Baffling cases of severe liver disease in children spark international investigation

Baffling cases of severe liver disease in children spark international investigation

A baby being treated with blue light, a preventive measure against jaundice.
Enlarge / A baby being treated with blue light, a preventive measure against jaundice.

Health officials in Scotland released the first results of a burgeoning international investigation into dozens of puzzling cases of severe liver inflammation in children on Thursday. A few cases have already led to acute liver failure and liver transplants.

Thursday’s report detailed 13 serious cases in Scotland, mostly in children aged 3 to 5 and almost all of which occurred in March and April this year alone. Scotland typically has fewer than four cases of unexplained liver inflammation – aka hepatitis – in children in an entire year. Of the 13 cases this year in Scotland, one led to a liver transplant and five are still in hospital. No deaths have been reported.

Meanwhile, health officials in England have reported around 60 unexplained cases of severe hepatitis in 2022, most of which were in children between the ages of 2 and 5. Some of these cases progressed to acute liver failure and a few also led to liver transplantation. Again, no deaths were reported.

In their report, Scottish officials said they had also been in contact with researchers from the US Centers for Disease Control and Prevention, who are investigating their own cluster of childhood hepatitis cases. The US CDC did not immediately respond to Ars’ request for more information about the cluster, including the number of children involved and the severity of their cases. This story will be updated as more information becomes available.

Health officials are racing to understand what lies behind acute illnesses. In the cases described so far, the most obvious infectious culprits that cause liver inflammation – the hepatitis viruses (A through E) – have been ruled out, as children have always tested negative. Health investigators also couldn’t find a common food, drink or personal care product to explain the illnesses. There are no clear links between the cases, and there is no link to travel. The researchers also did not see strong evidence of bacterial infection.

Hypotheses

Some children have tested positive for an adenovirus infection. For example, five of 13 children in Scotland have tested positive for adenovirus – two by throat swab, two by blood tests and one by stool samples. And according to health officials in Scotland who have been in contact with CDC researchers, the US cluster of unexplained hepatitis cases is also linked to adenovirus infections.

Adenoviruses are a large family of viruses that circulate widely and are often linked to respiratory and eye infections. However, they can cause various diseases, including gastrointestinal and disseminated infections. Adenoviruses are known to cause severe hepatitis in children, but are rare in those who are not immunocompromised.

Some of the children in the UK have also tested positive for SARS-CoV-2 infections. For example, five of 13 children in Scotland had recently tested positive. None of the children had been vaccinated against the virus.

According to health officials in Scotland, the main hypothesis is that the illnesses are caused by an infectious agent – rather than toxic exposure – and an adenovirus is the prime suspect. Officials note two possibilities if an adenovirus is causing the acute cases: a new adenovirus has evolved to cause severe liver damage, or an existing variant that regularly circulates in children is causing severe illness because they have not been previously exposed to adenoviruses and are immunologically naïve. “This latter scenario could be the result of restricted social mixing during the COVID-19 pandemic,” officials speculate.

But, it’s also possible that the clusters are linked to infections with the omicron BA.2 subvariant, which is sweeping the UK and US, or even a yet-to-be-identified variant. “A new or as yet undetected virus also cannot be ruled out at this time,” the officials wrote.

As researchers continue their investigation – which is still in its early stages – health officials in the UK are alerting doctors to watch children with symptoms of hepatitis, such as dark urine, pale stools, jaundice, itchy skin, nausea, vomiting, and lethargy.

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