Investigation of an outbreak of novel hepatitis of unknown aetiology in children and adolescents, Ireland, 2021 to 2023.

An outbreak of severe acute hepatitis of unknown aetiology in children (HUAC) was reported by the United Kingdom (UK) in spring 2022. Within days, a corresponding increase was identified in Ireland. A multi-agency incident management team (IMT), led by the Health Protection Surveillance Centre (HPSC), established a national case definition, trawling questionnaire, testing protocol and communications plan. Between 1 October 2021 and 12 May 2023, 44 probable and three possible cases of HUAC were identified in Ireland with a median age of 3 years. Adeno-associated virus 2 (AAV2), detected in 18 of 31 probable cases, and SARS-CoV-2 antibodies in 22 of 37 of probable cases were the most common infectious agents, followed by human herpes virus 7 (18/33) and adenovirus (20/44). Immunological findings included the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele in 17 of 32 cases. Autoantibodies were found in 15 of 40 patients. Our findings corroborate those of the UK, which suggested a link between HUAC and AAV2 and another virus, in children predisposed due to presence of a particular HLA class II type. Close collaboration with the UK, the European Centre for Disease Prevention and Control (ECDC) and World Health Organization (WHO) was invaluable in the investigation.