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Lookup NU author(s): Professor Marieke Emonts-le ClercqORCiD, Ashley Bell, Kathryn Bell, Dr Daniel Fabian, Professor John IsaacsORCiD, Dr Emma Lim, Dr Geoff Shenton, Owen Treloar, Fabian Van Der Velden
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland 1 in April 2022 and has now been identified in 35 countries 2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case–control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10−12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a ‘helper virus’ to support AAV2 replication) and disease susceptibility related to HLA class II status.
Author(s): Ho A, Orton R, Tayler R, Asamaphan P, herder V, Davis C, Tong L, Smollett K, Manali M, Allen J, Rawlik K, McDonald SE, Vink E, Pollock L, Gannon L, Evans C, McMenamin J, Roy K, Marsh K, Divala T, Holden MTG, Lockhart M, Yirrell D, Currie S, O'Leary M, Henderson D, Shepherd SJ, Jackson C, Gunson R, MacLean A, McInnes N, Bradley-Stewart A, Battle R, Hollenbach J, Henderson P, Odam M, Chikowore P, Oosthuyzen W, Chand M, Hamilton MS, Estrada-Rivadeneyra D, Levin M, Avramidis N, Pairo-Castineira E, Vitart V, Wilkie C, Ray S, Emonts,M, Bell,A, Bell,K, Fabian,D, Isaacs,J, Lim,E, Shenton,G, Treloar,O, Van Der Veldon,F, DIAMONDS Consortium, ISARIC4C Investigators
Publication type: Article
Publication status: Published
Journal: Nature
Year: 2023
Volume: 617
Issue: 7961
Pages: 555-563
Print publication date: 18/05/2023
Online publication date: 30/03/2023
Acceptance date: 10/03/2023
Date deposited: 13/06/2023
ISSN (print): 0028-0836
ISSN (electronic): 1476-4687
Publisher: Nature Research
URL: https://doi.org/10.1038/s41586-023-05948-2
DOI: 10.1038/s41586-023-05948-2
ePrints DOI: 10.57711/prbz-2n62
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