One of Canada’s largest children’s hospitals is reporting seven cases of severe acute hepatitis identified in recent months, which may be part of an unexplained outbreak impacting youth in multiple countries, CBC News has learned.
It’s still unclear how many cases have been reported across Canada, or whether any of the cases under investigation at the Hospital for Sick Children in Toronto — also known as SickKids — are linked to the mysterious instances of serious liver disease among children in the U.K., U.S., Israel and elsewhere.
A spokesperson for SickKids provided the tally in an email, saying the hospital is “closely monitoring” for any cases of severe acute hepatitis and has reported seven cases meeting the “probable case definition” to Public Health Ontario.
Those cases were identified between Oct. 1, 2021 and April 30, 2022.
“It remains to be seen whether this number represents an increase in cases of unknown origin compared to similar time periods in previous years or if any of these cases will be confirmed to be caused by a novel clinical entity,” SickKids spokesperson Jessamine Luck continued.
100+ cases reported in U.S.
The Public Health Agency of Canada has not yet provided specifics on how many cases are being investigated Canada-wide to determine if they’re related to the unexplained instances of hepatitis elsewhere.
Other countries, however, have been publicizing growing numbers of potentially connected cases, with hundreds of investigations underway globally to determine the root cause of unexplained liver issues among youth.
On Friday, the U.S. Centers for Disease Control and Prevention said 109 cases across various parts of the country are under investigation to determine any possible links. Fourteen per cent of those children required liver transplants, and five died from their illness.
Hepatitis — which refers to inflammation of the liver — is rare among children. It’s typically caused by the family of hepatitis viruses, but can also be sparked by alcohol use, exposure to toxins, or other pathogens.
The cases identified by health officials around the world in recent months don’t appear to have any of those usual causes.
Instead, researchers are probing other theories, including links to infections from an adenovirus or SARS-COV-2, the virus behind COVID-19.
WATCH | Mystery cases of hepatitis among children under investigation:
Leading hypothesis in U.K. involves adenovirus
In the U.K., where there have been at least 163 cases of acute, unexplained hepatitis identified in youth under 16 since the start of the year — including 11 cases which required a liver transplant — officials say the leading hypothesis remains focused on adenovirus.
“However, we continue to investigate the potential role of SARS-CoV-2 and to work on ruling out any toxicological component,” the U.K. Health Security Agency (UKHSA) said in a briefing note released on Friday.
Adenovirus — referring to a family of common viruses that typically cause mild cold- or flu-like illness — was the pathogen detected most often, found in more than 70 per cent of the U.K. cases and primarily detected in blood, the UKHSA said.
SARS-CoV-2 was detected in 18 per cent of cases. Serological testing, a method to determine if someone has antibodies from a prior infection, is also underway.
“A range of other possible pathogens have been detected in a low proportion of cases and are of uncertain significance,” the U.K. briefing note continued.
The UKHSA is investigating whether a normal adenovirus infection might be behind the instances of hepatitis, due to a variety of factors including a lack of exposure to the virus during the COVID-19 pandemic, an “exceptionally large wave” of infections causing a rare complication to present more often, or an abnormal response to the virus due to a prior or co-infection with SARS-CoV-2.
“I don’t think the answer is a simple smoking gun here,” said Hamilton, Ont.-based infectious diseases specialist Dr. Zain Chagla, of the global investigations into this mystery outbreak.
“Certainly we’ve seen adenoviruses cause hepatitis in immunocompromised populations. But even then: Why now, and why in the context of certain countries, and not others? The context of certain time frames, but not others?” he questioned.
“Is there a cofactor — a toxin, or genetics, or another infection like COVID-19 that might be involved in all of this?”
WATCH | Hepatitis cases among children a medical mystery, says specialist:
Israeli team exploring links to COVID-19
Unexplained cases of hepatitis have been identified in an array of countries, and at varying points in the pandemic, with significant numbers being reported in recent months following alerts sent out by officials in the U.S. and U.K.
What’s unclear, whether in global reports or the numbers under investigation in Toronto, is exactly how these tallies compare to the typical baseline rate for unexplained hepatitis in children.
“There’s just so much uncertainty,” said Chagla, including why certain regions are reporting more cases than others.
In Israel, Dr. Yael Mozer Glassberg — head of the liver transplant unit at Schneider Children’s Medical Center — said her team has treated multiple children who faced strange instances of hepatitis, but hasn’t seen a “huge jump” in overall numbers.
Medical staff analyzed those recent cases, including genetic testing, and the only link between them was that each one had faced a previous bout of COVID-19, identified through serological testing and each family’s medical history. None of the patients tested positive for adenovirus, Mozer Glassberg told CBC News.
“I can’t say that this is the same thing that happens right now around the world,” she said. “But we had seven definite cases like that [since Feb. 2021] and right now we’ve hospitalized the eighth one.”
Two infants required transplants, but Mozer Glassberg said it’s not uncommon for hepatitis in that age group to present with no clear cause, raising questions about whether those two cases were linked to the others.
Given variations in testing for COVID-19 around the world, it may also be tough to determine any possible links to prior infections from SARS-CoV-2, adding another layer of uncertainty to this global puzzle.
“Maybe it’s a new virus. Maybe it’s not [adenovirus]. Maybe it’s not even post-COVID… maybe it’s a combination of the two,” Mozer Glassberg said.
Physicians say possible symptoms of hepatitis can include jaundice — yellowing eyes and skin — dark urine, pale stool, abdominal pain, and vomiting.