Obesity was found to be associated with elevated markers of liver damage in children and adolescents, according to study results published in The Journal of Clinical Endocrinology & Metabolism.
While plasma concentrations of liver enzymes and bilirubin are frequently used as a marker of liver injury, the age- and sex-specific effects of childhood overweight and obesity on these liver enzymes are unclear. The goal of the current study was to determine age- and sex-specific reference values for liver enzymes in children and adolescents, as well as to assess the impact of adiposity.
The study included 2 cohorts: a population-based cohort with 1858 normal-weight children and adolescents and a cohort with 2155 children and adolescents with overweight/obesity, all aged 6 to 18 years. Children and adolescents with overweight, obesity, or underweight in the population-based cohort were excluded from the main analysis to ensure that the reference values were based on healthy normal-weight patients only.
Age- and sex-specific percentile curves were calculated for fasting plasma concentrations of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), gammaglutamyltransferase (GGT), bilirubin, and alkaline phosphatase (ALP) in both cohorts.
In the population-based cohort, concentrations of ALT and AST declined with age among normal-weight boys and girls. Increased standard deviation score for body mass index was associated with higher ALT in boys, but not in girls. LDH concentrations decreased with age. GGT concentrations showed no change with age in boys or girls, while bilirubin showed no change with age in girls, but a modest increase with age was evident in boys. For ALP, levels initially increased until reaching a peak at ages 11 to 12 years in girls and 13 to 14 years in boys, followed by a sharp decline in both sexes.
In the cohort of patients with overweight/obesity, ALT concentrations were higher in all age groups and in both boys and girls. Unlike the pattern in the population-based cohort, ALT levels increased markedly with age in children with overweight/obesity, and this trend was more pronounced in boys >13 years of age. In addition, compared with the population-based cohort, there was a modest age-associated increase in GGT in children with overweight or obesity, which was more pronounced in boys.
The researchers also assessed hepatic fat content by proton magnetic resonance spectroscopy in 458 patients and explored the ability of ALT to identify hepatic steatosis, as defined by liver fat content >5%. Based on this definition, 25 girls (9.9%) and 44 boys (21%) had evidence of hepatic steatosis. The optimal ALT cutoff point was 24.5 U/L for girls (sensitivity: 55.6%; specificity: 84.0%; area under the curve: 71.8%), and 34.5 U/L for boys (sensitivity: 83.7%; specificity: 68.2%; area under the curve: 79.1%).
The researched noted several limitations of the study, including no data on viral infections that might have affected liver enzymes, possible misreporting as alcohol consumption was based on self-report, and the fact the liver fat content quantification was not possible for all individuals.
“The increased plasma concentrations of ALT in girls and boys with overweight or obesity might reflect the presence of [nonalcoholic fatty liver disease] or [nonalcoholic] steatohepatitis in many of these children… These findings emphasize the need for both efficient preventive and treatment strategies in pediatric populations with overweight and obesity,” concluded the researchers.
Disclosure: This clinical trial was supported by The Novo Nordisk Foundation. Please see the original reference for a full list of disclosures.
Johansen MJ, Gade J, Stender S, et al. The effect of overweight and obesity on liver biochemical markers in children and adolescents [published online October 16, 2019]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgz010/5588552