Childhood hepatitis surge likely linked to two common viruses, say UK scientists

Simultaneous infection with two common viruses is thought to explain a recent surge in childhood hepatitis cases , which has led to 12 UK children requiring liver transplants so far. Two research groups have detected high levels of adeno-associated virus 2 (AAV2) – a little-known virus not previously associated with human disease – in almost all of the affected British children they have tested. AAV2 is unable to replicate by itself but can do so in the presence of a second virus.

Changes in the seasonal circulation of viruses, brought about by the pandemic, may have triggered a rise in co-infections that are usually less common, causing hepatitis in some of these cases. “My feeling is that this has probably happened before. But because there have been some changes in the seasonal trends of these viruses, we’ve seen a small collection of cases all at once, and that’s why we’ve picked them up,” said Prof Emma Thomson, a consultant in infectious diseases at the MRC-University of Glasgow Centre for Virus Research, who was involved in the new research.

Sign up to First Edition, our free daily newsletter – every weekday morning at 7am BST Since health authorities were first alerted to a sudden increase in cases of acute severe hepatitis of unknown origin in young children in early April, the World Health Organization (WHO) has reported at least 1,010 probable cases in 35 countries, including 22 deaths. Most of the UK’s 268 cases have involved children under the age of five, with 74 of them requiring admission to intensive care. The leading theory was that a surge in infections caused by a separate group of common viruses called adenoviruses was to blame, because they were commonly found in samples from affected children.

Another idea was that Covid infections had left children more susceptible to hepatitis. To investigate, Thomson and her colleagues carried out detailed genetic sequencing of samples from nine Scottish children with hepatitis of unknown origin. AAV2 was detected in all of them, but in none of the 58 children they also tested who did not have the condition.

Hepatitis cases rising among children globally but cause remains a mystery Read more Separately, researchers led by Prof Judith Breuer at Great Ormond Street hospital and University College London tested samples from a further 28 children with hepatitis, five of whom required liver transplants. They detected high levels of AAV2 in most of these children. Both studies were able to rule out recent or prior Covid infection as a direct cause for the acute hepatitis – although neither has been peer reviewed.

Since AAV2 cannot replicate without a “helper” virus, the researchers believe co-infection with a second virus – an adenovirus, or less often a herpes virus called HHV6 – may explain the onset of severe hepatitis. Whether AAV2 or the second virus is directly responsible for triggering this damage is still unclear. Thomson said larger studies were urgently needed to investigate this.

“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. ”.