Following the report shared by the United Kingdom regarding cases of severe acute hepatitis of unknown origin in young children, a standardized reporting system involving a network of clinicians and laboratories was established in France to detect any similar cases within the country. An initial case definition for healthcare professionals was thus published on May 3, 2022. Today, based on evolving knowledge and following further discussions with its network of partners (clinicians, laboratory specialists), Santé publique France is updating the case definition to improve its sensitivity and enable the identification of less severe cases, which may be more numerous. Additionally, the recommended procedures have been updated to reflect this new case definition.

A reporting system for suspected cases to complement syndromic surveillance

The formalized system for reporting and investigating possible cases, established in collaboration with the Ministry of Health, relies on a network of clinicians and laboratories, including the four liver transplant centers (Necker, Bicêtre, Marseille, Lyon) and pediatric intensive care units. Its objective is to detect any potential signal similar to that observed in the United Kingdom within the country.

The system is based on a new case definition developed in collaboration with pediatric hepatologists and the three National Reference Centers involved (for viral hepatitis B/C/Delta, gastroenteritis viruses, and respiratory infection viruses). The protocol for managing cases of severe acute hepatitis in children under 18 has consequently been updated and distributed by the Ministry of Health to the relevant healthcare professionals.

In addition, Santé publique France continues to regularly analyze:

• emergency department visit data from the OSCOUR® network for a selection of diagnostic codes consistent with acute hepatitis of unknown etiology (excluding, in particular, viral hepatitis A through E) in children under 18 years of age, in order to identify any unusual increase in such cases in the recent period;

• hospitalization data (PMSI) to detect any potential increase in the number of hospital stays consistent with acute hepatitis of unknown origin (data currently available through the end of January 2022).

Why are we updating the case definition?

The initial definition for pediatric cases of acute hepatitis was developed with the aim of rapidly identifying severe cases of unknown origin and characterizing them precisely. The investigation process established in collaboration with the Ministry of Solidarity and Health has identified two cases. Based on current knowledge, it is not possible to determine whether there is a link between these cases and the report from the United Kingdom.

Following further discussions with its network of partners (clinicians, biologists), Santé publique France is adapting the case definition to improve its sensitivity and be able to identify less severe cases, which may therefore be more numerous.

What’s new?

The main changes made to the case definition were discussed with the Agency’s network of partners, particularly pediatric hepatologists and virologists. They include, among other things:

• The systematic inclusion of cases of acute hepatitis with SARS-CoV-2 or adenovirus infection.

• The removal of the criterion of a prothrombin ratio below 50% (a severity criterion indicating major liver dysfunction) in order to expand data collection to include less severe cases of hepatitis.

• Clarification of the exclusion factors from the definition of a possible case, including: drug-induced hepatotoxicity, viruses typically responsible for acute hepatitis, and other well-known causes that can lead to acute hepatitis.

These changes are expected to result in the reporting of a greater number of cases. These cases are not unexpected in France, but their reporting will allow for in-depth investigation and, where appropriate, linking them to the alert in the United Kingdom.

The publication of this case definition is intended for investigative and epidemiological surveillance purposes but does not alter the medical management of the affected children.