Published: 31 March 2023
New NIHR-funded research has found that a common virus plays a key role in acute hepatitis in children who carry a certain gene.
Global perspective
The World Health Organisation estimates that since July 2022, there have been at least 1010 cases of unexplained acute hepatitis in 35 countries, including 22 deaths. The majority of the 270 UK cases were in children under the age of five. Many required admission to intensive care and 15 children required liver transplants as a result of their condition.
The new study, published in Nature, is the first detailed research investigation into the worldwide outbreak.
The adeno-associated virus 2 (AAV2) infects up to 90% of the population. The virus is not known to cause disease and most people become infected and develop immunity by the age of 18.
About the study
In the study, led by the University of Glasgow, researchers carried out tests on 32 children with acute hepatitis and 74 children without.
They compared blood samples and confirmed the presence of AAV2 in the liver of all children with acute hepatitis. 81% of acute hepatitis patients had AAV2 in their blood, compared with only 7% of the control group.
In July 2022, two UK pre-print studies made the first link between AAV2 and acute hepatitis in children. One examined cases from Scotland and the other looked at cases from all across the UK.
This peer-reviewed study involved more patients, samples and controls. It offers important new data which indicates that AAV2 infection in those with the gene variant HLA DRB1*04:01 is linked to the onset of acute hepatitis in children.
AAV2 and unexplained hepatitis
Professor Emma Thomson, Clinical Professor and Consultant in Infectious Diseases at the MRC-University of Glasgow Centre for Virus Research (CVR) and senior author of this Nature study, said:
“The presence of the AAV2 virus is associated with unexplained hepatitis in children. 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.”
Important discovery
Professor Paul Dimitri, NIHR Clinical Research Network National Specialty Lead for Children and Young People said:
“The findings of the new NIHR-funded study published in Nature are concerning, particularly given the high number of cases of acute hepatitis in children in multiple countries.
“The link between the adeno-associated virus 2 (AAV2) and acute hepatitis in children with the HLA DRB1*04:01 gene is an important discovery that may lead to better detection and treatment of the condition. The need for larger studies and a better understanding of the immune response and seasonal circulation of AAV2 are critical areas for future research.”