More than 100 cases of hepatitis of unknown origin among children in the USA: 5 of them died

The US Centers for Disease Control and Prevention (CDC) said it is investigating 109 cases of severe and unexplained hepatitis in children in 25 states that may be related to outbreak all over the world. Read more about this publication CNN.

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Among the infected children, 14% needed a transplant, more than 90% needed hospitalization, and five died.

Dr. Jay Butler, CDC Associate Director of Infectious Diseases, emphasized that not all of the hepatitis cases they are currently studying may end up being the result of the same problem.

Hepatitis can be caused by infections, autoimmune diseases, drugs, and toxins. A family of viruses well known for attacking the liver causes hepatitis A, hepatitis B, and hepatitis C.

It is not clear what causes these cases in young children. Butler said some of the common causes of viral hepatitis have been looked at but not found in any of the cases.

Adenovirus is detected in more than 50% of cases, although its role in the development of the disease is not clear.

Early reports of hepatitis

On April 21, the CDC alerted doctors to a group of unusual cases of hepatitis in nine children in Alabama.

Butler asked doctors and public health officials to notify the agency if they had similar cases of children under the age of 10 with elevated levels of liver enzymes and no obvious explanation for their hepatitis since October.

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Since then, health departments have been working with pediatricians to identify possible cases. The figures presented at the May 6 briefing are the first nationwide look at the cases.

The disease has been identified 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 warning follows reports that children from England, Wales, Scotland and Northern Ireland are being admitted to hospital with unexplained hepatitis.

As of May 1, there are 228 known probable cases associated with the outbreak in 20 countries, with more than 50 cases under investigation, said Dr Philippa Easterbrook, senior researcher at the World Health Organization's Global Hepatitis Program. According to her, among those infected, one child died, about 18 needed a liver transplant.

Most children were healthy when they developed symptoms, including fatigue, loss of appetite, vomiting, diarrhea, abdominal pain, dark urine, light-colored 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 has treated two children who are involved in the CDC investigation. One XNUMX-year-old from South Dakota received a liver transplant this week.

Bhatt says liver failure is "very rare" in children. And even before scientists began to track this outbreak, half of the cases had not been explained.

The doctors who treated these children say their cases were very unusual.

“Even during the first case, I thought it was weird,” says Dr. Markus Buchfelner, a pediatric infectious disease specialist at the University of Alabama at Birmingham (UAB), where staff began reporting outbreaks in October. “And then, when the second case appeared, I decided that I needed to report it somewhere.”

He reached out to senior physicians in his department, who contacted the state health department and the CDC.

What stood out about these cases, according to Buchfelner, was that the inflammation of the liver was very severe.

Sometimes common viruses, such as Epstein-Barr or even SARS-CoV-2, slightly increase a child's liver enzyme levels, indicating what Buchfelner calls "minor hepatitis," but children usually recover as their bodies fight off the infection.

“It is very strange to see a healthy child with the same liver damage as these children,” he is surprised.

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Nine children were initially seen at UAB with unexplained hepatitis, and all nine tested positive for adenovirus in their blood. Butler said none of them have tested positive for SARS-CoV-2 and have not previously had COVID-19.

After these cases were reported, two more children fell ill in Alabama. Their cases are under investigation, bringing the total number of cases in the state to 11, Dr. Wes Stubblefield said.

There are about 100 types of adenoviruses. Nearly 50 of them are known to infect humans, so experts needed to take a closer look at the virus to try to figure out if it was the same in all children.

When the researchers tried to read the adenovirus genes from infected children, only five had enough genetic material to obtain a complete sequence. In all five cases, the virus was of a specific type called adenovirus 41. It usually causes diarrhea and vomiting in children, sometimes with nasal congestion or cough, but has never before been associated with liver failure in otherwise healthy children.

Butler stated that adenoviruses 40 and 41 are associated with hepatitis, but almost exclusively in immunocompromised children.

UK cases

Researchers at the UK Health Security Agency have published an update on their hepatitis investigation. Of the 163 cases, 126 patients were tested for adenovirus and 91 (or 72%) tested positive for the pathogen.

The researchers attempted to sequence the entire adenovirus genome of 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 they were all adenovirus 41F, the same as in the US.

Many have wondered if these cases could have something to do with SARS-CoV-2, the virus that causes COVID-19.

British researchers say they are still exploring the possibility, but only 24 out of 132 patients tested (18%) were found to have SARS-CoV-2.

The report says they do not rule out some role for COVID-19 in these cases. It's possible that COVID-19 somehow activated the immune system, making these children extraordinarily susceptible, or perhaps co-infection of the two viruses together affects the liver.

Researchers want to know, among other things, whether hepatitis is part of a syndrome that affects children after being infected with SARS-CoV-2, such as a rare complication called multisystem inflammatory syndrome in children, or MIS-C.

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Another working theory from British researchers is that these children have some kind of excessive or irregular immune response, possibly because they were more protected than usual during the pandemic.

Another theory is that adenovirus may have always caused liver failure in a tiny percentage of infected children, and these rare cases are only being caught because it causes an exceptionally large wave of infections.

Researchers in the UK say they are still testing for drugs, toxins or possibly environmental exposure, though some kind of infection is most likely the cause.

Understanding the role of adenovirus 41

Another detail that puzzled the doctors, Buchfelner noted, 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 showed severe inflammation and hepatitis. But we didn't find the virus in the liver. We found the virus only in the blood,” he said.

If adenovirus 41 is somehow responsible for these cases - and it's still a big "if" - Buchfelner says he doesn't know why it's only found in blood and not in severely damaged liver tissue. True, he has some theories.

“Perhaps the liver destroys the virus before it is cleared from the blood,” he suggested. “So, by the time the liver is damaged and we do the biopsy, the immune system has already cleared the liver of the virus. And what's left is just inflammation."

His second theory is that it is not the virus itself that is responsible for the damage to the liver, but that the immune system may overreact in trying to fight the virus and eventually damage the liver.

Adenovirus infections are widespread, so it's possible that some of these patients were found to have the virus just by coincidence.

“We are not 100% sure that this is an adenovirus. There is still much to be learned,” Bhatt stressed.

Active investigation

An April 29 CDC statement said: "We believe adenovirus may be the cause of these reported cases, but other potential environmental and situational factors are still being studied."

Butler said experts are looking at a number of possibilities, including contact with animals.

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“We remain open-minded about whether the adenovirus data may reflect an innocent bystander or whether there may be cofactors that cause adenovirus infections to manifest in ways that have not been seen before,” he said.

The researchers say they know the news could worry parents.

According to Butler, researchers still believe that such cases are very rare. For example, there is no increase in the number of children admitted to emergency departments with hepatitis.

"We're still talking, at least to our families here in Alabama, and I would advise other families to do the same - don't worry too much about it just yet," Buchfelner said. “I mean, it’s still quite rare.”

According to the doctor, adenoviruses are usually distributed in kindergartens and schools. They usually don't cause anything worse than what looks like stomach flu for a few days.

“It has been around for a long time and it will continue. And in total we only have about 200 cases that have been reported worldwide. So it doesn’t look like a COVID-19 pandemic,” he concluded.

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