Human Adenovirus Prominently Found in Children With Acute Hepatitis

New data shows various clinical presenting features for pediatric patients in the UK with acute hepatitis of unknown causes.

A team, led by Chayarani Kelgeri, MD, the Liver Unit, Birmingham Women’s and Children’s NHS Foundation Trust, attempted to identify the causative agent or agents of acute hepatitis of unknown causes in pediatric patients in the UK.

An Increase in Cases

There has been increases in cases of acute hepatitis of unknown causes in pediatric patients since January 2022, the majority of which occurring in the UK.

In the retrospective study, the investigators examined pediatric patients 10 years of age or younger referred to a single pediatric liver-transplantation center in the UK between January 1 and April 11, 2022. Each of the 44 participants had hepatitis that met the case definition of the U.K. Health Security Agency for confirmed acute hepatitis that was not hepatitis A through E.

The patients also did not have a metabolic, inherited or genetic, congenital, or mechanical cause in the context of a serum aminotransferase level greater than 500 IU per liter.

The investigators reviewed medical records and documented demographic characteristics, clinical features, and results of liver biochemical, serologic, and molecular tests for hepatotropic and other viruses. They also documented radiologic and clinical outcomes that were classified as an improving condition, liver transplantation or death.

The Patients

All of the participants met the confirmed case definition and the majority were previously healthy. The median age was 4 years.

Some noticeable presenting features included jaundice, which occurred in 93% of patients, vomiting, which occurred in 54%, and diarrhea, which occurred in 32%. There were also 30 patients who underwent molecular testing for human adenovirus, 90% (n = 27) of which were positive. An additional 14% (n = 6) developed fulminant liver failure, all of whom received a liver transplant.

No patient died and each participant was discharged home, including the 6 who received liver transplants.

“In this series involving 44 young children with acute hepatitis of uncertain cause, human adenovirus was isolated in most of the children, but its role in the pathogenesis of this illness has not been established,” the authors wrote.

A CDC Report

A June US Centers for Disease Control and Prevention (CDC) report does not show an increase in pediatric acute hepatitis cases during the COVID-19 pandemic in comparison with pre-pandemic levels.

A team led by Anita K. Kambhampati, MPH, Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, CDC, assessed trends in hepatitis-associated emergency department visits and hospitalizations, liver transplantations, and adenovirus stool testing results in pediatric patients in the US.

The CDC first identified a cluster of previously healthy pediatric patients with hepatitis of unknown etiology at a single US hospital in November 2021.

In April 2022, the CDC requested additional data on pediatric hepatitis cases of unknown etiology, which resulted in test results positive for adenovirus, which is not known to cause hepatitis in immunocompetent pediatric patients.

The results did not show an increase in weekly emergency department visits with hepatitis-associated discharge codes during the pandemic among patients aged 0-4 years or 5-11 years compared to the pre-COVIID-19 figures.

Between January 2019 and March 2022 there was a median of 22 and 10 hepatitis-associated hospitalizations in those age groups, respectively, recorded each month.

There was also no significant changes observed in hepatitis-associated hospitalizations during the pandemic study period, compared to the same months prior to COVID-19 among pediatric patients aged 0–4 years (22 and 19.5, respectively, P = 0.26) or 5–11 years (12 and 10.5, respectively, P = 0.42).

The study, “Clinical Spectrum of Children with Acute Hepatitis of Unknown Cause,” was published online in The New England Journal of Medicine.