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Clinical Laboratories and Pathology Groups

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CDC asks physicians and clinical laboratories to be on the lookout and report symptoms of hepatitis to state health departments

Growing incidences of hepatitis in children are perplexing medical professionals and researchers in several countries around the world. The mysterious outbreak is occurring in otherwise healthy children and, to date, is of unknown origin, though an adenovirus may be involved.

Microbiologists and clinical laboratory scientists who perform virology testing may want to prepare for increased numbers of children presenting with hepatitis symptoms in the US.

On April 21, the Centers for Disease Control and Prevention (CDC) issued a nationwide health alert to notify the public about a cluster of children in Alabama who presented with hepatitis and adenovirus infections. The CDC asked physicians to watch for symptoms in children and to inform local and state health departments of any new suspected cases. 

Also in April, the World Health Organization (WHO) issued its own alert to an outbreak of acute hepatitis of unknown etiology among young children in several countries. In addition to the United States, cases were reported in the United Kingdom, Spain, Israel, Denmark, Ireland, the Netherlands, Italy, Norway, France, Romania, and Belgium.

All the cases reported to the WHO involved children between one month and 16 years of age with the majority of cases occurring in children under five.

According to NBC News, as of May 19, the worldwide number of cases “under investigation” had reached 600 in more than 25 countries. In the US, more than 90% of the patients required hospitalization and 14% of those patients needed a liver transplant. The CDC is investigating five pediatric deaths that may be attributed to the mysterious hepatitis outbreak. 

Jay Butler, MD
“Fifteen days ago, CDC issued a nationwide health alert to notify clinicians and public health authorities about an investigation involving nine children in Alabama identified between October of 2021 and February of 2022 with hepatitis or inflammation of the liver and adenovirus infection,” said pediatrician and epidemiologist Jay Butler, MD (above), Deputy Director for Infectious Diseases at the CDC. “We’re casting a broad net to increase our understanding,” he added. “As we learn more, we’ll share additional information and updates.” Hospital-based clinical laboratories that support emergency departments and urgent care centers with testing for hepatitis will want to monitor for upcoming CDC alerts. (Photo copyright: John Amis/AP/CNN.)

Adenovirus/SARS-CoV-2 May Be Linked to Hepatitis Outbreak

The cause of the hepatitis outbreak is as yet undetermined, but the pre-eminent theory among disease experts points to the presence of an adenovirus, which often causes cold and flu-like symptoms in addition to stomach issues. 

NBC News reported that more than half of the US patients, 72% of the UK patients, and 60% of the affected patients across Europe tested positive for human adenovirus type 41. This virus, however, is generally not associated with hepatitis in healthy children, and rarely impacts the liver so severely. 

Medical experts are also considering the possibility that COVID-19 infections could somehow be an underlying cause since the hepatitis outbreak occurred during the pandemic. The WHO is investigating whether exposure to the SARS-CoV-2 coronavirus might have prompted the immune systems in the infected children to react abnormally to adenoviruses that are typically non-life threatening. 

“The big focus over the next week is really looking at the serological testing for previous exposure and infections with COVID,” Phillipa Easterbrook, MD, a senior scientist at the WHO headquarters in Geneva, told NBC News.

Hepatitis, or inflammation of the liver, is typically caused by heavy alcohol use, exposure to toxins, certain medical conditions and medications, or a virus.

According to the CDC, symptoms of hepatitis include:

  • Fever
  • Fatigue
  • Loss of appetite
  • Nausea
  • Vomiting
  • Abdominal pain
  • Dark urine
  • Light-colored stools
  • Joint pain
  • Jaundice

The most recent children diagnosed with hepatitis presented with some or most of these symptoms, particularly stomach issues and fatigue. However, one symptom was present in all the children.

“The big symptom that made all of these kids different was that they all showed signs of jaundice, which is the yellowish coloration of the skin and eyes,” Markus Buchfellner, MD, a pediatric infectious disease fellow at the University of Alabama, told NBC News.

Buchfellner was the first person in the US to notice an unusual pattern of hepatitis among children. He reported his findings to the CDC last fall in 2021.

“We were able to uncover the possible association with the adenovirus 41 strain because it is our standard practice to screen patients diagnosed with hepatitis for adenovirus,” he said. “For us to dig deeper into this medical mystery and see if this strain is the cause of these severe hepatitis cases, we first need more data on how widespread the outbreak is.”

Adenovirus 41 is usually spread through fecal matter, which makes hand washing critical, especially after visits to the bathroom or diaper changes. This type of adenovirus typically presents as diarrhea, vomiting, and fever, and is often accompanied by respiratory issues.

Clinical Labs Performing Gene Sequencing Can Help

Medical scientists around the world are responding to this threat to the youngest and most vulnerable among us. Research is underway into identifying additional cases, determining what is causing the hepatitis globally among children, and establishing preventative measures.

Pathologists and clinical laboratory managers in the US will want to be on the alert for positive hepatitis tests in children whose specimens were tested at their facilities. With advances in gene sequencing that make testing economical and expeditious, more labs have the ability to not only detect hepatitis, but also to identify any genetic variants that may be associated with the increased number of pediatric hepatitis cases appearing around the world.

JP Schlingman

Related Information:

As Mysterious Child Hepatitis Cases Swell, Scientists Study Symptoms and Causes

With Usual Suspects Ruled Out, Disease Detectives Try to Crack Mystery of Viral Hepatitis Cases in Kids

CDC Alerts Providers to Hepatitis Cases of Unknown Origin

Hepatitis Outbreak in Children: What to Know

CDC Gives New Information about Mysterious Hepatitis Cases in Children

CDC Investigating 109 Unusual Hepatitis Cases in Kids in Outbreak

WHO: Multi-country—Acute, Severe Hepatitis of Unknown Origin in Children