Chest

Chest

Volume 133, Issue 1, January 2008, Pages 92-99
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Original Research
SLEEP MEDICINE
Elevated Serum Aminotransferase Levels in Children at Risk for Obstructive Sleep Apnea

https://doi.org/10.1378/chest.07-0773Get rights and content

Background

Fatty liver disease (FLD) is a highly prevalent condition in obese (Ob) children, who are at increased risk for obstructive sleep apnea (OSA). However, the contribution of OSA to FLD remains unknown.

Design

Prospective study.

Setting

Polysomnographic evaluation and assessment of plasma levels of insulin, glucose, and lipids, and liver function tests.

Participants

A total of 518 consecutive snoring children 4 to 17 years of age who were being evaluated for habitual snoring and suspected OSA.

Results

A total of 376 children had body mass index z score of < 1.20 (non-Ob children), 3 children (<1%) had elevated serum aminotransferase (LFT) levels, and 248 had OSA (65.9%). Among the 142 overweight/Ob children, 46 had elevated LFT levels (32.4%); of these children, 42 had OSA (91.3%). In contrast, OSA was present in only 71.8% of Ob children without elevated LFT level (p < 0.01). Insulin resistance and hyperlipidemia were more likely to occur in children with FLD. Furthermore, FLD was improved after treatment of OSA in 32 of 42 Ob children (p < 0.0001).

Conclusion

Increased liver enzyme levels are frequently found in Ob snoring children, particularly among those with OSA and/or metabolic dysfunction. Effective treatment of OSA results in improved liver function test results in the vast majority of these patients.

Section snippets

Materials and Methods

Five hundred eighteen children between the ages of 4 and 17 years who were consecutively evaluated at the Kosair Children's Hospital Sleep Medicine Center for habitual snoring and suspected OSA were recruited into the study. The study was approved by the University of Louisville Human Research Committee. Parental informed consent and child assent, in the presence of a parent, were obtained. Children were excluded if they had any chronic medical condition, were receiving medications known to

Results

Overall, 518 consecutive habitually snoring children with a mean age of 8.4 ± 1.3 years (age range, 4 to 17 years) were recruited into the study, and 343 had evidence of OSA (Table 1). The characteristics of children with and without OSA are shown in Table 1. Among those children with OSA, 44 children had elevated liver function test results (12.8%) compared to only 5 children with elevated serum transaminase levels among the 175 children without OSA (2.8%; p < 0.0001; odds ratio [OR], 5.15;

Discussion

This study shows that FLD is highly prevalent among Ob habitually snoring children. Furthermore, there is a more than threefold increase in the relative risk for FLD in the present cohort compared to previously reported FLD rates among Ob adolescents in the United States,6 suggesting that respiratory disturbances during sleep may contribute to the underlying mechanisms of hepatic steatosis in the context of obesity. Furthermore, we not only confirm previous observations on the increased

References (49)

  • HM Patton et al.

    Pediatric nonalcoholic fatty liver disease: a critical appraisal of current data and implications for future research

    J Pediatr Gastroenterol Nutr

    (2006)
  • JR Moran et al.

    Steatohepatitis in obese children: a cause of chronic liver dysfunction

    Am J Gastroenterol

    (1983)
  • M Rashid et al.

    Nonalcoholic steatohepatitis in children

    J Pediatr Gastroenterol Nutr

    (2000)
  • JP Molleston et al.

    Obese children with steatohepatitis can develop cirrhosis in childhood

    Am J Gastroenterol

    (2002)
  • JB Schwimmer et al.

    Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease

    J Pediatr

    (2003)
  • RS Strauss et al.

    Prevalence of abnormal serum aminotransferase values in overweight and obese adolescents

    J Pediatr

    (2000)
  • K Tominaga et al.

    Prevalence of fatty liver in Japanese children and relationship to obesity: an epidemiological ultrasonographic survey

    Dig Dis Sci

    (1995)
  • HS Park et al.

    Relation between elevated serum alanine aminotransferase and metabolic syndrome in Korean adolescents

    Am J Clin Nutr

    (2005)
  • JB Schwimmer et al.

    Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents

    Pediatrics

    (2005)
  • R Tauman et al.

    Obesity and obstructive sleep apnea in children

    Paediatr Respir Rev

    (2006)
  • D Gozal et al.

    Oxidant stress and inflammation in the snoring child: confluent pathways to upper airway pathogenesis and end-organ morbidity

    Sleep Med Rev

    (2006)
  • R Tauman et al.

    Plasma C-reactive protein in children with sleep-disordered breathing

    Pediatrics

    (2004)
  • L Kheirandish-Gozal et al.

    Plasma C-reactive protein in non-obese children with obstructive sleep apnea before and after adenotonsillectomy

    J Clin Sleep Med

    (2006)
  • S Ryan et al.

    Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome

    Circulation

    (2005)
  • H Singh et al.

    Symptoms of obstructive sleep apnea in patients with nonalcoholic fatty liver disease

    Dig Dis Sci

    (2005)
  • SW Tsang et al.

    Predictors of fibrosis in Asian patients with non-alcoholic steatohepatitis

    J Gastroenterol Hepatol

    (2006)
  • F Tanne et al.

    Chronic liver injury during obstructive sleep apnea

    Hepatology

    (2005)
  • K Chin et al.

    Effects of obstructive sleep apnea syndrome on serum aminotransferase levels in obese patients

    Am J Med

    (2003)
  • HE Montgomery-Downs et al.

    Polysomnographic characteristics in normal preschool and early school-age children

    Pediatrics

    (2006)
  • A Rechtschaffen et al.

    A manual of standardized terminology, techniques and scoring systems for sleep stages of human subject

    (1968)
  • American Thoracic Society

    Standards and indications for cardiopulmonary sleep studies in children

    Am J Respir Crit Care Med

    (1996)
  • American Sleep Disorders Association

    EEG arousals: scoring and rules and examples; Sleep Disorders Atlas Task Force of the American Sleep Disorders Association

    Sleep

    (1992)
  • MA Mograss et al.

    Movement/arousals: description, classification, and relationship to sleep apnea in children

    Am J Respir Crit Care Med

    (1994)
  • RJ Kuczmarski et al.

    CDC growth charts: United States

    Adv Data

    (2000)

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    This study was supported by National Institutes of Health grant HL-65270, by The Children's Foundation Endowment for Sleep Research, and by the Commonwealth of Kentucky Challenge for Excellence Trust Fund.

    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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    Copyright © 2008 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.