Top

BMC Pediatrics

Published in:

Open Access 01-12-2021 | Obesity | Research article

Clinical characteristics and risk factors of nonalcoholic fatty liver disease in children with obesity

Authors: Luting Peng, Su Wu, Nan Zhou, Shanliang Zhu, Qianqi Liu, Xiaonan Li

Published in: BMC Pediatrics | Issue 1/2021

Abstract

Background

With the increasing number of children with obesity worldwide, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease among children. It is necessary to recognize the risk factors of NAFLD for prevention in childhood since NAFLD is asymptomatic in the early stage. Objectives. The objective of this study was to investigate possible risk factors of NAFLD in children with obesity, providing evidence for monitoring and prevention strategies at an early stage for obese children with NAFLD.

Methods

Data were collected from 428 children and adolescents aged 6-16 years recruited from the Children’s Hospital at Nanjing Medical University from September 2015 to April 2018 and analyzed. Based on a combination of ultrasound results and alanine transaminase levels, subjects were divided into three groups: simple obesity (SOB), simple steatosis (SS), and nonalcoholic fatty hepatitis (NASH). Blood biochemical examination included glucose, insulin, uric acid, lipid profile and liver enzymes.

Results

Among 428 children with obesity, 235 (54.9%) had SS and 45 (10.5%) had NASH. Body mass index, body mass index standard deviation score (BMI-SDS), waist circumference, body fat, liver enzymes, uric acid and HOMA-IR level were significantly higher in the NASH group than in the SS and SOB groups (p < 0.001). 53.3% of the SS group and 49.8% of the NASH group had metabolic syndrome, significantly more than in the SOB group (19.6%, p < 0.001). After adjustment for confounding factors, logistic regression models revealed that NASH was associated with BMI-SDS ≥ 3, gender, hyperuricemia and insulin resistance.

Conclusions

The prevalence of NASH in children with obesity is closely related to high BMI-SDS, gender, insulin resistance and hyperuricemia. These findings provide evidence that monitoring risk factors of childhood obesity can assist in developing prevention strategies for liver disease at an early stage.

Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118:1388–93 https://doi.org/10.1542/peds.2006-1212.PubMedCrossRef

Zhang W, Wei L. Prevalence of nonalcoholic fatty liver disease in Asia. Chin J Hepatol. 2013;21:801–4.

Anderson EL, Howe LD, Jones HE, Higgins JP, Lawlor DA, Fraser A. The prevalence of non-alcoholic fatty liver disease in children and adolescents: a systematic review and meta-analysis. PLoS One. 2015;10:e0140908 https://doi.org/10.1371/journal.pone.0140908.PubMedPubMedCentralCrossRef

Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science. 2011;332:1519–23 https://doi.org/10.1126/science.1204265.PubMedPubMedCentralCrossRef

Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221–31 https://doi.org/10.1056/NEJMra011775.PubMedCrossRef

Roberts EA. Nonalcoholic steatohepatitis in children. Curr Gastroenterol Rep. 2003;5:253–9 https://doi.org/10.1007/s11894-003-0028-4.PubMedCrossRef

Schwimmer JB, McGreal N, Deutsch R, Finegold MJ, Lavine JE. Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics. 2005;115:e561–5 https://doi.org/10.1542/peds.2004-1832.PubMedCrossRef

Lavine JE, Schwimmer JB. Nonalcoholic fatty liver disease in the pediatric population. Clin Liver Dis. 2004;8:549–58, viii-ix https://doi.org/10.1016/j.cld.2004.04.010.PubMedCrossRef

Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut. 2009;58:1538–44 https://doi.org/10.1136/gut.2008.171280.PubMedCrossRef

10.

Molleston JP, White F, Teckman J, Fitzgerald JF. Obese children with steatohepatitis can develop cirrhosis in childhood. Am J Gastroenterol. 2002;97:2460–2 https://doi.org/10.1111/j.1572-0241.2002.06003.x.PubMedCrossRef

11.

Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation. 2008;118:277–83 https://doi.org/10.1161/CIRCULATIONAHA.107.739920.PubMedPubMedCentralCrossRef

12.

Schwimmer JB, Zepeda A, Newton KP, Xanthakos SA, Behling C, Hallinan EK, et al. Longitudinal assessment of high blood pressure in children with nonalcoholic fatty liver disease. PLoS One. 2014;9:e112569 https://doi.org/10.1371/journal.pone.0112569.PubMedPubMedCentralCrossRef

13.

Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129:113–21 https://doi.org/10.1053/j.gastro.2005.04.014.PubMedCrossRef

14.

