Viral infections and genetic variant are linked to cases of hepatitis in children

A complex combination of factors may be responsible for the cases of pediatric hepatitis that baffled the doctors in recent months, according to two little ones, new studies.

The studies are based on only a few dozen cases and have not yet been peer-reviewed or published in scientific journals. Yet they suggest that children who developed severe, unexplained cases of liver inflammation may have been simultaneously infected with two different viruses, including one known as adeno-associated virus 2 (AAV2), a usually mild virus. which requires a second “helper”. ” virus in order to replicate itself.

Adenovirus, that have already been found in many children with the mysterious hepatitis reported in the past year, are common helper viruses for AAV2.

Many of the children studied also had a relatively rare version of a gene that plays an important role in immune response, the scientists found.

Together, the results suggest a possible explanation for hepatitis cases: in a small subset of children who carry this particular gene variant, dual AAV2 infections. and a helper virus, often an adenovirus, trigger an abnormal immune response that damages the liver.

Still, the researchers acknowledged that the studies are based on a small number of children in just one region of the world (the UK) and that a causal link has not been proven.

“There are a lot of things we still don’t know,” said Dr Antonia Ho, clinical lecturer at the MRC-University of Glasgow Center for Virus Research and author of one of the new studies.

But, she added: ‘We felt – because there were very few answers about the causes – that we had to publish these findings so that other people could start researching AAV2. and study this in more detail.

The results are intriguing but preliminary, said Dr. Saul Karpen, a pediatric hepatologist at Emory University and Children’s Healthcare in Atlanta, who was not involved in the research. “It’s not a definitive study,” he said. “Thematically it can certainly make sense, but there’s no full support for it.”

Cases of pediatric hepatitis are extremely rare but can be serious. Since July 8, 1,010 probable cases had been reported from 35 countries, according to the World Health Organization. Five percent of these children required a liver transplant and 2% died.

Several early studies showed that many children were infected with an adenovirus, one of a group of common viruses that typically cause cold or flu symptoms. The new studies suggest that if adenoviruses are implicated in hepatitis cases, they might just be history.

In one of the new studies, scientists compared nine Scottish children with unexplained hepatitis to 58 children in control groups. The researchers used genomic sequencing to identify all the viruses present in the children’s blood, liver and other samples.

The scientists found adeno-associated virus 2 in the blood of the nine affected children and in liver samples from the four children from whom such samples were available. They also found adenovirus in six of the children and common herpes virus in three.

In contrast, the researchers did not detect AAV2 in healthy children, in children who had adenovirus infections but normal liver function, or in children who had hepatitis of known cause.

These findings are consistent with those of a second study, led by researchers in London, which looked at samples from 28 children with unexplained hepatitis across the UK. This scientific team also found high levels of AAV2 in the blood and liver of many children. Many also had low levels of adenovirus or herpes virus in their samples.

The Scottish researchers also found that eight of the nine children affected, or 89%, shared a relatively rare variant of a gene that codes for a protein essential in the body’s immune response. This particular variant is present in only 16% of Scottish blood donors.

The London team found the same genetic variant in four of the five transplant recipients they assessed.

“The two studies reached independent and remarkably similar results,” Sofia Morfopoulou, a computational statistician at University College London’s Great Ormond Street Institute of Child Health and author of the second paper, said in an email.

Although the idea remains preliminary, it is possible that a recent resurgence of the adenovirus after a drop in circulation during the coronavirus pandemic explains why doctors noticed a sudden spike in these rare cases, the scientists said.

“Maybe some of these infections that might have happened more spaced out, over a few years,” are happening all at the same time instead, said Dr. Emma Thomson, an infectious disease physician at the Center for Virus Research and senior author of the Scottish study.

More and larger studies are still needed, especially focusing on children from other countries, the researchers said.

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