biostudies-literatureHo ANIAID NIH HHSMedical Research CouncilNational Institute for Health Research (NIHR)Wellcome Trust555-563https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617659biostudies-literatureUnknown617(7961)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 wNatureAdeno-associated virus 2 infection in children with non-A-E hepatitis.PMC7617659MR/W005611/1MC_UU_00034/5MC_UU_00034/6NIHR200224MC_UU_00007/10206369/Z/17/Z223164/Z/21/ZMC_PC_22004NIHR201409MC_PC_20029MR/X010252/1206369R01 AI158861MC_UU_12014/1ACF-2018-18-022MR/W030454/1223164MC_PC_19025MC_PC_19059HDRUK2021.0125CO-CIN-01MC_UU_12014/12Armstrong LLeiner TNdure EVoice MArmstrong DSchroepf SMaclean AGardiner ELittle JPokhrel BRomaine SVermont CLHaas NFernandez SSRudzate ACeolotto ASwingler RAgyeman PMadelane MGonzalez FAFletcher TBerger CBohmova KShen CKKitanovski LLimb JMcGill FAbdulla Avan der Zee CCWFitchett EWhite MZachariasse JHarper RAebi CBirt MSchoen CTurner DHerder VSeal MMiller DWhite DMiller CBath Dvan den Berg JMMSchobi NPairo-Castineira EDanekova NGiannoni EMarquez SWallner ENichols SHickey NWellman PMcGenily LRusu ADorward DMachin FRajic GIjaz SCunnington AAvramoska TSchranz RLaivacuma SKohlfurst DSMichalis VOrton RBinder ARichmond 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Silva Filipe ASemple MGCabello LManali MNijman RPosfay-Barbe KMCohen LRodriguez LPMacFarlane SFerguson SMcInnes NHude CBenesch MHartshorn SVincek KPaulus SCTait SBernhard-Stirnemann SCohen JPilch HCresswell FManzano JRKolnik MSchonenberg DRoff AAgwuh KLoffler SPeters MStocker MRawlik KBories PEvans BDawson JPennisi IWellings LEvans CDaubney EStudents MRobbins CAvcin TGormley SLachaume NPokorn MLeitch KPfurtscheller KKeldorfer MMarjaneh MMAvramidis NTedder RSMorris CBont LJMomodou SReid RGunson RJackson CHolden JJackson HSalas ABeer STsolia MSpyridis NHopton SVazquez SRWeber KRoca ARedondo-Collazo LBell Ade Silva TBell CLubinda TXagorari MAgranoff DHamilton MSHauer AJarman HBell KKohlmaier BCollins ELim EVastert SJAllan JSarr ISmollett KNasher MSuarez CDHardwick HYeung SGrammatikopoulos TOosthuyzen WOra MSEstrada-Rivadeneyra DWillett BJGriese MHanson AAlba-Alejandre IWallia DBradley-Stewart ATurtle LCWBellini AKhanijau AMatthews PPalmarini MBranch NSrpcic ADiaba CKapper AIsaacs JGurung 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de Kuip MMStrle FReiter KElorrieta LEWilkie CDeep AMarkos Mde Groc TGoetschalckx ICandlish JGalassini RRubick LMommert-Tripon MBrotherton HSchlapbach LJDIAMONDS ConsortiumSchlapbach LLewis-Burke NISARIC4C InvestigatorsNiederer-Loher AfalseAdeno-associated virus 2 infection in children with non-A-E hepatitis.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 w2023-01-01T00:00:00Z2023 May2026-06-02T12:03:37.954Z2026-04-18T03:11:20.133ZS-EPMC76176593699687310.1038/s41586-023-05948-2