A global outbreak of child hepatitis has been linked to a common virus combined with an underlying genetic predisposition, a new study has suggested.
Researchers at the Universities of Edinburgh and Glasgow have conducted the first detailed investigation into the cause of the recent hepatitis outbreak.
The findings, published in Nature, strongly suggest that the outbreak was caused by the adeno-associated virus 2 (AAV2), which was found in a range of different samples taken from children with acute unexplained hepatitis.
Since April 2022, over 1,000 young children in 35 countries have developed jaundice and acute severe hepatitis with an unknown origin. In the UK, there were 270 cases, mostly in children under five years of age, many of whom required admission to intensive care and 15 children who needed liver transplants due to the infection.
The AAV2 virus is common but does not usually cause severe disease. It infects up to 90 percent of the population but requires co-infection with viruses like adenoviruses to cause gastroenteritis or flu-like symptoms.
The scientists found AAV2 in all children with hepatitis, but it was not commonly found in children without hepatitis, suggesting AAV2 may cause the illness or it may be a biomarker of recent adenovirus infection. In the latter case, the adenovirus may be the primary underlying pathogen but are usually harder to detect.
Building on earlier research which linked the AAV2 virus with hepatitis, the researchers examined the genetics of patients with unexplained hepatitis to determine whether any of the children may have been more susceptible to this type of acute hepatitis.
Detailed genomic testing revealed that children who developed hepatitis had differences in the Human Leukocyte Antigen gene. This gene helps the body distinguish between foreign invaders, such as viruses, and the body’s cells. The genetic difference may explain why some children become seriously unwell when infected with AAV2.
Working with Public Health Scotland, the National Institute for Health Research and the Medical Research Council, the researchers were able to act quickly at the start of the outbreak due to infrastructure and collaboration already in place.
Professor Kenneth Baillie, from the University of Edinburgh, said it was the ‘best example’ he had seen of academic researchers working with national public health agencies to tackle a new threat.
He added: ‘We were able to find strong evidence for the underlying cause of a completely new disease within a few months of the first case being reported.’
The researchers stated that although their research provides important new data, there is more work to be done.
Professor Emma Thomson, from the University of Glasgow, said: ‘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.’