Children with acute hepatitis of unknown etiology (International, April 2022)

Background

Pathogen: Acute hepatitis refers to sudden, severe inflammation of the liver. It can manifest with jaundice (yellowing of skin and sclera), dark urine, pale stools, abdominal pain, nausea, and vomiting. It can sometimes progress to liver failure, which may require liver transplantation or dialysis in extreme cases. Hepatitis in children is usually attributed to hepatitis A, B, D, or E. It can also be caused by other viruses (e.g. Epstein‑Barr virus, cytomegalovirus), toxins, or autoimmune issues. The acute hepatitis of unknown etiology affecting children during this outbreak was suspected to be caused by adenovirus.
Transmission: Adenoviruses are transmitted via fecal‑oral route, through contaminated surfaces, respiratory droplets, or contact with infected individuals. If an adenovirus was indeed the cause (or contributing factor) of this outbreak, transmission would likely follow known adenovirus transmissibility patterns (i.e. person‑to‑person, environmental contamination). Because the etiology remains unknown, transmission routes beyond adenovirus modes are not confirmed.
Sources and risk factors: As the causative agent is not definitively known, specific sources remain speculative. The outbreak primarily affected children under the age of 16.
Seasonality: Adenoviruses do show seasonal variation (late winter: Feb- March, early spring: April- May) in general. Whether that aligns with these hepatitis cases of unknown etiology is under investigation.

In April 2022, the UK detected several pediatric cases of severe acute hepatitis of unknown cause. Patients tested negative for hepatitis A–E and other known causes of hepatitis. The cases were reported through WHO’s International Health Regulations system, triggering global attention. Subsequently, several other countries (US, Japan, Ireland, Netherlands, Denmark, and Sweden) reported similar increases of acute hepatitis of unknown etiology in children. A matched case–control study in the UK (74 cases vs 225 controls) found that adenovirus was the pathogen most frequently detected in the cases of hepatitis. This suggests that it is the most likely cause. As the timeline of the outbreak overlapped with the COVID-19 pandemic, the possibility of association with COVID‑19 was considered, but no evidence was found. In Sweden, researchers conducted wastewater surveillance to monitor for the presence of adenovirus F41 variants.

YEAR	DATE	OBSERVATION
2022	April	Initial cases were reported in the UK for pediatric acute hepatitis of unknown etiology, patients tested negative for hepatitis A–E and other known agents.
2022	July	WHO stated that more countries (including Sweden) began reporting increased numbers of unexplained hepatitis cases in children.
2022	October	A matched case–control study in the UK identified adenovirus as the most likely cause.
2022	September	Researchers from Sweden conducted wastewater monitoring to detect adenovirus F41.
2022	November	ECDC launched a surveillance program to provide an overview of cases across countries.

Hepatitis of unknown origin in Children Surveillance Bulletin was launched by ECDC to provide an overview of cases reported across the countries during the outbreak in 2022.