Possible cause of mystery hepatitis in children identified in new study, but more research needed

A new small Israeli study describes a potential link between liver damage in children and long COVID. But it also highlights how little we still know about the mysterious childhood hepatitis outbreak.

The study’s lead author and experts agree that it’s too early to tell whether prior COVID-19 infection is behind the recent rise in childhood hepatitis cases with no known cause.

Mysterious hepatitis case: what we know so far

Since April 2022, health officials around the world have been monitoring a mysterious outbreak of acute hepatitis in children. There are at least 290 cases under investigation in the United States, according to the most recent data from the Centers for Disease Control and Prevention. Worldwide, at least 700 cases are being investigated in 34 countries, according to the World Health Organization.

What makes these cases of pediatric hepatitis so mysterious is that there is no known cause. Hepatitis, or inflammation of the liver, is often caused by viral infections, and the most common causes are hepatitis A, B, C, D, and E viruses. However, none of them are behind the recent outbreak of hepatitis in children around the world, which has left scientists baffled.

While cases of unexplained pediatric hepatitis appear every year, the number of cases detected since the fall of 2021 worries health officials and parents. The CDC recently released an analysis that found between October 2021 and March 2022 that there was no increase in hepatitis or adenovirus from pre-pandemic levels. But that was limited to US data, and The WHO has already said that other countries have experienced higher than usual rates of pediatric hepatitis of unknown cause.

Of the 700 cases of pediatric hepatitis reported worldwide, at least 38 children required liver transplantation and 10 died, according to the most recent WHO data.

Researchers have studied possible links between the current hepatitis epidemic and SARS-CoV-2, the virus that causes COVID-19, as well as adenovirus, a very common group of viruses that cause cold symptoms. and flu. Adenovirus has been identified in a number of these pediatric hepatitis cases, but it does not usually cause hepatitis in healthy children, according to the CDC.

Israeli researchers have published the results of a small study, which suggest that prior infection with COVID-19 and its impact on the immune system may play a role in the outbreak. The study, titled “Long COVID-19 Liver Manifestation in Children,” was published last week in the Journal of Pediatric Gastroenterology and Nutrition.

What did this new study find?

The study describes five children in Israel who recovered from COVID-19 and later presented with liver injury. This was a retrospective case series, meaning it looked at existing patient data.

“Basically, this is an observation we’ve made over the past two years, describing a type of liver injury that’s likely caused by a post-COVID phenomenon,” said gastroenterologist Dr. Orith Waisbourd-Zinman. pediatrician at Schneider Children’s Medical Center of Israel and the study’s principal investigator, said TODAY. Post-COVID liver damage has been well documented in adults, the scientists note in the study, but data on children is sparse.

The five patients, ages 3 months to 13 years, presented with liver damage after recovering from a mild or asymptomatic case of COVID-19. Two patients, both infants, had liver failure. They all had elevated liver enzymes, suggesting inflammation or damage, and the most common symptoms were jaundice, abdominal pain, nausea and weakness.

All of the subjects were previously healthy and tested negative for the usual culprits of liver damage during extensive blood workups, Waisbourd-Zinman said, prompting researchers to test for antibodies against SARS-CoV-2 and look into the long COVID.

The study describes a type of liver injury that was “not caused by the virus itself, but rather by the immune response after the virus is gone…which is similar to other long COVID phenomena,” Waisbourd said. -Zinman. These include prolonged fatigue, brain fog, gastrointestinal symptoms and more.

Scientists have postulated that after recovering from COVID-19, the immune system may be primed to react differently to infection, leading to liver damage.

Although the adenovirus was a leading theory, Waisbourd-Zinman said it was a “weak link”. Only one of the patients in this study tested positive for adenovirus. “But when we stained the liver for the presence of adenovirus, it was negative,” she added. Adenovirus was also not found in the livers of other patients in the study.

Multisystem inflammatory syndrome in children (MIS-C), a condition in which organs and other parts of the body become inflamed, has also been reported in children who have previously been infected with COVID and can cause liver damage. But the patients in the study did not meet the diagnostic criteria for MIS-C.

Three of the patients in the study recovered from hepatitis with treatment involving steroids, except for the two young children with liver failure, who required a transplant. Waisbourd-Zinman said none of the patients had been vaccinated against COVID-19.

The scientists concluded that the likely causes of acute hepatitis were “either a post-infectious immune reaction similar to MIS-C” or the immune system becoming dysregulated after infection with COVID-19, “priming the immune system against d ‘other infectious agents such as adenovirus’. .”

Long-COVID may or may not be the answer

Overall, the jury is still out on whether long COVID can trigger an immune response that leads to severe acute hepatitis in children.

Not all experts are convinced by the study, which had a number of limitations. First, the sample size was very small and the study was observational. He hasn’t studied the mechanisms of liver damage at the molecular level, so it may be too early to rule out other factors. Additionally, the cases occurred between December 2020 and September 2021, before the current outbreak.

“Any viral infection can cause your immune system to have a strange or aberrant reaction. … This is not unique to COVID-19,” said Dr. Rima Fawaz, a pediatric gastroenterologist at Yale Medicine, who did not participated in the study. says TODAY.

The liver is a very resilient organ, so when it comes to liver damage, especially in healthy children, “there is often a predisposing factor,” said Dr. Michael Wilsey, vice president of the division of gastroenterology at Johns Hopkins All Children’s Hospital in Florida. who was not involved in the study, TODAY said. Is this factor a previous COVID-19 infection, an adenovirus, a genetic component or a combination of these? We just don’t know.

Of note, one of the patients in the study was diagnosed with hemophagocytic lymphohistiocytosis (HLH), a systemic inflammatory syndrome, which Fawaz says can cause you to have a dysregulated immune reaction and cause a prolonged inflammatory response. , even fatal.

Although the common denominator for these patients is a pre-COVID infection, there could be another common cause that researchers are not yet able to identify with existing tests.

“These may be patients at risk for reasons we don’t fully understand of developing post-COVID liver injury,” Wilsey said. “We test everything we know how to test.”

Experts and study authors agree that more data and research is needed to fully understand these mysterious cases of pediatric hepatitis and the potential link to long COVID.

The bottom line: don’t panic

Another thing the experts have agreed on is that there is no need to panic. Acute hepatitis is still relatively rare. “I would like to reassure parents that they shouldn’t be stressed out,” Waisbourd-Zinman said.

If your child has had COVID-19, it does not mean they will develop hepatitis. Parents don’t need to proactively check for liver problems or ask the doctor for liver tests after their child recovers, Waisbourd-Zinman said.

But it is important to know how to recognize the symptoms of hepatitis. These include jaundice or yellowing of the skin and eyes, abdominal pain, dark-colored urine, light-colored stools, nausea, joint pain, fever, and fatigue.

Although this study may leave us with more questions than answers, it is certainly a step in the right direction. “Basically, that’s what we were hoping for: to gather more information so that we can further investigate the mechanisms and understand this disease,” Waisbourd-Zinman said.


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