{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T04:04:31Z","timestamp":1763006671156,"version":"3.45.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JPGN rep."],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In April 2022, the United Kingdom and the United States reported alarming increases in cases of severe acute hepatitis of unknown etiology in children, indicating a multicountry outbreak. We aimed to determine if Germany was affected by the outbreak.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cases were defined as patients 0\u201316 years with severe acute hepatitis (aspartate transaminase and\/or alanine transaminase\u2009&gt;\u2009500\u2009IU\/l), with adenovirus detection or unknown etiology. Severely impaired liver function resulting in listing for liver transplant, undergoing liver transplant or death was defined as \u201cfulminant\u201d pediatric acute liver failure (pALF). We compared the 2017\u20132021 case numbers reported by German pediatric liver transplant centers (pLTxCs) with 05\/2022\u201305\/2023. Numbers of pediatric inpatients diagnosed with any of 12 selected hepatological ICD\u201010 codes and number of liver transplants from national hospital discharge data in 2022 were compared with 2015\u20132021, using a two\u2010sample Poisson test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From 5\/2022\u20135\/2023, eight pLTxCs reported nine hepatitis cases with fulminant pALF, compared to 5\u201314 cases annually from 2017 to 2021, and a total of 26 hepatitis cases without pALF (no baseline data available). The number of pediatric inpatients diagnosed with any of 12 selected hepatological ICD\u201010 codes was 373 in 2022, compared to 333\u2013422 annually in 2015\u20132021. There were 85 liver transplants in 2022, compared to 91\u2013114 annually in 2015\u20132021.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>According to available data, there was no apparent increase in severe acute hepatitis cases of unknown etiology with fulminant pALF in children in Germany, 2022. We recommend implementing syndromic surveillance at pediatric emergency units and timely access to hospital discharge data.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jpr3.70083","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T14:33:10Z","timestamp":1757687590000},"page":"498-507","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["No apparent increase in cases of severe acute hepatitis of unknown etiology with fulminant liver failure in children in Germany, 2022"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8118-7051","authenticated-orcid":false,"given":"Anna\u2010Lisa","family":"Behnke","sequence":"first","affiliation":[{"name":"Department of Infectious Disease Epidemiology Robert Koch Institute Berlin Germany"},{"name":"Postgraduate Training for Applied Epidemiology (PAE), Robert Koch Institute Berlin Germany"},{"name":"ECDC Fellowship Programme, Field Epidemiology path (EPIET), European Centre for Disease Prevention and Control (ECDC) Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9297-3675","authenticated-orcid":false,"given":"Achim","family":"D\u00f6rre","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology Robert Koch Institute Berlin Germany"},{"name":"Postgraduate Training for Applied Epidemiology (PAE), Robert Koch Institute Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6108-1498","authenticated-orcid":false,"given":"Julia","family":"Enkelmann","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology Robert Koch Institute Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"Knoppke","sequence":"additional","affiliation":[{"name":"University Children's Hospital Regensburg Regensburg Germany"},{"name":"Spokesperson of the Working Group for Pediatric Liver Transplantation, German Society for Pediatric Gastroenterology and Nutrition (GPGE) Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Working Group for Pediatric Liver Transplantation of the German Society for Pediatric Gastroenterology and Nutrition (GPGE)","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3635-2692","authenticated-orcid":false,"given":"Ruth","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology Robert Koch Institute Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9196-570X","authenticated-orcid":false,"given":"Mirko","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology Robert Koch Institute Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"unstructured":"World Health Organization (WHO). Severe acute hepatitis of unknown aetiology in children: multi\u2010country.Disease Outbreak News. 2022. Accessed 12 March 12 2024.https:\/\/www.who.int\/emergencies\/disease-outbreak-news\/item\/2022-DON400.","key":"e_1_2_8_2_1"},{"unstructured":"UK Health Security Agency. Investigation into acute hepatitis of unknown aetiology in children in England: case update.Reserach and Analysis; 2023. Accessed June 13 2024.https:\/\/www.gov.uk\/government\/publications\/acute-hepatitis-technical-briefing\/investigation-into-acute-hepatitis-of-unknown-aetiology-in-children-in-england-case-update.","key":"e_1_2_8_3_1"},{"unstructured":"Public