Global childhood hepatitis on the rise, researchers rush to unravel the mysteries of these mysterious cases

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About half of these cases are from two countries, the United States and the United Kingdom. On Thursday, investigators in both countries said they were working to find answers.

One of their first tasks was to try to determine whether the sudden and often severe cases of liver injury in these children represented a real increase in recent years. The answer is that it depends on where you look.

The UK has better hepatitis case data than many other countries because it only admits children with liver disease in three national hospitals.

“Caring for these children is highly centralized,” Diedre Kelly, professor of pediatric hepatology at the University of Birmingham, UK, said on a conference call with reporters on Thursday hosted by the independent nonprofit Science Media Centre.

They see, on average, about 20 children each year who suddenly develop hepatitis with no apparent cause for liver inflammation, Kelly said. This year, they saw 176 such cases, almost eight times as many.

This is in stark contrast to European countries. Kelly said she was recently involved in a study that counted childhood hepatitis cases in European specialist liver centers, “and they found absolutely no increase in the number of cases compared to previous years. “Acute and severe hepatitis” or liver transplantation.

Kelly said they are still trying to figure out what that means. “Either Europe is behind us but still has to catch up, or that’s not happening in Europe,” she said.

In the U.S., unexplained hepatitis cases are not typically reported to public health authorities, so it’s unclear whether the 180 cases under investigation here are an increase from what doctors normally see.

When the CDC called clinicians on Thursday, Amanda Ingram, an epidemiologist with the Alabama Department of Public Health, said state investigators found that hepatitis , jaundice, and liver failure in children with ER visits increased by about 1 year. The month between November 21st and December 25th, 2021. Alabama was the first state to report nine cases of unexplained childhood hepatitis.

Investigators have no irrefutable evidence. But they were able to limit some of the things they were thinking about.

So far, they say, based on questionnaires collected from cases, they have been able to rule out contact with dogs as a potential contributor to these diseases, said Dr. Calum Semple, a pediatrician and professor of child health. the University. Liverpool.

Many of the children in the study had pet dogs or reported recent contact with dogs, so this possibility was initially listed, but after further research, the researchers said it was ruled out. postman.

“We looked very carefully at the case-control data and those with and without severe disease, and these children did not differ in their exposure to dogs,” Simple said.

Although Covid-19 has not been completely ruled out, it seems increasingly unlikely that it will play a role.

“I don’t think we’ve completely ruled out Covid-19,” Semple said. “I mean, I think Covid-19 is on the list of ‘possibilities under consideration’ and adenoviruses and adeno-associated viruses and other viruses like that are moving the list. on the list,” he said.

That’s not to say, however, that the pandemic and its social distancing, masks and other behavioral changes may not play a role in all of this. In all likelihood, our immune system behaves differently after barely two years from being infected.

Researchers in the UK are studying T-cell responses in affected children to see if these immune defences are abnormally activated in these otherwise common infections.

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

But the researchers weren’t sure if they tested children of the same age and sex who didn’t have hepatitis, they would find the same amount of adenovirus in their blood. This is known as a case-control study, and Will Owen, a professor of virology at the University of Nottingham, UK, said data could be available soon.

“Adenovirus is the main contender here, but we need more data to convince, at least I am,” Owen said.

Scientists are skeptical because adenovirus 41 is not usually a major player in viral infection. It’s not even in the top 10 adenoviruses that make people sick each year, Ingram said.

“It’s hard to know if that’s why we instinctively think this isn’t the case, or if it’s a trigger for kids who are susceptible for other reasons,” Kelly said.

In Alabama’s cases, the sickest children — those who eventually needed a liver transplant — had the highest levels of adenovirus in their blood, suggesting a dose response — and researchers were trying to figure out two related things Research whether it is related because one leads to the other or is purely coincidental.

Curiously, however, while many children tested positive for adenovirus in their blood, samples of their damaged liver tissue often showed no virus.

The researchers said they didn’t know what that meant, but said it was unusual. For example, when adenovirus 5 attacks the liver, you look at the liver cells under a microscope.

“Liver cells are absolutely full of new adenovirus particles. So there’s no question that the virus itself infects liver cells and kills them. We don’t have that link yet,” Owen said.

So there are several factors to consider, Owen said. Maybe the virus won’t act alone. Or it could trigger a devastating immune response.

In Alabama, more than one virus was detected at the time of illness in 75 percent of cases (9 of 12 children currently identified as having unexplained flare-up hepatitis).

In addition to adenovirus 41, these children tested positive for viruses known to cause upper respiratory tract infections, including rhinovirus, enterovirus, respiratory syncytial virus (RSV), OC43-like coronavirus, human metapneumovirus, and usually Rotavirus that causes diarrhea. None of the current Covid-19 infections have been positive.

A detailed study of children in Alabama clearly shows that these children are very sick.

Almost all vomited, and more than half suffered from diarrhea and fever. Almost all people have yellow whites of the eyes or yellow-orange skin, a condition called jaundice. –

Reassuringly, at least in the UK, the cases do not appear to have any geographic or social connection, meaning the children do not know each other or live in the same area. “It’s really sporadic,” Kelly said.

What does it mean if hepatitis is caused by one or more infections, but it doesn’t affect children in the same area?

Virologist Owen said he thinks this could mean that many children and even adults are infected, but in most cases, these infections do not cause serious liver problems.

“That begs the question, what’s so special about these young kids? They’ve been diagnosed with liver problems,” Owen said.

To that end, researchers are turning to genetics to try to unravel the mystery behind these cases, and several projects are already underway to study the genetic profiles of affected children and their parents to see if they have any unidentified livers Problem risk factors.

While the mysteries of these cases are fascinating, the researchers say they’re trying to put the affected families at the center of their work.

“We cannot forget that there are 170 families [in the UK] They are very distressed by this mysterious disease that causes these kinds of problems in their children, and receiving a liver transplant is a life-changing event,” Semple said.



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