Abstract

An outbreak of acute hepatitis of unknown aetiology in children was first reported in Scotland in April 2022. Cases aged <16 years have since been identified in 35 countries. Here we report a detailed investigation of 9 early cases and 58 control subjects. Using next-generation sequencing and real-time PCR, adeno-associated virus 2 (AAV2), was detected in the plasma of 9/9 and liver of 4/4 patients but in 0/13 sera/plasma of age-matched healthy controls, 0/12 children with adenovirus (HAdV) infection and normal liver function and 0/33 children admitted to hospital with hepatitis of other aetiology. AAV2 typically requires a coinfecting ‘helper’ virus to replicate, usually HAdV or a herpesvirus. HAdV (species C and F) and human herpesvirus 6B (HHV6B) were detected in 6/9 and 3/9 affected cases, including 3/4 and 2/4 liver biopsies, respectively. The class II HLA-DRB1*04:01 allele was identified in 8/9 cases (89%), compared with a background frequency of 15.6% in Scottish blood donors, suggestive of increased susceptibility in affected cases. Acute non-A-E paediatric hepatitis is associated with the presence of AAV2 infection, which could represent a primary pathogen or a useful biomarker of recent HAdV or HHV6B infection. Population and mechanistic studies are required to explore these findings further.

Rights

The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. http://creativecommons.org/licenses/by/4.0/

Cite as

Ho, A., Orton, R., Tayler, R., Asamaphan, P., Tong, L., Smollett, K., Davis, C., Manali, M., McDonald, S., Pollock, L., Evans, C., McMenamin, J., Roy, K., Marsh, K., Divala, T., Holden, M., Lockhart, M., Yirrell, D., Currie, S., Shepherd, S., Jackson, C., Gunson, R., MacLean, A., McInnes, N., Battle, R., Hollenbach, J., Henderson, P., Chand, M., Hamilton, M., Estrada-Rivadeneyra, D., Levin, M., DIAMONDS Consortium, ISARIC4C Investigators, Robertson, D., Filipe, A., Willett, B., Breuer, J., Semple, M., Turner, D., Baillie, J. & Thomson, E. 2022, 'Adeno-associated virus 2 infection in children with non-A-E hepatitis'. To be published in medRxiv [Preprint]. Available at: https://doi.org/10.1101/2022.07.19.22277425

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Last updated: 15 September 2022
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