Viral infection, genetic factors may be linked to mysterious hepatitis in children, study suggests

As scientists around the world race to find the cause of previously unexplained hepatitis in children, including those requiring liver transplants, two new British studies offer new clues. increase.

Both papers implicated an unusual virus called adeno-associated virus-2 (AAV2) as one aspect of a complex mechanism that may cause rare and severe liver problems.

Preprint studies are by research teams. London When Glasgow, has not yet been formally published or peer-reviewed. The team looked at a small number of children suffering from liver inflammation, along with healthy control subjects, rather than being caused by an obvious culprit, such as a normal family member of the hepatitis virus.

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

The findings suggest that simultaneous infection with two viruses, AAV2 and adenovirus, and possibly herpes virus, may cause hepatitis in certain children. The Scottish team also noted that the majority of affected children shared a specific gene, DRB1-0401.

“Eight out of nine children carried this particular gene … whereas in the Scottish background it was present in only 15.6%,” said one of the authors of the Glasgow study, MRC. Antonia Ho, Clinical Senior Lecturer at the University of Glasgow Centre, said. virus research.

“Therefore, we suspect that perhaps co-infection of children with this special gene with AAV2 and adenovirus makes them more susceptible to infection with these viruses and develops an aberrant immune response against them.”

Trio of possible factors

This is a complex theory, combining three possible factors.

Ho’s team acknowledged that initial findings had not identified an underlying cause, and they were unable to determine exactly what caused over 1,000 probable cases of acute severe hepatitis of unknown cause in 35 countries. More global research is needed because we need to dig deeper. According to the latest figures from the World Health Organization.

The overall number of cases soared this year and, after first coming to the attention of British authorities, declined and included 22 deaths.No children have died in Canada this year. 24 cases of acute severe hepatitis were reported nationwidewhile two children required liver transplants.

There was a heated debate with scientists around the world about what might have been point the finger at the virus They range from the common adenovirus known to cause stomach upset to the widespread SARS-CoV-2, the virus behind COVID-19.

So far, no theory has turned into a slam dunk. Clinicians are also questioning whether this is a new phenomenon.Medical teams have warned that even before this year’s surge in cases has given global health officials high marks, children with no clear cause are at risk of serious illness. I have long noticed sporadic cases of liver problems.

It leaves more questions than answers, but a recent British study explores some intriguing possibilities, offering even more potential pieces to this puzzle.

Some scientists told CBC News that what was particularly fascinating and unexpected was the potential connection with AAV2. It is known as the dependoparvovirus and does not normally self-replicate in the human body.

Watch | The causes of rare liver disease outbreaks are a mystery to experts:

Causes of rare liver disease outbreaks in children remain a mystery to experts

Doctors have not pinpointed what is causing the mysterious outbreak of liver disease in children in more than a dozen countries around the world. At least one child has died, but experts say most They claim that the child will make a full recovery from the illness.

“It’s essentially a parasite. It needs another DNA virus to replicate its genome,” says virologist Charlotte Holdcroft of the University of Cambridge’s Department of Genetics.

A significant proportion of the population may be infected with AAV2, but may not be aware of it.

The virus is generally not thought to cause disease on its own. Because there needs to be a “helper virus,” Houldcroft said.However, some studies suggest Infection with AAV2or the Use as a vector in gene therapy It may be associated with liver-related health problems to treat certain ailments.

Houldcroft noted that specific genes identified in patients by the Scottish team may be another important factor, as they are already associated with certain autoimmune conditions.

“Genetic susceptibility would explain why this is rare,” she said.

“And perhaps two different infections are required, and the fact that adenovirus 41 surged in the UK from December 2021 to spring 2022 may explain why these rare cases have clustered over time. No. And why did I suddenly become aware of this disease?”

More research, larger studies needed

Dr. Jordan Feld, a clinician and scientist at the Toronto Western Hospital River Clinic, agreed that the papers made interesting points and linked the data. These data may explain the rare but concerning cases emerging this year, and perhaps even childhood hepatitis of unknown origin. Examples so far.

But given all the potential factors at work, he stressed it was important to validate the results beyond these two small studies.

“When adenovirus was first proposed and SARS-CoV-2 was first proposed as its cause, everyone in the world went back and carefully examined their samples. That’s not the whole story.” Feld said.

Papers also have major limitations, such as small sample sizes and unclear cause and effect, noted by both external experts and the authors themselves.

The role of COVID-19 also remains unclear.

The Glasgow team’s Ho said her team found no clear link to SARS-CoV-2, and if that virus was the cause, it was more likely than childhood hepatitis during the early waves of the pandemic. He said he should have seen many cases.

The authors of the UK paper, on the other hand, concluded that their data alone were insufficient to rule out an effect of Omicron variants that “appeared prior to the onset of hepatitis of unknown cause” and that large case-control studies emphasized the need for more results of

Feld stressed that whatever could cause unexplained hepatitis in children, despite the close monitoring of cases by medical professionals, it remains an incredibly rare phenomenon.

Parents can look for obvious symptoms such as jaundice (yellowing of the child’s eyes and skin), dark urine, pale stools, abdominal pain, and vomiting.

“It’s certainly not an epidemic of severe acute hepatitis,” Feld said. “So the first thing to do is take a deep breath. Most kids will be perfectly fine.”