[1][2] The outbreak led to a significant interest in adenoviruses, though as of 2023 no definite explanation has been agreed on the cause of the hepatitis.

[3] In October 2021, a cluster of cases of severe hepatitis of unknown origin were identified at a children's hospital in the U.S. state of Alabama.

[4] Between 5 April and 8 July 2022, 35 countries had reported 1,010 probable cases of acute hepatitis of unknown cause in children.

[11] On 5 April, the International Health Regulations (IHR) National Focal Point (NFP) for the UK informed the WHO of 10 cases of sudden severe hepatitis of unknown origin in children across Scotland, one whose symptoms began in January while the others first became unwell in March.

[16] Most did not have a fever, and many presented with diarrhoea, vomiting and abdominal pain, before finding raised levels of liver enzymes in their blood and jaundice.

[14] On 26 April 2022, the Public Health Agency of Canada announced it was investigating reports of the disease affecting children in the country.

[22] On 2 May 2022, Indonesia's Ministry of Health reported that 3 children died of acute hepatitis in April 2022.

[23][24] On 6 May 2022, Malaysia reported a case of hepatitis of unknown origin in a 4-year-old boy who sought treatment in March 2022 and subsequently underwent liver transplantation.

[37] In August 2022, 9 children in a U.S. case series of hepatitis of unknown cause[38] and 27 of 30 children in a U.K. case series with hepatitis of unknown cause who underwent molecular testing[39] tested positive for human adenovirus 41 in a sample.

One possibility is that restrictions imposed during the COVID-19 pandemic led to young children being exposed to adenovirus at a later point than normal in their lives, leading to a stronger immune response.

[37] Another suggestion is that there has been a change in the genetic make-up of adenovirus, so that it causes liver inflammation more readily,[40] although data is lacking to support this.