Children’s Physicians Identify Adenovirus as Common Link in Hepatitis Outbreak

Adenovirus in the blood was a common link between cases during a recent hepatitis outbreak, according to researchers at Children’s of Alabama.

When a cluster of Alabama children were diagnosed with severe hepatitis in the fall of 2021, pediatric physicians at Children’s of Alabama and the University of Alabama at Birmingham (UAB) notified public health leaders and began investigating. As a result of their efforts, the Centers for Disease Control and Prevention (CDC) issued a health alert to warn the public about the spread of the illness. Hundreds more cases were subsequently discovered across the United States and Europe, many with a common link: adenovirus within the blood.

Researchers at Children’s and UAB discovered the link in the Alabama cases through a routine screening.

“We were able to uncover the possible association with the adenovirus-41 strain because it is our standard practice to screen patients diagnosed with hepatitis for adenovirus,” said Markus Buchfellner, M.D., a pediatric infectious disease physician at Children’s and UAB.

But the outbreak was something of a mystery to doctors. The nine patients in the Alabama cluster—all between 2 and 11 years old—were previously healthy. They lived in different parts of Alabama, and none attended the same day care or had known contact with any of the others. All developed severe hepatitis, with some experiencing acute liver failure and even requiring liver transplants.

“The adenovirus is typically associated with respiratory infections as well as gastrointestinal infections,” said Helena Gutierrez, M.D., Medical Director of the UAB and Children’s Pediatric Liver Transplant Program. “It is very rare for a healthy person to develop a severe illness that requires hospitalization from this virus.”

Gutierrez investigated the cases alongside Buchfellner and their colleague Henry Shiau, M.D., a pediatric hepatologist at Children’s and UAB. She served as lead author of the study, which was ultimately published in the New England Journal of Medicine. It showed that while the adenovirus was a common finding among the Alabama cases, it was unclear whether adenovirus infection itself, or a combination of the virus with other factors, led to the pediatric hepatitis outbreak.

Researchers noted that the timing of the outbreak during the COVID-19 pandemic should be considered, but it’s role also was unclear. COVID-19 is known to cause elevation of liver enzymes and multisystem inflammatory syndrome in children. The nine children tested negative for COVID-19 upon hospital admittance but did not receive antibody testing. While the outbreak remains a mystery, it’s clear that the work done by researchers at Children’s and UAB made an impact on the worldwide medical community. They led the way in researching the outbreak and alerting the public about symptoms and protective measures.

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