CDC investigating 109 unusual hepatitis cases in kids in outbreak

The Centers for Disease Control and Prevention said Friday it is investigating 109 reported cases of unusual hepatitis in previously healthy young children, 14% of whom needed liver transplants and five of whom have died. A total of 25 states and territories have reported cases.

Half of the children had confirmed adenovirus infections, the leading suspected cause of these illnesses. But the CDC warned that the investigations are in an early stage and it is too soon to draw conclusions.

“We really are casting a broad net and keeping an open mind in terms of whether the adenovirus data may reflect an innocent bystander or whether there may be co-factors that are making the adenovirus infections manifest in a way that’s not been commonly seen before,” Jay Butler, the CDC’s deputy director for infectious diseases, said during a news conference.

Butler said the CDC is suggesting that doctors treating children who have unexplained hepatitis should consider testing their patients for adenovirus.

Anticipating that parents may be spooked by news of severe hepatitis in young children, the CDC officials tried to put the numbers in context. Butler said the country isn’t seeing increased rates of pediatric hepatitis — though he acknowledged national figures aren’t kept on pediatric hepatitis of unknown etiology. As a consequence, CDC is mining what’s known as syndromic surveillance data, trying to see if there are changes in rates of children presenting for care with jaundice, a sign of liver disorder.

Changes in the number of rare events are easier to spot in countries with single-payer health systems, he suggested. “If we had data coming in for 330 million people that was real time, that would make it a lot easier,” he said. “We are working hard to come up with good data.”

One metric the CDC does have access to, though, is the number of children who undergo liver transplants. To date there hasn’t been an increase in reported transplants, said Umesh Parashar, chief of CDC’s viral gastroenteritis branch, despite the 15 or so children with hepatitis of unknown etiology who received transplants.

“We have not noticed an increase in the past few months compared with even the pre-Covid baseline for children requiring transplantation,” Parashar said, though he noted there is a two- to three-month reporting lag on this data.

Upward of 300 pediatric hepatitis cases of unknown etiology or origin have been reported by more than two dozen countries, according to information drawn from the CDC, the European Center for Disease Prevention and Control, and the United Kingdom Health Security Agency (UKHSA).

The phenomenon was first observed in Alabama last October, but came to broader global attention in early April when the UKHSA alerted the world to the fact that the U.K. was seeing an unexpected number of unexplained hepatitis cases in very young children. While some of the patients are as old as 16, most are under the age of 5. The CDC said the median age of the U.S. cases is 2 years.

The UKHSA reported Friday that its case count has risen to 163 children, all diagnosed since the start of 2022. Eleven of the U.K. children have needed liver transplants, but none to date has died.

Smaller numbers of cases have been reported by Argentina, Austria, Belgium, Costa Rica, Cyprus, Denmark, France, Germany, Indonesia, Ireland, Israel, Italy, Japan, the Netherlands, Norway, Palestine, Panama, Poland, Portugal, Romania, Serbia, Singapore, Slovenia, and Spain. Five of the cases reported by European countries have received liver transplants.

Experts have cautioned that some of the reported cases may turn out to have another explanation. In an update also published on Friday, the ECDC noted that one suspected case reported by Romania was struck from the list when the child was diagnosed with a genetic condition that can trigger hepatitis.

Hepatitis is rare in very young children; rarer still are cases like these, for which an obvious cause is not apparent. The condition — inflammation of the liver — can be triggered by a host of pathogens as well as by exposure to toxins, some medications, and alcohol misuse. But most cases are caused by the hepatitis viruses labeled A through E. Those have been ruled out in these cases.

Suspicion has focused on an adenovirus, type 41, which has been seen in a number of children, including five of the Alabama patients. A larger number of children in multiple countries have tested positive for adenoviruses more generically; in some cases samples are inadequate to perform tests to try to type which kind of adenovirus was present, while in others the work is still underway. But other hypotheses are also being explored, including the possibility that there is a combination of factors — for instance, that a prior infection with another virus such as SARS-CoV-2, which causes Covid-19, might have primed some children to become more ill when they were infected with adenoviruses.

In fact, the UKHSA said Friday it had revised its working hypotheses.

“The leading hypotheses remain those which involve adenovirus,” it said in a technical brief published online. “However, we continue to investigate the potential role of SARS-CoV-2 and to work on ruling out any toxicological component.”

The U.K. report’s leading hypotheses focus around infection with an adenovirus — though there are a number of explanations for why it might be causing hepatitis being explored. One thought is that some children have heightened susceptibility because they hadn’t been exposed to the viruses during the Covid pandemic; another is that there may have been an exceptionally large wave of adenovirus infections that has allowed a hitherto unrecognized rare association — hepatitis caused by adenoviruses — to be recognized.

Other theories include that prior infection with SARS-2 — or perhaps specifically the Omicron variant — primed some children to become seriously ill when infected later with adenovirus, or that co-infection with SARS-2 or another virus and adenovirus can trigger liver inflammation. Still another option under consideration is that exposure to a drug, a toxin, or something in the affected children’s environment predisposed them to have an abnormal reaction to adenovirus infection.

Butler said this event could reveal that adenovirus 41 is responsible for a portion of pediatric hepatitis cases of unknown etiology, small numbers of which occur annually.

“That’s certainly in the hypothesis list,” he said. “Is it a catch up, because now kids are being exposed once again after a period of not being exposed? I think that’s a very plausible explanation.”

Scientists are also trying to see if there have been changes in adenovirus 41 that might explain why a virus not previously known to cause hepatitis in healthy children may now be doing so. But neither the UKHSA nor the CDC has managed yet to sequence a whole virus from one of the affected children. “The viral load in these children, by the time they’re diagnosed, tends to be fairly low,” Butler said.

There is at least one thing public health officials have ruled out. They are certain this phenomenon is not linked to Covid-19 vaccines. Most of the affected children are too young to have been vaccinated. The Covid vaccines are not authorized for use in children under the age of 5, who make up 75% of the British cases.

“There are fewer than five older case-patients recorded as having had a Covid-19 vaccination prior to hepatitis onset,” the UKHSA report said. “There is no evidence of a link between Covid-19 vaccination and the acute hepatic syndrome.”

Correction: An earlier version of this story misstated the number of affected children who have required liver transplants.