What Scientists Know About the Unusual Hepatitis Cases in Children

Officials are exploring the possibility that a common adenovirus might be responsible for the unexplained cases, which remain rare.

A transmission electron micrograph of adenovirus, which was present in at least 74 of the 169 hepatitis cases described in a recent W.H.O. report. But experts cautioned that adenovirus might not be the cause.

Credit...Biophoto Associates/Science Source


By Emily Anthes
May 3, 2022

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

The cases remain extremely rare, with about 200 children affected worldwide, according to a report issued last week by the European Centre for Disease Prevention and Control.

But even these small clusters are unusual. In Britain, where most of the cases have been reported, two pediatric liver units have already had at least as many admissions for acute, unexplained hepatitis in 2022 as they typically have in an entire year, according to a briefing from the U.K. Health Security Agency.

Most children should recover fully, experts said, but some cases have been severe. In nearly 10 percent of reported cases, children have required liver transplants, according to the World Health Organization. There has been at least one death, the W.H.O. said.

The cause remains unknown, but scientists are exploring the possibility that an adenovirus may be responsible. Adenoviruses are common, but they are not usually associated with hepatitis in healthy children. And with many nations only now beginning to look for cases in earnest, the scope of the problem remains unknown.

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

Here’s what scientists know so far.

What is hepatitis?

Hepatitis is an inflammation of the liver and 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.

Understanding Hepatitis

An inflammation of the liver generally caused by a virus, hepatitis carries a host of complicating factors, side effects and stigma. Personal Accounts: What is it like to live with the disease? Six individuals shared their experience.

Symptoms in Children: Hepatitis symptoms in children overlap with many common illnesses. Here are the warning signs parents should watch out for.

Preventing Transmission: With infections on the rise, most adults should be getting screened for hepatitis.

Pandemic’s Effect: A wave of diagnostics ushered in by Covid could help revive flagging efforts to eliminate hepatitis C, one of the most common forms of the disease.

Heavy drinking, as well as certain medications and toxic substances, can also cause hepatitis. In autoimmune hepatitis, the body’s own immune system attacks the liver.

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

Where have the new cases been reported?

In early April, Britain became the first country to notify the W.H.O. of a cluster of unexplained hepatitis cases in children. The cases were unusual because they occurred over a short period of time in otherwise healthy children, and because clinicians 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 might explain the outbreak, according to the U.K. Health Security Agency’s briefing.

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 E.C.D.C. said.

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

“The two that received the transplant are actually doing quite well,” said Dr. Henry Shiau, a pediatric transplant hepatologist at the University of Alabama at Birmingham and the Children’s of Alabama hospital.

The cases prompted the C.D.C. to issue a nationwide alert, asking health care providers to keep an eye out for similar cases.

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

In many of the cases, children developed gastrointestinal symptoms, including 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 liver inflammation or damage.

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

“The likelihood of your child developing hepatitis is extremely low,” Dr. Meera Chand, the director of clinical and emerging infections at the U.K. Health Security Agency, said in a statement. “However, we continue to remind parents to be alert to the signs of hepatitis — particularly jaundice, which is easiest to spot as a yellow tinge in the whites of the eyes — and contact your doctor if you are concerned.”
What’s causing it?

“That’s the million-dollar question,” Dr. Shiau said. “I want to be up front about this: We don’t know.”

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

Adenovirus infections have been on the rise in Britain, where most of the hepatitis cases have been reported, the W.H.O. said.

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

It is possible that a new adenovirus strain has emerged or that adenovirus infections are occurring in conjunction with some other risk factor — such as a toxic exposure or an infection with another pathogen — causing these unusually severe outcomes, the U.K. Health Security Agency said.

Or the adenovirus infections could be a red herring. Because the viruses are so common among children, it is difficult to determine whether they are the cause of these hepatitis cases or whether many of the children have been infected incidentally. “Somebody could be infected with adenovirus and then develop hepatitis based on something else,” Dr. Malley said. “For proof of causality you really need a lot of data, which we just don’t have.”

Is this connected to Covid-19?

Probably not directly, experts said. Of the 169 patients identified by the W.H.O., 20 tested positive for the coronavirus. That is not surprising, given how widely the virus has been spreading in recent months, scientists said.

And there is no evidence that the hepatitis is linked to the Covid-19 vaccines; the “vast majority” of the children in question had not been vaccinated, the W.H.O. said.

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

But that, too, is speculative.

“At this point,” Dr. Shiau said, “we still don’t know what’s going on.”


Emily Anthes is a reporter for The New York Times, where she focuses on science and health and covers topics like the coronavirus pandemic, vaccinations, virus testing and Covid in children.