A possible cause of mysterious hepatitis in children identified in a new study, but more research is needed

A small, new Israeli study describes a potential link between liver injury in children and chronic COVID. But it also underscores how little we still know about the mysterious hepatitis that continues in children.

The study’s lead author and experts say it is too early to say whether COVID-19 is the leading cause of the recent increase in hepatitis in children.

Mysterious cases of hepatitis: We already know

Since April 2022, health workers around the world have been monitoring the mysterious spread of acute hepatitis among children. At least 290 cases are being investigated in the United States, according to the latest Centers for Disease Control and Prevention. According to the World Health Organization, at least 700 cases are being investigated in 34 countries around the world.

There is no known reason why these cases of hepatitis in children are so mysterious. Hepatitis or inflammation of the liver is usually caused by a viral infection and the most common causes are hepatitis A, B, C, D and E. However, none of this is behind the recent spread of hepatitis among children around the world. surprised scientists.

Despite the fact that cases of unexplained childhood hepatitis occur every year, the number of cases detected since the fall of 2021 worries health workers and parents. The CDC recently published an analysis that found no increase in the incidence of hepatitis or adenovirus relative to pre-pandemic levels from October 2021 to March 2022. However, this was limited to data from the United States and Earlier, the WHO said In other countries, higher rates of hepatitis in children for unknown reasons have been reported.

Of the 700 reported cases of hepatitis worldwide, at least 38 have had liver transplants and 10 have died. According to the latest data from the WTO.

The researchers looked at possible links between the current hepatitis epidemic and the SARS-CoV-2, COVID-19 virus, as well as adenoviruses, a group of viruses that cause symptoms such as the flu and the common cold. Adenovirus has been identified in a number of cases of this pediatric hepatitis, but according to the CDC, it does not cause hepatitis in healthy children.

Researchers in Israel have published the results of a small study that previously linked infection with COVID-19 and its effects on the immune system could play a role in an epidemic. The study, titled “Long COVID-19 Liver Appearance in Children,” was published last week in the Journal of Pediatric Gastroenterology and Nutrition.

What did this new study reveal?

The study described five children in Israel who were cured of COVID-19 and later suffered liver damage. It was a series of retrospective studies, so it reviewed current patient data.

“Basically, this is due to our observations over the last year or two, which describe the type of liver injury and may be due to the post-COVID phenomenon,” the doctor said. Orit Weisburd-Zinman, a pediatric gastroenterologist and chief researcher at Israel’s Schneider Children’s Medical Center, said today. The study found that liver injury after COVID was well documented in adults, but data in children were rare.

All five patients, aged 3 months to 13 years, presented with liver injury after recovering from mild or asymptomatic COVID-19. Both patients and infants had liver failure. In all of them, liver enzymes were elevated, indicating inflammation or damage, and the most common symptoms were jaundice, abdominal pain, dizziness, and weakness.

Weisburd-Zinman said all subjects were previously healthy and tested negatively for normal culprits for liver damage, Weisburd-Zinman said, which prompted researchers to test for antibodies to SARS-CoV-2 and to study long-term COVID.

The study describes a type of liver injury that is “not from the virus itself, but from the immune response after the virus is gone … similar to other long-term COVID phenomena,” Weisburd-Zinman said. These include chronic fatigue, dizziness, symptoms of gastrointestinal disorders, and more.

Researchers have suggested that after recovering from COVID-19, the immune system may react differently to the infection, leading to liver damage.

Although adenovirus is a leading theory, Weisburd-Zinman said it is a “weak link.” Only one of the patients in this study tested positive for adenovirus. “But when we stained the liver with adenovirus, it was negative,” he added. The adenovirus was not found in the livers of other patients in the study.

Multi-systemic inflammatory syndrome (MIS-C), inflammation of organs and other parts of the body in children, as well as children with a previous COVID infection, have also been reported and liver damage may occur. However, the patients in the study did not meet the MIS-C diagnostic criteria.

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

The researchers concluded that the possible causes of acute hepatitis were “post-MIS-C-like immune response” or “failure of the immune system to regulate after COVID-19 infection,” “preparing the immune system for other infectious agents, such as adenovirus.” . “

Prolonged COVID may or may not be a response

In general, the panel of judges is considering whether long-term COVID can trigger an immune response that leads to acute hepatitis in children.

Not all experts are convinced of the study, which has a number of limitations. First, the sample size was very small and the study was observational. He has not studied the mechanisms of liver damage at the molecular level, so it may be too early to rule out other factors. There were also cases from December 2020 to September 2021, before the current epidemic.

“Any viral infection can cause your immune system to have a surprising or aberrant reaction … It’s not just about COVID-19,” he said. Rima Fawaz, a pediatric gastroenterologist at Yale Medicine, who did not participate in the study, said today.

The liver is a very flexible organ, so when it comes to liver damage, especially in healthy children, “there is often an inflammatory factor,” says the doctor. Michael Wilsie, deputy director of gastroenterology at Johns Hopkins Children’s Hospital in Florida, who did not participate in the study, said today. Is this a pre-COVID-19 infection factor, an adenovirus, a genetic component, or a combination of these? We just don’t know.

One of the patients in the study was diagnosed with hemophagocytic lymphohystiocytosis (HLH), a systemic inflammatory syndrome that, according to Fawaz, can trigger an unregulated immune response that can lead to a prolonged, even fatal, inflammatory reaction.

Although the common denominator among these patients is COVID infection, there may be another common cause that researchers are unable to identify using current tests.

“These patients may be at risk due to a lack of understanding of post-COVID liver injury,” Wilsey said. “We’ll check everything we can 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 between long-term COVID.

Corollary: Don’t panic

According to experts, there is no need to panic. Acute hepatitis is still relatively rare. “I would reassure parents that there should be no stress,” Weisburd-Zinman said.

If your child has COVID-19, it does not mean that they have hepatitis. Weissburd-Zinman said parents should actively look for liver problems or ask a doctor for a liver test once their child is healed.

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

This study may leave us with more questions than answers, but it is certainly a step in the right direction. “Basically, this is what we expect: to further study the mechanisms and gather more information to understand this disease,” Weisburd-Zinman said.

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