Ho, A. et al. (2023) Adeno-associated virus 2 infection in children with non-A-E hepatitis. Nature, (doi: 10.1038/s41586-023-05948-2) (PMID:36996873) (Early Online Publication)
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Abstract
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.
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