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Abstract

An outbreak of severe acute hepatitis of unknown aetiology in children (HUAC) was reported by the United Kingdom (UK) in spring 2022. Within days, a corresponding increase was identified in Ireland. A multi-agency incident management team (IMT), led by the Health Protection Surveillance Centre (HPSC), established a national case definition, trawling questionnaire, testing protocol and communications plan. Between 1 October 2021 and 12 May 2023, 44 probable and three possible cases of HUAC were identified in Ireland with a median age of 3 years. Adeno-associated virus 2 (AAV2), detected in 18 of 31 probable cases, and SARS-CoV-2 antibodies in 22 of 37 of probable cases were the most common infectious agents, followed by human herpes virus 7 (18/33) and adenovirus (20/44). Immunological findings included the human leukocyte antigen (HLA) class II allele in 17 of 32 cases. Autoantibodies were found in 15 of 40 patients. Our findings corroborate those of the UK, which suggested a link between HUAC and AAV2 and another virus, in children predisposed due to presence of a particular HLA class II type. Close collaboration with the UK, the European Centre for Disease Prevention and Control (ECDC) and World Health Organization (WHO) was invaluable in the investigation.

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/content/10.2807/1560-7917.ES.2025.30.14.2400536
2025-04-10
2025-04-14
/content/10.2807/1560-7917.ES.2025.30.14.2400536
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References

  1. Squires RH Jr, Shneider BL, Bucuvalas J, Alonso E, Sokol RJ, Narkewicz MR, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr. 2006;148(5):652-8.  https://doi.org/10.1016/j.jpeds.2005.12.051  PMID: 16737880 
  2. Mendizabal M, Dip M, Demirdjian E, Lauferman L, Lopez S, Minetto J, et al. Changing etiologies and prognostic factors in pediatric acute liver failure. Liver Transpl. 2020;26(2):268-75.  https://doi.org/10.1002/lt.25658  PMID: 31606931 
  3. Braccio S, Irwin A, Riordan A, Shingadia D, Kelly DA, Bansal S, et al. Acute infectious hepatitis in hospitalised children: a British Paediatric Surveillance Unit study. Arch Dis Child. 2017;102(7):624-8.  https://doi.org/10.1136/archdischild-2016-311916  PMID: 28377449 
  4. World Health Organization (WHO). Severe acute hepatitis of unknown aetiology in children—multi-country. Geneva: WHO; 12 July 2022. Available from: https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON400
  5. European Centre for Disease Prevention and Control (ECDC) and World Health Organization Regional Office for Europe. (WHO/Europe). Joint ECDC-WHO Regional Office for Europe Hepatitis of Unknown Origin in Children Surveillance Bulletin. Stockholm: ECDC and Copenhagen: WHO/Europe; 25 Nov 2022. Available from: https://cdn.ecdc.europa.eu/novhep-surveillance
  6. Marsh K, Tayler R, Pollock L, Roy K, Lakha F, Ho A, et al. Investigation into cases of hepatitis of unknown aetiology among young children, Scotland, 1 January 2022 to 12 April 2022. Euro Surveill. 2022;27(15):2200318.  https://doi.org/10.2807/1560-7917.ES.2022.27.15.2200318  PMID: 35426362 
  7. Mandal S, Simmons R, Ireland G, Charlett A, Desai M, Coughlan L, et al. Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK. Lancet Child Adolesc Health. 2023;7(11):786-96.  https://doi.org/10.1016/S2352-4642(23)00215-8  PMID: 37774733 
  8. Kelgeri C, Couper M, Gupte GL, Brant A, Patel M, Johansen L, et al. Clinical spectrum of children with acute hepatitis of unknown cause. N Engl J Med. 2022;387(7):611-9.  https://doi.org/10.1056/NEJMoa2206704  PMID: 35830627 
  9. Baker JM, Buchfellner M, Britt W, Sanchez V, Potter JL, Ingram LA, et al. Acute hepatitis and adenovirus infection among children - Alabama, October 2021–February 2022. MMWR Morb Mortal Wkly Rep. 2022;71(18):638-40.  https://doi.org/10.15585/mmwr.mm7118e1  PMID: 35511732 
