Treating Obstructive Sleep Apnea and Chronic Intermittent Hypoxia Improves the Severity of Nonalcoholic Fatty Liver Disease in Children

J Pediatr. 2018 Jul:198:67-75.e1. doi: 10.1016/j.jpeds.2018.03.028. Epub 2018 May 8.

Abstract

Objective: To determine the effects of treating obstructive sleep apnea/nocturnal hypoxia on pediatric nonalcoholic fatty liver disease (NAFLD) severity and oxidative stress.

Study design: Biopsy proven participants (n = 9) with NAFLD and obstructive sleep apnea/hypoxia were studied before and after treatment with continuous positive airway pressure (CPAP) for sleep disordered breathing, including laboratory testing and markers of oxidative stress, urine F(2)-isoprostanes.

Results: Adolescents (age 11.5 ± 1.2 years; body mass index, 29.5 ± 3.8 kg/m2) with significant NAFLD (mean histologic necroinflammation grade, 2.3 ± 0.9; fibrosis stage, 1.4 ± 1.3; NAFLD Activity Score summary, 4.8 ± 1.6) had obstructive sleep apnea/hypoxia by polysomnography. At baseline, they had severe obstructive sleep apnea/hypoxia, elevated aminotransferases, the metabolic syndrome, and significant oxidative stress (high F(2)-isoprostanes). Obstructive sleep apnea/hypoxia was treated with home CPAP for a mean 89 ± 62 days. Although body mass index increased, obstructive sleep apnea/hypoxia severity improved on CPAP and was accompanied by reduced alanine aminotransferase, metabolic syndrome markers, and F(2)-isoprostanes.

Conclusions: This study provides strong evidence that treatment of obstructive sleep apnea/nocturnal hypoxia with CPAP in children with NAFLD may reverse parameters of liver injury and reduce oxidative stress. These data also suggest CPAP as a new therapy to prevent progression of NAFLD in those children with obesity found to have obstructive sleep apnea/nocturnal hypoxia.

Keywords: CPAP; F(2)-isoprostanes; NASH; hypoxia; reactive oxygen species; sleep apnea.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Biomarkers / metabolism
  • Body Mass Index
  • Child
  • Chronic Disease
  • Cohort Studies
  • Continuous Positive Airway Pressure*
  • F2-Isoprostanes / urine
  • Female
  • Humans
  • Hypoxia / complications
  • Hypoxia / therapy*
  • Male
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / therapy*
  • Oxidative Stress
  • Pilot Projects
  • Severity of Illness Index
  • Sleep Apnea, Obstructive / complications
  • Sleep Apnea, Obstructive / therapy*

Substances

  • Biomarkers
  • F2-Isoprostanes