The investigation on the acute, severe hepatitis of unknown origin in children
YAO Kai-Hu, MENG Qing-Hong, YU Dan
National Center for Children's Health/Beijing Children's Hospital, Capital Medical University/Laboratory of Microbiology, Beijing Pediatric Research Institute/National Key Discipline of Pediatrics (Capital Medical University)/Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 100045, China
Abstract:In April 2022, the United Kingdom notified the World Health Organization (WHO) of an unexpected increase in acute hepatitis of unknown origin in children. Subsequent investigations have found more than 400 cases in more than 20 countries and regions around the world. Although the potential role of adenovirus type 41 in the pathogenesis of these cases is one hypothesis, it is probably not the only pathogenic factor, and other infectious and non-infectious causes cannot be completely ruled out. For hepatitis caused by non-hepatitis A, B, C, D and E viruses, there is a lack of systematic monitoring and research, and many unknowns still exist. According to the current etiology speculation and epidemiological characteristics of adenovirus in China, cases of acute hepatitis with unknown origin may be found in China in the future. There is also a risk of imported cases. This article systematically sorts out the reports and studies on child acute hepatitis of unknown origin, hoping to attract the attention of pediatric clinicians in China, raise awareness and vigilance, and calmly prepare for possible abnormal situations.
1 World Health Organization. Acute hepatitis of unknown aetiology—the United Kingdom of Great Britain and Northern Ireland[EB/OL]. (2022-04-15)[2022-04-30]. https://www.who.int/emergencies/disease-outbreak-news/item/acute-hepatitis-of-unknown-aetiology---the-united-kingdom-of-great-britain-and-northern-ireland.
2 World Health Organization. Multi-country—acute, severe hepatitis of unknown origin in children[EB/OL]. (2022-04-23)[2022-04-30]. https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON376.
3 European Centre for Disease Prevention and Control. Increase in acute hepatitis of unknown origin among children—United Kingdom[EB/OL]. (2022-04-12)[2022-04-30]. https://www.ecdc.europa.eu/en/news-events/increase-acute-hepatitis-unknown-origin-among-children-united-kingdom.
4 European Centre for Disease Prevention and Control. Update: hepatitis of unknown origin in children[EB/OL]. (2022-04-19)[2022-04-30]. https://www.ecdc.europa.eu/en/news-events/update-hepatitis-unknown-origin-children.
5 Centers for Disease Control and Prevention. Recommendations for adenovirus testing and reporting of children with acute hepatitis of unknown etiology[EB/OL]. (2022-04-21)[2022-04-30]. https://emergency.cdc.gov/han/2022/pdf/CDC_HAN_462.pdf?ACSTrackingID=USCDC_511-DM80338&ACSTrackingLabel=HAN%20462-%20Professional%20and%20Media%20Partners&deliveryName=USCDC_511-DM80338%20(.
6 Centers for Disease Control and Prevention. CDC alerts providers to hepatitis cases of unknown origin[EB/OL]. (2022-04-21)[2022-04-30]. https://www.cdc.gov/media/releases/2022/s0421-hepatitis-alert.html.
7 Thomas N, Ahmed T. UK, US health officials investigating cases of severe hepatitis with unknown causes in children[EB/OL]. (2022-04-15)[2022-04-30]. https://edition.cnn.com/2022/04/15/health/pediatric-hepatitis-cases/index.html.
10 UK Health Security Agency. Increase in hepatitis (liver inflammation) cases in children under investigation[EB/OL]. (2022-05-06)[2022-05-10]. https://www.gov.uk/government/news/increase-in-hepatitis-liver-inflammation-cases-in-children-under-investigation.
11 European Centre for Disease Prevention and Control. Increase in severe acute hepatitis cases of unknown aetiology in children[EB/OL]. (2022-04-28)[2022-04-30]. https://www.ecdc.europa.eu/sites/default/files/documents/RRA-20220420-218-erratum.pdf.
12 European Centre for Disease Prevention and Control. Epidemiological update: hepatitis of unknown aetiology in children[EB/OL]. (2022-05-11) [2022-05-17]. https://www.ecdc.europa.eu/en/news-events/epidemiological-update-hepatitis-unknown-aetiology-children.
Baker JM, Buchfellner M, Britt W, et al. Acute hepatitis and adenovirus infection among children—Alabama, October 2021-February 2022[J]. MMWR Morb Mortal Wkly Rep, 2022, 71(18): 638-640. PMID: 35511732. DOI: 10.15585/mmwr.mm7118e1.
