Symptoms and Possible Causes of Mysterious Cases of Childhood Hepatitis in the US and Around the World

Worldwide, the number of mysterious cases of hepatitis being investigated in children has reached 450, the European Center for Disease Prevention and Control said this week.

That’s more than double the number the group reported two weeks ago, and significantly higher than the World Health Organization’s latest count of 348.

Cases of this liver inflammation have been reported in more than 25 countries, although the majority are in the UK (about 160) and the US (about 110). Most affected children are under 5 years old. More than 90 percent of US patients have been hospitalized and 14 percent have had a liver transplant. The Centers for Disease Control and Prevention are investigating five pediatric deaths that may be related.

Disease experts aren’t sure what’s behind these cases, though several hypotheses have emerged. The leading theory is an adenovirus, which often causes cold or flu-like symptoms or stomach problems.

More than half of U.S. cases tested positive for adenovirus, the CDC said Wednesday. So did about 72 percent of cases in the UK and 60 percent across Europe.

But it is rare for an adenovirus to affect the liver so severely.

Tissue and liver samples recently taken in the UK “do not show any of the typical features you would expect in adenovirus liver inflammation, but we are awaiting further examination of biopsies”, Dr. Phillipa Easterbrook, a senior scientist at WHO, said Tuesday.

This is what is known so far.

What Causes These Severe Hepatitis Cases?

In general, there can be hundreds of possible causes of hepatitis: Liver inflammation can be the result of toxins, viruses, or contaminated food and water.

But in these recent cases, experts have turned their eye to a particular adenovirus, type 41, which has been identified in most cases in Europe and in many cases in the US. Adenovirus 41 usually results in stomach upset but is not usually associated with hepatitis in otherwise healthy children.

dr. Markus Buchfellner, a pediatric infectious disease researcher at the University of Alabama at Birmingham, was the first to notice the unusual pattern of unexplained hepatitis in children in the US and report it to the CDC. He and other experts have questioned whether pandemic lockdowns resulted in reduced exposure to adenoviruses in general, perhaps making young children more vulnerable to them.

But experts have also not ruled out the possibility that Covid-19 could be an underlying cause, as the wave of cases appears to have originated during the pandemic.

“That’s one of the biggest unanswered questions,” Buchfellner said.

There is no evidence that the coronavirus directly causes hepatitis in children.

Still, the WHO is also looking at whether a previous Covid infection — even a mild or asymptomatic case — could have somehow prompted children’s immune systems to respond abnormally to otherwise harmless adenoviruses.

“The big focus in the coming week is really looking at the serology tests for past exposure and infections with Covid,” Easterbrook said Tuesday.

What Are Common Hepatitis Symptoms in Children?

“The big symptom that made all these kids different was that they all showed signs of jaundice, which is the yellowish discoloration of the skin and eyes,” Buchfellner said.

Aside from that notable symptom of these unusual cases of hepatitis, he said, a majority of patients had nausea and vomiting and experienced severe fatigue and loss of appetite.

Other symptoms may include fever, stomach pain, dark urine, and light-colored stools.

How did the children with long-term hepatitis fare?

This unusual form of hepatitis can be fatal, although deaths appear to be rare so far. The CDC has not yet determined whether the five US deaths under investigation were indeed caused by hepatitis.

Of the 109 cases studied, 14 percent required a liver transplant, according to the CDC. They will have to take medication for the rest of their lives to keep their bodies from rejecting the new organ.

The majority of the children had to be hospitalized, but Buchfellner said it was mainly to make sure doctors could monitor them and do more testing.

But for the most part, the illnesses were mild. The liver is a robust organ that can often heal itself over time, with proper hydration and nutrition. As such, many of these young patients have made a full recovery and continue to do well, Buchfellner said.

“All of our nine children are doing well, even those who needed a transplant,” he said.

Can this hepatitis disease be prevented with a vaccine?

Some forms of hepatitis can be prevented with routine vaccines, such as those against hepatitis A and B viruses. But those viruses are excluded in these cases, as are the other typical viruses that can cause hepatitis: C, D, and E.

There is no publicly available vaccine for adenoviruses, but the US has approved an adenovirus vaccine for military personnel that protects against two subtypes: type 4 and type 7.

Adenovirus 41 is generally spread through feces, so proper hand washing is critical, especially after diaper changes and visits to the bathroom.

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