As in most of the African continent, the status of hepatitis E virus (HEV) infection in domestic animals in São Tomé and Príncipe, an archipelago off the western equatorial coast of Central Africa, is also completely unknown. In the present study, we investigated the presence of HEV among domestic animals in São Tomé and Príncipe. A total of 93 stool samples from different animal species (goat, cow, pig, chicken, duck, and monkey) were tested for HEV RNA using two real-time RT-PCR assays, followed by a nested RT-PCR assay for sequencing and phylogenetic analysis. A total of six samples (1 cow stool and 5 pig stools) were found to be positive for HEV RNA of which one pig stool was positive by broad spectrum nested RT-PCR. Phylogenetic analysis showed that the retrieved sequence clustered within HEV subgenotype 3f, similar to zoonotic strains of European countries and posing interesting questions on past introduction of European HEV into São Tomé and Príncipe archipelago. This is the first report describing the presence and molecular characterization of HEV in São Tomé and Príncipe.
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Affiliation(s)
- João Rodrigo Mesquita
- Escola Superior Agrária de Viseu (ESAV), Centro de Estudos em Educação, Tecnologias e Saúde (CI&DETS), Instituto Politécnico de Viseu, Quinta da Alagoa, Estrada de Nelas, Ranhados, 3500-606, Viseu, Portugal. .,Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, 4050-313, Porto, Portugal.
| | - Claudia Istrate
- Global Health and Tropical Medicine (GHTM), Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Lisbon, Portugal
| | - Nânci L Santos-Ferreira
- Laboratório de Microbiologia, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal
| | - Ana S Ferreira
- Laboratório de Microbiologia, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal
| | - Joana Abreu-Silva
- Laboratório de Microbiologia, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal
| | - José Veiga
- Instituto Marquês de Valle Flor, São Tomé, São Tomé and Príncipe.,Ministério da Saúde, São Tomé, São Tomé and Príncipe
| | - Wim H M van der Poel
- Wageningen Bioveterinary Research, Edelhertweg 15, 8219 PH, Lelystad, The Netherlands
| | - Maria S J Nascimento
- Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, 4050-313, Porto, Portugal.,Laboratório de Microbiologia, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal
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