Adenovirus should be considered when diagnosing acute hepatitis in children

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Several cases of acute, severe hepatitis in children in Alabama have provided additional evidence to support a possible link between the disease and adenovirus, according to a report published in the Weekly Morbidity and Mortality Report.

“This cluster, together with the recently identified possible cases in Europe, suggests that adenovirus should be considered in the differential diagnosis of acute hepatitis of unknown etiology in children,” said Julia M. Baker, Ph.D. epidemic intelligence at the CDC National Center for Immunization and Respiratory Diseases and colleagues wrote. “Clinicians and laboratory technicians should be aware of possible differences in the sensitivity of the adenovirus test for different types of samples; whole blood tests may be more sensitive than plasma tests.

“The CDC is closely monitoring the situation to understand the possible cause of the disease and to identify potential efforts to prevent or mitigate the disease. Increased monitoring is under way in coordination with the public health jurisdictional partners. ”

From October to November 2021, five pediatric patients with severe hepatitis and adenovirus infection were identified at the Children’s Hospital of Alabama, prompting an investigation by hospital clinicians, state and county health departments and the CDC.

Baker and colleagues reviewed hospital records to identify patients with hepatitis and adenovirus infection diagnosed by PCR testing observed on or after October 1, 2021. Four additional children were identified between October 2021 and February 2022, leading to up to a total of nine (mean age, 2 years, 11 months; seven patients). All children are immunocompetent without clinically significant medical comorbidities. No additional patients have been identified since the state’s health council was issued in February 2022.

The researchers noted that before admission, seven patients reported vomiting, six reported diarrhea and three reported upper respiratory symptoms. On admission, eight patients had scleral jaundice, seven had hepatomegaly, six had jaundice, and one had encephalopathy. All patients had elevated transaminases, and total bilirubin ranged from normal to elevated (range = 0.23-13.5 mg / dL elevated in eight patients). All patients were negative for hepatitis A, B, and C viruses and several other causes of pediatric hepatitis and infections, including autoimmune hepatitis, Wilson’s disease, bacteremia, urinary tract infections, and SARS-CoV-2 infection.

According to the researchers, real-time PCR detected adenovirus in whole blood samples from all patients, and sequencing the hypervariable region of the hexon gene identified adenovirus type 41 in five patients. In addition, seven patients were co-infected with other viral pathogens, including enterovirus / rhinovirus, metapneumovirus, respiratory syncytial virus, and human coronavirus OC43. Six patients tested positive for Epstein-Barr virus (EBV) by PCR testing; however, these patients were tested negative for EBV immunoglobulin M antibodies, suggesting a possible low reactivation of a previous infection rather than an acute infection.

Six patients underwent liver biopsies that revealed varying degrees of hepatitis without viral involvement or immunohistochemical evidence of adenovirus. Acute liver failure developed in three patients, two of whom were treated with cidofovir and off-label steroids and later underwent liver transplantation. Both patients initially tested negative for adenovirus by real-time PCR on plasma samples, but were later tested positive with whole blood samples.

All patients, including the two LT recipients, recovered or are recovering.

“Clinicians are encouraged to report possible cases of pediatric hepatitis of unknown etiology that occurred on or after October 1, 2021, to public health authorities for further investigation,” the authors conclude.

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