In the July 13 issue of the New England Journal of Medicine, there are two reports of clusters of pediatric hepatitis of unknown etiology, one from Birmingham, UK, and one from Birmingham, AL. Just as a check, there have been no reports of childhood hepatitis from Birmingham, Saskatchewan.
The story of this outbreak began in April 2022 when the World Health Organization (WHO) was notified of 10 cases of acute hepatitis in previously well children (range 11 months to 5 years) in Scotland. All of these children were hospitalized with elevated transaminases (>500 IU/L), and all were negative for hepatitis A-E. WHO published an “Outbreak News” alert. Since then, reports have flooded in from all over the world.
There are a number of possible explanations for these reports. First, this may not represent anything new. At least 50% of hepatitis in young children is of unknown etiology. In these “unknown” cases, a virus is often suspected, thus explaining the cluster effect of this outbreak. Yet there appears to be something different here. In both the United Kingdom and the United States, the children were well and became acutely and severely ill, requiring hospitalization, and some received liver transplants.
With the SARS-Co-2 on everyone’s mind, another immediate thought was that the outbreak of hepatitis could be COVID-19 related. At least as a straightforward explanation, COVID-19 does not appear to be the answer. Most of the cases tested negative for SAR-Co-2 antibodies and, where performed, tested negative by PCR. These results, however, do not rule out the possibility COVID-19 could interact with another virus or could alter the immune system.
The commonality between the UK and the US cases was positive testing for adenovirus. In the UK series, of the 30 cases tested for adenovirus, 27 were positive. Of the US cases, 9 of 9 had blood tests positive for adenovirus, and 6 of 9 had liver tissue test positive for adenovirus. So, it seems possible that adenovirus is the etiologic agent. Adenovirus 41 is known to cause gastrointestinal illness and hepatitis in immunocompromised children. However, adenovirus is a common infectious virus, usually causing mild and self-limited symptoms. There are no increased reports of adenovirus in the communities where the hepatitis cases occurred. In an editorial that accompanied the two Birmingham reports, Saul Karpen stated “…these studies are not yet sufficient to declare that human adenovirus 41 a firm cause of acute hepatitis that can lead to liver failure.”
So, while the cause of these unusual case of acute hepatitis has not yet been found, it has become very clear that we need to know a lot more about hepatitis in young children. We need a registry.
In the meantime, for what we do know of hepatitis in pediatrics, including the broad differential diagnosis, signs and symptoms, and evaluation and management, visit September’s Pediatric in Review for General Hepatitis by Ellis et al.