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

Matthews, PC; Campbell, C; Săndulescu, O; Matičič, M; Ruta, SM; Rivero-Juárez, A; van Welzen, BJ; ... Şahin, GÖ; + view all (2022) Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain? Frontiers in Pharmacology , 13 , Article 1062408. 10.3389/fphar.2022.1062408. Green open access

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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.

Type: Article
Title: Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fphar.2022.1062408
Publisher version: https://doi.org/10.3389/fphar.2022.1062408
Language: English
Additional information: © 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. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: Adeno-associated virus, adenovirus, aetiology, epidemiology, hepatitis, liver, outbreak, paediatric
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10162374
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