Research points to common infections as cause of liver disease outbreak in kids

Scientists think they may have pinpointed the cause of a mysterious outbreak of liver disease that affected children worldwide last year.

In a study published Thursday in the scientific journal Nature, researchers from the University of California and the New York State Department of Public Health present new evidence linking the outbreak of hepatitis with adenoviruses – which can cause a range of illnesses including the common cold -- and adeno-associated viruses.

Last April, scientists and health officials were puzzled when children in the U.K., Spain, Israel, the U.S., Denmark, Ireland, the Netherlands, Italy, Norway and France began suddenly developing severe cases of hepatitis with no known cause. By May, hospitals in Canada were reporting cases of rare pediatric hepatitis, too.

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By August 2022, clusters of cases were reported in 35 countries.

To date, the outbreak has been linked to 1,000 cases of acute pediatric hepatitis globally. As a result of the outbreak, 50 children have needed liver transplants and at least 22 have died.

Hepatitis is an inflammation of the liver. Acute hepatitis occurs when the liver function is impaired for less than six months. It's usually associated with viruses like hepatitis A, B, or C, but can have other triggers.

At the time of the initial outbreak, close to half of the hepatitis cases had been tied to an adenovirus infection. With funding from the U.S. Centers for Disease Control and Prevention, senior author Dr. Charles Chiu and his co-researchers set out to explore the link further.

“We were surprised by the fact that the infections we detected in these children were caused not by an unusual, emerging virus, but by common childhood viral pathogens,” Chiu, professor of laboratory medicine and medicine at the University of California, said in a media release.

Adenoviruses make up a large family of viruses that can spread from person to person, causing a range of illnesses including colds, pinkeye and gastroenteritis. Adeno-associated viruses are also widespread in the human population. While they are not known to cause disease on their own, they can replicate in the liver, causing liver inflammation, when paired with a "helper" virus such as an adenovirus.

The timing of the outbreak not long after schools had reopened for in-person learning hinted that students affected by the outbreak had been exposed to a combination of adenoviruses and adeno-associated viruses in school, and had developed hepatitis as a result.

What Chiu and his co-authors discovered through their research supports this theory.

The team used PCR and several other testing methods to examine plasma, whole blood, nasal swab and stool samples from 16 pediatric cases in six states — Alabama, California, Florida, Illinois, North Carolina and South Dakota — from Oct. 1, 2021, to May 22, 2022. They compared those specimens with 113 control samples.

When they genotyped the blood samples, they found adeno-associated virus 2 (AAV2) in 93 per cent of the cases and found adenoviruses in all of the cases. Eleven of those cases were specifically linked to a type of adenovirus associated with gastroenteritis. On top of those infections, they found additional infections with Epstein-Barr, herpes and enterovirus in 88 per cent of the samples.

"Our results suggest that co-infection with AAV2 may cause more severe liver disease than infection by an adenovirus and/or herpesvirus alone," the authors wrote, adding that the severity of the disease caused by co-infection with AAV2 could be compared to the liver failure caused by hepatitis D virus.

Their findings were consistent with those of two other studies conducted in the United Kingdom, which found the same AAV2 strain in samples from affected children. All three studies identified co-infections from multiple viruses, and 75 per cent of the children in the Chiu's study had three or four viral infections.

While clusters of acute severe hepatitis in children have declined, Chiu said the best way to protect children from the condition in the future is to help prevent the spread of common childhood infections in general, by practising good hand hygiene and staying home when sick.

– With files from Solarina Ho and Rhythm Sachdeva