BOSTON, Mass. — In an age of medical mysteries, here’s another: why have more than 100 children in the United States across two dozen states developed hepatitis, or liver inflammation, in recent months — and why is the same thing happening in other countries?
“For years, we’ve seen cases of acute hepatitis,” said William Balistreri, MD, Director Emeritus of the Pediatric Liver Care Center at Cincinnati Children’s Hospital in Ohio. “But this seems to be a unique cluster.”
It is a cluster that started with a single case in Alabama — and, at latest count, had swelled to 109 cases in the U.S.
“This whole thing started back in October,” said Markus Buchfellner, MD, a pediatric infectious disease specialist at the University of Alabama in Birmingham. “We saw our first case of a child who came in with clinical signs of hepatitis.”
Those signs included vomiting and a yellowish tint to the skin known as jaundice.
“And then on lab work she had elevated liver function enzymes,” Buchfellner said. “As part of our initial work-up we had recommended to the GI doctors to send testing for adenovirus from the blood. And when it came back positive, we all stopped and paused because that was unusual, even that one case.”
Adenoviruses, first isolated in the early 1950s, tend to cause a variety of mild flu-like illnesses, especially in children. Buchfellner said they have been known to cause hepatitis, but only rarely in kids.
“Case Number 2 came in a few weeks later and that’s when I initiated contact with the Alabama Health Department,” Buchfellner said.
In all, he would treat nine children with hepatitis from October to February.
“Most of them presented with vomiting, diarrhea. Some of them presented with fever,” said Buchfellner. “And all of them had very elevated liver function tests.”
In addition, all nine tested positive for adenovirus.
“Five of those nine were subtyped to adenovirus 41.” Buchfellner said. “The remaining four, we did not have enough virus in the sample to do subtype testing.”
So is the conclusion that adenovirus is causing this hepatitis wave in kids? That is still under investigation.
“It’s hard to say right now that the adenovirus is exactly what’s causing these kids to get hepatitis,” Buchfellner said. “Because we haven’t been able to find the virus in the liver tissue of the biopsies in our nine cases in Alabama.”
That would seem to suggest the virus may not be causing direct damage to the liver.
Given this wave of hepatitis cases is happening as the pandemic rages on, it’s only natural to suspect COVID-19 may be playing a role. That hasn’t been ruled out, either, although all nine children in Alabama tested negative for SARS-CoV2. But, Buchfellner said further testing is underway to potentially detect antibodies from a past infection.
Balistreri said one hypothesis has SARS-CoV2 essentially ‘teaming up’ with an adenovirus to cause liver damage.
“Is it a synergy with SARS-CoV2?,” he said. “Is it an immune response that was generated by SARS-CoV2? We know we’re seeing all kinds of immunologic features of SARS-CoV2 both short term and long term So I think that’s what’s intriguing everybody. That conundrum.”
Another possibility, he said, is that a mutant adenovirus is on the loose — or that the hepatitis cases are linked to something environmental.
Whatever the cause — there have been sometimes devastating effects. The CDC reports 90 percent of children who’ve come down with this hepatitis required hospitalization — with 14 percent needing liver transplants. And, sadly, five have died with the disease.
Given the potential seriousness, Balistreri recommended parents not be quick to dismiss viral infections in children — and to keep pediatricians in the loop should a child fall ill. Handwashing and basic hygiene can also help prevent spread of adenoviruses — again, if they are even the cause.
Finally, Balistreri said it’s important to know the signs the liver may be in trouble.
“If the patient develops jaundice, yellowing of the eyes, darkening of their urine — then that should be assigned that this child needs a little deeper investigation,” he said. “Because that may well be the first sign of this acute liver injury.”
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