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This briefing is produced to share data useful to other public health investigators and academic partners undertaking related work. Although a detailed clinical case review is also taking place, that data is not shared here as, given the small number of cases, there are some risks to confidentiality.
Cases
As of 3 May 2022, there have been 163 cases of acute non-A-E hepatitis with serum transaminases greater than 500 IU/l identified in children aged under 16 years old in the UK since 1 January 2022. This is the result of an active case finding investigation commencing in April which identified retrospective as well as prospective cases. Eleven cases have received a liver transplant. No cases resident in the UK have died. New cases continue to be identified. Whilst there is some apparent reduction in confirmed cases in the past 2 weeks overall in the UK, there are continued new case reports in Scotland, the number of cases pending classification in England is substantial and the likely reporting lags mean that we cannot yet say there is a decrease in new cases. Cases pending classification are usually those in which laboratory testing to rule out known causes of hepatitis has not been completed.
Working hypotheses
The working hypotheses have been refined. The leading hypotheses remain those which involve adenovirus. However, we continue to investigate the potential role of SARS-CoV-2 and to work on ruling out any toxicological component.
Associated pathogens
Adenovirus remains the most frequently detected potential pathogen. Amongst 163 UK cases, 126 have been tested for adenovirus of which 91 had adenovirus detected (72%). Amongst cases the adenovirus has primarily been detected in blood. On review of some of the adenovirus negative cases it was notable that some had only been tested on respiratory or faecal samples, and some had been tested on serum or plasma rather than whole blood (whole blood being the optimal sample). It is therefore not possible to definitively rule out adenovirus in these cases. SARS-CoV-2 has been detected in 24 cases of 132 with available results (18%). SARS-CoV-2 serological testing is in process. A range of other possible pathogens have been detected in a low proportion of cases and are of uncertain significance, although the inclusive nature of the UKHSA case definition intentionally will pick up some cases of non-A-E hepatitis with recognised causes.
Adenovirus characterisation
Typing by partial hexon gene sequencing consistently shows that the adenovirus present in blood is type 41F (18 of 18 cases with an available result). Whole genome sequencing (WGS) has been attempted on multiple samples from cases but the low viral load in blood samples, and limited clinical material from historic cases, mean that it has not been possible to get a good quality full adenovirus genome from a case as yet.
Metagenomics
Metagenomics undertaken on blood and liver tissue has detected primarily adeno-associated virus 2 (AAV-2) in high quantities. Whilst contamination was originally suspected, AAV-2 is now detected in multiple samples from different hospital sources and tested in more than one sequencing laboratory. This finding is of uncertain significance and may represent a normal reactivation of AAV-2 during an acute viral infection (for example, adenovirus) or during liver injury of another cause. It is not unusual to detect bystander, reactivating or other incidental species during metagenomic sequencing. However, given the presence of AAV-2 in a number of cases, the significance will be further explored through testing of additional sets of controls.
Toxicology
Toxicological investigations continue with no positive findings to date. Detection of paracetamol is likely to be related to appropriate therapeutic use (also noted in the trawling questionnaires) which would not be a concern, however verification work is being undertaken to confirm this.
Host investigations
Host (for example, immunological) investigations require full research consent and are undertaken under the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Clinical Characterisation Protocol. Thirty-seven cases have been recruited to the ISARIC clinical characterisation protocol to date and retrospective and prospective recruitment continues...
Update 2 (May 6, 2022):
