The Effect of Overweight and Obesity on Liver Biochemical Markers in Children and Adolescents

Magnus J. Johansen; Julie Gade; Stefan Stender; Christine Frithioff-Bøjsøe; Morten A. V. Lund; Elizaveta Chabanova; Henrik S. Thomsen; Oluf Pedersen; Cilius E. Fonvig; Torben Hansen; Jens-Christian Holm

Disclosures

J Clin Endocrinol Metab. 2020;105(2) 

In This Article

Abstract and Introduction

Abstract

Background: Elevated plasma concentrations of liver enzymes are routinely used as markers of liver injury in adults and children. Currently, the age- and sex-specific effects of adiposity on pediatric liver enzyme concentrations are unclear.

Methods: We included participants from 2 cohorts of Danish children and adolescents: 1858 from a population-based cohort and 2155 with overweight or obesity, aged from 6 to 18 years. Age- and sex-specific percentile curves were calculated for fasting plasma concentrations of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), bilirubin, and alkaline phosphatase (ALP) in both cohorts. Hepatic fat content was assessed by proton magnetic resonance spectroscopy in 458 participants.

Results: Concentrations of ALT, AST, LDH, and ALP decreased with age in both girls and boys, while GGT and bilirubin were comparable across age groups in girls and increased slightly with age in boys. Children and adolescents with overweight or obesity exhibited higher concentrations of ALT in all age groups. Concentrations of ALT, and to a lesser degree GGT, increased with age in boys with overweight or obesity. Optimal ALT cut-points for diagnosing hepatic steatosis (liver fat content > 5%) was 24.5 U/L for girls (sensitivity: 55.6%, specificity: 84.0%), and 34.5 U/L for boys (sensitivity: 83.7%, specificity: 68.2%).

Conclusions: Pediatric normal values of liver enzymes vary with both age and sex. Overweight and obesity is associated with elevated biochemical markers of liver damage. These findings emphasize the need for prevention and treatment of overweight and obesity in children and adolescents.

Introduction

The prevalence of obesity in children and adolescents has increased worldwide in the past decades.[1,2] Overweight and obesity in children increase the risk of developing diseases linked to the metabolic syndrome, including nonalcoholic fatty liver disease (NAFLD). NAFLD is among the most common comorbidities in children with obesity, with reported prevalence rates of 30% to 70%.[3–8] NAFLD covers a spectrum of disease activity in the absence of high alcohol consumption, beginning with its main characteristic, accumulation of fat in the liver (hepatic steatosis). Hepatic steatosis may cause inflammation and subsequent liver cell damage (steatohepatitis), progress to fibrosis and scarring, and potentially result in end-stage liver disease as childhood-onset cirrhosis.[9–11] Furthermore, hepatocellular carcinomas may occur, even in the absence of cirrhosis.[12,13] It is important to detect liver damage, both at an early age and at an early stage of NAFLD, in order to avoid disease progression to an irreversible stage.[14,15] Liver biopsy is the gold standard for assessing liver damage, but the invasiveness and risks associated with this procedure makes it unsuitable for routine clinical screening and monitoring.[11]

In daily clinical practice, plasma concentrations of liver enzymes and bilirubin are routinely used as a marker of liver injury. The most frequently measured biochemical markers include alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), bilirubin, and alkaline phosphatase (ALP).[16] Plasma concentrations of ALT are commonly used to screen for NAFLD in children with overweight or obesity worldwide.[10,17,18] However, the specific screening methodology, including cutoff values and whether additional biochemical markers are also evaluated, varies between countries and studies.[10,17–19]

Assessing biochemical markers in a pediatric cohort requires not only consideration of age, but also of sex, growth, and pubertal development.[15,20] It is essential that reference values are defined from a healthy, large, and representative population recruited outside the hospital setting.[21] This establishes reliable cutoff values, which are able to identify liver disease in children and adolescents with overweight or obesity.[22,23]

In the present study, we provide age- and sex-specific reference values for ALT, AST, GGT, LDH, bilirubin, and ALP in a population-based cohort of Danish children and adolescents aged 6 to 18 years. Furthermore, we examine how the values in a large cohort of children and adolescents with overweight or obesity compare with this reference. In addition we assess the hepatic fat content by proton magnetic resonance spectroscopy (1H-MRS) in a subsample of the cohort with overweight or obesity and the populationbased cohort, and calculate optimal cutoffs of plasma ALT concentrations for identifying hepatic steatosis.

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