On 5 April, the UK reported an unexpected and significant increase in cases of severe, acute hepatitis of unknown origin in young, previously healthy children, all under the age of 10.
Since then, an increase in cases has been reported to the World Health Organization (WHO) by 11 other countries including Ireland, the US, Israel, the Netherlands, Romania, and as of Tuesday, Japan. On Wednesday, it was reported Canada is also investigating an undisclosed number of cases to see if they are linked to the outbreak.
The children affected range from one month old to 16 years old. One child has died, and about 10% of cases have required a liver transplant, the WHO said.
The majority of cases are in the UK (114 cases), with approximately 200 cases reported in total. It is possible the true number may be greater if there are children affected who are not showing serious symptoms and therefore will not have been taken to hospital for testing.
What is hepatitis?
Hepatitis is inflammation of the liver, which can lead to a range of health problems including cancer and liver failure, and can be fatal. The liver is crucial as it removes toxins from the blood, is involved in metabolism and regulates blood clotting, among other functions.
Hepatitis has a number of causes.
The most common are viruses, with hepatitis A, B, C, D and E being the key virus strains involved. These viruses differ in terms of how they are transmitted, their geographical spread, symptoms (not everyone develops symptoms) and severity, but all lead to hepatitis. There are vaccines against some of these virus strains.
Alcohol, certain medications and immune system disorders can also cause hepatitis.
Sometimes, hepatitis has no known cause, which is what is being seen in the cases in children reported to the WHO. However, such severe cases resulting in liver failure are especially rare in children, so when clinicians in the UK saw a rise in such cases with no cause, they became concerned. This led to the report to the WHO, and other countries becoming alert to the issue.
The common hepatitis viruses have not been detected in any of the children affected.
Associate Prof Asha Bowen, a clinician at Perth children’s hospital in Australia and an infectious diseases researcher at Telethon Kids Institute said: “This is definitely unusual, and I can’t think of many times in my career where we have faced something like this.”
“What’s unusual is that it’s fulminant hepatitis, which basically means the liver has failed completely in these children,” Bowen said. “That’s extremely rare in childhood. And it has put us all on high alert.”
What do we know about this mystery hepatitis?
The children were generally healthy before becoming sick and being diagnosed. The WHO described their hepatitis as “severe and acute”.
Many of the children suffered from gastrointestinal symptoms such as abdominal pain, diarrhoea and vomiting just before being diagnosed. Many also had jaundice, a condition which can make the skin and eyes appear yellow, and which can be caused by liver damage.
A number of investigations are occurring into potential causes of the mystery hepatitis, but nothing has been confirmed.
Adenoviruses – which are common and lead to what people describe as a cold, and symptoms such as a sore throat, fever and diarrhoea – were detected in more than 70 of the children. Covid-19 was also detected in 20 cases.
But the WHO said in its latest report on the cases that while adenovirus is currently one hypothesis as the underlying cause, “it does not fully explain the severity of the clinical picture”. The strain of adenovirus, known as type 41, seen in many of the children has not previously been linked to severe hepatitis.
“While there have been case reports of hepatitis in immunocompromised children with adenovirus infection, adenovirus type 41 is not known to be a cause of hepatitis in otherwise healthy children,” the WHO said.
Bowen, who is also co-chair of the Australasian Society for Infectious Diseases, said the adenovirus theory is the most likely explanation so far, but that “whether that’s the absolute causative agent, there’s still a quite a bit of uncertainty about that”.
Other investigations are examining whether environmental factors, or other viruses or organisms may be involved.
Director of the European Centre for Disease Prevention and Control, Dr Andrea Ammon, told reporters during a briefing on Tuesday that another hypothesis being investigated is whether lockdowns may have weakened children’s immunity due to lower exposure to pathogens.
The WHO said “hypotheses related to side effects from the Covid-19 vaccines are currently not supported” given the majority of affected children did not receive a Covid-19 vaccination, as they were too young.
What’s the health advice in the meantime?
Countries have been urged to be alert to any hepatitis cases in children with no apparent cause. The WHO recommends that blood, urine, stool and respiratory samples, as well as liver biopsy samples, should be taken from these children.
“Other infectious and non-infectious causes need to be thoroughly investigated,” the WHO said.
