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U.K. health officials are investigating dozens of cases of unexplained hepatitis, or liver inflammation, that have recently emerged among young children there. Similar cases of pediatric hepatitis have also been reported in the U.S. and Spain.

Some of the affected children in the U.K. have required assessment at specialized centers and a "small number" of kids have undergone liver transplantation procedures, the U.K. Health Security Agency (UKHSA) announced on April 8. Although hepatitis viruses (hepatitis A, B, C, D and E) are often the cause of hepatitis, these viruses have been ruled out, the statement said. Potential complications of hepatitis include liver failure and death, and liver transplants are typically used to treat end-stage liver failure, according to Stanford Children's Health.

"That's the only definitive treatment for acute liver failure," said Dr. Rachel Tayler, a pediatric gastroenterologist at the Royal Hospital for Children in Glasgow.

Tayler and her colleagues authored a report about recent hepatitis cases among children in Scotland, which was published Thursday (April 14) in the journal Eurosurveillance. In most of these cases, the children recovered with only supportive care in the hospital, which involved maintaining their fluid levels and nutrition and monitoring for blood clots. However, in a minority of cases, children needed to be assessed for potential liver transplants, and in some cases, underwent transplant surgery, Tayler told Live Science.

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As officials continue to investigate the cause of these severe acute hepatitis cases, clinicians have been urged to look out for potential signs and symptoms of liver inflammation in pediatric patients, the UKHSA statement reads. The condition is sometimes preceded by gastrointestinal symptoms, including vomiting and abdominal pain, and affected children often develop jaundice, meaning yellowing of the skin or the whites of the eyes. "In milder cases, it can be quite difficult to see," Tayler noted.

Other potential symptoms of hepatitis include dark urine, pale feces, itchy skin, joint stiffness, muscle pain, fever, nausea, abdominal pain, lethargy and loss of appetite, according to the UKHSA statement.

"Parents should be cautioned to take seriously children who have severe vomiting or who develop jaundice and should seek medical attention immediately if these occur," Dr. Jeremiah Levine, director of the Division of Pediatric Gastroenterology at NYU Langone Health, who was not involved in the investigation, told Live Science in an email. Children should wash their hands to prevent potential exposure to viruses that can cause hepatitis, Tayler said. If any kids catch an infection, they should be kept home to prevent spread of the germ, she added.

As the investigation unfolded in the U.K., another cluster of unexplained pediatric hepatitis cases was reported in the United States.

Dr. Hannah Kirking, a medical epidemiologist for the Centers for Disease Control and Prevention (CDC), informed the Eurosurveillance report authors that the U.S. agency is investigating a cluster of hepatitis and adenovirus cases among children in the country. Specifically, nine such cases have been reported in children ages 1 to 6 in Alabama, according to STAT. These cases occurred between October 2021 and now.

Three additional hepatitis cases have been reported in Spain, in children between 22 months and 13 years old, the World Health Organization (WHO) reported Friday (April 15). Five more confirmed or possible cases have been reported in Ireland and are now under investigation, the WHO noted.

In general, severe acute liver disease in children is "relatively uncommon but occurs occasionally," Levine said. These bouts of severe liver disease tend to be caused by an infectious agent, like a virus, but that said, affected children should undergo a complete evaluation to check that they don't have an underlying metabolic disorder, Levine added.

In regard to the hepatitis cases in U.K. children, "what is unusual is the number of patients affected and the clustering of cases in the U.K.," Levine said. "The severity is unfortunately relatively typical."

In England, there are 60 cases of pediatric hepatitis under investigation, most in children ages 2 to 5, according to UKHSA. And so far, 13 cases have been identified among young children in Scotland, according to the Eurosurveillance report.

The first cases in Scotland were reported on March 31 by the Scottish NHS. Within a three-week period, five children, ages 3 to 5, had been brought to the Royal Hospital for Children in Glasgow with severe hepatitis of unknown cause. In a typical year, fewer than four unexplained hepatitis cases are reported in Scotland, the report notes.

"Very quickly, over the course of a week, I had seen four, and then five [cases]," Tayler told Live Science. "The initial cases all presented with jaundice ... what the parents picked up is that the children had just gone yellow."

After the NHS issued its alert about the cases, Public Health Scotland (PHS) launched an investigation into these first five cases, which are described in detail in the Eurosurveillance report. Clinicians tested the children's blood upon admission and found "exceptionally high" levels of alanine aminotransferase, a liver enzyme whose quantity tends to increase in the blood after liver damage.

Three out of the five children were transferred to specialized centers in England to be evaluated for liver transplant, and one child received a transplant.

After investigating these five cases, the PHS team launched a wider investigation to see if any other children had been admitted to Scottish hospitals with unusually high liver enzyme levels or jaundice of unknown cause. Through this search, they identified eight additional cases of acute hepatitis of unknown origin in children between 3 and 5 years old, bringing the total number of cases to 13. Twelve of these cases occurred in March and April, and the other case occurred in January.

All the children had been admitted to a hospital for at least six days as of April 14, and five were still hospitalized, including the one who'd undergone transplant surgery in England.

Four of the 13 children had tested positive for SARS-CoV-2, the virus that causes COVID-19, in the weeks or months before their hospitalization; and one tested positive on a rapid test for the coronavirus upon their admission, but this result was not confirmed with a PCR test. Five of 13 children tested positive for adenovirus on a PCR test of their blood, stool or throat swabs at the time of admission.

What is causing these cases?

The cause of these hepatitis cases remains unknown, but officials suspect that the culprit to be an infectious pathogen or a toxic exposure to contaminated food, drinks or toys, the Eurosurveillance report noted. An infectious agent is considered the more likely cause at this point, based on the nature of the cases and their timing, the report added. Levine told Live Science that he also thinks "an infectious etiology is more likely than a toxic exposure."

The leading hypothesis, for now, is that an adenovirus might be the underlying cause, the Eurosurveillance report authors wrote. This adenovirus might be "either a new variant with a distinct clinical syndrome or a routinely circulating variant that is more severely impacting younger children who are immunologically naïve," they noted.

"With all the social distancing, children for the last two years may not have been exposed to the common viral pathogens and that may lead them to be more susceptible to adenovirus or other similar viral infectious [agents]," Levine told Live Science.

Comment: Children weren't just suffering social distancing, many were under enforced lockdown and obligatory mask wearing for months on en, the impact of which had already begun to take its toll last summer: US infants struck by winter virus in summer after lockdowns disrupt immunity & transmission

"We have a group of children [whose] immune system has evolved in a very different way to what it would have done normally, in terms of exposure to common viruses," Tayler said, echoing Levine's sentiment.

That said, as an alternate theory, "this may be related to some new SARS-CoV-2 variant," Levine suggested. U.K. children below age 5 are not currently cleared to receive any COVID-19 vaccines, so none of the children in their report had been vaccinated against the virus, Tayler noted.

Comment: True, but children will be exposed to tripled boosted parents or teachers who might be carriers and super shedders..

Analyzing samples of liver tissue from the children, especially those who required transplants, may help reveal the underlying cause of the disease, Levine said. These sorts of analyses are being conducted in England, Tayler confirmed.