Infectious Disease

Adenovirus common in pediatric hepatitis cases, but role still unclear

Source/Disclosures

Disclosures:
Karpen reports receiving grants, personal fees and other support from Albireo, personal fees from Intercept, personal fees and other support from Mirum, and personal fees from Vertex, outside the submitted editorial. Please see the studies for all other authors’ relevant financial disclosures.

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Although adenovirus was isolated from most children with unexplained acute hepatitis, its role in the illnesses remains unclear, according to the authors of two new studies published in The New England Journal of Medicine.

Adenovirus infection has been implicated – but not proven – as the cause of a spate of pediatric hepatitis cases with an unknown cause in multiple countries, including the United States.

As of July 13, there were 338 cases under investigation in 42 states and territories in the US since Oct. 1, according to the CDC. WHO said it has received reports of 1,010 probable cases from 35 countries, including 22 deaths.

The two new studies reviewed 53 cases admitted to two hospitals — one in Birmingham, Alabama, and one in Birmingham, United Kingdom.

Among nine pediatric patients with acute hepatitis of an unknown cause at the Children’s Hospital of Alabama, eight tested positive for human adenovirus, according to the authors.

“Although we do not know whether human adenovirus infection was the cause of their hepatitis, the remainder of the diagnostic investigations did not identify other common possible causes,” they wrote.

The second study reviewed the cases of 44 children referred to the Birmingham Women’s and Children’s NHS Foundation Trust liver unit. Of the 30 patients tested for adenovirus, 27 were positive. Six of the 44 patients — 14% — required a transplant after developing liver failure, “underscor[ing] the severity of the illness,” the authors wrote. They said an investigation into the cause of the illnesses was ongoing.

Sequencing identified adenovirus subtype 41 in specimens from both studies, although the authors of the US study noted that testing uncovered three adenovirus 41 variants, suggesting “that if human adenovirus was causative in this group of patients with hepatitis, it was not driven by an outbreak a single new strain of human adenovirus 41,” they wrote.

In an accompanying editorial, Saul J Karpen, MD, PhDprofessor of pediatrics at Emory University School of Medicine and division chief of pediatric gastroenterology at Children’s Healthcare of Atlanta, said the underlying cause of acute hepatitis “is often elusive even with the application of modern gene-based and antigen-based rapid diagnostic methods. ”

“What is of interest here is the discovery that all nine of the children in the US case series and 27 of the 30 children who underwent molecular testing in the UK study tested positive for human adenovirus type 41, a finding consistent with other reports,” Karpen wrote.

He ultimately concluded that “there is not yet completely convincing evidence of a causal link, since at least in the United States there has not been an increase in reported cases of adenoviral hepatitis.”

“Appropriate studies and data are needed before speculation about pandemic-related alterations in immunologic reactivity to childhood illnesses can be supported or refuted,” Karpen wrote.

References:

CDC. Children with acute hepatitis of unknown etiology. https://www.cdc.gov/ncird/investigation/hepatitis-unknown-cause/updates.html. Accessed July 14, 2021.

Karpen S.N Engl J Med. 2022;doi:10.1056/NEJMe2208409.

Kelgeri C, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2206704

Sanchez L, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2206294.

WHO. Severe acute hepatitis of unknown etiology in children – multi-country. https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON400. Published July 12, 2022. Accessed July 14, 2022.

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