Adenovirus linked to mysterious cases of severe childhood hepatitis

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A Adenovirus linked to mysterious cases of severe infantile hepatitis

Co-infection with other viruses could explain this wave of cases.

Most children affected by this mysterious ailment have experienced vomiting and diarrhea; some also experienced respiratory symptoms.

The high number of unexplained cases of severe acute childhood hepatitis observed since 2022 may be linked to a common virus, adeno-associated 2 (AAV2), confirm three new studies published in the journal Nature Thursday.

Since 2022, more than 1,010 cases of severe childhood hepatitis have been reported in 235 countries. About 7% of these young people required a liver transplant.

In Canada, from April to September 2022, there have been 28 cases of severe acute hepatitis in children aged 1 to 13 years, including 14 in Ontario, 5 in Alberta and 4 in Quebec. Normally, we see two or three cases each year in Canada. All of the Canadian children have been hospitalized. Four of them needed liver transplants. No deaths were reported.

The abnormally high number of cases had raised many questions.

At the start of this wave, researchers hypothesized that adeno-associated 2 (AAV2) could be involved. However, doubts persisted, since AAV2 is known to replicate in the liver, but does not normally cause hepatitis and cannot replicate without a helper virus (a co-infection).

But these three new studies published in Nature, one American and two British, confirm that AAV2 played a key role in the development of this serious hepatitis.

Hepatitis is an inflammation of the liver that can be caused by viral infections (including Hep-A, Hep-B and Hep-C viruses), alcohol consumption, toxins, drugs and some abnormalities.

Symptoms are nausea, vomiting, abdominal pain, dark urine, jaundice, fever and fatigue.

Acute hepatitis rarely occurs in children and its exact cause is often difficult to circumscribe.

American researchers detected the presence of AAV2 in the blood of 93% of children studied with severe acute hepatitis of unknown origin. In comparison, AAV2 was detected in only 3.5% of children in the control group.

According to one of the British studies, AAV2 was detected in 81% of hepatitis cases, compared to 7% of people in the control group.

While the three studies observed a link between AAV2 and these forms of hepatitis, the researchers do not know if this adenovirus is the sole cause of the hepatitis or if a co-infection would explain the wave of severe hepatitis cases.

Among most of the children affected and infected with AAV2, researchers in these three studies detected the presence of helper viruses, including human adenovirus and human beta-herpesvirus 6B (HHV-6B).

Adenoviruses are generally common viruses that cause respiratory symptoms, conjunctivitis or even digestive disorders.

Human herpes virus 6B (HHV-6B) causes roseola infantum in infants and toddlers.

The researchers also found that 93% of children with severe hepatitis have a particular gene, suggesting that some children are genetically more likely to develop a severe form of the disease.

The British researchers detected in few children the presence of a previous infection of COVID-19.

The authors point out that the circulation of viruses, including adenoviruses, was largely interrupted during the pandemic. When health restrictions were lifted, it is possible that genetically predisposed children were at greater risk of being co-infected with HAdV and AAV2, creating a synchronized wave of severe hepatitis cases.

While researchers do not currently believe that COVID-19 is involved, they do not completely rule out this link.

Incidentally, in a comment published in Nature, Frank Tacke, a researcher from the Department of Hepatology and Gastroenterology at the Medical University Charité-Berlin, argues that one should conduct more studies to see if SARS-CoV-2 triggered a superantigen-like mechanism causing a strong immune response in some infected children and particularly affecting the liver.

SARS-CoV-2 cannot be completely ruled out, given that this wave of hepatitis occurred in the midst of the COVID-19 pandemic.

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