U.S. reports 180 cases of unexplained hepatitis in children, as researchers investigate potential causes

U.S. health officials said Friday they were investigating 180 reported cases of unusual hepatitis in children in 36 states and territories dating from the past seven months.

The number is an increase from the 109 reported two weeks ago, but Jay Butler of the Centers for Disease Control and Prevention told reporters Friday that the “vast majority” of the newly accounted for cases have been retrospectively identified as health authorities expanded their investigation. Some go back to October, and just 7% occurred in the past two weeks, said Butler, the CDC’s deputy director for infectious diseases.

There was one additional death reported this week, bringing the total to six. Fifteen of the reported cases of hepatitis — liver inflammation — have required liver transplants. Cases are more common in preschool-age children, and there does not appear to be a difference in rates by sex.


The phenomenon of unexplained pediatric hepatitis cases gained global attention when U.K. officials in April reported an unexpected number of cases. In the United States, where national data on unexplained pediatric hepatitis cases aren’t kept, CDC officials said they are still investigating whether this represents a true increase in cases or if the numbers are a result of more comprehensive reporting. They’ve been looking to hospital discharge data to gather information on the usual rate of pediatric hepatitis cases of unknown etiology (meaning there’s not a clear cause).

Globally, more than 600 cases of unexplained hepatitis have been identified; at least 14 children have died.


Hepatitis has multiple causes, but the usual suspects — including a number of hepatitis viruses — have been ruled out in these cases.

Much of the focus has centered on the potential role of an adenovirus, specifically adenovirus 41, which has been detected in many of the cases. The virus is common and typically causes gastrointestinal illnesses, and has not been known to cause liver damage in otherwise healthy children.

“The leading hypothesis remains an important role for adenovirus 41,” Butler said. “However, we continue to keep looking for multiple causes.” Butler added: “It does take time to assess the evidence.”

As scientific sleuths investigate, they are considering a range of possibilities. Was this phenomenon previously occurring but at such low numbers that it wasn’t detected? Did the adenovirus somehow change to become able to cause this type of liver condition? Is there a combination of factors at play, such as the effect of another virus or toxin in tandem with an adenovirus infection? Are kids more susceptible to the effects of an adenovirus infection because of a lack of exposure to common viruses during the Covid-19 pandemic?

And is an adenovirus really involved at all?

Butler said that preliminary genomic evidence suggests that it’s not just one strain of adenovirus 41 that has been found in children who’ve tested positive for the virus. That indicates there’s not some new variant of the virus that’s causing these cases of hepatitis, though Butler said more comprehensive genetic testing needed to be done.

One factor that has been ruled out is the Covid-19 vaccines. Many of the children are under 5, who are not eligible for the shots.

Separately Friday, U.K. health officials released an updated report about cases there, with 197 detected as of earlier this week, 11 of which have required a transplant. Cases appear to be on the decline.

On Thursday, the European Centre for Disease Prevention and Control said 125 cases had been identified in 14 European countries.

Some two-thirds of the U.K. children had adenovirus detected, though testing limitations meant that the portion could be higher. SARS-CoV-2, the coronavirus that causes Covid-19, was diagnosed in 15% of cases with available results.

Experts have noted that it’s difficult to analyze the significance of those rates of adenovirus and SARS-2 in children with these hepatitis cases. The viruses are not uncommon, so how do those rates compare to those in children who don’t have hepatitis? “Case control” studies that can answer that question are being launched.

Some researchers have urged scientists to put more weight on a possible connection to Covid-19 infections.

One hypothesis is that the cases of hepatitis are a result of a past Covid-19 infection followed by another viral infection, possibly from adenovirus 41. Under that theory, some children don’t completely clear the coronavirus after a mild infection and have a viral reservoir in their GI tract, essentially keeping their immune systems in a heightened state. Prompted by the second viral infection, components of the immune system go into overdrive and damage the liver — a process called “superantigen-mediated immune activation.” Essentially, the second infection triggers a cascade of effects that results in hepatitis.

“If a child has such a viral reservoir lingering for a while and then has an intestinal viral infection” — perhaps from the adenovirus — “then one can imagine that this could potentiate this superantigen effect,” Petter Brodin, a professor of pediatric immunology at Imperial College London, told STAT. Brodin has written about that hypothesis in the journal The Lancet Gastroenterology and Hepatology.

Other scientists, however, are not sold on the idea, at least not yet. “It’s too early to answer that question” about the possible contribution of a latent Covid infection, Deirdre Kelly, a professor of pediatric hepatology at the University of Birmingham, told reporters this week.

And Calum Semple, a professor in child health and outbreak medicine at the University of Liverpool, said he leaned away from a possible tie to Covid. “I don’t think we’re ruling out Covid completely,” he said. “It’s just I’m saying I think Covid is moving down that list” of hypotheses.

The latest report from the U.K. Health Security Agency lists hypotheses for the cases, but they haven’t changed much in recent weeks. But there was one potential factor the agency had previously mentioned that’s now off the board: dogs.

In a past report, health authorities noted that many of the cases came from dog-owning families, or had other exposure to dogs, and said “the significance of this finding is being explored.” But in the report Friday, they wrote that “there is no difference between children with dog contact and those without dog contact in either the patterns of illness or virological detections.”

“This is no longer an active line of investigation by public health agencies,” they wrote.

Helen Branswell contributed reporting. 

Source: STAT