Viral Infections and Gene Variant Are Linked to Child Hepatitis Cases

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

The studies are based on only a few dozen cases and have not yet been peer-reviewed or published in scientific journals. Nevertheless, they suggest that children who develop severe, unexplained cases of liver inflammation may be simultaneously infected with two different viruses, one of which is called adeno-associated virus 2 (AAV2). ), a generally benign virus that requires a second “helper”. “Virus to replicate.

Adenoviruses, which have been found in several children with mysterious hepatitis previously reported within the past year, are common adjuvant viruses for AAV2.

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

Together, the findings suggest a possible explanation for the hepatitis cases: double infection with AAV2, in a small subset of children with this particular gene variant. And a helper virus, often an adenovirus, triggers an abnormal immune response that damages the liver.

Nevertheless, the researchers acknowledged that the studies are based on a small number of children in just one region of the world (United Kingdom) and that a causal link was not proven.

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

But, she adds: “We realized – because there is little in the way of an answer to the cause – that we needed to release these findings so that others can start looking for AAV2. And examine it in more detail.” “

The findings are intriguing but preliminary, said pediatrician at Emory University and Children’s Healthcare of Atlanta, Dr. Saul Karpen, who was not involved in the research. “This is not a definitive study,” he said. “Thematically, it certainly makes sense, but there isn’t full support for it.”

Cases of pediatric hepatitis are extremely rare but can be serious. According to the World Health Organization, as of 8 July, 1,010 probable cases were reported from 35 countries. Five percent of those children required a liver transplant, and 2 percent died.

Several early studies found that many children were infected with adenovirus, one of a group of common viruses that commonly cause cold or flu-like symptoms. New studies suggest that if adenoviruses are involved in hepatitis cases, they may be part of the story.

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 any viruses present in the children’s blood, liver and other samples.

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

On the other hand, the researchers did not detect AAV2 in healthy children, children who had adenovirus infection but had normal liver function or in children who had hepatitis from a known cause.

Those findings are in line with a second study led by researchers in London, which examined samples from 28 children with unexplained hepatitis from across the United Kingdom. That scientific team also found high levels of AAV2 in the blood and liver of several children. Several people also had low levels of adenovirus or herpes virus in their samples.

Scottish researchers also found that eight of the nine affected children, or 89 percent, shared a relatively unusual variant of a gene that codes for a protein important 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, have reached remarkably similar results,” Sofia Morphopolu, 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.

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

“Perhaps some of these infections that may occur over a greater distance in a few years,” said Dr. Emma Thomson, an infectious disease physician and a senior at the Center for Virus Research, “instead of occurring all at once.” The author of the Scottish study.

The researchers said additional, larger studies are still needed, specifically focusing on children in other countries.