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Adenovirus was detected in the blood specimens of all nine children with acute hepatitis infection identified in Alabama from October 2021 to February 2022, researchers found.

The nine children were 0 to 6 years old and previously healthy, and most had gastrointestinal symptoms prior to admission, reported Julia Baker, PhD, of the CDC, and colleagues.

Low levels of other viruses were detected, including evidence of Epstein-Barr virus in six kids; enterovirus/rhinovirus in four; and metapneumovirus, respiratory syncytial virus, and human coronavirus OC43 in one apiece, the authors noted in an early edition of the

Notably, neither SARS-CoV-2 nor hepatitis A, B, or C were detected during testing, they added.

Gene sequencing was performed on five specimens, and adenovirus type 41 -- which commonly causes pediatric gastritis, but can also cause respiratory symptoms -- was detected in all five samples.

On April 21, the CDC issued a health alert, recommending that physicians test for adenovirus in cases of hepatitis with an unknown etiology. As of April 28, cases have been reported in , and 12 countries around the world.

Among the nine Alabama children, median age at admission was about 3, seven patients were girls, and all were white. All were immunocompetent with "no clinically significant comorbidities." Three initially presented with upper respiratory symptoms. Upon physical examination, eight patients presented with scleral icterus, or yellowing in the eye, seven with hepatomegaly, and six with jaundice.

Six patients underwent liver biopsies with "various degrees of hepatitis," no viral inclusions, nor "immunohistochemical evidence of adenovirus." Three patients had acute liver failure, and two were treated with off-label antiviral cidofovir and steroids prior to liver transplantation.

Interestingly, plasma specimens from two patients requiring transplant were negative for adenovirus via RT-PCR when they arrived for surgery, but their whole blood specimens tested positive via PCR. All nine patients have either recovered or are recovering.

Adenovirus type 41 is a cause of hepatitis among immunocompromised children, Baker's team said, and may be "an underrecognized contributor to liver injury among healthy children."

They encouraged clinicians not only to include adenovirus in a differential diagnosis for unknown hepatitis, but to test using whole blood versus plasma, as the former may be more sensitive.

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