Viral infections, genetic factors may be linked to mystery hepatitis in kids, studies suggest

As scientists around the world are racing to understand what caused a spate of so-far unexplained cases of hepatitis in children — including some who needed liver transplants — two new U.K. studies are offering fresh clues.

In both papers, an unusual virus called adeno-associated virus-2 (AAV2) is implicated as one aspect of a complex mechanism that might be sparking rare and serious liver issues, including two dozen cases this year among Canadian children.

The preprint studies are from research teams in London and Glasgow, and not yet formally published or peer-reviewed. The teams looked at small numbers of children who suffered from liver inflammation which wasn't caused by the obvious culprits, such as the usual family of hepatitis viruses, alongside healthy control subjects.

Researchers in both regions identified high levels of AAV2 in blood samples taken from young patients with unexplained hepatitis and indications of other viral infections.

The findings suggest co-infection with two viruses at once — AAV2, plus an adenovirus or, in some cases, a herpes virus — could be triggering hepatitis in certain kids. The Scottish team also noted the majority of children impacted shared a specific gene, DRB1-0401.

"Eight of the nine kids had this special gene … whereas in the background in Scotland, it's only present in 15.6 per cent," said one of the Glasgow study's authors, Antonia Ho, a clinical senior lecturer at MRC-University of Glasgow Centre for Virus Research.

"So we wonder whether, perhaps, it's co-infection with AAV2 and an adenovirus, in kids that have this special gene, that makes them more susceptible to getting these viruses and having an abnormal immune response to them."

It's a complicated theory, linking together a trio of possible factors. 

The early findings also don't confirm a root cause, Ho's team acknowledged, with more global research needed to drill into exactly what sparked more than 1,000 probable cases of acute severe hepatitis of unknown origin in young children across 35 countries, according to the latest figures from the World Health Organization.

The overall case count spiked this year, including a rise that first caught the attention of U.K. officials, then dropped off, and included 22 deaths. No children have died in Canada this year out of 24 cases of acute severe hepatitis reported across the country, though two children did require liver transplants.

There's been intense debate over what could be at play, with scientists around the globe pointing the finger at viruses ranging from a common adenovirus that's known for causing stomach upset, to the widely circulating SARS-CoV-2, the virus behind COVID-19.

So far, no theory has been a slam dunk. Clinicians have also raised questions over whether this is even a new phenomenon, since medical teams have long noticed sporadic instances of serious liver issues in children that don't have any obvious cause — even before this year's rash of cases put global health officials on high alert.

Though there are still more questions than answers, the latest U.K. research investigates some intriguing possibilities, offering more potential pieces to this puzzle. 

Particularly fascinating — and unexpected — was the possible connection to AAV2, several scientists told CBC News. It's what's known as a dependoparvovirus, which doesn't usually replicate on its own inside the human body.