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The exterior of the Hospital for Sick Children in Toronto, on Jan. 21, 2021.Fred Lum/The Globe and Mail

Canadian health officials investigating several cases of severe acute hepatitis of unknown origin in children say there is no evidence to date that the cases represent an increase or departure from what is seen in a typical year.

They are advising parents to be aware, but not alarmed, as the World Health Organization (WHO) confirms about 350 cases globally, with reports of deaths in the United States and Indonesia.

“It’s important to underscore that at every large children’s hospital, it is not uncommon to see such cases,” said Vicky Ng, a pediatric gastroenterologist at the Hospital for Sick Children in Toronto, commonly called SickKids. “The importance is that, because some of them have been serious, as reported in the world literature, this is why this is under investigation.”

SickKids has identified seven cases of children with severe acute hepatitis of unknown origin, meeting the WHO’s probable case definition, between Oct. 1, 2021, and April 30, 2022. All seven are “doing well” and none are currently in hospital, Dr. Ng said.

The Public Health Agency of Canada, through the Canadian National Public Health Intelligence platform, on April 14 alerted provinces and territories to increase vigilance of acute hepatitis of unknown origin in children. On Tuesday, the agency said it is not yet known if there has been an increase of such cases. British Columbia investigated one possible case that turned out to be unrelated.

The WHO was first notified on April 5 of 10 cases of the disease in children under 10 across central Scotland. By April 8, 74 cases had been identified in the United Kingdom.

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On Tuesday, Philippa Easterbrook, a senior scientist with the WHO’s Global Hepatitis Programme, said there are now 348 probable cases globally, with 70 additional cases pending confirmation. Twenty countries have reported probable cases, 13 others are investigating cases and only six countries have reported more than five cases, she said.

Hepatitis viruses A through E have been excluded after laboratory testing and further investigations are ongoing. Symptoms of the disease include jaundice and gastrointestinal issues. Some cases have required transfer to specialist children’s liver units and, as of April 8, six children had undergone liver transplantation, according to the WHO. The U.S. has reported five deaths, and India three.

The U.K. reported about 163 probable cases as of Tuesday, and the UK Health Security Agency has been leading and co-ordinating investigations with nation states, Dr. Easterbrook said.

“At present, the leading hypotheses remain those which involve adenovirus,” she said at a WHO briefing in Geneva. “But, I think, with also still an important consideration about the role of COVID as well, either as a co-infection or as a past infection.”

Of cases that had been tested in the U.K., about 70 per cent have tested positive for adenovirus, with a particular type – F type 41 – being the most prevalent, Dr. Easterbrook said.

Upton Allen, head of infectious diseases at SickKids, noted that adenovirus can linger dormant in the body long after an infection without problem.

“If you get a serious illness, if your immune system gets a jolt for whatever reason, then you might have the virus waking up, and you might detect it in the blood, and you might think it’s the cause of your illness, but it isn’t,” he said. “So that is something that we are carefully trying to get across and evaluate, so that we get a clear understanding of whether adenovirus happens to be an innocent bystander who just woke up, or if it is the culprit.”

Dr. Allen said all seven children are being tested for adenovirus but was not able to confirm Tuesday how many had tested positive.

Dr. Easterbrook said the examination of tissue specimens over the past week in the U.K. have not shown typical features one might expect from a liver inflammation due to adenovirus, but that experts are awaiting further examinations of biopsies.

COVID-19 testing has found that 18 per cent of the U.K. cases were PCR-positive, and a focus in the coming week will be serological testing for previous exposure and infections, Dr. Easterbrook said.

Dr. Allen said is no evidence to date that either adenovirus or COVID-19 are a “smoking gun” in the cases currently under investigation.

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