Health Agency of Canada. Acute severe hepatitis in children; 2022. Accessed March 12 2024.https:\/\/www.canada.ca\/en\/public-health\/services\/diseases\/acute-hepatitis-children.html#a3.","key":"e_1_2_8_4_1"},{"doi-asserted-by":"publisher","key":"e_1_2_8_5_1","DOI":"10.1016\/j.jpeds.2005.12.051"},{"volume-title":"Rapid Risk Assessment: Increase in Severe Acute Hepatitis Cases of Unknown Aetiology in Children \u2013 28 April 2022","author":"European Centre for Disease Prevention and Control","first-page":"2022","key":"e_1_2_8_6_1"},{"doi-asserted-by":"publisher","key":"e_1_2_8_7_1","DOI":"10.1001\/jamanetworkopen.2022.37091"},{"doi-asserted-by":"publisher","key":"e_1_2_8_8_1","DOI":"10.1038\/s41586-023-05948-2"},{"doi-asserted-by":"publisher","key":"e_1_2_8_9_1","DOI":"10.1038\/s41586-023-06003-w"},{"doi-asserted-by":"publisher","key":"e_1_2_8_10_1","DOI":"10.1038\/s41586-023-05949-1"},{"doi-asserted-by":"publisher","key":"e_1_2_8_11_1","DOI":"10.1016\/S2468-1253(23)00118-8"},{"doi-asserted-by":"publisher","key":"e_1_2_8_12_1","DOI":"10.2807\/1560-7917.ES.2022.27.15.2200318"},{"doi-asserted-by":"publisher","key":"e_1_2_8_13_1","DOI":"10.2807\/1560-7917.ES.2022.27.31.2200483"},{"unstructured":"European Centre for Disease Prevention and Control\/WHO Regional Office for Europe. Hepatitis of unknown aetiology in children joint epidemiological overview; 2022. Accessed February 3 2023.https:\/\/www.ecdc.europa.eu\/en\/hepatitis\/joint-hepatitis-unknown-origin-children-surveillance-bulletin.","key":"e_1_2_8_14_1"},{"unstructured":"European Centre for Disease Prevention and Control. TESSy \u2010 The European surveillance system. Hepatitis of unknown origin reporting protocol 2022 version 2.0; 2022. Accessed May 08 2024.https:\/\/www.ecdc.europa.eu\/sites\/default\/files\/documents\/Hepatitis-of-unknown-origin-Reporting-Protocol_1.pdf.","key":"e_1_2_8_15_1"},{"unstructured":"Federal Ministry of Justice. German infection protection act (IfSG). \u00a76 Notifiable Diseases; 2001. Accessed September 18 2024.https:\/\/www.gesetze-im-internet.de\/ifsg\/__6.html.","key":"e_1_2_8_16_1"},{"unstructured":"ZimmermannR FaberM. F\u00e4lle akuter Hepatitis unklarer \u00c4tiologie (non A\u2010E) bei Kindern [Cases of acute hepatitis of unknown aetiology (non A\u2010E) in children]; 2022. Accessed May 8 2024.https:\/\/edoc.rki.de\/bitstream\/handle\/176904\/9658\/EB-17-2022-F%C3%A4lle%20akuter%20Hepatitis-ONLINE%20VORAB.pdf?sequence=1&isAllowed=y.","key":"e_1_2_8_17_1"},{"doi-asserted-by":"publisher","key":"e_1_2_8_18_1","DOI":"10.1016\/j.dld.2021.03.004"},{"doi-asserted-by":"publisher","key":"e_1_2_8_19_1","DOI":"10.1097\/MPG.0000000000003268"},{"doi-asserted-by":"publisher","key":"e_1_2_8_20_1","DOI":"10.1016\/j.cld.2018.06.009"},{"unstructured":"DESTATIS \u2010 Statistisches Bundesamt [Federal Statistical Office]. Statistischer Bericht \u2010 Diagnosen der Krankenhauspatienten 2022 [Statistical Report \u2010 Diagnoses of hospital inpatients 2022]; 2023. Accessed November 9 2023.https:\/\/www.destatis.de\/DE\/Themen\/Gesellschaft-Umwelt\/Gesundheit\/Krankenhaeuser\/Publikationen\/Downloads-Krankenhaeuser\/statistischer-bericht-diagnosedaten-5231301227015.html.","key":"e_1_2_8_21_1"},{"volume-title":"Protocol for Assessment of Exceedances Around Severe Acute Cases of Hepatitis of Unknown Origin in Children in EU\/EEA Countries","year":"2022","author":"European Centre for Disease Prevention and Control","key":"e_1_2_8_22_1"},{"doi-asserted-by":"publisher","key":"e_1_2_8_23_1","DOI":"10.14745\/ccdr.v49i06a02"},{"unstructured":"Gesellschaft f\u00fcr P\u00e4diatrische Gastroenterologie und Ern\u00e4hrung (GPGE e.V.). [German Society for Pediatric Gastroenterology and Nutrition (GPGE e.V.)]. Kein geh\u00e4uftes Vorkommen unklarer schwerer Hepatitis im Kindesalter in Deutschland. [No clustered occurrence of unclear severe hepatitis in children in Germany]. Press Release. Accessed July 3 2024.https:\/\/www.gpge.eu\/gpge-news\/span-classsqsrte-text-color-accentkein-gehuftes-vorkommen-unklarer-schwerer-hepatitis-im-kindesalter-in-deutschlandspan.","key":"e_1_2_8_24_1"},{"unstructured":"aerzteblatt.de. Unklare Hepatitis bei Kindern hierzulande bisher nicht auff\u00e4llig [Unexplained hepatitis in children in Germany has not been conspicuous to date]; 2022. Accessed June 13 2024.https:\/\/www.aerzteblatt.de\/nachrichten\/133518\/Unklare-Hepatitis-bei-Kindern-hierzulande-bisher-nicht-auffaellig.","key":"e_1_2_8_25_1"},{"doi-asserted-by":"publisher","key":"e_1_2_8_26_1","DOI":"10.15585\/mmwr.mm7124e1"},{"doi-asserted-by":"publisher","key":"e_1_2_8_27_1","DOI":"10.2807\/1560-7917.ES.2022.27.19.2200369"},{"doi-asserted-by":"publisher","key":"e_1_2_8_28_1","DOI":"10.1016\/j.jhep.2022.06.026"},{"doi-asserted-by":"publisher","key":"e_1_2_8_29_1","DOI":"10.1016\/j.jhep.2022.12.012"},{"unstructured":"Frankfurter Allgemeine Zeitung (Lucia Schmidt). Warum Kinder schwer an Leberentz\u00fcndungen erkranken [Why children fall seriously ill with liver inflammation]; 2023. 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