Mysterious child hepatitis continues to plague researchers

For months after a British doctor warned about a mysterious case of hepatitis that seemed to have hit an infant, researchers struggled to find the cause — and a possible link to the coronavirus pandemic. Is one of the main hypotheses.

However, on June 17, researchers at the US Centers for Disease Control and Prevention (CDC) provided data suggesting that the incidence of unexplained hepatitis or liver inflammation has not changed among children since 2017. Announced. 11 years old or younger¹.. If true, the findings could confuse the pandemic link theory.

However, not everyone is convinced by the data, and it is unclear if the same findings will emerge from other countries. “I’ve been working as a liver doctor in this country for 30 years, so there were a huge number of cases in 2022,” said Deirdre Kelly, a pediatric hepatologist at the University of Birmingham, UK. “And I think the confirmation of the UK case is very good.”

Despite the US results, the CDC continues to investigate possible connections to the pandemic. According to an analysis released on June 24, 26% of 123 children with unexplained hepatitis in the United States had a positive history of COVID-19 testing prior to liver disease.².. The CDC is currently working to collect the samples needed to test antibodies against SARS-CoV-2 and to see if other hepatitis children were previously undetected to be infected. Says David Sugerman, Head of Medical Care for the Viral Diseases Division. At the CDC’s National Center for Immune and Respiratory Diseases. “We are still very much interested in SARS-CoV-2,” he says.

Known and unknown causes

Hepatitis in children has many known causes, including infection with viruses such as hepatitis A and exposure to certain drugs such as paracetamol. However, every year, several cases of unexplained childhood hepatitis occur.

In early April, the UK Health and Safety Agency (UKHSA) informed the public that the number of infants suffering from severe liver inflammation was clearly increasing. At that time, the agency reported 60 possible cases in children under the age of 10 in 2022. Doctors usually see about 20 such cases a year in the UK, says Kelly.

Since the beginning of this year, more than 250 UK children have had hepatitis — and by May 26, a total of about 650 cases in 33 countries had been reported to the World Health Organization. Twelve of the British children needed a liver transplant. No one is dead. In the United States, 11 out of 296 children believed to be in this condition have died.

Adenovirus infection

In the United Kingdom and the United States, many children with mysterious liver inflammation were also infected with members of a family of common viruses known as adenoviruses. This led to the speculation that hepatitis is caused by adenovirus. However, while this is the UKHSA’s main hypothesis, it is not a widespread hypothesis. Researchers have pointed out the lack of statistical control. Adenovirus infections often peak in winter and spring, and the prevalence of children who do not develop hepatitis is unknown.

There is also a lack of precedent: adenovirus is not known to cause hepatitis in children with a healthy immune system. And the levels of the virus found in most children with liver inflammation are low. “I don’t think it’s an adenovirus,” says Orit Waisbourd-Zinman, a pediatric hepatologist at the Schneider Children’s Medical Center in Petachikva, Israel.

On June 10, Waisbourd-Zinman published a series of cases of five children with unexplained hepatitis.³.. She says that only one of them is positive for adenovirus. Sumit Rawat, a microbiologist at Bundelkhand Medical College in Sargal, India, tested samples from 17 children with unexplained hepatitis and found adenovirus in only three of them.

However, Waisbourd-Zinman and Rawat both state that all the children they saw were previously positive for SARS-CoV-2 or positive for their families. UKHSA also consistently lists COVID-19 as a possible explanation. However, only 15% of children with hepatitis in the UK are actively infected with SARS-CoV-2 at the time of diagnosis, and authorities are concerned with the number of people who had antibodies to the virus suggesting a previous infection. No data has been released.

COVID connection

Neither hypothesis is yet a clear winner, but the timing of the apparent outbreak of hepatitis strongly suggests some link to a pandemic, says virologist William Irving of the University of Nottingham, UK. The increase in cases may be the result of direct damage from past SARS-CoV-2 infections, reduced exposure to the virus during blockade, or an abnormal immune response caused by the coronavirus. “This is all a gesture,” he says. “But I feel that the COVID pandemic must be significant.”

One of the obviouss is that this condition has nothing to do with COVID-19 vaccination. That is, only a handful of British children who developed hepatitis were vaccinated.

The 2017-22 CDC survey asks for pandemic-related explanations. The team selected data from medical records, organ transplant records, and clinical examination of adenovirus fecal samples.In the end, researchers did not find a recent increase in the number of cases of childhood hepatitis, transplants, or adenovirus-positive fecal samples.¹..

Hidden diagnosis

However, Waisbourd-Zinman states that a simple analysis of electronic health records may not reveal the true incidence of unexplained hepatitis in children. She tried a similar study in Israel, but soon realized she had to manually look at her health records to find the buried diagnosis. For example, one case of hepatitis was found to be the result of medication used during a kidney transplant. The other was an infection with a known hepatitis-causing virus. These causes were not so coded in health records, and a rough examination would have grouped them together with cases of unexplained liver inflammation.

That noise makes it hard to find really unexplained cases, she says. “It’s impossible to see an increase,” she says. “It’s very different.”

In April, researchers also determined that the incidence of unexplained hepatitis in children in mainland Europe did not exceed the regional baseline.^Four.. However, Kelly, who consulted on the analysis, states that it is also limited. As in the United States, European medical data was fragmented and the European survey included only specialized hospitals.

In some countries, including Israel and the United Kingdom, doctors are asked to report cases of childhood hepatitis not explained by known causes to public health authorities to assist in tracking the condition. In addition to this, various research studies initiated to determine the cause of symptoms shed light on a small number of mysterious cases of pediatric liver inflammation that appear each year, whether related to COVID-19 or not. I can. Kelly.

“I think there may be something special about those kids that makes them sensitive,” she says. “Perhaps one of the nice things about this is that you can see what it is.”