The U.S. Centers for Disease Control and Prevention said Friday it is investigating 109 cases of severe and unexplained hepatitis in children in 25 states and territories that may be linked to an outbreak worldwide.
Among them, 14 percent needed transplants, and five children died.
Almost all children – more than 90 percent – had to be hospitalized.
Dr Jay Butler, CDC’s deputy director of infectious diseases, emphasized that the investigation – a partnership between the CDC and public health departments – was an evolving situation. Not all cases of hepatitis that are being studied now can ultimately be caused by the same thing.
“It’s important to note that this is an evolving situation, and we’re throwing a wide net to help broaden our understanding,” Butler said.
Hepatitis or swelling of the liver can be caused by infections, autoimmune diseases, drugs and toxins. A family of viruses well known to attack the liver, causing hepatitis A, hepatitis B and hepatitis C.
It is not clear what drives these cases in young children. Butler said some of the common causes of viral hepatitis have been examined but not found in any of the cases.
Adenovirus is found in more than 50% of cases, although its role is unclear.
EARLY REPORTS ON HEPATITIS
On April 21, the CDC warned doctors about a group of unusual cases of hepatitis in nine children in Alabama.
He asked doctors and public health officials to notify the agency if they had had similar cases in children under the age of 10 with elevated liver enzymes and no apparent explanation for their October hepatitis.
Since then, health services have been working with pediatricians in their countries to identify possible cases. The figures shared at Friday’s news briefing are the first national look at the cases.
Cases are being investigated in Alabama, Arizona, California, Colorado, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Louisiana, Michigan, Minnesota, Missouri, North Carolina, North Dakota, Nebraska, New York, and Ohio. Tennessee, Texas, Washington and Wisconsin.
The CDC signal followed reports of children from England, Wales, Scotland and Northern Ireland going to hospitals with unexplained hepatitis.
As of May 1, there are 228 possible cases related to the outbreak in 20 countries, and more than 50 cases have been investigated, said at a briefing on Wednesday Dr. Philippa Easterbrook, a senior scientist in the World Health Organization’s Global Hepatitis Program. Among those cases, one child died and about 18 needed a liver transplant, she said.
Most children were healthy when they developed symptoms that included fatigue, loss of appetite, vomiting, diarrhea, abdominal pain, dark urine, light stools, and yellowing of the skin and eyes – a sign called jaundice.
Unusually severe inflammation of the liver
Pediatric gastroenterologist Dr. Heli Bhatt of the M Health Fairview Masonic Children’s Center in Minneapolis is treating two children who are part of the CDC investigation. One, a 2-year-old South Dakota child, had a liver transplant this week.
Bhat says liver failure in children is “super rare.” And even before scientists began tracking the outbreak, half of the cases were never explained.
Doctors who have treated these children say their cases stand out.
“Even during the first case, I thought it was weird,” said Dr. Marcus Buchfelner, a pediatric infectious disease specialist at the University of Alabama at Birmingham, where staff began seeing cases in October.
“And then when the second one came in, I said, ‘Okay, we need to talk to someone about this.’ He turned to senior doctors in his department, who contacted the state health department and the CDC.
Buchfelner says the cases stand out because the inflammation of the liver is so severe.
Sometimes common viruses like Epstein-Barr or even SARS-CoV-2 will slightly increase a child’s liver enzymes, which shows what Buchfellner calls “small parts of hepatitis,” but children usually recover as their bodies fight infection. .
“But it’s very strange to see a healthy child come with the amount of liver damage these children have,” he said.
UAB initially 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 told a briefing.
After these cases were reported, two more children were identified in Alabama. Their cases are under investigation, with a total of 11 in the state, said Dr. Wes Stubblefield, a medical officer for the northern and northeastern counties of Alabama.
There are about 100 types of adenoviruses. About 50 of them are known to infect humans, so experts needed a closer look at the virus to see if all the children had the same.
When the researchers tried to read the adenovirus genes in infected children, only five had enough genetic material to get a complete sequence. In all five, the virus is a special type called adenovirus 41. It usually causes diarrhea and vomiting in children, sometimes with obstruction or cough, but has never been associated with liver failure in otherwise healthy children.
Butler said Friday that adenoviruses 40 and 41 are linked to hepatitis, but almost exclusively in children with weakened immune systems.
EVIDENCE FROM THE UK
Also Friday, researchers from the UK Health Security Agency published a new technical briefing updating the hepatitis investigation. Of the 163 cases, 126 patients were tested for adenovirus and 91, or 72 percent, were positive for this pathogen.
The researchers tried to sequence the entire adenovirus genome from one of the patients, but were unable to obtain a sample with enough of the virus to do so. There were 18 cases in which they were able to partially sequence the genome, and all of them were adenovirus 41F, the same found in the United States.
Many wondered if the cases could be related in any way to SARS-CoV-2, the virus that causes COVID-19.
Researchers in the United Kingdom say they are still considering the possibility, but only 24 of the 132 patients tested – 18 per cent – had SARS-CoV-2 detected.
The report says they do not rule out any role in COVID-19 infection in these cases. Maybe a previous COVID-19 infection has somehow prepared the immune system to make these children unusually susceptible, or maybe a co-infection of the two viruses together is taking over the liver.
Researchers also want to know if hepatitis is part of some kind of syndrome that strikes children after infection with SARS-CoV-2, such as the rare complication called multisystemic inflammatory syndrome in children or MIS-C.
Another working theory of UK researchers is that there is some kind of oversized or irregular immune response in these children, perhaps because they were sheltered more than usual during the pandemic.
Another theory is that the adenovirus has always caused liver failure in a small percentage of infected children, and these rare cases come to light only because it causes an extremely large wave of infections.
And UK investigators say they are still being tested for drugs, toxins or perhaps exposure to the environment, although an infection is more likely to be the cause.
DISTRIBUTION OF THE ROLE OF ADENOVIRUS 41
Another thing that puzzled doctors, Buchfelner said, was that they found adenovirus in blood samples, but not in liver tissue samples taken during biopsies of patients in Alabama.
“All nine of them have liver biopsies that show a lot of inflammation and hepatitis. But we didn’t find the virus in the liver. We only found the virus in the blood,” he said.
The case of Bhat, a South Dakota child, was also positive for adenovirus in her blood, but not in her liver.
If adenovirus 41 is somehow responsible in these cases – and that’s still a big deal if – Buchfelner says he doesn’t know why it would only appear in the blood but not in severely damaged liver tissue. But he has some theories.
“Maybe the liver clears the virus before it clears the blood,” he said. “So, while the damage has been done to the liver and we’re doing a biopsy, the immune system has 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 damaging the liver, but perhaps the immune system overreacts when trying to fight the virus and ultimately damages the liver.
Adenovirus infections are common, so perhaps the detection of the virus in some of these patients is a coincidence. “We are not 100 percent sure that this is exactly the adenovirus. There is still a lot to know,” Bhatt said.
ACTIVE INVESTIGATION
In a statement on April 29 on the cases, the CDC wrote, “We believe that adenovirus may be the cause of these reported cases, but other potential environmental factors and the situation are still being investigated.”
Butler said Friday that experts are considering a number of options, including exposing animals.
“We are indeed launching a wide network and maintaining an open opinion as to whether adenovirus data may reflect an innocent bystander or whether there may be cofactors that cause adenovirus infections to manifest in a way that has not been common before.” he said.
Investigators say they know the news may worry parents.
Butler says investigators still believe these cases are very rare. They have not seen an increase, for example, in children coming to the emergency department with hepatitis.
“We are still telling at least our families here in Alabama – and I would encourage others …
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