The investigation on the acute, severe hepatitis of unknown origin in children

YAO Kai-Hu; MENG Qing-Hong; YU Dan

doi:10.7499/j.issn.1008-8830.2205024

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Chinese Journal of Contemporary Pediatrics ›› 2022, Vol. 24 ›› Issue (6) : 604-613. DOI: 10.7499/j.issn.1008-8830.2205024

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The investigation on the acute, severe hepatitis of unknown origin in children

YAO Kai-Hu, MENG Qing-Hong, YU Dan

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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.

Key words

Acute hepatitis / Unknown origin / Child

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YAO Kai-Hu, MENG Qing-Hong, YU Dan. The investigation on the acute, severe hepatitis of unknown origin in children[J]. Chinese Journal of Contemporary Pediatrics. 2022, 24(6): 604-613 https://doi.org/10.7499/j.issn.1008-8830.2205024

References

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.
8 中华人民共和国国家卫生健康委员会宣传司. 关于不明原因儿童急性肝炎有关问题解答[EB/OL]. (2022-05-07)[2022-05-10]. http://www.nhc.gov.cn/xcs/s7847/202205/d1a3f433743144ddaca5e40b232820b1.shtml.
9 Marsh K, Tayler R, Pollock L, et al. Investigation into cases of hepatitis of unknown aetiology among young children, Scotland, 1 January 2022 to 12 April 2022[J]. Euro Surveill, 2022, 27(15): 2200318. PMID: 35426362. PMCID: PMC9012090. DOI: 10.2807/1560-7917.ES.2022.27.15.2200318.
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.
13 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.
15 连建奇, 白雪帆. 人腺病毒感染[M]. 北京: 人民卫生出版社, 2021.
16 谢立, 刘社兰, 丁华, 等. 腺病毒感染[M]. 北京: 科学出版社, 2013.
17 Lee B, Damon CF, Platts-Mills JA. Pediatric acute gastroenteritis associated with adenovirus 40/41 in low-income and middle-income countries[J]. Curr Opin Infect Dis, 2020, 33(5): 398-403. PMID: 32773498. PMCID: PMC8286627. DOI: 10.1097/QCO.0000000000000663.
18 Wang LP, Zhou SX, Wang X, et al. Etiological, epidemiological, and clinical features of acute diarrhea in China[J]. Nat Commun, 2021, 12(1): 2464. PMID: 33927201. PMCID: PMC8085116. DOI: 10.1038/s41467-021-22551-z.
19 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.
20 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.
21 Yang Z, Zhu Z, Tang L, et al. Genomic analyses of recombinant adenovirus type 11a in China[J]. J Clin Microbiol, 2009, 47(10): 3082-3090. PMID: 19675212. PMCID: PMC2756911. DOI: 10.1128/JCM.00282-09.
22 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.
24 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.
25 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.
26 Hayto?lu Z, Canan O. Bocavirus viremia and hepatitis in an immunocompetent child[J]. Balkan Med J, 2017, 34(3): 281-283. PMID: 28443581. PMCID: PMC5450871. DOI: 10.4274/balkanmedj.2015.1492.
27 Kirin BK, Topi? RZ, Dodig S. Hepatitis during respiratory syncytial virus infection: a case report[J]. Biochem Med (Zagreb), 2013, 23(1): 112-116. PMID: 23457772. PMCID: PMC3900097. DOI: 10.11613/bm.2013.014.
28 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.
29 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.
30 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.
31 Boettler T, Csernalabics B, Salié H, et al. SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis[J]. J Hepatol, 2022. Epub ahead of print. PMID: 35461912. PMCID: PMC9021033. DOI: 10.1016/j.jhep.2022.03.040.
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.
33 余真君, 何泽宝. 自身免疫性肝炎研究进展[J]. 中国免疫学杂志, 2019, 35(22): 2813-2818. DOI: 10.3969/j.issn.1000-484X.2019.22.025.
34 Sokollik C, McLin VA, Vergani D, et al. Juvenile autoimmune hepatitis: a comprehensive review[J]. J Autoimmun, 2018, 95: 69-76. PMID: 30344030. DOI: 10.1016/j.jaut.2018.10.007.
35 邹婷婷, 詹学. 儿童自身免疫性肝炎研究进展[J]. 中华实用儿科临床杂志, 2016, 31(20): 1598-1600. DOI: 10.3760/cma.j.issn.2095-428X.2016.20.022.
36 Osborn J, Szabo S, Peters AL. Pediatric acute liver failure due to type 2 autoimmune hepatitis associated with SARS-CoV-2 infection: a case report [J]. JPGN Rep, 2022,3(2): e204. PMID: 35505826. DOI: 10.1097/PG9.0000000000000204.
37 Brodin P, Arditi M. Severe acute hepatitis in children: investigate SARS-CoV-2 superantigens[J]. Lancet Gastroenterol Hepatol, 2022. Epub ahead of print. PMID: 35576952. DOI: 10.1016/S2468-1253(22)00166-2.
38 Hu CY, Tang YW, Su QM, et al. Public health measures during the COVID-19 pandemic reduce the spread of other respiratory infectious diseases[J]. Front Public Health, 2021, 9: 771638. PMID: 34858936. PMCID: PMC8631357. DOI: 10.3389/fpubh.2021.771638.
39 Cevik M, Rasmussen AL, Bogoch II, et al. Acute hepatitis of unknown origin in children[J]. BMJ, 2022, 377: o1197. PMID: 35580879. DOI: 10.1136/bmj.o1197.
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.
43 江载芳, 申昆玲, 沈颖. 诸福棠实用儿科学[M]. 8版. 北京: 人民卫生出版社, 2015: 870.
44 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.
45 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.