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The CDC is still searching for the cause of mysterious liver illness in kids

With data on nearly 300 cases, experts are confident that the culprit will soon be uncovered.
Transmission electron microscopic (TEM) image of some of the ultrastructural details exhibited by a small cluster of adenovirus virions.
Transmission electron microscopic (TEM) image of adenovirus virions.Dr. G. William Gary, Jr. / CDC

The search for the cause behind the cluster of mysterious, severe hepatitis cases in young children continues.

Reports of potential cases have poured in since the Centers for Disease Control and Prevention issued a nationwide alert to physicians in April, asking them to be on the lookout for unexplained cases of liver inflammation in kids. 

Those cases haven’t led to any direct answers yet, but experts are confident that further research over the coming months will be fruitful. 

A total of 296 potential cases of unexplained hepatitis in young children have been identified so far, the CDC reported Friday. Most of the cases are not new; many were identified in retrospect, with doctors looking as far back as October. And while the number may sound high, they haven’t exceeded the expected yearly number of severe pediatric hepatitis cases.

In fact, cases have been falling in recent weeks, according to Dr. Markus Buchfellner, a pediatric infectious diseases fellow at the University of Alabama at Birmingham. Buchfellner first alerted the CDC to unusual back-to-back cases of pediatric hepatitis last year.

But falling case numbers don’t mean scientists are taking their eye off the ball. The situation is “still alarming enough that we need to know more about it,” he said.

Most cases were in children under 5 years old; the average age was 2, the CDC reported. Nearly 90% of the children required hospitalization, 6% needed a liver transplant, and 11 children died.

None of the children tested positive for any of the common causes of hepatitis, including the viruses that cause hepatitis A, B and C. Hepatitis refers to inflammation of the liver in general and can have hundreds of causes, including other viruses, toxins and food poisoning.

In 224 of the cases, patients received a test for an adenovirus infection — a virus that’s considered to be a prime suspect. Just under half, 45%, tested positive. 

Adenoviruses are common among children and can cause a range of symptoms, from colds to pink eye to vomiting and diarrhea. But they’re not a known cause of severe hepatitis in healthy children.

Adenovirus is known to cause hepatitis in immunocompromised children, said Dr. David Sugerman, a medical officer in the Division of Viral Diseases at the CDC and an author of the new report. But the recent spate of cases differs from cases in immunocompromised children in two ways, he said. First, they’re in children with healthy immune systems, and second, the virus was found in stool and blood samples, but has not yet been detected in liver tissue. 

“The pathology in the liver tissue [in the new cases] is not what we usually see with adenovirus liver disease. That’s what’s different,” said Sugerman, who is also the deputy incident manager for the CDC’s pediatric hepatitis of unknown etiology response task force. 

According to the report, adenovirus was not the only virus detected in samples from the children, though it was by far the most common. Around 26% of the children previously had Covid, and 10% tested positive for Covid at the same time they had hepatitis. A smaller number of kids had other viruses, such as RSV.

A poorly understood problem

It isn’t unusual that viruses go undetected until they cause severe problems, said Dr. Alice Sato, a pediatric infectious diseases specialist at Children’s Hospital and Medical Center in Omaha, Nebraska. For that reason, doctors do not have a clear understanding of how much adenovirus, and which specific ones, are circulating in communities at any given time. 

It’s possible, she said, that the adenovirus infections in children with hepatitis could be a coincidence, given that cases do not seem to be any higher than pre-pandemic levels of pediatric hepatitis. 

That said, “there is enough suspicion that the CDC has enlisted states to keep a very close eye on it to see if it really is something so we can prevent it,” Sato said. “It’s not taking off like wildfire, but several states have reported cases that could be concerning.” 

One theory is that adenovirus has always been a cause of pediatric hepatitis in some kids, but because kids weren’t socializing during the pandemic, they weren’t exposed to adenovirus early on in life. According to Sugerman, most kids are exposed to adenovirus before age 4. Quarantine also threw off the normal virus cycle — with things like influenza and RSV, which were previously considered winter viruses, now appearing in summer months.

“There might be a rapid re-exposure, and it’s possible that this is something that has always been there, but we didn’t see it before because there wasn’t this re-exposure,” he said, noting that if re-exposure is the cause, it is not triggering a wave of hepatitis cases. 

Still, Sugerman said that acute liver failure in children is not well understood, and about 30% of cases historically have had no known cause. “It’s possible that adenovirus was one of the causes of those cases that wasn’t previously detected,” he said.

Sugerman said Covid infection does not appear to be an underlying cause of the hepatitis, but the possibility is still being investigated. 

Buchfellner, of the University of Alabama at Birmingham, said that a link to long Covid hasn’t completely been ruled out, since experts have not yet been able to detect traces of the virus in the liver tissue. 

“There are a lot of theories floating around about why this happened, and we don’t have solid evidence to say one way or another,” he said. “What we have been able to show is that there is something unusual going on.”

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