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Ho, A; Orton, R; Tayler, R; Asamaphan, P; Herder, V; Davis, C; Tong, L; Smollett, K; Manali, M; Allan, J; Rawlik, K; McDonald, SE; Vink, E; Pollock, L; Gannon, L; Evans, C; McMenamin, J; Roy, K; Marsh, K; Divala, T; Holden, MTG; Lockhart, M; Yirrell, D; Currie, S; O'Leary, M; Henderson, D; Shepherd, SJ; Jackson, C; Gunson, R; MacLean, A; McInnes, N; Bradley-Stewart, A; Battle, R; Hollenbach, JA; Henderson, P; Odam, M; Chikowore, P; Oosthuyzen, W; Chand, M; Hamilton, MS; Estrada-Rivadeneyra, D; Levin, M; Avramidis, N; Pairo-Castineira, E; Vitart, V; Wilkie, C; Palmarini, M; Ray, S; Robertson, DL; da, Silva, Filipe, A; Willett, BJ; Breuer, J; Semple, MG; Turner, D; Baillie, JK; Thomson, EC; DIAMONDS Consortium; ISARIC4C Investigators.
Adeno-associated virus 2 infection in children with non-A-E hepatitis.
Nature. 2023; 617(7961): 555-563. Doi: 10.1038/s41586-023-05948-2
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Study Group Members Med Uni Graz:: Binder Alexander; Kohlfürst Daniela; Kohlmaier Benno; Schweintzger Nina; Zenz Werner; Zurl Christoph Johann
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Abstract:: An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland¹ 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.
Find related publications in this database (using NLM MeSH Indexing): Child - administration & dosage; Humans - administration & dosage; Acute Disease - epidemiology; Adenovirus Infections, Human - epidemiology, genetics, virology; Alleles - administration & dosage; Case-Control Studies - administration & dosage; CD4-Positive T-Lymphocytes - immunology; Coinfection - epidemiology, virology; Dependovirus - isolation & purification; Genetic Predisposition to Disease - administration & dosage; Helper Viruses - isolation & purification; Hepatitis - epidemiology, genetics, virology; Hepatocytes - virology; HLA-DRB1 Chains - genetics, immunology; Liver - virology