Comparison of three pediatric studies investigating acute hepatitis of unknown etiology

Table 1 Characteristics of cases of acute hepatitis of unknown etiology and controls in the United Kingdom and United States studies

	England	Scotland	United States
Case definition of acute hepatitis of unknown etiology	A person presenting since January 1, 2022 with acute hepatitis which is not due to hepatitis A-E viruses, or an expected presentation of metabolic, inherited or genetic, congenital or mechanical cause with serum transaminase greater than 500 IU/L (AST or ALT), who is 10 years old and under	A person presenting with a serum transaminase greater than 500 IU/L (AST or ALT) without known cause (excluding hepatitis A-E, CMV and EBV), who is 10 years of age and under or a contact of any age of a confirmed case, since 1 January 2022	Children < 10 years of age with elevated (> 500 U/L) AST or ALT since October 1, 2021 who have an unknown etiology for their hepatitis (with or without any adenovirus testing results, irrespective of the results)
Number of cases	n = 38	n = 32	n = 16
	Male: 12, Female: 15, Unknown: 11	Male: 11, Female: 21	Male: 9, Female: 7
	1-9 years of age (median 3)	2.7-5.5 years of age (median 4.1)	Mean age: 3.8 ± 2.0 (median 3)
	Liver transplantation, n = 12	Liver transplantation, n = 1	Liver transplantation, n = 2
	Treatment with cidofovir, n = 14	Treatment with cidofovir, n = 1	Treatment with cidofovir, no data
	Blood HAdV PCR was positive in 22/23 cases	All routine blood tests for A-E hepatitis, EBV, CMV, HHV-6, HHV-7 and HSV were negative. Of 30 cases, 5 were positive for plasma HAdV PCR	All 16 cases had positive testing for HAdV from blood
Controls (comparators)	Immunocompetent control: n = 65	Group 1: Age-matched healthy control = 13	Group 1: Without hepatitis, n = 42 (non-inflammatory, non-hepatitis hospitalized control, n = 27, inflammatory, non-hepatitis hospitalized control, n = 15)
	Healthy control, n = 13	Group 2: HAdV infection (HAdV PCR positive with normal ALT) control, n = 12	Group 2: Acute hepatitis (ALT > 100 U/L, defined etiology), n = 30
	HAdV infection, normal ALT, n = 17	Group 3: Hepatitis control (HAdV PCR negative with increased ALT), if reactivation of AAV-2 in severe hepatitis, n = 33	Group 3: Acute gastroenteritis, n = 23 (HAdV positive stool, n = 12)
	HAdV infection, normal ALT (HAdV in blood), n = 8	Group 4: Contemporaneous control, if circulating widely across Scotland, n = 16	Group 4: Blood donor, n = 18
	HAdV infection, raised ALT, n = 5
	Critical illness, raised ALT, n = 11
	Non-HAdV infection, raised ALT, n = 5
	Other hepatitis, n = 6
	Immunocompromised comparator: n = 17
	HAdV infection, raised ALT > 500 U/L, n = 14
	CMV infection, raised ALT > 500 U/L, n = 3

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; CMV: Cytomegalovirus; EBV: Epstein-Barr virus; HAdV: Human adenovirus; HHV: Human herpes virus; PCR: Polymerase chain reaction.