As scientists around the world race to understand what caused a spate of previously unexplained cases of hepatitis in children, including some requiring liver transplants, two new studies in the UK 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 be causing rare and serious liver problems, including two dozen cases this year among Canadian children.
Preliminary studies are from research teams in London Y 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 was not caused by obvious culprits, such as the usual hepatitis family of viruses, along with healthy control subjects.
Researchers from both regions identified high levels of AAV2 in blood samples drawn from young patients with unexplained hepatitis and evidence of other viral infections.
The findings suggest that co-infection with two viruses at the same time (AAV2, plus an adenovirus or, in some cases, a herpes virus) could trigger hepatitis in certain 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 Scotland, it is only present in 15.6 percent,” said one of the study’s authors from Glasgow, Antonia Ho, senior clinical professor at the MRC- University of Glasgow Center for Virus Research.
“So we wonder if, perhaps, it is coinfection with AAV2 and an adenovirus, in children who have this special gene, that makes them more susceptible to getting these viruses and having an abnormal immune response to them.”
Trio of possible factors
It’s a complicated theory, bridging a trio of possible factors.
The early findings also don’t confirm a root cause, Ho’s team acknowledged, and more global research is needed to delve into exactly what triggered 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 overall case count soared this year, including a spike that first caught the attention of UK officials, then dropped to include 22 deaths. No child has died in Canada this year outside of 24 cases of severe acute hepatitis reported throughout the countryalthough two children required liver transplants.
There has been an intense debate about what could be at stake, with scientists from all over the world. pointing the finger at viruses ranging from a common adenovirus that is known to cause stomach upset to SARS-CoV-2, the virus behind COVID-19, which circulates widely.
So far, neither theory has been successful. Doctors have also raised questions about whether this is a new phenomenon, as medical teams have long noted sporadic cases of serious liver problems in children that have no obvious cause, even before this series of cases year put global health officials on high. alert.
Although there are still more questions than answers, the latest research from the UK investigates some interesting possibilities and offers 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 within the human body.
CLOCK | The cause of the rare liver disease outbreak is a mystery to experts: 
Cause of rare liver disease outbreak in children remains 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. While at least one child has died, experts insist most children will fully recover from the disease.
“It is effectively a parasite. It has to have another DNA virus present to replicate its genome,” said Charlotte Houldcroft, a virologist at the University of Cambridge’s department of genetics who was not involved in any of the new studies.
A high percentage of the population is likely to be infected with AAV2, but may never realize it.
The virus is not generally thought to cause illness on its own, as it also requires the presence of a “helper virus,” Houldcroft said. However, some studies suggest infection with AAV2or your use as a vector in gene therapy to treat certain diseases, it can be related to health problems related to the liver.
Houldcroft noted that the specific gene identified in the patients by the Scottish team could be another key factor, since it is already associated with certain autoimmune conditions.
“Genetic susceptibility would explain why this is rare,” he said.
“And then the fact that you need maybe two different infections, and we’ve had this big increase in adenovirus 41, in the UK from December 2021 to spring 2022, that could explain why these rare cases were clustered in time, and why we suddenly became aware of this disease.
More research, larger studies needed
Dr. Jordan Feld, a physician and scientist at Toronto Western Hospital Liver Clinic, agreed that the articles make interesting points, linking data that may, over time, explain the rare but concerning cases that have emerged this year. , and perhaps even some cases of unexplained childhood hepatitis. cases that came before.
But it’s important to validate the results beyond these two small studies, he stressed, given all the potential factors at play.
“When people first proposed adenovirus and they first proposed SARS-CoV-2 as the cause of this, everyone around the world went back to their samples and looked carefully to see and, I would say, largely showed that probably weren’t is not the whole story,” Feld said.
There are also important limitations in the papers, both external experts and the authors themselves pointed out, including small sample sizes and unclear cause and effect.
The role of COVID-19 remains murky as well.
Ho, from the Glasgow team, said his team found no clear links to SARS-CoV-2, saying more cases of childhood hepatitis should have been seen during earlier waves of the pandemic if that virus was the cause.
Meanwhile, the authors of the UK paper stressed that their data alone are not enough to rule out an impact of the Omicron variant, “whose appearance preceded the outbreak of unexplained hepatitis,” and more results from large case studies are needed. and controls.
Feld stressed that regardless of what is causing unexplained hepatitis in children, it remains an incredibly rare phenomenon, even as cases are being closely watched by more medical professionals.
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 take a deep breath first. Most kids will be completely fine.”
Source: www.cbc.ca