What scientists know about the rare cases of hepatitis in children around the world

At least 16 countries and 10 US states have identified or are investigating reports of unusual cases of hepatitis in healthy children.

Cases remain extremely rare, with around 200 children affected worldwide, according to a report released last week by the European Center for Disease Prevention and Control.

But even these small nuclei are unusual. In Britain, where the majority of cases have been reported, two pediatric units have had at least as many hospitalizations for acute and unexplained hepatitis in 2022 as they normally would in an entire year, according to a report from the UK Health Safety Agency.

Most children are expected to make a full recovery, experts said, but some cases were serious. In nearly 10% of reported cases, children required liver transplants, and there was at least one death, the World Health Organization said.

The cause remains unknown, but scientists are looking into the possibility that an adenovirus is responsible. Adenoviruses are common but not usually associated with hepatitis in healthy children. And because many countries are only now starting to look seriously at cases, the scope of the problem is not known.

“It’s still early days,” said Dr. Richard Malley, an infectious disease specialist at Children’s Hospital Boston. “It is difficult to predict whether this will become more common or if, in fact, it will be just a small sign in our infectious disease track record in 2022.”

Here’s what scientists know so far.

What is hepatitis? Hepatitis is an inflammation of the liver that can have a wide range of causes. Viral infections can cause the condition; the viruses known as hepatitis A, B, C, D and E are all known triggers.

Excessive consumption of alcohol, as well as certain drugs and toxic substances, can also cause hepatitis. In autoimmune hepatitis, the body’s own immune system attacks the liver.

Sudden, severe hepatitis in previously healthy children is uncommon, which is why the new clusters of cases have raised concern.

Where were the new cases reported? In early April, Britain became the first country to notify the WHO (World Health Organization) of a cluster of unexplained cases of hepatitis in children. The cases were unusual because they occurred over a short period of time in healthy children and because doctors quickly ruled out any of the common hepatitis viruses as the cause. They did not identify any patterns in travel, diet, chemical exposures or other risk factors that could explain the outbreak, according to the UK Health Safety Agency’s statement.

Since then, Austria, Belgium, Denmark, France, Germany, Ireland, Israel, Italy, Japan, the Netherlands, Norway, Poland, Romania, Spain and the United States have reported similar cases, the European CDC said.

In the United States, Alabama recorded nine cases between October and February. Three of the children developed liver failure and two needed liver transplants, the US Centers for Disease Control and Prevention noted in a recent report. All the children have recovered or are recovering, the agency noted.

“The two who received the transplant are doing very well,” said Dr. Henry Shiau, a pediatric transplant hepatologist at the University of Alabama at Birmingham and Children’s Hospital of Alabama.
The cases prompted the CDC to issue a national alert, urging healthcare workers to be on the lookout for similar cases.

Illinois and Wisconsin have since announced possible cases. North Carolina, Delaware, Minnesota, California, New York, Georgia and Louisiana have also identified or are investigating potential cases, state officials told The New York Times.

What are the symptoms? In many of the cases, the children developed gastrointestinal symptoms such as vomiting, diarrhea and abdominal pain, followed by a yellowing of the skin or eyes known as jaundice. They also had abnormally high levels of liver enzymes, a sign of inflammation or liver damage.

Gastrointestinal symptoms are common in children and should not, in isolation, be cause for alarm, Shiau said. But yellowing of the skin or eyes is a more telltale sign of liver problems, she said.

“The likelihood that your child will develop hepatitis is extremely low,” Dr. Meera Chand, director of clinical and emerging infections at the UK Health Safety Agency, said in a statement. “However, we continue to remind parents to be on the lookout for signs of hepatitis — particularly jaundice, which is easier to detect by the yellow tint to the whites of the eyes — and to contact their doctors if they are concerned.”

What is causing this? “That’s the million dollar question,” Shiau said. “I want to be honest about this: we don’t know.”

But one of the leading hypotheses is that an adenovirus — a group of common viruses that often cause cold symptoms — is responsible. Of the 169 cases included in a recent WHO report, at least 74 had adenovirus infection, the organization said. Eighteen of those children were infected with what is known as adenovirus type 41, which normally causes gastrointestinal and respiratory symptoms.

Adenovirus infections are on the rise in Britain, where most cases of hepatitis have been reported, the WHO said.

But the explanation doesn’t quite fit. Not all children have tested positive for adenovirus, and while viruses can cause liver inflammation, this symptom is more common in immunocompromised people. “It’s not a common cause of liver failure in children,” said Dr. Aaron Milstone, a specialist in pediatric infectious diseases at the Johns Hopkins Children’s Center.

It is possible that a new strain of adenovirus has emerged or that adenovirus infections are occurring in conjunction with some other risk factor — such as a toxic exposure or infection by another pathogen — producing exceptionally severe results, the Health Safety Agency said. United Kingdom.

Or adenovirus infections could be a distracting factor. Because these viruses are common among children, it is difficult to determine whether they caused these cases of hepatitis or whether many of the children were accidentally infected. “Someone could be infected with adenovirus and develop hepatitis based on something else,” Malley said. “To prove causality, you really need a lot of data, which we just don’t have.”

Is this related to Covid-19? Probably not directly, experts said. Of the 169 patients identified by the WHO, 20 tested positive for coronavirus. This is not surprising given the extent to which the virus has spread in recent months, the scientists explained.

And there is no evidence that hepatitis is linked to Covid-19 vaccines; the “great majority” of the children in question were not vaccinated, the WHO said.

Still, a connection to the coronavirus cannot be entirely ruled out, experts have warned, and hepatitis cases could be linked to the pandemic in less direct ways. For example, public health measures implemented over the past two years may have left fewer children exposed to common adenoviruses. That, in turn, may have made them more susceptible now, according to one of the British agency’s working hypotheses.

But that too is speculative.

“Right now,” Shiau said, “we still don’t know what’s going on.”

Translated by Luiz Roberto M. Gonçalves.