  10. Irish Statute Book (ISB). S.I. No. 707/2003 - Infectious Diseases (Amendment) (No. 3) Regulations 2003. Dublin: ISB; 2003. Available from: https://www.irishstatutebook.ie/eli/2003/si/707/made/en/print
  11. Health Protection Surveillance Centre (HPSC). Severe acute hepatitis of unknown aetiology in Ireland. Dublin: HPSC; 15 Feb 2022. Available from: https://www.hpsc.ie/a-z/hepatitis/acutehepatitisofunknownaetiology/dataandreports/archivedacutehepatitisofunknownaetiologyreports/20230215_Epi%20summary%20of%20cases%20hepatitis%20unknown%20aetiology%20_WEBSITE.pdf
  12. World Health Organization (WHO). Laboratory testing for severe acute hepatitis of unknown aetiology in children: interim guidance, 17 June 2022. Geneva: WHO;17 June 2022. Available from: https://www.who.int/publications/i/item/who-unkhep-laboratory-2022.1
  13. Martin NA, Gonzalez G, Reynolds LJ, Bennett C, Campbell C, Nolan TM, et al. Adeno-associated virus 2 and human adenovirus F41 in wastewater during outbreak of severe acute hepatitis in children, Ireland. Emerg Infect Dis. 2023;29(4):751-60.  https://doi.org/10.3201/eid2904.221878  PMID: 36957994 
  14. Mieli-Vergani G, Vergani D, Baumann U, Czubkowski P, Debray D, Dezsofi A, et al. Diagnosis and Management of Pediatric Autoimmune Liver Disease: ESPGHAN Hepatology Committee Position Statement. J Pediatr Gastroenterol Nutr. 2018;66(2):345-60.  https://doi.org/10.1097/MPG.0000000000001801  PMID: 29356770 
  15. European Centre for Disease Prevention and Control (ECDC). Hepatitis of unknown origin - Reporting protocol 2022. Stockholm: ECDC; 29 Apr 2022. Available from: https://www.ecdc.europa.eu/en/publications-data/hepatitis-unknown-origin-reporting-protocol-2022#:~:text=This%20reporting%20protocol%20is%20intended,Area%20(EEA)%2C%20to%20the
  16. Independent Health and Aged Care Pricing Authority (IHPA). ICD-10-AM/ACHI/ACS Tenth Edition. Sydney: IHPA; 1 Jul 2017. Available from: https://www.ihacpa.gov.au/resources/icd-10-amachiacs-tenth-edition
  17. Eurostat. Population and population change statistics. Luxembourg: Eurostat; 6 Jul 2024. Available from: https://ec.europa.eu/eurostat/statistics-explained/index.php?title=Population_and_population_change_statistics
  18. Morfopoulou S, Buddle S, Torres Montaguth OE, Atkinson L, Guerra-Assunção JA, Moradi Marjaneh M, et al. Genomic investigations of unexplained acute hepatitis in children. Nature. 2023;617(7961):564-73.  https://doi.org/10.1038/s41586-023-06003-w  PMID: 36996872 
  19. Ho A, Orton R, Tayler R, Asamaphan P, Herder V, Davis C, et al. Adeno-associated virus 2 infection in children with non-A-E hepatitis. Nature. 2023;617(7961):555-63.  https://doi.org/10.1038/s41586-023-05948-2  PMID: 36996873 
  20. Dunne C, Crowley J, Hagan R, Rooney G, Lawlor E. HLA-A, B, Cw, DRB1, DQB1 and DPB1 alleles and haplotypes in the genetically homogenous Irish population. Int J Immunogenet. 2008;35(4-5):295-302.  https://doi.org/10.1111/j.1744-313X.2008.00779.x  PMID: 18976432 
  21. Health Protection Surveillance Centre (HPSC). Seroprevalence of SARS-CoV-2 antibodies in children. Dublin: HPSC;4 October 2022. Available from: https://www.hpsc.ie/a-z/nationalserosurveillanceprogramme/reports/NSP%20combined%20adult%20paeds%20cycle%201%20report_final.pdf
  22. United Kingdom Health Security Agency (UKHSA). Investigation into acute hepatitis of unknown aetiology in children in England: case update. London: UKHSA;23 May 2023. Available from: https://www.gov.uk/government/publications/acute-hepatitis-technical-briefing/investigation-into-acute-hepatitis-of-unknown-aetiology-in-children-in-england-case-update
  23. World Health Organization (WHO). Acute hepatitis of unknown aetiology in children - Multi-country. Geneva: WHO; 27 May 2022. Available from: https://www.who.int/emergencies/disease-outbreak-news/item/DON-389
  24. de Kleine RH, Lexmond WS, Buescher G, Sturm E, Kelly D, Lohse AW, et al. Severe acute hepatitis and acute liver failure of unknown origin in children: a questionnaire-based study within 34 paediatric liver centres in 22 European countries and Israel, April 2022. Euro Surveill. 2022;27(19):2200369.  https://doi.org/10.2807/1560-7917.ES.2022.27.19.2200369  PMID: 35551705 
