About half of those cases come from just two countries: the United States and the UK. On Thursday, researchers from both countries said they were working diligently to get answers.
One of their first tasks was to find out whether these cases of sudden and often severe liver damage in children represent a real increase in recent years. The answer is that it depends on where you look.
The UK has better data on its hepatitis cases than many other countries as it only sees children with liver disease in three national hospitals.
“Care for these children is highly centralised,” Diedre Kelly, a professor of pediatric hepatology at the University of Birmingham, in the UK, said in a press call for reporters on Thursday organized by the independent non-profit Science Media Centre.
Kelly says that in an average year, they would see about 20 children who suddenly develop hepatitis with no apparent cause for their liver inflammation. This year, they’ve seen 176 such cases, a nearly 8-fold increase.
That in contrast to European countries. Kelly said she was recently part of a study of childhood hepatitis cases at liver specialty centers across Europe, and “they saw absolutely no increase in the number of acute, severe hepatitis” or in liver transplants compared to previous years.
Kelly says they’re still trying to figure out what that means. “Either Europe is behind us and has yet to catch up, or it is a phenomenon that is not happening 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 investigated 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 room visits across the state for children with hepatitis, jaundice and liver failure for about a year. month between November 21 and December 25, 2021. Alabama was the first state to signal a cluster of 9 unexplained cases of childhood hepatitis.
Investigators don’t have a smoking gun. But they have some things that they can limit looking at.
So far, they say, based on questionnaires collected from cases where they’ve been able to rule out contact with dogs as a possible contributor to the diseases, said Dr. Calum Semple, a pediatrician and professor of pediatric health and outbreak medicine at the university. from Liverpool.
Many of the children studied had dogs or reported contact with dogs recently, so that possibility was initially on the list, but after further investigation, researchers say it has been ruled out as a factor.
“We’ve looked very carefully at the control data on cases as well as those with severe disease and those without severe disease and there is no difference at all between these children in terms of dog contacts,” Semple said.
Although Covid-19 has not been completely ruled out, it seems less and less likely that it will play a role.
“I don’t think we’re completely ruling out Covid,” Semple said, “I’m saying I think Covid’s list of ‘considered possibilities’ and adenovirus and adeno-associated viruses and other similar viruses are rising on the list,” he said.
However, that’s not to say that the pandemic, with its social distancing, masks and other behavioral changes, may not have a hand in this. After nearly two years of minimal exposure to infections, our immune system may very well behave differently.
Researchers in the UK are looking at T-cell responses in affected children to see if there’s any unusual activation of these immune defenders in these otherwise mundane 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 difficult to ignore.
But researchers aren’t sure if they tested age-and-sex children who didn’t have hepatitis, they’d find just as many with adenovirus in their blood. That’s called a case-control study, and Will Irving, a professor of virology at the University of Nottingham, in the UK, said data will be forthcoming soon.
“Adenovirus is the biggest contender here, but we need more data to be convinced, at least I am,” Irving said.
Scientists are skeptical because adenovirus 41 is usually not a big player when it comes to viral infections. It doesn’t even rank in the top 10 in terms of adenoviruses that make people sick every year, Ingram said.
“It’s very difficult to know if this is the cause, which we would instinctively think it wasn’t, or if it was a trigger in the child who was predisposed for some other reason,” Kelly said.
In the Alabama cases, the sickest kids — those who eventually needed a liver transplant — had the highest levels of adenovirus in their blood, suggesting a dose response — something researchers are looking for when trying to understand either two things related related because one caused the other or by sheer coincidence.
Strangely enough, although many of the children test positive for adenovirus in their blood, samples of their destroyed liver tissue usually do not find any virus.
Researchers say they don’t know what that means, but say it’s unusual. For example, if adenovirus 5 attacks the liver, and you look at liver cells under a microscope.
“The liver cells are absolutely full of new adenovirus particles, so there’s no question that the virus itself infects and kills the hepatocytes. We don’t have that link yet,” Irving said.
So there are a number of factors to consider, Irving said. Perhaps the virus does not act alone. Or maybe it triggers a harmful immune response.
In Alabama, in 75% of cases — nine out of 12 children currently diagnosed with sudden, unexplained hepatitis — more than one virus was discovered at the time of their illness.
In addition to adenovirus 41, the children tested positive for viruses known to cause upper respiratory tract infections, including rhinovirus, enterovirus, respiratory syncytial virus (RSV), a type of coronavirus OC43, human metapneumovirus, and rotavirus, which typically causes diarrhea. None were positive for a current Covid-19 infection.
What becomes clear from the detailed study of the children in Alabama is that the children were very ill.
Almost all of them had vomited, more than half had diarrhea and fever. Almost all of them had yellow in the whites of their eyes or a yellowish orange tint to their skin, a symptom called jaundice.
It’s reassuring that, at least in the UK, there don’t seem to be any geographic or social links between the business, meaning the kids don’t know each other or live in the same areas. “It’s really sporadic,” Kelly says.
If the hepatitis is caused by an infection or infections, but it doesn’t happen in children in the same area, what does that mean?
Irving, the virologist, said he thinks this could mean many, many children and maybe adults are infected, but for most those infections don’t lead to serious liver problems.
“Which then begs the question, what’s so special about these young children?” those diagnosed with liver problems, Irving said.
For that, researchers are turning to genetics to try to unravel the mystery behind these cases, and several projects are already underway to study genetic traits of the affected children and their parents to see if they had unrecognized risk factors for their liver problems.
While the puzzle of these cases is fascinating, the researchers say they try to keep affected families at the center of their work.
“We must not forget that there are 170 families [in the UK] who are deeply saddened by this mysterious disease that is causing such problems with their children, and getting a liver transplant is a life-changing event,” Semple said.
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