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Etiology of acute liver failure in children in North America and Europe (final diagnosis as percent of cases in each age group)

Diagnosis	Percent of cases in age group (n)
Diagnosis	All ages (n = 986)	0 to 90 days (n = 181)	91 days to 3 years (n = 274)	4 to 17 years (n = 531)
Indeterminate	45 (444)	35 (64)*	59 (162)*	41 (218)*
APAP	12 (123)	1 (1)	4 (12)	21 (110)*
Metabolic	10 (100)	17 (31)*	11 (30)*	7 (39)*
Tyrosinemia	1 (9)	2 (3)	2 (6)	0 (0)
Wilson disease	4 (36)	0 (0)	0 (0)	7 (36)*
Fatty acid oxidation	<1 (5)	0 (0)	2 (5)	0 (0)
Alpha₁-antitrypsin	<1 (2)	0 (0)	1 (2)	0 (0)
Mitochondrial	<1 (20)	5 (9)*	4 (10)	<1 (1)
Galactosemia	<1 (13)	7 (13)*	0 (0)	0 (0)
Niemann-Pick type C	<1 (4)	2 (4)	0 (0)	0 (0)
Urea cycle defect	<1 (8)	1 (2)	2 (5)	<1 (1)
Glycosylation defect	<1 (1)	0 (0)	<1 (1)	0 (0)
Reye syndrome	<1 (1)	0 (0)	0 (0)	<1 (1)
Fructose intolerance	<1 (1)	0 (0)	<1 (1)	0 (0)
Viral hepatitis	8 (77)*	20 (36)*	5 (14)*	5 (27)*
Hepatitis A	<1 (5)	0 (0)	0 (0)	1 (5)
Hepatitis B	<1 (3)	0 (0)	<1 (1)	<1 (2)
Hepatitis C	<1 (1)	0 (0)	0 (0)	<1 (1)
Hepatitis E	<1 (2)	0 (0)	0 (0)	<1 (2)
Epstein-Barr virus	<1 (8)	0 (0)	1 (3)	1 (5)
Cytomegalovirus	<1 (3)	1 (2)	<1 (1)	0 (0)
Herpes simplex	3 (31)	15 (28)*	<1 (1)	<1 (2)
Enterovirus	<1 (8)	3 (6)	<1 (1)	<1 (1)
Adenovirus	<1 (5)	0 (0)	1 (2)	1 (3)
Human herpesvirus 6	<1 (2)	0 (0)	<1 (1)	<1 (1)
Parvovirus	<1 (1)	0 (0)	0 (0)	<1 (1)
Influenza/parainfluenza	<1 (5)	0 (0)	1 (3)	<1 (2)
Paramyxovirus	<1 (3)	0 (0)	<1 (1)	<1 (2)
Autoimmune	7 (68)	0 (0)	7 (20)*	9 (48)*
Shock/ischemia	3 (31)	3 (6)	3 (8)	3 (17)
Non-APAP drug-induced	3 (29)	15 (27)*	1 (2)	5 (27)*
GALD	3 (27)	3 (6)	0 (0)	0 (0)
HLH	3 (25)	1 (2)	4 (10)	2 (9)
Multiple	2 (20)	0 (0)	2 (5)	2 (13)
Veno-occlusive disease	1 (12)	0 (0)	2 (6)	1 (6)
Other	3 (30)	4 (8)	2 (5)	3 (17)
Budd-Chiari	<1 (3)	0 (0)	0 (0)	1 (3)
Mushroom toxicity	<1 (5)	0 (0)	0 (0)	1 (5)
Leukemia	<1 (3)	<1 (1)	0 (0)	<1 (2)
Sepsis	<1 (4)	1 (2)	<1 (1)	<1 (1)
Other	2 (15)	3 (5)	1 (4)	1 (6)

Data from the Pediatric Acute Liver Failure Study Group, 2000 to 2012.

APAP: acetaminophen; GALD: gestational alloimmune liver disease; HLH: hemophagocytic lymphohistiocytosis.
* Denotes the more common causes in each age group (≥5% of cases).

Original table modified for this publication. From: Narkewicz MR, Horslen S, Hardison RM, et al. A Learning Collaborative Approach Increases Specificity of Diagnosis of Acute Liver Failure in Pediatric Patients. Clin Gastroenterol Hepatol 2018; 16:1801. Table used with the permission of Elsevier Inc. All rights reserved.

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