Allen J

Asamaphan P

Avramidis N

Battle R

Bell

Bradley-Stewart A

Chand M

Chikowore P

Currie S

Davis C

DIAMONDS Consortium

Divala T

Emonts

Estrada-Rivadeneyra D

Evans C

Fabian

Gannon L

Gunson R

Hamilton MS

Henderson D

Henderson P

herder V

Ho A

Holden MTG

Hollenbach J

Isaacs

ISARIC4C Investigators

Jackson C

Levin M

Lockhart M

MacLean A

Manali M

Marsh K

McDonald SE

McInnes N

McMenamin J

O'Leary M

Odam M

Oosthuyzen W

Orton R

Pairo-Castineira E

Pollock L

Rawlik K

Ray S

Roy K

Shenton

Shepherd SJ

Smollett K

Tayler R

Tong L

Treloar

Van Der Veldon

Vink E

Vitart V

Wilkie C

Yirrell D

\ua9 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 
7 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

Newcastle University E-Prints

English

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

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

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