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      The global epidemiology of hepatitis E virus infection: A systematic review and meta‐analysis

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          Abstract

          Background and aims

          Hepatitis E virus (HEV), as an emerging zoonotic pathogen, is a leading cause of acute viral hepatitis worldwide, with a high risk of developing chronic infection in immunocompromised patients. However, the global epidemiology of HEV infection has not been comprehensively assessed. This study aims to map the global prevalence and identify the risk factors of HEV infection by performing a systematic review and meta‐analysis.

          Methods

          A systematic searching of articles published in Medline, Embase, Web of science, Cochrane and Google scholar databases till July 2019 was conducted to identify studies with HEV prevalence data. Pooled prevalence among different countries and continents was estimated. HEV IgG seroprevalence of subgroups was compared and risk factors for HEV infection were evaluated using odd ratios (OR).

          Results

          We identified 419 related studies which comprised of 1 519 872 individuals. A total of 1 099 717 participants pooled from 287 studies of general population estimated a global anti‐HEV IgG seroprevalence of 12.47% (95% CI 10.42‐14.67; I 2 = 100%). Notably, the use of ELISA kits from different manufacturers has a substantial impact on the global estimation of anti‐HEV IgG seroprevalence. The pooled estimate of anti‐HEV IgM seroprevalence based on 98 studies is 1.47% (95% CI 1.14‐1.85; I 2 = 99%). The overall estimate of HEV viral RNA‐positive rate in general population is 0.20% (95% CI 0.15‐0.25; I 2 = 98%). Consumption of raw meat ( P = .0001), exposure to soil ( P < .0001), blood transfusion ( P = .0138), travelling to endemic areas ( P = .0244), contacting with dogs ( P = .0416), living in rural areas ( P = .0349) and receiving education less than elementary school ( P < .0001) were identified as risk factors for anti‐HEV IgG positivity.

          Conclusions

          Globally, approximately 939 million corresponding to 1 in 8 individuals have ever experienced HEV infection. 15‐110 million individuals have recent or ongoing HEV infection. Our study highlights the substantial burden of HEV infection and calls for increasing routine screening and preventive measures.

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          Most cited references40

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          ICTV Virus Taxonomy Profile: Hepeviridae

          The family Hepeviridae includes enterically transmitted small non-enveloped positive-sense RNA viruses. It includes the genera Piscihepevirus, whose members infect fish, and Orthohepevirus, whose members infect mammals and birds. Members of the genus Orthohepevirus include hepatitis E virus, which is responsible for self-limiting acute hepatitis in humans and several mammalian species; the infection may become chronic in immunocompromised individuals. Extrahepatic manifestations of Guillain–Barré syndrome, neuralgic amyotrophy, glomerulonephritis and pancreatitis have been described in humans. Avian hepatitis E virus causes hepatitis–splenomegaly syndrome in chickens. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Hepeviridae, which is available at www.ictv.global/report/hepeviridae.
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            Hepatitis E Seroprevalence in Europe: A Meta-Analysis

            There have been large numbers of studies on anti-HEV IgG seroprevalence in Europe, however, the results of these studies have produced high variability of seroprevalence rates, making interpretation increasingly problematic. Therefore, the aim of this study was to develop a clearer understanding of anti-HEV IgG seroprevalence in Europe and identify risk groups for HEV exposure by a meta-analysis of published studies. Methods: All European HEV-seroprevalence studies from 2003 to 2015 were reviewed. Data were stratified by assay, geographical location, and patient cohort (general population, patients with HIV, solid-organ transplant recipients, chronic liver disease patients, and individuals in contact with swine/wild animals). Data were pooled using a mixed-effects model. Results: Four hundred thirty-two studies were initially identified, of which 73 studies were included in the analysis. Seroprevalence estimates ranged from 0.6% to 52.5%, increased with age, but were unrelated to gender. General population seroprevalence varied depending on assays: Wantai (WT): 17%, Mikrogen (MG): 10%, MP-diagnostics (MP): 7%, DiaPro: 4%, Abbott 2%. The WT assay reported significantly higher seroprevalence rates across all cohorts (p < 0.001). Individuals in contact with swine/wild animals had significantly higher seroprevalence rates than the general population, irrespective of assay (p < 0.0001). There was no difference between any other cohorts. The highest seroprevalence was observed in France (WT: 32%, MP: 16%) the lowest in Italy (WT: 7.5%, MP 0.9%). Seroprevalence varied between and within countries. The observed heterogeneity was attributed to geographical region (23%), assay employed (23%) and study cohort (7%). Conclusion: Seroprevalcence rates primarily depend on the seroassy that is used, followed by the geographical region and study cohort. Seroprevalence is higher in individuals exposed to swine and/or wild animals, and increases with age.
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              Test performance characteristics of Anti-HEV IgG assays strongly influence hepatitis E seroprevalence estimates.