Ekstedt M, Hagstrom H, Nasr P, Fredrikson M, Stal P, Kechagias S, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61:1547–54 https://doi.org/10.1002/hep.27368.PubMedCrossRef

15.

Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the expert committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017;64:319–34 https://doi.org/10.1097/MPG.0000000000001482.PubMedPubMedCentralCrossRef

16.

Schwimmer JB, Newton KP, Awai HI, Choi LJ, Garcia MA, Ellis LL, et al. Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2013;38:1267–77 https://doi.org/10.1111/apt.12518.PubMedPubMedCentralCrossRef

17.

Farrell GC, Wong VW, Chitturi S. NAFLD in Asia--as common and important as in the west. Nat Rev Gastroenterol Hepatol. 2013;10:307–18 https://doi.org/10.1038/nrgastro.2013.34.PubMedCrossRef

18.

Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44:865–73 https://doi.org/10.1002/hep.21327.PubMedCrossRef

19.

Mullen MC, Shield J. Pocket guide to pediatric weight management. 2nd ed; 2018.

20.

McCarthy HD, Jarrett KV, Crawley HF. The development of waist circumference percentiles in British children aged 5.0–16.9 y. Eur J Clin Nutr. 2001;55:902–7 https://doi.org/10.1038/sj.ejcn.1601240.PubMedCrossRef

21.

Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–50 https://doi.org/10.1053/gast.2002.35354.PubMedCrossRef

22.

Dhuper S, Cohen HW, Daniel J, Gumidyala P, Agarwalla V, St Victor R, et al. Utility of the modified ATP III defined metabolic syndrome and severe obesity as predictors of insulin resistance in overweight children and adolescents: a cross-sectional study. Cardiovasc Diabetol. 2007;6:4 https://doi.org/10.1186/1475-2840-6-4.PubMedPubMedCentralCrossRef

23.

Song P, Li X, Gasevic D, Flores AB, Yu Z. BMI, waist circumference reference values for Chinese school-aged children and adolescents. Int J Environ Res Public Health. 2016;13 https://doi.org/10.3390/ijerph13060589.

24.

Subspecialty Group of Endocrinologic H, Metabolic Diseases, The Society of Pediatrics Chinese Medical Association, Subspecialty Group of Cardiology TSoPCMA, Subspecialty Groups of Child Health Care TSoPCMA. The definition of metabolic syndrome and prophylaxis and treatment proposal in Chinese children and adolescents. Chin J Pediatr. 2012;50:420–2.

25.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9 https://doi.org/10.1007/bf00280883.PubMedCrossRef

26.

Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics. 2005;115:e500–3 https://doi.org/10.1542/peds.2004-1921.PubMedCrossRef

27.

Ford ES, Li C, Cook S, Choi HK. Serum concentrations of uric acid and the metabolic syndrome among US children and adolescents. Circulation. 2007;115:2526–32 https://doi.org/10.1161/CIRCULATIONAHA.106.657627.PubMedCrossRef

28.

Denzer C, Thiere D, Muche R, Koenig W, Mayer H, Kratzer W, et al. Gender-specific prevalences of fatty liver in obese children and adolescents: roles of body fat distribution, sex steroids, and insulin resistance. J Clin Endocrinol Metab. 2009;94:3872–81 https://doi.org/10.1210/jc.2009-1125.PubMedCrossRef

29.

Alp H, Eklioglu BS, Atabek ME, Karaarslan S, Baysal T, Altin H, et al. Evaluation of epicardial adipose tissue, carotid intima-media thickness and ventricular functions in obese children and adolescents. J Pediatr Endocrinol Metab. 2014;27:827–35 https://doi.org/10.1515/jpem-2013-0306.PubMedCrossRef

30.

Jain V, Jana M, Upadhyay B, Ahmad N, Jain O, Upadhyay AD, et al. Prevalence, clinical & biochemical correlates of non-alcoholic fatty liver disease in overweight adolescents. Indian J Med Res. 2018;148:291–301 https://doi.org/10.4103/ijmr.IJMR_1966_16.PubMedPubMedCentralCrossRef

31.

Pacifico L, Celestre M, Anania C, Paolantonio P, Chiesa C, Laghi A. MRI and ultrasound for hepatic fat quantification:relationships to clinical and metabolic characteristics of pediatric nonalcoholic fatty liver disease. Acta Paediatr. 2007;96:542–7 https://doi.org/10.1111/j.1651-2227.2007.00186.x.PubMedCrossRef

32.

