Mystery outbreak of severe hepatitis in children prompts worldwide surveillance

Kadakkal Radhakrishnan, MD

There has been much interest recently on outbreaks of unexplained hepatitis and the potential association with adenoviral infection reported from different parts of the world, including the United States.

At this point, the causality of this unexplained hepatitis by adenovirus has not been proven. Adenoviral hepatitis and sepsis have previously been reported in immunocompromised children and are not usually seen in healthy children. Adenoviral infection in children typically causes respiratory symptoms, sometimes associated with gastrointestinal symptoms including nausea, vomiting and abdominal pain as well as diarrhea. In the United Kingdom, where most of the cases were reported, there has been an increased prevalence of adenoviral infection on stool testing in children.

The question that needs to be addressed is whether these cases of hepatitis are randomly associated with incidental diagnosis of adenovirus in the samples, due to enhanced laboratory testing for adenovirus, and whether adenovirus is the true cause of hepatitis. It is also possible that with improved testing for adenovirus, a rare association of hepatitis is being identified in children that was not previously recognized. Another possibility is that these children may have other unknown underlying causes that may enhance the effect of adenoviral infection on the liver. Therefore, more investigations and testing will be required to clearly prove a cause-and-effect with adenoviral infection and this recent increased outbreak of hepatitis.

At this time, it is prudent to test for adenovirus infection in cases of unexplained hepatitis in children as recommended by the CDC, while looking for other known causes. Most cases of infective hepatitis resolve on their own and only require supportive care. Occasionally, patients may deteriorate, and clinicians should be aware of symptoms and signs, as well as biochemical indicators of worsening status. In that setting, a consultation with a pediatric gastroenterologist/hepatologist or referral to a center with transplant capabilities should be considered. It is important that any positive isolation of adenoviral infection in these patients be reported to the state public health agencies as well as the CDC. NASPAGHAN and AASLD have put out a guidance document to better inform the clinicians, providing a reasonable approach to the diagnosis and management of acute hepatitis in children.

Potential symptoms/signs/testing of worsening includes:

• International normalized ratio more than 1.5
• ALT greater than 500 IU/L
• Rising bilirubin and INR
• Suggestion of hepatic encephalopathy (increasing fatigue, sleepiness or altered mental status)
• New onset of jaundice/icterus
• New onset of easy bleeding or bruising

References:

Children with acute hepatitis of unknown etiology. https://www.cdc.gov/ncird/investigation/hepatitis-unknown-cause/updates.html. Accessed June 8, 2022.

NASPGHAN/AASLD guidance for acute hepatitis outbreak in children. https://naspghan.org/recent-news/naspghan-aasld-guidance-for-acute-hepatitis-outbreak-in-children/. Published May 24, 2022. Accessed June 8, 2022.