Acute severe hepatitis outbreak in children: a perfect storm. What do we know, and what questions remain?

Matthews, P. C. et al. (2022) Acute severe hepatitis outbreak in children: a perfect storm. What do we know, and what questions remain? Frontiers in Pharmacology, 13, 1062408. (doi: 10.3389/fphar.2022.1062408) (PMID:36506522) (PMCID:PMC9732095)

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Abstract

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.

Item Type:Articles
Additional Information:PM receives core funding from the Francis Crick Institute, holds a Wellcome fellowship (grant ref 110110/Z/15/Z), and has funding support from UCL NIHR Biomedical Research Centre. CC receives PhD fellowship funding from the Nuffield Department of Medicine and GSK.
Keywords:Paediatric, hepatitis, outbreak, adenovirus, adeno-associated virus, epidemiology, aetiology, liver.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Herder, Dr Vanessa
Authors: Matthews, P. C., Campbell, C., Săndulescu, O., Matičič, M., Ruta, S. M., Rivero-Juárez, A., van Welzen, B. J., Tan, B. K., Garcia, F., Gherlan, G. S., Çınar, G., Hasanoğlu, İ., Gmizić, I., Nicolini, L. A., Santos, L., Sargsyants, N., Velikov, P., Habibović, S., Fourati, S., Židovec-Lepej, S., Herder, V., Dudman, S., Miron, V. D., Irving, W., and Şahin, G. Ö.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Frontiers in Pharmacology
Publisher:Frontiers Media
ISSN:1663-9812
ISSN (Online):1663-9812
Copyright Holders: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
First Published:First published in Frontiers in Pharmacology 13: 1062408
Publisher Policy:Reproduced under a Creative Commons License

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