Rajindrajith S, Pathmeswaran A, Jayasinghe C, Kottahachchi D, Kasturiratne A, de Silva ST, et al. Non-alcoholic fatty liver disease and its associations among adolescents in an urban, Sri Lankan community. BMC Gastroenterol. 2017;17:135 https://doi.org/10.1186/s12876-017-0677-7.PubMedPubMedCentralCrossRef

33.

Tominaga K, Fujimoto E, Suzuki K, Hayashi M, Ichikawa M, Inaba Y. Prevalence of non-alcoholic fatty liver disease in children and relationship to metabolic syndrome, insulin resistance, and waist circumference. Environ Health Prev Med. 2009;14:142–9 https://doi.org/10.1007/s12199-008-0074-5.PubMedPubMedCentralCrossRef

34.

Schwimmer JB, Deutsch R, Rauch JB, Behling C, Newbury R, Lavine JE. Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr. 2003;143:500–5 https://doi.org/10.1067/S0022-3476(03)00325-1.PubMedCrossRef

35.

Bugianesi E, Gastaldelli A, Vanni E, Gambino R, Cassader M, Baldi S, et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia. 2005;48:634–42 https://doi.org/10.1007/s00125-005-1682-x.PubMedCrossRef

36.

Neuschwander-Tetri BA. Non-alcoholic fatty liver disease. BMC Med. 2017;15:45 https://doi.org/10.1186/s12916-017-0806-8.PubMedPubMedCentralCrossRef

37.

Ouyang X, Cirillo P, Sautin Y, McCall S, Bruchette JL, Diehl AM, et al. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol. 2008;48:993–9 https://doi.org/10.1016/j.jhep.2008.02.011.PubMedPubMedCentralCrossRef

38.

Sirota JC, McFann K, Targher G, Johnson RJ, Chonchol M, Jalal DI. Elevated serum uric acid levels are associated with non-alcoholic fatty liver disease independently of metabolic syndrome features in the United States: liver ultrasound data from the National Health and Nutrition Examination Survey. Metabolism. 2013;62:392–9 https://doi.org/10.1016/j.metabol.2012.08.013.PubMedCrossRef

39.

Sullivan JS, Le MT, Pan Z, Rivard C, Love-Osborne K, Robbins K, et al. Oral fructose absorption in obese children with non-alcoholic fatty liver disease. Pediatr Obes. 2015;10:188–95 https://doi.org/10.1111/ijpo.238.PubMedCrossRef

40.

Mosca A, Nobili V, De Vito R, Crudele A, Scorletti E, Villani A, et al. Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents. J Hepatol. 2017;66:1031–6 https://doi.org/10.1016/j.jhep.2016.12.025.PubMedCrossRef

41.

Petta S, Camma C, Cabibi D, Di Marco V, Craxi A. Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2011;34:757–66 https://doi.org/10.1111/j.1365-2036.2011.04788.x.PubMedCrossRef

42.

Choi YJ, Shin HS, Choi HS, Park JW, Jo I, Oh ES, et al. Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes. Lab Investig. 2014;94:1114–25 https://doi.org/10.1038/labinvest.2014.98.PubMedCrossRef

43.

Wan X, Xu C, Lin Y, Lu C, Li D, Sang J, et al. Uric acid regulates hepatic steatosis and insulin resistance through the NLRP3 inflammasome-dependent mechanism. J Hepatol. 2016;64:925–32 https://doi.org/10.1016/j.jhep.2015.11.022.PubMedCrossRef

Title: Clinical characteristics and risk factors of nonalcoholic fatty liver disease in children with obesity
Authors: Luting Peng
Su Wu
Nan Zhou
Shanliang Zhu
Qianqi Liu
Xiaonan Li
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Obesity
Obesity
Insulins
Fatty Liver
Insulins
Published in: BMC Pediatrics / Issue 1/2021
Electronic ISSN: 1471-2431
DOI: https://doi.org/10.1186/s12887-021-02595-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Clinical characteristics and risk factors of nonalcoholic fatty liver disease in children with obesity

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Mothers’ experiences of parenting and everyday life of children born at 23 weeks of gestation – a qualitative descriptive study

Epidemiology, risk factors and outcomes of bloodstream infection caused by ESKAPEEc pathogens among hospitalized children

Factors affecting rehabilitation of infants with Central Coordination Disorders during a three-month-long observation

A cross-sectional, exploratory survey on health-relevant free-time activities and body mass index in preschool children in urban and rural settings of Austria

Endoscopic features for early decision to evaluate superior mesenteric artery syndrome in children

A randomized EPIREMED protocol study on the long-term visuo spatial effects of very preterm children with a working memory deficit