Mystery child hepatitis outbreak 'due to AAV2 virus and genes', University of Glasgow scientists find

University of Glasgow scientists have found “strong evidence” that a recent hepatitis outbreak in children was caused by a virus and genetic factors.

Researchers said that AAV2, alongside an underlying genetic predisposition, played a key role in cases of acute hepatitis in children amid a worldwide outbreak.

Since April 2022, a number of young children worldwide have developed jaundice and acute severe hepatitis of unknown origin.

While the outbreak has now largely subsided, the World Health Organisation estimates there have been at least 1010 probable cases in 35 countries.

In the UK, the majority of the 270 cases were under the age of five years old, with many requiring admission to intensive care and 15 children requiring liver transplants as a result of their condition.

According to a new study published in Nature, which was led by researchers at the University of Glasgow, found that the common virus AAV2 (adeno-associated virus 2) was present in a range of different samples taken from children with acute unexplained hepatitis.

The Glasgow team was the first in the world to identify the AAV2 connection with recent childhood hepatitis cases.

The virus was first identified by scientists in 1965 and infects up to 90% of the population, with most people being infected and developing immunity by the age of 18.

AAV2 is not known to normally cause disease and require co-infection with certain viruses, such as herpes viruses and adenoviruses, the latter cause gastroenteritis as well as cold or flu-like symptoms.

The peer-reviewed study carried out a detailed investigation of 32 cases and 74 control subjects.

Of the 32 children with acute hepatitis, four children needed to be treated in a specialist liver unit and one child required a liver transplant.

“The presence of the AAV2 virus is associated with unexplained hepatitis in children,” said prof Emma Thomson, clinical professor and consultant in Infectious Diseases at the MRC-University of Glasgow Centre for Virus Research (CVR) and senior author of the study.

“This virus replicates in the presence of another virus, usually an adenovirus. AAV2 may cause disease itself or it may be a useful biomarker of recent adenovirus infection which may be the main underlying pathogen, but which can be harder to detect.

“There are many unanswered questions and larger studies are urgently needed to investigate the role of AAV2 in paediatric hepatitis cases, particularly the role of the immune response in the disease process.

“We also need to understand more about seasonal circulation of AAV2, a virus that is not routinely monitored – it may be that a peak of adenovirus infection has coincided with a peak in AAV2 exposure, leading to an unusual manifestation of hepatitis in susceptible young children who carry the HLA DRB1*04:01 gene, a relatively common gene in Scotland.”

Dr Antonia Ho, clinical senior Lecturer and consultant in Infectious Diseases at the MRC-University of Glasgow Centre for Virus Research, said: “With the inclusion of more cases, addition of control children that were recruited at the same time as cases, as well as antibody data demonstrating that most cases had evidence of AAV2 IgM antibodies (indicating recent infection) and liver staining that shows the presence of AAV2 in the liver, our updated peer-reviewed paper provides convincing evidence that AAV2, along with a genetic predisposition play an important role in the onset of acute hepatitis in children.”

The paper, ‘Adeno-associated virus 2 infection in children with non-A-E hepatitis’ , is published in Nature. The work was funded by Public Health Scotland, the National Institute for Health Research (NIHR) and the Medical Research Council.

The study was carried out in collaboration with the Royal Hospital for Children in Glasgow, Public Health Scotland (PHS) and ISARIC (International Severe Acute Respiratory and emerging Infections Consortium).