Alexandra Ramos
(CNN) – The US Centers for Disease Control and Prevention (CDC) said Friday that it is investigating 109 cases of severe and unexplained hepatitis in children in 25 states and territories that may be related to a global outbreak.
Among them, 14% needed transplants and five children have died.
Nearly all of the children—more than 90%—needed to be hospitalized.
Dr. Jay Butler, deputy director for infectious diseases at the CDC, stressed that the research — a partnership between the CDC and state health departments — is an evolving situation. Not all of the hepatitis cases they are studying now may ultimately be caused by the same thing.
“It’s important to note that this is an evolving situation, and we’re casting a wide net to help broaden our understanding,” Butler said.
What is hepatitis? Symptoms, treatment and risks
Hepatitis, or liver swelling, can be caused by infections, autoimmune diseases, drugs, and toxins. A family of viruses known to attack the liver causes hepatitis A, hepatitis B, and hepatitis C.
It is not clear what is driving these cases in young children. Butler said that some of the common causes of viral hepatitis have been considered, but were not found in any of the cases.
Adenovirus has been detected in more than 50% of cases, although its role is unclear.
Outbreak of childhood hepatitis, what are the risks? 1:59
Early hepatitis reports
On April 21, the CDC alerted doctors to a cluster of unusual cases of hepatitis in nine Alabama children.
Since October, the CDC has asked doctors and public health officials to notify the agency if they have similar cases of children under 10 with elevated liver enzymes and no apparent explanation for their hepatitis.
Since then, health departments have been working with pediatric specialists in their states to identify possible cases. The numbers shared at Friday’s press conference are the first national look at the cases.
CDC Releases Details on Hepatitis Cases of Unknown Cause in Children: Some Have Vomiting, Diarrhea, Respiratory Symptoms and Enlarged Liver
The cases are under investigation in Alabama, Arizona, California, Colorado, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Louisiana, Michigan, Minnesota, Missouri, North Carolina, North Dakota, Nebraska, New York, Ohio, Pennsylvania. , Puerto Rico, Tennessee, Texas, Washington and Wisconsin.
The CDC alert came following reports of children from England, Wales, Scotland and Northern Ireland going to hospitals with unexplained hepatitis.
As of May 1, there are 228 probable cases linked to the outbreak in 20 countries, with more than 50 cases under investigation, Dr. Philippa Easterbrook, a senior scientist with the World Organization’s Global Hepatitis Program, said at a briefing on Wednesday. Of the health. Among these cases, one child died and regarding 18 needed liver transplants, she said.
Most of the children were healthy when they developed symptoms that included fatigue, loss of appetite, vomiting, diarrhea, stomach pain, dark urine, light-colored stools, and yellowing of the skin and eyes, a sign called jaundice.
Unusually severe liver inflammation
Pediatric gastroenterologist Dr. Heli Bhatt of the M Health Fairview Masonic Children’s Center in Minneapolis has treated two children who are part of the CDC investigation. One, a 2-year-old boy from South Dakota, received a liver transplant this week.
Bhatt says liver failure in children is “super rare.” And even before scientists started tracking this outbreak, half of the cases were never explained.
Doctors who have treated these children say their cases stood out.
“Even during the first case, I thought it was weird,” says Dr. Markus Buchfellner, a pediatric infectious disease specialist at the University of Alabama (UAB) in Birmingham, where staff began seeing cases in October.
“And then when the second came, that’s when I was like, ‘Okay, we need to talk to someone regarding this.'” He reached out to senior doctors in his department, who contacted the state health department and the CDC.
Buchfellner says the cases stood out because the liver inflammation was so severe.
Sometimes common viruses like Epstein-Barr or even SARS-CoV-2 raise a child’s liver enzymes a bit, indicating what Buchfellner calls “small bits of hepatitis,” but children usually recover as their bodies fight infection.
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“But it is very rare to see a healthy child come in with the amount of liver damage that these children had,” he said.
Initially, UAB saw nine children with unexplained hepatitis, and all nine tested positive for adenovirus in their blood. None of them tested positive for COVID-19 during their hospitalization or had a documented history of COVID-19, Butler said at the news conference.
Since those cases were reported, two more children have been identified in Alabama. Their cases are under investigation, bringing the state’s total to 11, said Dr. Wes Stubblefield, medical officer for the North and Northeast districts of Alabama.
There are regarding 100 types of adenoviruses. About 50 of them are known to infect humans, so experts needed to take a closer look at the virus to try to find out if all children had the same one.
