Children with Hepatitis of Unknown Cause

About the Investigation

Alabama

In October 2021, five pediatric patients with hepatitis (inflammation of the liver) of unknown cause were identified in children at a hospital in Alabama. The children had significant liver illness, including some with liver failure, with no known cause. The five children tested negative for hepatitis A, hepatitis B, and hepatitis C viruses and tested positive for adenovirus, a common virus that typically causes cold- or flu-like illness, or more rarely stomach or intestine problems. An additional review of hospital records later identified four additional patients, all of whom had hepatitis and adenovirus infection.

All of the children were previously healthy and ranged in age from one to six years old at the time of hospitalization. The children were from different parts of the state. No known contact or common exposures were found among the children. None of the children had significant underlying medical conditions.

Global Investigation Led by WHO

CDC is also aware of an increase in pediatric patients with hepatitis of unknown cause recently reported in other countries, and CDC is working with public health officials around the world to understand what they are learning. Adenovirus has been detected in some of these patients throughout the United Kingdom and Europe, but not among all of them. Investigators are considering other possible causes and identifying other possible contributing factors.

Nationwide Investigation

In addition to looking for more cases in Alabama, the CDC issued a notice calling for state and local health departments nationwide to report potential cases. CDC is working with states to support them when patients under investigation are reported and is updating investigation numbers regularly.

Some of the Children with Hepatitis in Alabama also had Adenovirus

Laboratory tests identified that some of the children in Alabama had adenovirus type 41, which is more likely to cause severe stomach illness in children. Although there have been previous reports of hepatitis in children with suppressed immune systems who were infected with adenovirus, adenovirus type 41 is not a common cause of hepatitis in otherwise healthy children.

Other common causes of viral hepatitis, such as infection with hepatitis A, B, C, D, and E viruses were considered, but evidence for these infections were not found in any of the patients. Some other causes have been ruled out for the children in Alabama, including:

• The virus that causes COVID-19
• Bacteria
• Autoimmune hepatitis
• Wilson disease

We Don’t Know the Cause

At this time, the cause of the reported illnesses in these children is still unknown. While adenovirus has been detected in some children, we do not know if it is the cause of the illness.

We do not know and are investigating what role other factors play in this illness, such exposure to toxins or other infections that the children might have.

We don’t know the normal prevalence (number of cases)

Cases of hepatitis in children over the past few years appear stable and are small numbers overall. CDC continues to look at data to understand the expected numbers of children with hepatitis. It is not unusual for the cause of some hepatitis cases in children to remain unknown; some estimates suggest 30-50% of hepatitis cases in children are from unknown causes.

CDC is looking at overall trends in hepatitis in children.

During this investigation, as reports come in from states, it may seem like there is a growing number of children with hepatitis, but this might not be the full picture. These may not be new cases of hepatitis, and they may not be linked to this current investigation.

CDC is also examining national data sources to look at trends in hepatitis in children (including disease requiring liver transplants), as well as any trends in adenovirus infection over several years, including before the COVID-19 pandemic.

What CDC Is Doing

CDC is leading the investigation

CDC is working with state and local health departments to learn more about potential cases and what may be causing these illnesses. At this time, we believe adenovirus could be the cause of some of these reported illnesses, but investigators are still learning more – including ruling out other possible causes and identifying other possible contributing factors.

To learn more about the potential causes of hepatitis in this investigation, investigators are working with state and local health departments to examine the medical records of children who had hepatitis in the past. Many of the reports are from records many months ago, so some details may be missing and certain recommended tests may not have been completed.

CDC and state public health officials will continue to work in close collaboration with healthcare providers to identify and detect unusual patterns or clusters of hepatitis in children to determine the cause.

CDC is working closely with laboratories around the country to determine the best testing practices

CDC is asking healthcare providers to consider testing for adenovirus in pediatric patients with hepatitis of unknown origin, and to report any possible cases of hepatitis to their local or state public health authorities.

CDC will share additional information as it becomes available. We made recommendations for healthcare providers and laboratories on how to submit specimens for testing.

CDC is also engaging medical organizations to share information with healthcare providers.

Sharing information

• CDC sent  HAN (Health Alert Network) notifications to healthcare providers and public health partners to help clinicians and state health departments learn about the pediatric hepatitis cases of unknown cause, including how to report any other potential cases they identify. Additional HAN notifications are planned when there are clinical or laboratory updates.
• CDC will continue to update healthcare providers and public health partners, including through planned Clinician Outreach and Communication Activity (COCA)
• CDC will continue to release data and analyses quickly, including through MMWR publications, and continue to provide updated information to the public.