14 Alabama's Health. Investigations of nine young children with adenovirus are underway[EB/OL]. (2022-04-15)[2022-04-30]. https://www.alabamapublichealth.gov/blog/2022/04/nr15.html.
Huang D, Wang Z, Zhang G, et al. Molecular and epidemiological characterization of human adenoviruses infection among children with acute diarrhea in Shandong Province, China[J]. Virol J, 2021, 18(1): 195. PMID: 34579757. PMCID: PMC8474830. DOI: 10.1186/s12985-021-01666-1.
Tang X, Hu Y, Zhong X, et al. Molecular epidemiology of human adenovirus, astrovirus, and sapovirus among outpatient children with acute diarrhea in Chongqing, China, 2017-2019[J]. Front Pediatr, 2022, 10: 826600. PMID: 35311045. PMCID: PMC8929441. DOI: 10.3389/fped.2022.826600.
Du J, Zhao X, Tang F, et al. Outbreaks of acute respiratory disease associated with human adenovirus infection in closed camps, China, December 2011-March 2014[J]. China CDC Wkly, 2021, 3(38): 793-798. PMID: 34594992. PMCID: PMC8477058. DOI: 10.46234/ccdcw2021.197.
23 UK Health Security Agency. Increase in acute hepatitis cases of unknown aetiology in children[EB/OL]. (2022-04-08)[2022-04-30]. https://www.gov.uk/government/publications/hepatitis-increase-in-acute-cases-of-unknown-aetiology-in-children/increase-in-acute-hepatitis-cases-of-unknown-aetiology-in-children.
Leon LAA, Alves ADR, Garcia RCNC, et al. Parvovirus B19 infection in a fatal case of acute liver failure[J]. Pediatr Infect Dis J, 2017, 36(12): e355-e358. PMID: 28787384. DOI: 10.1097/INF.0000000000001731.
Ishige M, Fuchigami T, Furukawa M, et al. Primary carnitine deficiency with severe acute hepatitis following rotavirus gastroenteritis[J]. J Infect Chemother, 2019, 25(11): 913-916. PMID: 31189503. DOI: 10.1016/j.jiac.2019.04.020.
Han SB, Seo YE, Kim SK, et al. Varicella with rapidly progressive hepatitis presenting with multiple hepatic nodules in a child with acute leukemia[J]. J Infect Chemother, 2016, 22(12): 822-825. PMID: 27496601. DOI: 10.1016/j.jiac.2016.07.005.
Gur I, Shapira Y, Amitai Y, et al. Renal failure, hepatitis and encephalitis following measles[J]. Isr J Med Sci, 1984, 20(5): 441-442. PMID: 6469565.
Gonzales-Gustavson E, Timoneda N, Fernandez-Cassi X, et al. Identification of sapovirus GV.2, astrovirus VA3 and novel anelloviruses in serum from patients with acute hepatitis of unknown aetiology[J]. PLoS One, 2017, 12(10): e0185911. PMID: 28982120. PMCID: PMC5628893. DOI: 10.1371/journal.pone.0185911.
32 Centers for Disease Control and Prevention. Investigation of acute non-viral hepatitis of unknown etiology potentially associated with an alkaline water product[EB/OL]. (2021-11-23)[2022-04-30]. https://www.cdc.gov/nceh/hsb/chemicals/nonviralhepatitis.htm.
40 European Centre for Disease Prevention and Control. Hepatitis of unknown origin reporting protocol 2022: version 2.0[EB/OL]. (2022-04-29)[2022-05-04]. https://www.ecdc.europa.eu/sites/default/files/documents/Hepatitis-of-unknown-origin-Reporting-Protocol_1.pdf.
41 European Centre for Disease Prevention and Control. ECDC and WHO publish joint surveillance bulletin on hepatitis outbreak[EB/OL]. (2022-05-13) [2022-05-17]. https://cdn.ecdc.europa.eu/novhep-surveillance/.
42 UK Health Security Agency. Research and analysis acute hepatitis: technical briefing. Technical briefing document on the investigation into acute hepatitis cases of unknown aetiology in children in England[EB/OL]. (2022-04-25)[2022-04-30]. https://www.gov.uk/government/publications/acute-hepatitis-technical-briefing.
van Beek J, Fraaij P, Giaquinto C, 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[J]. Euro Surveill, 2022, 27(19). PMID: 35551703. DOI: 10.2807/1560-7917.ES.2022.27.19.2200370.
de Kleine RH, Lexmond WS, Buescher G, 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[J]. Euro Surveill, 2022, 27(19). PMID: 35551705. DOI: 10.2807/1560-7917.ES.2022.27.19.2200369.