Wisconsin DHS Health Alert #42: Recommendations for Adenovirus Testing and Reporting of Children with Acute Hepatitis of Unknown Etiology

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Wisconsin DHS Health Alert #42: Recommendations for Adenovirus Testing and Reporting of Children with Acute Hepatitis of Unknown Etiology

Bureau of Communicable Diseases

April 27, 2022


The  Wisconsin Department of Health Services (DHS) is issuing this Health Alert Network (HAN) Health Advisory to notify clinicians and public health authorities of a recent increase in cases of acute hepatitis and adenovirus infection in children.

From November 2021 to February 2022, clinicians at a large children’s hospital in Alabama identified nine pediatric patients with significant liver injury, including three with acute liver failure, who also tested positive for adenovirus. All children were previously healthy. All five of the nine specimens that were sequenced had adenovirus type 41 infection identified. Two patients required liver transplant; no patients died.

Since being notified of this adenovirus-associated hepatitis cluster, DHS is now investigating at least four similar cases among children in Wisconsin. This includes two children who had severe outcomes, one liver transplant, and one fatality.


A possible association between pediatric hepatitis and adenovirus infection in children who tested negative for hepatitis viruses A, B, C, D, and E is currently under investigation worldwide. This Health Alert serves to notify U.S. clinicians who may encounter pediatric patients with hepatitis of unknown etiology to consider adenovirus testing and to elicit reporting of such cases to state public health authorities and to the Centers for Disease Control and Prevention (CDC). Nucleic acid amplification testing (NAAT, e.g., PCR) is preferred for adenovirus detection and may be performed on respiratory specimens, stool or rectal swabs, or blood.

CDC issued an official Health Advisory describing a cluster of cases in Alabama and provided recommendations for testing and reporting on April 21. The World Health Organization has also published a Disease Outbreak News report on April 23 describing 169 cases of acute hepatitis of unknown etiology, of these, adenovirus had been detected in at least 74 cases.


Hepatitis is inflammation of the liver that can be caused by viral infections, alcohol use, toxins, medications, and certain other medical conditions. In the U.S, the most common causes of viral hepatitis are hepatitis A, hepatitis B, and hepatitis C viruses.

Signs and symptoms of hepatitis include fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, light-colored stools, joint pain, and jaundice. Treatment of hepatitis depends on the underlying etiology. Adenoviruses are doubled-stranded DNA viruses that spread by close personal contact, respiratory droplets, and fomites. There are more than 50 types of immunologically distinct adenoviruses that can cause infections in humans. Adenoviruses most commonly cause respiratory illness. However, some adenovirus types can cause other illnesses, such as gastroenteritis, conjunctivitis, cystitis, and, less commonly, neurological disease.

There is no specific treatment for adenovirus infections. Adenovirus type 41 commonly causes pediatric acute gastroenteritis, which typically presents as diarrhea, vomiting, and fever; it can often be accompanied by respiratory symptoms. While there have been case reports of hepatitis in immunocompromised children with adenovirus type 41 infection, adenovirus type 41 is not known to be a cause of hepatitis in otherwise healthy children.


  1. Clinicians should consider adenovirus testing in pediatric patients with hepatitis of unknown etiology. NAAT (e.g., PCR) is preferable and may be done on respiratory specimens, stool or rectal swabs, or blood.
  2. Anecdotal reports suggest that testing whole blood by PCR may be more sensitive than testing plasma by PCR; therefore, testing of whole blood could be considered in those without an etiology who tested negative for adenovirus in plasma samples.
  3. If patients are still under medical care or have residual specimens available, please save and freeze specimens for possible additional testing and contact DHS at 608-267-9003.

Clinical Criteria for Case Reporting

  1. Children under age 16, presenting with hepatitis of unknown etiology (with or without any adenovirus testing results) since January 1, 2021, AND
  2. Elevated liver function tests (i.e., aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >500 U/L).

Suspect cases should be reported to public health electronically via the Wisconsin Electronic Disease Surveillance System (WEDSS) and selecting “hepatitis unknown” as the disease type, or by contacting DHS at 608-267-9003.


Ryan Westergaard, MD, PhD, MPH
Chief Medical Officer and State Epidemiologist
Bureau of Communicable Diseases
Division of Public Health
Wisconsin Department of Health Services