Adeno-associated virus 2 infection in children with non-A-E hepatitis

, , Antonia Ho, Richard Orton, Rachel Tayler, Patawee Asamaphan, Vanessa Herder, Chris Davis, Lily Tong, Katherine Smollett, Maria Manali, Jay Allan, Konrad Rawlik, Sarah E. McDonald, Elen Vink, Louisa Pollock, Louise Gannon, Clair Evans, Jim McMenamin, Kirsty RoyKimberly Marsh, Titus Divala, Matthew T. G. Holden, Michael Lockhart, David Yirrell, Sandra Currie, Maureen O'Leary, David Henderson, Samantha J. Shepherd, Celia Jackson, Rory Gunson, Alasdair MacLean, Neil McInnes, Amanda Bradley-Stewart, Richard Battle, Jill Hollenbach, Paul Henderson, Miranda Odam, Primrose Chikowore, Wilna Oosthuyzen, Meera Chand, Melissa Shea Hamilton, Diego Estrada-Rivadeneyra, Michael Levin, Nikos Avramidis, Erola Pairo-Castineira, Veronique Vitart, Craig Wilkie, Massimo Palmarini, Surajit Ray, David L. Robertson, Ana da Silva Filipe, Brian J. Willett, Judith Breuer, Malcolm G. Semple, David Turner, J. Kenneth Baillie, Emma C. Thomson (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review


An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland in April 20221 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus (HAdV), a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing (NGS), reverse transcription-polymerase chain reaction (RT-PCR), serology and in situ hybridisation (ISH), we detected recent infection with AAV2 in the plasma and liver samples of 26/32 (81%) hepatitis cases versus 5/74 (7%) of controls. Further, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsies. In keeping with a CD4+ T-cell-mediated immune pathology, the Human Leucocyte Antigen (HLA) class II DRB1*04:01 allele was identified in 25/27 cases (93%), compared with a background frequency of 10/64 (16%; p=5.49 x 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a coinfection with HAdV which is required as a "helper virus" to support AAV2 replication) and HLA class II-related disease susceptibility.

Original languageEnglish
Pages (from-to)555–563
Number of pages9
Early online date30 Mar 2023
Publication statusPublished - 18 May 2023


  • Viral genetics
  • Virology


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