Viral infections and gene variant linked to cases of childhood hepatitis

A complex combination of factors may be responsible for cases of childhood hepatitis that puzzled doctors in recent months, according to two small, new research.

The studies are based on only a few dozen cases and have not yet been peer-reviewed or published in scientific journals. However, they suggest that children who develop 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 normally benign virus that needs a second “helper.” . virus to replicate.

adenoviruses, that have been previously discovered many children with mysterious hepatitis reported within the past year are common AAV2 helper viruses.

The scientists found that many of the children studied also had a relatively unusual version of a gene that plays an important role in the immune response.

Taken together, the findings suggest a possible explanation for hepatitis cases: A small subset of children with this particular gene variant have dual AAV2 infection. and a helper virus, often an adenovirus, causes an abnormal immune response that damages the liver.

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

“There are many things that we still do not know,” the doctor said. Antonia Ho, Clinical Senior Lecturer at the MRC-University of Glasgow Center for Viral Research and author of one of the new studies.

But she added: “We felt — as there were very few answers or reasons — that we needed to publish these results so that other people could start looking for AAV2. and explore it in more detail.”

The findings are intriguing but preliminary, the doctor said. Saul Karpen, a pediatric hepatologist at Emory University and Atlanta Children’s Health, was not involved in the study. “This is not a definitive study,” he said. “Thematically, it could certainly make sense, but it doesn’t have full support.”

Cases of pediatric hepatitis are extremely rare but can be severe. As of July 8, 1010 probable cases were reported from 35 countries, according to the World Health Organization. Five percent of these children required a liver transplant, and 2 percent died.

Several early studies showed that many children were infected with adenovirus, one of a group of common viruses that commonly cause cold or flu symptoms. New research suggests that if adenoviruses are linked to cases of hepatitis, then they may just be part of the story.

In one new study, researchers compared nine Scottish children with unexplained hepatitis with 58 control children. The researchers used genome sequencing to detect any viruses present in the blood, liver and other samples of the children.

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

On the other hand, researchers did not find AAV2 in healthy children, children with adenovirus infection but normal liver function, or children with hepatitis for a known cause.

These results are consistent with those of a second study by researchers in London, which examined samples of 28 children with unexplained hepatitis from across the UK. This research 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 out of nine sick children, or 89 percent, have a relatively unusual gene variant that codes for a critical protein in the body’s immune response. This particular variant is present in only 16 percent of Scottish blood donors.

The London team found the same gene variant in four of the five transplant recipients they evaluated.

“Both studies independently achieved remarkably similar results,” Sophia Morfopoulou, a computational statistician at the Great Ormond Street Institute of Child Health at University College London and author of the second paper, said in an email.

While this idea remains tentative, it’s possible that the recent resurgence of adenovirus following a decline in its circulation during the coronavirus pandemic explains why doctors have noticed a sudden spike in these rare cases, scientists say.

“It’s possible that some of these infections, which could have happened more sparsely, over several years,” instead happen at the same time, the doctor said. Emma Thomson, infectious disease physician at the Center for Viral Research and senior author of the Scottish study.

The researchers said more, larger studies are still needed, especially with a focus on children in other countries.