title: Children's liver chemistries vary with age and gender and require customized pediatric reference ranges.
abstract: Used to detect liver disease and injury, baseline liver chemistry distributions were evaluated by age and gender in children without known liver disease. Baseline liver chemistries [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL)] were analyzed from 24 randomized controlled pediatric clinical trials. Using quantile regression, liver chemistry distributions were examined by age and gender; upper limit normal (ULN) ranges were compared to the 97.5th percentiles of the distributions for the specified ages and genders. 5410 subjects without known liver disease (0-18 years; 60% male) were studied. The median ALT varied little with age. In males age 5-18, the ALT 97.5th percentile increased from 34 to 63 IU/L. In both genders, the median and 97.5th percentile AST decreased with age. After age 9, ALP decreased. TBIL increased with age. Despite most liver chemistry 97.5th percentiles changing substantively with age and gender, the reference lab ULN generally changed minimally and did not correlate with the 97.5th percentile. Gender and age specific 97.5th percentile data should therefore be considered for the reference laboratory ULN in children to more accurately detect liver injury and disease.
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Stockley Park, UK. Electronic address: heide.a.stirnadel@gsk.com.
authors.forename: Heide A
authors.initials: HA
authors.lastname: Stirnadel-Farrant
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Stockley Park, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Galwey
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Stockley Park, UK.
authors.forename: Chanchal
authors.initials: C
authors.lastname: Bains
authors.affiliation: Department of Epidemiology, University of North Carolina, Gillings School of Global Public Health, Chapel Hill, NC, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Yancey
authors.affiliation: Division of Gastroenterology, Duke University Medical Center, Durham, NC, USA; Durham Veterans Administration Medical Center, Durham, NC, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hunt
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000378:metabolism* / Q000502:physiology*; D008107:Liver Diseases / Q000378:metabolism / Q000503:physiopathology; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D012016:Reference Values; D055815:Young Adult
chemical_list: D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin
keywords: Alanine aminotransferase; Alkaline phosphatase; Laboratory reference ranges; Liver chemistries; Pediatric clinical trials