Severe acute hepatitis of unknown origin in children

Keith Alcorn
25 April 2022

Cases of severe acute hepatitis in children are being reported in an increasing number of countries and the cause is unknown, the World Health Organization said on Saturday.

A total of 169 cases of acute severe hepatitis in children had been reported in eleven countries by 21 April. The children affected range in age from one month to 16 years old.

So far, one death and 17 liver transplants have been reported as a result of the hepatitis outbreak, the World Health Organization revealed on Saturday.

Most cases have been reported in the United Kingdom (114), where the condition was first identified.

The syndrome presents in the form of acute hepatitis with elevated liver enzymes. In many cases gastrointestinal symptoms such as abdominal pain, diarrhoea and vomiting have preceded the development of severe hepatitis. AST and/or ALT levels above 500 IU/ml have been accompanied by jaundice. Fever is absent in most cases.

Viral hepatitis has not been detected in any of the cases and all the children presenting with the syndrome were described as previously healthy.

Very few of the affected children had been vaccinated against SARS-CoV-2, ruling out an adverse vaccine reaction as a cause of the syndrome.

Adenovirus has been detected in at least 74 cases, 20 cases have been diagnosed with SARS-CoV-2 and in 19 cases, SARS-CoV-2 was detected alongside adenovirus. Further information on testing for each infection is needed.

Although an adenovirus infection has been proposed as a cause of the syndrome, no adenovirus type has been linked to an acute hepatitis syndrome. Adenovirus F type 41, detected in 18 cases, may cause gastrointestinal symptoms, fever and respiratory symptoms.

The World Health Organization says that “other infectious and non-infectious explanations need to be excluded to fully assess and manage the risk.”

Several working hypotheses are being investigated, including the possibility that a lack of prior adenovirus exposure due to the COVID-19 lockdowns may have left children more susceptible to the effects of resurgent adenovirus infections. The United Kingdom has observed an increase in adenovirus infections in the community in recent months.

Another possibility is that prior SARS-CoV-2 infection or another viral infection could result in a severe reaction to infection by another virus. A novel pathogen cannot be ruled out.

Alternatively, the syndrome may have a non-infectious cause, either a drug, toxin or environmental exposure.

Investigations to date have been hampered by a lack of consistent testing. In England, 40% of cases have not been tested for adenoviruses and the majority have not been tested for enteroviruses or other common viral causes of childhood illnesses, according to a technical briefing issued by the UK Health Security Agency on 25 April.