https://pubmed.ncbi.nlm.nih.gov/36822480/ Acute liver failure

J Hepatol. 2023 Feb 21;S0168-8278(23)00101-0.
doi: 10.1016/j.jhep.2023.02.013.Online ahead of print.

Outbreak of indeterminate acute liver failure in children with adenoviraemia - Not a new disease

Barath Jagadisan 1, Anita Verma 2, Maesha Deheragoda 3, Akash Deep 4, Tassos Grammatikopoulos 5, Malur Sudhanva 6, Sanjay Bansal 7, Nedim Hadzic 8, Sunitha Vimalesvaran 9, Nigel Heaton 10, Anil Dhawan 11

Abstract
Background & aims: In the year 2022, United Kingdom (UK) reported an outbreak of indeterminate acute hepatitis and indeterminate paediatric acute liver failure (ID-PALF) in immunocompetent children in association with adenoviraemia. We postulate that this association is not a new disease in immunocompetent children.

Methods: Children with acute hepatitis during the outbreak referred to King's College Hospital, London for advice and management. The frequency of ID-PALF in 2022, their transplantation rates and association with adenovirus infection were obtained from electronic health records. The clinical presentation, histology and outcomes of children with ID-PALF with adenoviraemia in 2017-2021 were compared with that in 2022.

Results: From January to June 2022, 65 patients with acute hepatitis were referred. Ten children were admitted with ID-PALF. ID-PALF constituted 26% of all PALF in 2017-2021, in contrast to 58.8% during the 2022 outbreak. During the outbreak, adenoviraemia was present in 52% of children with acute hepatitis without liver failure in whom adenoviraemia test results were available and in 100% of ID-PALF. Adenoviraemia was seen in immunocompetent children in 6/13 (46%) of all ID-PALF between 2017-2019 with a clear absence of adenoviraemia in the 6 ID-PALF cases during 2020-2021. ID-PALF with adenoviraemia during the outbreak (n=10) when compared with ID-PALF with adenoviraemia in 2017-2019 (n=6), showed more frequent hepatic encephalopathy, hypotension requiring vasoactive medications and higher plasma ammonia levels (admission and peak), with similar native liver survival.

Conclusions: The recent outbreak of ID-PALF with adenoviraemia in immunocompetent children does not appear to be a new disease unlike what was perceived and reported. The frequency of such cases over the years could possibly be linked to background rates of adenovirus infections.