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A Case Series of Children with Acute Hepatitis and Human Adenovirus Infection
L Helena Gutierrez Sanchez1, Henry Shiau1, Julia M Baker1
1From the Division of Pediatric Gastroenterology, Hepatology, and Nutrition (L.H.G.S., H.S., S.S.) and the Division of Pediatric Infectious Diseases, (M.B., W.B., V.S., J.L.P.), Department of Pediatrics, and the Department of Pathology (D.K.), University of Alabama at Birmingham, Children's of Alabama (L.H.G.S., H.S., S.S., M.B., D.K.), and Jefferson County Department of Health (S.A.-M., W.G.W.), Birmingham, and the Alabama Department of Public Health, Montgomery (L.A.I., A. Martin) - all in Alabama; the Division of Viral Diseases (J.M.B., X.L., A.J.H., U.P., A. MacNeil, J.E.T., H.L.K.), the Epidemic Intelligence Service (J.M.B.), and the Division of High-Consequence Pathogens and Pathology (N.R., J.B., H.B., S.R.-S.), Centers for Disease Control and Prevention, Atlanta, and Synergy America, Duluth (H.B.) - both in Georgia; the Department of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center (M.E.R.), and the Department of Pediatrics, University of Cincinnati College of Medicine (M.E.R.) - both in Cincinnati; the Division of Pediatric Gastroenterology, Hepatology and Nutrition (A.M.B.-H., S.H., D.H.L.) and the Division of Pediatric Infectious Diseases (E.A.M.), Texas Children's Hospital, and the Department of Pediatrics, Baylor College of Medicine (A.M.B.H., S.H., D.H.L., E.A.M.) - both in Houston; and the Wadsworth Center, New York State Department of Health (D.M.L., K.S.G.), and the Department of Biomedical Sciences, University at Albany (K.S.G.) - both in Albany.
Insights
Human adenovirus viremia was detected in children with acute hepatitis of unknown cause. While the causative link remains unclear, sequencing revealed diverse adenovirus type 41 variants, not a single outbreak strain.
Area of Science:
- Pediatric Gastroenterology
- Infectious Diseases
- Hepatology
Background:
- Human adenoviruses commonly cause mild infections in children.
- An increase in acute hepatitis cases with human adenovirus viremia was observed in previously healthy children in late 2021/early 2022.
Purpose of the Study:
- To investigate the association between human adenovirus and acute hepatitis in children.
- To identify the adenovirus types involved in these cases.
Main Methods:
- Utilized ICD-10 codes to identify pediatric hepatitis admissions.
- Included children with acute hepatitis and positive whole-blood PCR for human adenovirus.
- Collected demographic, clinical, laboratory, and treatment data; performed diagnostic confirmation and adenovirus typing.
Main Results:
- Eight of nine children with unexplained acute hepatitis tested positive for human adenovirus.
- Liver biopsies showed mild-to-moderate hepatitis; adenovirus was detected in 50% of liver tissues via PCR.
- Sequencing identified three distinct human adenovirus type 41 hexon variants.
Conclusions:
- Human adenovirus viremia was common in children with unexplained acute hepatitis during the study period.
- The causative role of human adenovirus in these hepatitis cases requires further investigation.
- The observed cases were not linked to a single adenovirus strain, suggesting diverse origins.
Background:
Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia.
Methods:
We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing.
Results:
A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care.
Conclusions:
Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).
