Guidance

Increase in acute hepatitis cases of unknown aetiology in children

Published 8 April 2022

UKHSA is working with the NHS and public health colleagues across the UK to investigate the potential cause of an unusually high number of acute hepatitis cases being seen in children from England, Scotland and Wales in the past few weeks. There is no known association with travel, and hepatitis viruses (A to E) have not been detected in these children.

The clinical syndrome in identified cases is of severe acute hepatitis with markedly elevated transaminases, often with jaundice, sometimes preceded by gastrointestinal symptoms including vomiting as a prominent feature, in children up to the age of 16 years. In England, there are approximately 60 cases under investigation with most cases being 2 to 5 years old. Some cases have required transfer to specialist children’s liver units and a small number of children have undergone liver transplantation. Based on reports from the specialist units, no child has died. The underlying cause of this increase in presentation since early 2022 currently remains unknown.

Clinicians are asked to be alert to this emerging situation, and to be vigilant to children presenting with signs and symptoms potentially attributable to hepatitis that may require liver function testing. These include:

• discolouration of urine (dark) and/or faeces (pale)
• jaundice
• pruritis
• arthralgia/myalgia
• pyrexia
• nausea, vomiting or abdominal pain
• lethargy and or loss of appetite

GPs should be alert to children presenting with symptoms compatible with acute hepatitis and seek advice from their local Trust.

Clinicians are asked to be aware of potential new cases of unexplained acute hepatitis in children aged 16 years or under, with a serum transaminase >500 IU/L (AST or ALT). All staff involved in the care of these children should use standard IPC precautions with optimal placement in a single en-suite room whilst the patient is considered infectious and until resolution of symptoms. Follow protocols that would normally apply in the investigation of acute hepatitis and handling of specimens. There should be a low threshold for seeking expert clinical support from, or specialist referral to one of the three paediatric liver centres (King’s College, Birmingham Women’s and Children’s and Leeds Teaching Hospitals) for children who are clinically unwell or deteriorating.

Cases of acute hepatitis in children up to the age of 16 years with a serum transaminase >500 IU/L, in which hepatitis A to E has been excluded, should be notified to local health protection teams by telephone between 9am and 5pm, including weekends.

The following investigations should be performed locally where available. Referral for specialist testing should be via normal arrangements:

Sample type	Test	Pathogen
Blood*	PCR	Adenovirus, Enterovirus, CMV, EBV, HSV, Hepatitis A, Hepatitis C, Hepatitis E, HHV6 and 7
Blood*	Serology	Hepatitis A, B, C, E, CMV, EBV, SARS-CoV-2 anti-S, SARS-CoV-2 anti-N (only if locally available)
Blood	Culture	Standard culture for bacteria/fungi (only if clinically indicated i.e. fever)
Throat swab*	PCR	Respiratory virus panel (including adenovirus/enterovirus/influenza, SARS-CoV-2)
Stool*	PCR	Adenovirus, sapovirus, norovirus, enterovirus Standard bacterial stool pathogen panel to include Salmonella spp (or stool culture depending on local test availability)
Blood* (whole blood in EDTA and plasma separated specimens)	Toxicology	Local investigations according to history Store samples locally - UKHSA will contact laboratories to request samples
Urine*	Toxicology	Local investigations according to history Store samples locally - UKHSA will contact laboratories to request samples

*earliest possible sample.

Positive results should be reported following usual process.

In addition, please consider the following additional tests if relevant clinical history: leptospirosis PCR (blood and urine) and serology (blood), throat swab for group A streptococci, serum for anti-streptolysin O titre (ASOT).

Further testing may be required. If possible, the following additional samples should be stored for future testing as soon as an acute case of unexplained hepatitis with serum transaminase >500 IU/L (AST or ALT) in a child aged 16 years or under is identified:

• serum and EDTA samples
• nose and throat swabs (bacterial and viral)
• faecal sample for further testing as required
• urine sample for further testing as required

Any sample positive for a pathogen should be stored for typing.

Clinicians wishing to discuss testing for any acute case of unexplained hepatitis with serum transaminase >500 IU/L (AST or ALT) in a child aged 16 years or under should contact the Imported Fever Service on 0844 778 8990.

Please see UKHSA for the latest updates on this emerging incident.