              Hepatitis E virus (HEV) seroprevalences of 0.3%-53% were reported from industrialized countries. Because these estimates may be influenced by detection assays, this study compares 3 frequently used tests for HEV detection: the MP Diagnostics HEV immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), the Axiom Diagnostics HEV IgG enzyme immunoassay (EIA), and the Mikrogen recomLine HEV IgG assay. Sera from 200 healthy healthcare workers and 30 individuals with acute HEV infection were analyzed. Among the healthy individuals, HEV IgG was found in 4.5% by the MP Diagnostics assay, in 29.5% by the Axiom Diagnostics assay, and in 18% by the Mikrogen assay. Among individuals with acute HEV infection, positive results were obtained for 83.3%, 100%, and 96.7%, respectively. Thus, the 3 assays show clear differences in diagnostic sensitivity.
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                Author and article information

                Contributors
                j.liu.2@erasmusmc.nl
                q.pan@erasmusmc.nl
                Journal
                Liver Int
                Liver Int
                10.1111/(ISSN)1478-3231
                LIV
                Liver International
                John Wiley and Sons Inc. (Hoboken )
                1478-3223
                1478-3231
                24 April 2020
                July 2020
                : 40
                : 7 ( doiID: 10.1111/liv.v40.7 )
                : 1516-1528
                Affiliations
                [ 1 ] Department of Gastroenterology and Hepatology Erasmus MC‐University Medical Center Rotterdam The Netherlands
                [ 2 ] Biomedical Research Center Northwest Minzu University Lanzhou China
                [ 3 ] Medical Library Erasmus MC‐University Medical Center Rotterdam The Netherlands
                Author notes
                [*] [* ] Correspondence

                Jiaye Liu, Department of Gastroenterology and Hepatology, Erasmus MC‐University Medical Center, Rotterdam, The Netherlands.

                Email: j.liu.2@ 123456erasmusmc.nl

                Qiuwei Pan, Department of Gastroenterology and Hepatology, Erasmus MC, room Na‐1011, ’sGravendijkwal 230, NL‐3015 CE Rotterdam, The Netherlands.

                Email: q.pan@ 123456erasmusmc.nl

                Author information
                https://orcid.org/0000-0001-9982-6184
                Article
                LIV14468
                10.1111/liv.14468
                7384095
                32281721
                6ee41cf6-656c-48e3-b1f1-491000c8bb26
                © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 January 2020
                : 29 March 2020
                : 01 April 2020
                Page count
                Figures: 4, Tables: 1, Pages: 13, Words: 9210
                Funding
                Funded by: KWF (Dutch Cancer Society)
                Award ID: 10140
                Funded by: Netherlands Organisation for Scientific Research (NWO)
                Award ID: 91719300
                Funded by: Changjiang Scholars and Innovative Research Team in University
                Award ID: IRT_17R88
                Funded by: China Scholarship Council , open-funder-registry 10.13039/501100004543;
                Award ID: 201808370170
                Award ID: 201606240079
                Award ID: 201703250073
                Award ID: 201708535017
                Award ID: 201307060013
                Categories
                Original Article
                Reviews
                Custom metadata
                2.0
                July 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.6 mode:remove_FC converted:27.07.2020

                Gastroenterology & Hepatology
                epidemiology,hepatitis e virus,prevalence,risk factors,seroprevalence

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