Acute Hepatitis and Adenovirus in Children


Insights from a CDC study on challenges and research direction in pediatric hepatitis.

Doctor checking on child in hospital | Image credits: Unsplash

The study, led by the Centers for Disease Control and Prevention (CDC), investigated 392 cases of acute hepatitis of unknown etiology in US children from October 2021 to June 2023. It highlights the significance of adenovirus testing in cases of acute hepatitis to understand the virus's role and inform public health strategies and clinical management. Notably, the presence of adenovirus in several patients, including one without any pre-existing health conditions, suggests a potential connection between adenovirus and acute hepatitis.

In the study of 8 cases, the progression of illness varied, including among 2 children who were immunocompromised when it began. Of these cases, 4 children were positive for adenovirus, with 2 undergoing complete virus typing. The case of 1 child who tested positive for adenovirus without any pre-existing health conditions, suggests a possible direct link between adenovirus infection and the development of acute hepatitis in children who were previously healthy.

“The United States is one of the few countries to report fatalities associated with pediatric acute hepatitis of unknown etiology, which may reflect minor differences in the case definitions implemented by countries, variation in the application of those definitions for case finding, or the large size of the US population, enabling identification of rare outcomes,” according to the CDC. “Of note, more than half of the initially reported fatalities in young children with hepatitis were later determined not to meet the case definition, most commonly because an etiology for their hepatitis was ultimately identified.”

3 Key Takeaways

  1. The detection of adenovirus in several children with acute hepatitis, including those without any pre-existing health conditions, suggests a potential association between adenovirus infection and the development of acute hepatitis.
  2. The study found a significant progression of illnesses among the children, including those who are immunocompromised at the onset.
  3. The investigation highlights the critical need for ongoing research into adenovirus, adenovirus-associated virus type 2, and other potential viruses that could influence liver damage and the course of hepatitis, particularly in children without known pre-existing conditions.

The investigation faced limitations, including partial access to medical records and variability in illness progression and testing, complicating the analysis and comparison. Determining the specific contribution of detected pathogens, including adenovirus, to hepatitis or death was challenging due to variations in testing methods, specimen types, and timing. All children underwent adenovirus testing across multiple specimen types. There is a need for further investigation into adenovirus-associated virus type 2's impact on liver disease, alone or with adenovirus. It could not account for factors like genetic or autoimmune predispositions, socioeconomic status, or behavioral patterns, affecting illness risk, progression, or treatment.

“The deaths reported during the US investigation of pediatric hepatitis of unknown etiology likely represent a diverse range of etiologies in both the cause of hepatitis and cause of death,” according to the CDC. “This report describes 3 children who demonstrated a recognized relationship between adenovirus and acute hepatitis in immunocompromised persons; it also contributes to the growing evidence suggestive of a potential relationship between adenovirus and acute hepatitis in previously healthy children and the importance of testing for adenovirus early in the course of illness.”

This study underscores the critical need for ongoing research into adenovirus and other potential viruses to understand liver damage mechanisms and co-infection effects, especially in children without pre-existing conditions. Such efforts could significantly improve our ability to diagnose and treat hepatitis.


Almendares O, Baker JM, Sugerman DE, et al. Deaths Associated with Pediatric Hepatitis of Unknown Etiology, United States, October 2021–June 2023. Emerging Infectious Diseases. Published April 2024. Accessed March 26, 2023. doi:10.3201/eid3004.231140.

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