As global cases rise, researchers race to solve puzzle of mysterious hepatitis cases in children - CNN

Kelly said she was recently part of a study that counted children's hepatitis cases at liver specialty centers across Europe, and "they saw absolutely no increase in the numbers of acute, severe hepatitis" or in liver transplants compared to previous years.

"Either Europe is behind us and has still got to catch up, or it's a phenomenon that's not occurring in Europe," she said.

In the United States, unexplained cases of hepatitis are not routinely reported to public health authorities, making it difficult to know whether the 180 cases under investigation here are an increase over what doctors normally see.

On a CDC call for clinicians on Thursday, Amanda Ingram, an epidemiologist with the Alabama Department of Public Health said state investigators there had seen an increase in emergency department visits across the state for children presenting with hepatitis, jaundice, and liver failure for roughly a month between November 21 and December 25, 2021.

Many of the children under study had pet dogs or reported recent contact with dogs, so that possibility was initially on the list, but after further study, researchers say it's been ruled out as a factor.

"We've looked very carefully at case control data and also those with severe disease and those without severe disease and there's no difference at all between these children regarding dog contacts," Semple said

Though Covid-19 has not been fully ruled out, it seems less and less likely to be playing a role.

"I don't think we're ruling out Covid completely," Semple said, "I'm saying I think Covid is moving down that list" of possibilities under consideration, "and adenovirus and adeno-associated viruses and other viruses like it are moving up the list," he said.

That's not to say, however, that the pandemic, with its social distancing, masks and other behavioral changes, may not have a hand in all this.

It could very well be that after nearly two years of minimal exposure to infections, our immune systems are behaving differently.

Investigators in the UK are looking at the T-cell responses in affected children to see if there's some unusual activation of these immune defenders in these otherwise run-of-the-mill infections.

About 70% of children in the UK and more than half of children in the US have tested positive for adenovirus 41F in their blood, making the association hard to ignore.

"It's sporadic really," Kelly says.

If the hepatitis is being caused by an infection, or infections, but there it's not happening to children in the same area, what does that mean?

Irving, the virologist, said he thinks that could mean that many, many children and maybe adults too are being infected, but for most, those infections aren't resulting in serious liver problems.

"Which then begs the question, what is special about these young children?" who are being diagnosed with liver problems, Irving said.

For that, researchers are turning to genetics to try to unravel the mystery behind these cases, with several projects already underway to study genetic traits of the affected children and their parents to see if they had any unrecognized risk factors for their liver problems.

While the puzzle of these cases is fascinating, the researchers say they're trying to keep the affected families at the center of their work.

"We mustn't forget that there's 170 families [in the UK] who are highly distressed about this mystery disease that is causing such problems with their kids, and to get a liver transplant is a life changing event," Semple said.