What we know about unexplained inferior hepatitis cases in children

As health officials continue to investigate cases of unknown cause of liver inflammation in children, what is known is being overtaken by what is not yet known.

At least 500 cases of unexplained hepatitis have been reported in children in about 30 countries, according to health agencies in Europe and the United States. As of May 18, 180 proceedings are under consideration in 36 US states and territories.

Many of the children have recovered. However, some cases are severe and more than 20 children require a liver transplant. At least 12 children have died, including five in the United States.

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The disease is mainly found in children under the age of five. So far, health agencies have ruled out common causes of hepatitis, while reporting that some children have tested positive for adenovirus. The pathogen infects basically everyone, usually not a serious problem, but is not known to be the main cause of liver damage. For positive children, authorities have identified certain adenoviruses: type 41.

However, researchers say there are several reasons why fixing adenovirus as the only cause of hepatitis is not completely combined. It is not clear whether recent cases show an increase in hepatitis illness or are more focused. The case seems to have appeared out of nowhere, but “children had such a rare and severe liver disease,” says Anna Peters, a pediatric hepatologist at the Cincinnati Children’s Hospital Medical Center.

Above all, it’s important for parents to remember that the cases described so far are “rare phenomena,” Peters says. “Parents don’t have to panic.”

Hepatitis in children

Hepatitis is an inflammation of the liver that can interfere with many functions of organs, such as filtering blood and regulating coagulation. Three hepatitis viruses, called hepatitis A, hepatitis B, and hepatitis C, are common causes of illness in the United States. Hepatitis A spreads when infected feces reach the mouth. When transmitted from a pregnant person to an infant, the child can get B and C. A and B have vaccines, but C does not. Overdose of acetaminophen can also cause hepatitis in children.

Symptoms of hepatitis include nausea, malaise, yellowing of the skin and eyes, darker urine than usual, and light-colored stools. Rapidly occurring hepatitis usually resolves, but it progresses slowly and can cause liver damage over time.

It is rare for a child to develop sudden liver failure.Estimated 500-600 cases occur each year in the United StatesAnd about 30% of them are “uncertain”, which means that no cause can be found, according to the North American Pediatric Gastroenterology, Liver and Nutrition Society.

The uncertain category of sudden liver failure has long been known, and a subset of cases are similar to the hepatitis under investigation, says Peters. No data have yet been reported as to whether recent cases represent an increase beyond what has been seen in the last few years, Peters says. “Maybe this just raised awareness of what’s happening.”

Adenovirus as a suspect

Not all children with hepatitis are positive for adenovirus, and not all children are tested. European Disease Control and Management Center (ECDC) Of the 151 cases tested, 90 were positive, Or 60 percent. The final dispatch from the UK Health and Security Agency from early May pointed out that 126 out of 163 samples were tested and 91 or 72 percent were positive. Further analysis of 18 cases Identified adenovirus type 41..

Adenoviruses commonly infect people and usually cause colds, bronchitis, or other respiratory illnesses. Two types of adenovirus, 40 and 41, target the intestine and cause gastrointestinal symptoms such as vomiting and diarrhea.

“All of these types, including this prime suspect type 41, have been continuously detected everywhere,” says Adriana Kajon, a virologist at the Love Race Institute for Biomedical Sciences in Albuquerque. “They all exist and have been continuously reported for decades.”

People usually recover from an adenovirus infection. The exception is that the immune system is not functioning properly. In that case, the infection can be serious. Children who are immune-protected have cases of hepatitis due to adenovirus, but the child under investigation is not immune-protected.

There are some interesting details about the discovery of adenovirus. For example, children who tested positive for the virus had lower blood levels. In the case of adenovirus-induced hepatitis, “the virus levels are very high,” says Peters.

Adenovirus has also not been found in the liver. In a study of nine children with hepatitis in Alabama who were positive for adenovirus in blood samples, researchers studied liver tissue from six children.was No signs of virus in the liverResearchers report May 6th Weekly morbidity and mortality reports..

“It’s very difficult to involve a virus that can’t be found at the crime scene,” Cajon said at a clinical virology symposium on May 3 in West Palm Beach, Florida.

Another strange thing: There seems to be no way for the virus to spread from one place to another. Unlike SARS-CoV-2, the virus that causes COVID-19, it “originally spread clearly from an epicenter,” said Andrew Tai, a virologist and clinician at the University of Michigan School of Medicine who treats patients. Says. With liver disease.

The perpetrators of adenovirus are not out of the question, but “it’s always difficult to identify and prove the link between the virus and the disease,” says Catherine Spindler, a virologist at the University of Michigan School of Medicine. “It’s hard to say that this is due to adenovirus 41, not to mention adenovirus.”

Consider COVID-19

All of this is approaching that COVID-19, a much larger outbreak of infectious disease, may be involved.

Researchers have found that SARS-CoV-2 affects the liver in mild and more severe cases of COVID-19. There is evidence that the livers of children and adults become inflamed during infection. Liver failure can occur with severe attacks of COVID-19.And developing children Pediatric multisystem inflammatory syndrome, or MIS-C, after COVID-19 can become hepatitis As part of that syndrome.

Peters and her colleagues explained yet another way SARS-CoV-2 can endanger the liver. The team reported a case of a young female patient from the fall of 2020 who developed sudden liver failure approximately 3 weeks after SARS-CoV-2 infection. She didn’t have MIS-C. A Liver biopsy showed signs of autoimmune hepatitisThe type of body that attacks his liver, Peters and colleagues report in May Journal of Pediatric Gastroenterology and Nutrition Reports.. The patient recovered after treatment with anti-inflammatory drugs.

Some children with hepatitis tested positive for SARS-CoV-2, but many did not. The ECDC reported that 20 of the 173 cases tested were SARS-CoV-2 positive, while the UK Health and Security Agency detected the virus in 24 of the 132 cases tested.

However, few data have been reported on whether children have antibodies to SARS-CoV-2, which may be evidence of past infections. (Most of these infants are not vaccinated.) ECDC found that 14 of the 19 tested were positive for antibodies to the virus.

One theory is that early SARS-CoV-2 infection set the stage for an unexpected response to adenovirus or other infections. The epidemic of adenovirus and other respiratory viruses has returned to pre-epidemic levels as people no longer minimize contact.

“These forgotten pathogens may have seen, so to speak, exacerbate the disease or cause severe inflammation due to certain existing conditions,” Kahon said on May 3. There is. “

“I can’t think of anything else that has had a global impact that could explain cases of hepatitis in remote areas like the United Kingdom and Argentina,” says Cajon.

According to Peters, SARS-CoV-2 gives researchers a better understanding of how it causes illness during active infections. But when it comes to long-term implications, “everyone is still organizing things.”