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

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/m(2)) 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.