Health

Viral infections and gene variants are associated with cases of hepatitis in children


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

The studies are based on only a few dozen cases and have not been peer-reviewed or published in scientific journals. However, they suggest that children who have developed severe, unexplained cases of hepatitis may have been infected with two different viruses simultaneously, including one known as adeno-associated virus. 2 (AAV2), a generally benign virus that needs a “second helper” to replicate.

Adenovirus, previously found in many children with mysterious hepatitis reported last year, is the common helper virus for AAV2.

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

Taken together, the findings suggest a possible explanation for cases of hepatitis: In a small group of children with this particular gene variant, dual infection with AAV2. and helper viruses, usually adenoviruses, trigger an abnormal immune response that damages the liver.

However, the researchers acknowledge that the studies were based on only a small number of children in one region of the world (United Kingdom) and that a cause-and-effect link has not been proven.

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

However, she added: “We felt – because there is so little answer as to what the cause was – that we needed to publish these findings so that others could start looking for AAV2. and investigate the matter in more detail”.

Dr. Saul Karpen, a pediatric hepatologist at Emory University and Children’s Healthcare of Atlanta, who was not involved in the study, said the findings are intriguing but preliminary. “This is not an exact study,” he said. “Thematically, it can certainly make sense, but there’s not enough support for it.”

Cases of hepatitis in children are extremely rare but can be severe. As of July 8, 1,010 possible cases have been reported from 35 countries, according to the World Health Organization. Five percent of those children required a liver transplant, and 2 percent died.

Some early research has found that many children are infected with adenoviruses, one of the common groups of viruses that often cause cold symptoms or hot flashes. New studies suggest that if adenoviruses are involved in hepatitis cases, they may be only part of the story.

In one of the new studies, scientists compared nine Scottish children with hepatitis of unknown cause with 58 children in a control group. The researchers used gene 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 for whom those samples were available. They also found an adenovirus in six children and a common herpes virus in three.

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

These findings are consistent with those from a second study, led by researchers in London, which examined samples from 28 children with hepatitis of unknown cause from across the UK. The same team also found high levels of AAV2 in the blood and liver of many children. Many people also have low levels of adenovirus or the herpes virus in their samples.

The Scottish researchers also found that eight out of nine affected children, or 89%, share a relatively uncommon variant of a gene encoding a protein important in the body’s immune response. body. This particular variant is present in only 16% of Scottish blood donors.

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

Sofia Morfopoulou, a computational statistician at the Great Ormond Street Institute for Children’s Health at University College London and author of the second paper, said: “Both studies yielded similar, independent results. significantly similar to each other.

Although the idea is still in its infancy, scientists say it is possible that the recent resurgence of the adenovirus after a decline in circulation during the coronavirus pandemic, explains why doctors have noticed a sudden increase variable in these rare cases, the scientists said.

Dr Emma Thomson, an infectious disease physician at the Center for Virology and a senior fellow, said: ‘Perhaps some infections could have occurred further apart, in a few years’ time. The author of the Scottish study.

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



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