Age‐ and Sex‐related Reference Ranges of Alanine Aminotransferase Levels in Children: European Paediatric HCV Network

Abstract

Serum alanine aminotransferase (ALT) levels are commonly used to indicate liver damage. Although elevated levels indicate possible liver injury, abnormalities, or disease, some patients with "normal" ALT levels have minimal to mild liver disease. Recently, ALT reference ranges for adults were queried and revised ranges proposed with lower upper limits of normality. The appropriateness of current paediatric ALT reference ranges is unclear. Hepatitis C virus (HCV)-uninfected children from the European Paediatric HCV Network represent a large population of healthy children born to HCV-infected mothers, with ALT observations collected prospectively from birth. Linear regression identified factors associated with ALT levels while accounting for within-child repeated measurements. ALT centiles stratified by sex were calculated using maximum penalized likelihood methods and LMS software. A total of 1293 HCV-uninfected children had 5011 ALT measurements during follow-up. ALT levels significantly decreased with increasing age, whilst ALT levels were significantly lower in girls than boys. Reference cutoffs representing the 95th centiles before 18 months of age were 60 U/L for boys and 55 U/L for girls, decreasing to 40 U/L for boys and 35 U/L for girls after 18 months of age. These reference ranges represent a unique investigation of ALT levels in a healthy child population. We show lower and more detailed age-related cutoffs of normality than available. Additionally, we demonstrate a significant effect of sex on ALT reference ranges, which has not previously been described in children younger than 5 years of age.