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

• Published in: The Journal of pediatrics Vol. 198; pp. 67 - 75.e1
• Main Authors: Sundaram, Shikha S., Halbower, Ann C., Klawitter, Jelena, Pan, Zhaoxing, Robbins, Kristen, Capocelli, Kelley E., Sokol, Ronald J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2018
• Subjects: Adolescent; Biomarkers - metabolism; Body Mass Index; Child; Chronic Disease; Cohort Studies; Continuous Positive Airway Pressure; CPAP; F-isoprostanes; F2-Isoprostanes - urine; Female; Humans; hypoxia; Hypoxia - complications; Hypoxia - therapy; Male; NASH; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - therapy; Oxidative Stress; Pilot Projects; reactive oxygen species; Severity of Illness Index; sleep apnea; Sleep Apnea, Obstructive - complications; Sleep Apnea, Obstructive - therapy; CRP; hypoxia; NAS; AHI; AST; NAFLD; CPAP; ALT; NASH; ΔAHI; HDL; PDSS; SaO2; reactive oxygen species; sleep apnea; F-isoprostanes; BMI
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2018.03.028

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