As scientists around the world scramble to understand what caused a wave of previously unexplained hepatitis cases in children, including some requiring liver transplants, two new studies from the United Kingdom offer new clues.
In both papers, an unusual virus called adeno-associated virus-2 (AAV2) is implicated as one aspect of a complex mechanism that could lead to rare and serious liver problems, including two dozen cases this year among Canadian children.
Preprint studies are from research teams London i Glasgow, and has not yet been formally published or peer-reviewed. The teams looked at a small number of children suffering from liver inflammation that wasn’t caused by the obvious culprits, such as the usual family of hepatitis viruses, alongside healthy control subjects.
Researchers from both regions identified high levels of AAV2 in blood samples taken from young patients with unexplained hepatitis and evidence of other viral infections.
The results suggest that coinfection with two viruses at the same time (AAV2, plus an adenovirus or, in some cases, a herpes virus) could be triggering hepatitis in some children. The Scottish team also noted that most of the affected children shared a specific gene, DRB1-0401.
“Eight of the nine children had this special gene … whereas in the background in Scotland, it is only present in 15.6 per cent,” said one of the authors of the Glasgow study, senior lecturer Antonia Ho clinic of the MRC Center of the University of Glasgow. Virus research.
“So we’re wondering if, perhaps, it’s the co-infection with AAV2 and an adenovirus, in children who have this particular gene, that makes them more susceptible to having these viruses and having an abnormal immune response.”
Choice of possible factors
It’s a complicated theory, bringing together a trio of possible factors.
The early findings also do not confirm a root cause, Ho’s team acknowledged, with more global research needed to investigate exactly what caused more than 1,000 likely cases of severe acute hepatitis of unknown origin in young children in 35 countries. according to the latest figures from the World Health Organization.
The total number of cases rose this year, including a spike that caught the attention of UK officials, then dropped to include 22 deaths. No children have died in Canada this year 24 cases of severe acute hepatitis reported throughout the countryalthough two children required liver transplants.
There has been intense debate about what might be at stake, with scientists around the world pointing the finger at viruses ranging from a common adenovirus known to cause stomach upset, to the widely circulating SARS-CoV-2, the virus behind COVID-19.
So far, neither theory has been a slam dunk. Doctors have also raised questions about whether this is even a new phenomenon, as medical teams have long seen sporadic cases of severe liver problems in children that have no obvious cause, even before the This year’s rash of cases has world health officials concerned. alert
While there are still more questions than answers, the latest research from the UK 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 is what is known as dependoparvovirus, which does not usually replicate on its own inside the human body.
LOOK | The cause of the rare liver disease outbreak is a mystery to experts:
The cause of the rare liver disease outbreak in children is a mystery to experts
Doctors aren’t sure what’s causing a mysterious outbreak of liver disease that has been seen in children in a dozen countries around the world. Although at least one child has died, experts insist that most children will make a full recovery from the disease.
“It is effectively a parasite. It has to have another DNA virus present in order to replicate its genome,” said Charlotte Houldcroft, a virologist in the University of Cambridge’s genetics department who was not involved in any of the new studies.
A high percentage of the population is likely infected with AAV2, but may never realize it.
The virus is not usually thought to cause disease by itself, as it also requires the presence of a “helper virus,” Houldcroft said. However, some studies do suggest AAV2 infectionor his use as a vector in gene therapy to treat certain diseases, it may be related to health problems related to the liver.
Houldcroft noted that the specific gene identified in patients by the Scottish team may prove to be another key factor, as it is already associated with certain autoimmune conditions.
“Genetic susceptibility would explain why this is rare,” he said.
“And then the fact that you might need two different infections, and we’ve had this huge increase in adenovirus 41, in the UK from December 2021 to spring 2022, that could explain why these rare cases clustered in time, and why we suddenly noticed this disease.”
More research, larger studies are needed
Dr. Jordan Feld, a scientist and clinician at Toronto’s Western Hospital Liver Clinic, agreed that the papers present interesting points, linking data that may, over time, explain the rare but troubling cases emerging this year. and maybe even some unexplained childhood hepatitis. previous cases.
But it’s important to validate the results beyond these two small studies, he stressed, taking into account all the potential factors at play.
“When people first proposed adenovirus and first proposed SARS-CoV-2 as the cause of it, everyone around the world went back to their samples and looked carefully to see and, I would say, they largely showed that they probably weren’t the whole story,” Feld said.
There are also important limitations to the papers, both outside experts and the authors themselves noted, including small sample sizes and unclear cause and effect.
The role of COVID-19 also remains murky.
Ho, of the Glasgow team, said his team found no clear links to SARS-CoV-2 and said more cases of childhood hepatitis should have been seen during earlier waves of the pandemic if this virus was the cause.
Meanwhile, the authors of the UK paper stressed that their data alone are not sufficient to rule out an impact of the Omicron variant, “the onset of which preceded the unexplained hepatitis outbreak,” with further results needed from large, case-controlled studies.
Feld emphasized that whatever is causing unexplained hepatitis in children remains an incredibly rare phenomenon, although more medical professionals are keeping a close eye on cases.
Parents can look for telltale symptoms, such as jaundice (yellowing of the child’s eyes and skin), dark urine, pale stools, abdominal pain, and vomiting.
“There is certainly not a rampant epidemic of severe acute hepatitis,” Feld said. “So I would say the first thing is to take a deep breath. Most kids will be completely fine.”