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

Antonia Ho, DIAMONDS consortium, ISARIC4C investigators, Brian J. Willett, Judith Breuer, Malcolm G. Semple, David Turner, J. Kenneth Baillie, Emma C. Thomson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)
7 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)555-563
JournalNature
Volume617
Early online date30 Mar 2023
DOIs
Publication statusPublished - 18 May 2023

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