Browsing by Author "Thomson, Emma C."

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    Adeno-associated virus 2 infection in children with non-A–E hepatitis
    (2023-05-18) Ho, Antonia; Orton, Richard; Tayler, Rachel; Thomson, Emma C.; DIAMONDS Consortium; ISARIC4C Investigators; Zavadska, Dace; Laivacuma, Sniedze; Rudzate, Aleksandra; Stoldere, Diāna; Barzdina, Arta; Barzdina, Elza; Madelane, Monta; Grāvele, Dagne; Rīga Stradiņš University
    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 countries2. 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.