Studies Link Common Childhood Viruses to Rare Hepatitis Cases

Last year, reports of severe, unexplained hepatitis in previously healthy children puzzled health experts around the world.

Now, a small new study The number of US children adds to evidence that such cases, which remain extremely rare, may be caused by simultaneous infection with several common viruses, including one known as adeno-associated virus type 2, or AAV2. .

AAV2 is not usually associated with disease, and requires a second “helper” virus to replicate. The researchers found that many children with unexplained hepatitis, or inflammation of the liver, were infected with multiple helper viruses.

Although this idea remains speculative, the timing of the outbreak may be related to a loosening of epidemiological precautions, exposing large numbers of young children to common viruses they may not have previously encountered.

“This could result in a population that was highly susceptible to becoming infected with multiple viral infections,” Dr. Charles Chiu, an infectious disease specialist and microbiologist at the University of California, San Francisco, and author of the new study.

The research was published Thursday in the journal Nature two british studies he was also trapped AAV2 in cases of hepatitis. Early versions of the British study were posted online last summer.

The consistent findings are “quite striking,” Dr. Frank Tacke, head of the department of gastroenterology and hepatology at the Charité University Medical Center in Berlin, who was not involved in the research but wrote an accompanying commentary. “The fact that three independent groups found it from different regions of the world makes it really reassuring.”

Still, the findings are not definitive, and many uncertainties remain, including how these infections may trigger hepatitis and whether AAV2 plays a causal role or is “just a bystander,” Dr. Taake said. (There has also been some debate about whether cases actually became more common last year or whether they were part of a previously recognized phenomenon.)

cases are prior fall 2021 That peaked last spring and summer before easing, experts said. until last July, more than a thousand possible cases was reported in 35 countries, including the United States, according to the World Health Organization. Roughly 5 percent of the children required liver transplants, and 2 percent died.

In several early studies, scientists found that many affected children were infected with adenoviruses, specifically adenovirus 41, which typically causes gastrointestinal symptoms. Adenoviruses are not generally known to cause hepatitis in healthy children, but they are common helper viruses for AAV2.

The new study was a collaboration between the Centers for Disease Control and Prevention, among academic researchers, state health departments and other institutions. Researchers studied biological samples from 16 US children from six states with unexplained hepatitis. All had previously tested positive for adenovirus. They also studied samples from 113 control children, a group that included healthy children, children with gastroenteritis and children with hepatitis of no known cause.

Blood samples were available from 14 children with unexplained hepatitis. The researchers found AAV2 in 13 of those children, or 93 percent of them, compared to 3.5 percent of the control children. Of the 30 children who had hepatitis associated with a known cause, none tested positive for AAV2.

Most children with unexplained hepatitis tested positive for at least one herpes virus, meaning many were infected with at least three viruses: AAV2, an adenovirus, and a herpes virus.

In the British studies, which were very small, scientists found AAV2 in the blood and liver of affected children. Many were also infected with adenovirus or herpes virus. In one study, 25 of 27 affected children shared an immune-related genetic variant that is relatively uncommon in the general population. The finding suggests that this variant may predispose some children to hepatitis when they are infected with AAV2 and one or more helper viruses.

“It may turn out that in rare cases, you have a perfect storm of events where there is a subset of children who were uniquely susceptible,” Dr. Chiu said.

He said more research is needed to determine whether one or more of these viruses were directly injuring the liver.

An alternative explanation is that, in a small subset of children, infection with multiple viruses triggers an overly strong immune response, which damages the liver.

Pinning down the mechanism would have important implications for treatment, Dr. Stitches added. If viruses are causing liver damage, antivirals may be the best course of treatment; He added that if an immune overreaction is to blame, suppressing the immune response with steroids may be a better option.

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