When the researchers attempted to read the adenovirus genes in infected children, only five had enough genetic material to obtain a complete sequence. In all five, the virus was a particular type called adenovirus 41. It usually causes diarrhea and vomiting in children, sometimes with congestion or cough, but has never before been associated with liver failure in otherwise healthy children.
Butler said Friday that adenoviruses 40 and 41 have been linked to hepatitis, but almost exclusively in immunocompromised children.
Hepatitis regrowth in children raises alert 0:34
UK tracks
Also on Friday, researchers from the UK’s Health Security Agency published a new white paper with an update on their hepatitis research. Of 163 cases, 126 patients have been tested for adenovirus and 91, or 72%, tested positive for that pathogen.
The researchers attempted to sequence the entire genome of an adenovirus from one of the patients, but were unable to obtain a sample with enough virus to do so. There were 18 cases where they were able to partially sequence the genome, and all of them have been adenovirus 41F, the same one that was found in the US cases.
Many have wondered if the cases may be related in some way to SARS-CoV-2, the virus that causes covid-19.
The UK researchers say they are still considering that possibility, but only 24 of the 132 patients examined — 18% — had SARS-CoV-2 detected.
The report says that they do not rule out any role of a covid-19 infection in these cases. Perhaps a previous Covid-19 infection somehow primed the immune system to make these children unusually susceptible, or perhaps a co-infection of the two viruses together overwhelms the liver.
The researchers also want to know if hepatitis is part of some kind of syndrome that affects children following SARS-CoV-2 infection, such as the rare complication called multisystem inflammatory syndrome in children, or MIS-C.
Another working theory of the UK researchers is that there is some kind of outsized or irregular immune response in these children, perhaps because they were protected more than usual during the pandemic.
Yet another theory is that the adenovirus may always have caused liver failure in a small percentage of infected children, and these rare cases come to light only because it is causing an unusually large wave of infections.
And researchers in the UK say they are still testing for drugs, toxins or perhaps an environmental exposure, though some kind of infection is likely to be the cause.
Classifying the role of adenovirus 41
Another thing that puzzles doctors, Buchfellner says, is that they found adenoviruses in blood samples but not in liver tissue samples taken during biopsies from patients in Alabama.
“All nine had liver biopsies that showed a lot of inflammation and hepatitis. But we didn’t find the virus in the liver. We only found the virus in the blood,” she said.
The case of Bhatt, a girl from South Dakota, also tested positive for adenovirus in her blood but not in her liver.
If adenovirus 41 is somehow responsible in these cases — and that’s still just a possibility — Buchfellner says he doesn’t know why it would only show up in blood but not in severely damaged liver tissue. But he has some theories.
“Perhaps the liver is clearing the virus before it is cleared in the blood,” he said. “So, by the time the damage has been done to the liver and we do the biopsy, the immune system will have already cleared the virus from the liver. And what’s left is just inflammation.”
His second theory is that it is not the virus itself that is responsible for the liver damage, but perhaps the immune system overreacts when trying to fight the virus and ends up damaging the liver.
Adenovirus infections are common, so perhaps finding the virus in some of these patients is just a coincidence. “We are not 100% sure that it is just that adenovirus. There is still a lot to know,” said Bhatt.
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active research
In an April 29 statement on the cases, the CDC wrote: “We believe that adenovirus may be the cause of these reported cases, but other possible environmental and situational factors are still being investigated.”
Butler said Friday that experts are considering a variety of possibilities, including animal exposure.
“We’re really casting a wide net and keeping an open mind in terms of whether the adenovirus data may reflect an innocent bystander or whether there may be cofactors that cause adenovirus infections to manifest in a way that hasn’t been commonly seen before.” , said.
The researchers say they know this news may worry parents.
Butler says that researchers still believe these cases are very rare. They haven’t seen an increase, for example, in children coming to emergency rooms with hepatitis.
“We’re still telling at least our families here in Alabama — and I encourage other families in the same way — not to worry too much regarding this yet,” Buchfellner said. “I mean, at the end of the day, this is still a pretty rare phenomenon.”
Buchfellner says that adenoviruses are commonly spread in day care centers and schools. They usually don’t cause anything worse than something that feels like viral gastroenteritis for a few days.
“It has been around for a long time and will continue to exist. And in total, we only have regarding 200 cases that have been reported worldwide. So this is not a covid pandemic-like situation where everyone needs to be really worried regarding this,” he said.
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