Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?
adeno-associated virus
adenovirus
aetiology
epidemiology
hepatitis
liver
outbreak
paediatric
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2022
2022
Historique:
received:
05
10
2022
accepted:
04
11
2022
entrez:
12
12
2022
pubmed:
13
12
2022
medline:
13
12
2022
Statut:
epublish
Résumé
During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and worldwide, although in most countries incidence did not increase above the expected baseline. There were no consistent epidemiological links between cases, and microbiological investigations ruled out known infectious causes of hepatitis. In this review, we explore the evidence for the role of viral infection, superimposed on a specific host genetic background, as a trigger for liver pathology. This hypothesis is based on a high prevalence of Human Adenovirus (HAdV) 41F in affected children, together with metagenomic evidence of adeno-associated virus (Adeno-associated viruses)-2, which is a putative trigger for an immune-mediated liver injury. Roles for superantigen-mediated pathology have also been explored, with a focus on the potential contribution of SARS-CoV-2 infection. Affected children also had a high frequency of the MHC allele HLA-DRB1*04:01, supporting an immunological predisposition, and may have been vulnerable to viral coinfections due to disruption in normal patterns of exposure and immunity as a result of population lockdowns during the COVID-19 pandemic. We discuss areas of ongoing uncertainty, and highlight the need for ongoing scrutiny to inform clinical and public health interventions for this outbreak and for others that may evolve in future.
Identifiants
pubmed: 36506522
doi: 10.3389/fphar.2022.1062408
pii: 1062408
pmc: PMC9732095
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
1062408Subventions
Organisme : Medical Research Council
ID : MC_UU_12014/1
Pays : United Kingdom
Informations de copyright
Copyright © 2022 Matthews, Campbell, Săndulescu, Matičič, Ruta, Rivero-Juárez, van Welzen, Tan, Garcia, Gherlan, Çınar, Hasanoğlu, Gmizić, Nicolini, Santos, Sargsyants, Velikov, Habibović, Fourati, Židovec-Lepej, Herder, Dudman, Miron, Irving and Şahin.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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