  25. van Beek J, Fraaij P, Giaquinto C, Shingadia D, Horby P, Indolfi G, et al. Case numbers of acute hepatitis of unknown aetiology among children in 24 countries up to 18 April 2022 compared to the previous 5 years. Euro Surveill. 2022;27(19):2200370.  https://doi.org/10.2807/1560-7917.ES.2022.27.19.2200370  PMID: 35551703 
  26. Di Dato F, Di Giorgio A, Mandato C, Maggiore G, Iorio R, Aloi M, et al. Italian children seem to be spared from the mysterious severe acute hepatitis outbreak: A report by SIGENP Acute Hepatitis Group. J Hepatol. 2022;77(4):1211-3.  https://doi.org/10.1016/j.jhep.2022.06.026  PMID: 35809865 
  27. Leiskau C, Tsaka S, Meyer-Ruhnke L, Mutschler FE, Pfister E-D, Lainka E, et al. Acute severe non-A-E-hepatitis of unknown origin in children - A 30-year retrospective observational study from north-west Germany. J Hepatol. 2023;78(5):971-8.  https://doi.org/10.1016/j.jhep.2022.12.012  PMID: 36572350 
  28. Kambhampati AKBR, Burke RM, Dietz S, Sheppard M, Almendares O, Baker JM, et al. Trends in acute hepatitis of unspecified etiology and adenovirus stool testing results in children - United States, 2017–2022. MMWR Morb Mortal Wkly Rep. 2022;71(24):797-802.  https://doi.org/10.15585/mmwr.mm7124e1  PMID: 35709071 
Investigation of an outbreak of novel hepatitis of unknown aetiology in children and adolescents, Ireland, 2021 to 2023
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Emer+Liddy&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Liddy Emer</a>, <a href="/search?value1=Niamh+Murphy&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Murphy Niamh</a>, <a href="/search?value1=Jolita+Mereckiene&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Mereckiene Jolita</a>, <a href="/search?value1=Emer+Fitzpatrick&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Fitzpatrick Emer</a>, <a href="/search?value1=Annemarie+Broderick&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Broderick Annemarie</a>, <a href="/search?value1=R%C3%B3isin+Egan&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Egan Róisin</a>, <a href="/search?value1=Tiarn%C3%A1n+Fallon+Verbruggen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Verbruggen Tiarnán Fallon</a>, <a href="/search?value1=Julie-Anne+Houlihan&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Houlihan Julie-Anne</a>, <a href="/search?value1=Christine+Campbell&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Campbell Christine</a>, <a href="/search?value1=Michael+Carr&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Carr Michael</a>, <a href="/search?value1=Gabriel+Gonzalez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Gonzalez Gabriel</a>, <a href="/search?value1=Jonathan+Dean&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Dean Jonathan</a>, <a href="/search?value1=Richard+Hagan&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Hagan Richard</a>, <a href="/search?value1=Cillian+De+Gascun&option1=author&noRedirect=true" class="nonDisambigAuthorLink">De Gascun Cillian</a>, <a href="/search?value1=Suzanne+Cotter&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Cotter Suzanne</a>, <a href="/search?value1=on+behalf+of+the+Incident+Management+Team&option1=author&noRedirect=true" class="nonDisambigAuthorLink">on behalf of the Incident Management Team</a></span>. Investigation of an outbreak of novel hepatitis of unknown aetiology in children and adolescents, Ireland, 2021 to 2023. <a href="/content/ecdc">Euro Surveill.</a> 2025;30(14):pii=2400536. <a href="https://doi.org/10.2807/1560-7917.ES.2025.30.14.2400536" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2025.30.14.2400536</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 12 Aug 2024;&nbsp;&nbsp; <span class="generated">Accepted</span>: 08 Nov 2024 </span> </p>
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