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)

Conclusion

This study provides age- and sex-specific reference values for plasma concentrations of ALT, AST, LDH, GGT, bilirubin, and ALP derived from a populationbased cohort of Danish children and adolescents aged 6 to 18 years. We found that age and sex influence the patterns of these biochemical markers throughout childhood and adolescence. Obesity in children and adolescents is associated with elevated biochemical markers of liver damage, likely reflecting the effects of NAFLD. These findings emphasize the need for both efficient preventive and treatment strategies in pediatric populations with overweight and obesity.

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Abbreviations
ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; AUC, area under the curve; BMI, body mass index; GGT, gamma-glutamyltransferase; ¹H-MRS, proton magnetic resonance spectroscopy; LDH, lactate dehydrogenase; MR, magnetic resonance; NAFLD, nonalcoholic fatty liver disease; ROC, receiver operating characteristic; SDS, standard deviation score.

Acknowledgments
This study is part of the research activities in TARGET, BIOCHILD, Novo Nordisk Foundation Challenge Programme "MicrobLiver," and The Danish Childhood Obesity Biobank. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at Copenhagen University partially funded by the Novo Nordisk Foundation. The authors wish to thank Oda Troest and Birgitte Holløse for logistical support.

Financial Support
This study received funding from the Innovation Fund Denmark (grant numbers 0603-00484B (TARGET) and 0603-00457B (BIOCHILD), The Novo Nordisk Foundation (grant number NNF15OC0016544 and NNF15OC0016692), and The Region Zealand Health Scientific Research Foundation.

Table 1. Comparison of anthropometrics and liver biochemical markers between the population cohort and the cohort with overweight or obesity. Values are medians and interquartile ranges. Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; BMI-SDS, body mass index standard deviation score; GGT, gammaglutamyltransferase; LDH, lactate dehydrogenase. P values are by Wilcoxon rank sum test. P values below 0.001 are bold.
	Population-based cohort	Cohort with overweight and obesity	P	Population-based cohort	Cohort with overweight and obesity	P	Population-based cohort	Cohort with overweight and obesity	P
	6–9 years			10–13 years			14–18 years
	Girls
Age	8 [7–9]	8 [7–9]	0.151	12 [11–12]	12 [11–12]	0.399	15 [14–17]	15 [14–16]	0.008
Height, cm	131 [124–138]	136 [131–142]	<0.001	152 [146–159]	154 [148–160]	0.042	166 [162–171]	165 [161–170]	0.031
Weight, kg	27 [23–30]	42 [37–48]	<0.001	40 [36–45]	62 [54–80]	<0.001	55 [51–60]	85 [76–95]	<0.001
Waist, cm	58 [55–60]	78 [73–84]	<0.001	63 [60–67]	90 [84–98]	<0.001	71 [66–75]	102 [94–111]	<0.001
Hip, cm	68 [64–71]	82 [78–88]	<0.001	78 [74–83]	96 [89–103]	<0.001	91 [87–96]	110 [104–118]	<0.001
BMI kg/m²	16 [15–17]	23 [21–25]	<0.001	17 [16–18]	26 [24–29]	<0.001	20 [19–21]	31 [28–34]	<0.001
BMI-SDS	0.01 [-0.53 - 0.58]	3 [2–3]	<0.001	0.06 [-0.40–0.56]	3 [2–3]	<0.001	0.17 [-0.38–0.7]	3 [2–3]	<0.001
ALT, U/L	21 [17–24]	23 [20–28]	<0.001	18 [15–22]	23 [18–30]	<0.001	18 [14–22]	22 [17–30]	<0.001
AST, U/L	31 [27–36]	27 [23–32]	<0.001	25 [22–30]	25 [21–29]	0.163	20 [17–24]	21 [18–26]	0.020
LDH, U/L	228 [208–254]	251 [230–274]	<0.001	201 [180–219]	221 [196–252]	<0.001	161 [143–175]	181 [162–202]	<0.001
GGT, U/L	17 [14–19]	16 [13–18]	0.034	16 [11–18]	16 [13–19]	0.009	16 [11–18]	17 [13–22]	<0.001
Bilirubin, μmol/L	7 [6–9]	7.00 [5–9]	0.111	7 [6–9]	7 [5–9]	0.100	8 [6–10]	7 [5–10]	0.119
ALP, U/L	262 [223–303]	280 [238–325]	<0.001	275 [224–331]	265 [217–316]	0.088	101 [76–157]	107 [85–144]	0.113
Boys
Age	8 [7–9]	9 [8–9]	<0.001	11 [11–12]	12 [11–12]	0.077	15 [14–16]	15 [14–16]	0.075
Height, cm	131 [125–137]	139 [132–144]	<0.001	150 [144–156]	154 [149–160]	<0.001	174 [166–180]	172 [165–189]	0.115
Weight, kg	27 [24–30]	45 [39–53]	<0.001	38 [34–43]	62 [54–70]	<0.001	60 [51–65]	92 [77–108]	<0.001
Waist, cm	58 [56–61]	81 [75–87]	<0.001	64 [61- 67]	92 [85–98]	<0.001	73 69–76]	105 [97–115]	<0.001
Hip, cm	68 [65–72]	84 [80–90]	<0.001	78 [73- 81]	95 [89–100]	<0.001	91 [84–95]	108 [101–117]	<0.001
BMI kg/m²	16 [15–17]	24 [22–26]	<0.001	17 [16–18]	26 [24–29]	<0.001	19 [18–21]	31 [27–34]	<0.001
BMI-SDS	0.03 [-0.41–0.54]	3 [3–4]	<0.001	0.03 [-0.46–0.62]	2.98 [2.52, 3.43]	<0.001	0.21 [-0.34–0.66]	3 [3–4]	<0.001
ALT, U/L	21 [18–25]	22 [18–29]	<0.001	19 [17–23]	23 [19–31]	<0.001	20 [17–24]	29 [21–43]	<0.001
AST, U/L	32 [29–37]	29 [25–33]	<0.001	27 [24–31]	26 [22–31]	0.113	25 [21–30]	25 [21–31]	0.307
LDH, U/L	233 [210–253]	252 [232–275]	<0.001	212 [193–229]	234 [213–254]	<0.001	184 [161–205]	206 [184–229]	<0.001
GGT, U/L	17 [13–19]	16 [13–18]	0.081	17 [12–19]	17 [14–20]	0.012	18 [14–20]	20 [16–28]	<0.001
Bilirubin, μmol/L	6 [5–8]	6 [5–8]	0.101	7 [5–9]	7 [5–9]	0.685	9 [7–12]	8 [6–11]	0.002
ALP, U/L	247 [213–285]	266 [228–315]	<0.001	271 [227–319]	269 [238–327]	0.453	233 [153–310]	239 [163–306]	0.683