An outbreak of acute hepatitis of unknown aetiology in kids was first reported in Scotland in April 2022.1 Instances aged <16 years have since been recognized in 35 international locations.2 Right here we report an in depth investigation of 9 early instances and 58 management topics. Utilizing next-generation sequencing and real-time PCR, adeno-associated virus 2 (AAV2), was detected within the plasma of 9/9 and liver of 4/4 sufferers however in 0/13 sera/plasma of age-matched wholesome controls, 0/12 kids with adenovirus (HAdV) an infection and regular liver perform and 0/33 kids admitted to hospital with hepatitis of different aetiology. AAV2 usually requires a coinfecting ‘helper’ virus to duplicate, often HAdV or a herpesvirus. HAdV (species C and F) and human herpesvirus 6B (HHV6B) had been detected in 6/9 and three/9 affected instances, together with 3/4 and a couple of/4 liver biopsies, respectively. The category II HLA-DRB1*04:01 allele was recognized in 8/9 instances (89%), in contrast with a background frequency of 15.6% in Scottish blood donors, suggestive of elevated susceptibility in affected instances. Acute non-A-E paediatric hepatitis is related to the presence of AAV2 an infection, which might signify a main pathogen or a helpful biomarker of latest HAdV or HHV6B an infection. Inhabitants and mechanistic research are required to discover these findings additional.