Interim Analysis of Acute Hepatitis of Unknown Etiology in Children Aged <10 Years - United States, October 2021-June 2022.

On April 21, 2022, CDC issued a health advisory† encouraging U.S. clinicians to report all patients aged <10 years with hepatitis of unknown etiology to public health authorities, after identification of similar cases in both the United States (1) and Europe.§ A high proportion of initially reported patients had adenovirus detected in whole blood specimens, thus the health advisory encouraged clinicians to consider requesting adenovirus testing, preferentially on whole blood specimens. For patients meeting the criteria in the health advisory (patients under investigation [PUIs]), jurisdictional public health authorities abstracted medical charts and interviewed patient caregivers. As of June 15, 2022, a total of 296 PUIs with hepatitis onset on or after October 1, 2021, were reported from 42 U.S. jurisdictions. The median age of PUIs was 2 years, 2 months. Most PUIs were hospitalized (89.9%); 18 (6.1%) required a liver transplant, and 11 (3.7%) died. Adenovirus was detected in a respiratory, blood, or stool specimen of 100 (44.6%) of 224 patients.¶ Current or past infection with SARS-CoV-2 (the virus that causes COVID-19) was reported in 10 of 98 (10.2%) and 32 of 123 (26.0%) patients, respectively. No common exposures (e.g., travel, food, or toxicants) were identified. This nationwide investigation is ongoing. Further clinical data are needed to understand the cause of hepatitis in these patients and to assess the potential association with adenovirus.

Trends in Acute Hepatitis of Unspecified Etiology and Adenovirus Stool Testing Results in Children - United States, 2017-2022.

In November 2021, CDC was notified of a cluster of previously healthy children with hepatitis of unknown etiology evaluated at a single U.S. hospital (1). On April 21, 2022, following an investigation of this cluster and reports of similar cases in Europe (2,3), a health advisory* was issued requesting U.S. providers to report pediatric cases† of hepatitis of unknown etiology to public health authorities. In the United States and Europe, many of these patients have also received positive adenovirus test results (1,3). Typed specimens have indicated adenovirus type 41, which typically causes gastroenteritis (1,3). Although adenovirus hepatitis has been reported in immunocompromised persons, adenovirus is not a recognized cause of hepatitis in healthy children (4). Because neither acute hepatitis of unknown etiology nor adenovirus type 41 is reportable in the United States, it is unclear whether either has recently increased above historical levels. Data from four sources were analyzed to assess trends in hepatitis-associated emergency department (ED) visits and hospitalizations, liver transplants, and adenovirus stool testing results among children in the United States. Because of potential changes in health care-seeking behavior during 2020-2021, data from October 2021-March 2022 were compared with a pre-COVID-19 pandemic baseline. These data do not suggest an increase in pediatric hepatitis or adenovirus types 40/41 above baseline levels. Pediatric hepatitis is rare, and the relatively low weekly and monthly counts of associated outcomes limit the ability to interpret small changes in incidence. Ongoing assessment of trends, in addition to enhanced epidemiologic investigations, will help contextualize reported cases of acute hepatitis of unknown etiology in U.S. children.