LAUSR

Since January 2022, there have been increasing reports of children with acute hepatitis of unknown cause world-wide, mostly in the UK. A retrospective study reported 44 children aged ≤10 years old (median 4 years, range 1–7) referred to the Birmingham, UK paediatric liver-transplantation centre who met the national case definition of confirmed acute hepatitis with serum aminotransferase level > 500 IU/L that was not hepatitis A to E and did not have a metabolic, inherited or genetic, congenital, or mechanical cause. Common presenting features were jaundice (93%), vomiting (54%), and diarrhoea (32%). 27 (90%) of 30 patients tested using molecular testing were positive for human adenovirus. Six patients (14%) developed fulminant liver failure requiring liver transplant. No patients died. A case series from Alabama, USA reported 15 children in 6 months with acute hepatitis: 6 (40%) had hepatitis with an identified cause and 9 (60%) had hepatitis without a known cause. Eight (89%) of the nine patients with hepatitis of unknown cause tested positive for human adenovirus by wholeblood polymerase chain reaction (PCR). These eight and one additional patients referred to the facility (age range 1–6 years) were included in the case series. Two children required liver transplantation. Six children had mild-to-moderate active hepatitis on liver biopsy, with or without cholestasis; none had immunohistochemical evidence of human adenovirus, but PCR testing of liver tissue for human adenovirus was positive in three of six children. Sequencing of specimens from five children showed three distinct human adenovirus type 41 variants. Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause but sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. The role of human adenovirus in the pathogenesis of acute hepatitis of unknown cause has not been established.