Interim support for ISARIC4C Clinical Characterisation Protocol (CCP) activation for acute severe hepatitis in children of unknown cause

A number of young children in the UK, and across the world, are developing severe acute hepatitis. The cause is unknown. We are a group of doctors and scientists who do research in outbreaks in close partnership with public health agencies. Because our study (called ISARIC4C) is already set up across the whole country, we can recruit patients everywhere, collate data and samples and gain consent for research and development. The ISARIC4C approach brings the scalable capacity and cutting-edge capabilities of the academic sector to help the nation respond to public health challenges in time to make a difference to outcome.

We have already shown the strongest evidence for the underlying cause of this disease - a combination of common viruses - by reading the DNA sequence of viruses in samples of blood and liver from children with the disease.

We have put together a rapid research plan to tackle the key questions identified by UK public health agencies. To do this, the first thing we need to do is recruit patients and their families into research studies to look for the cause of the disease, understand the role of the immune system, find genetic factors that may explain the disease processes, and suggest new treatments.

A series of cases of severe hepatitis in young children of unknow cause were recognised in Central Scotland in March 2022. As of 11 May 2022, there have been 176 such cases across the UK, predominantly in children under 5 years old. The aetiology is unknown but an infection or co-infection is a strong possibility and preliminary data from ISARIC CCP work suggests that co-infection with adenovirus 41F and an adeno-associated virus 2 (AAV2) may be responsible.

The CCP is a “sleeping” research protocol, established nationwide in 2013 to provide a rapid research response to new outbreaks and exposures of public health interest. It is managed by a broad consortium of experts with a proven track record of high-quality outbreak research. In partnership with medical and scientific experts and public health agencies including UKHSA and PHS, we responded immediately to this outbreak by using the existing ISARIC CCP-UK.