Obstructive Sleep Apnea Syndrome Affects Liver Histology and Inflammatory Cell Activation in Pediatric Nonalcoholic Fatty Liver Disease, Regardless of Obesity/Insulin Resistance

• DOI: 10.1164/rccm.201307-1339oc
• Publication Date: 2013-11-21T03:21:01Z
• Authors: Valerio Nobili; Renato Cutrera; Daniela Liccardo; Martino Pavone; Rita Devito; Valentina Giorgio; Elisabetta Verrillo; Giuseppe Baviera; Giovanni Musso
• Keywords: Male; 2. Zero hunger; Sleep Apnea, Obstructive; Keratin-18; Interleukin-6; Tumor Necrosis Factor-alpha; Polysomnography; 3. Good health; Fatty Liver; 03 medical and health sciences; C-Reactive Protein; 0302 clinical medicine; Liver; Non-alcoholic Fatty Liver Disease; Humans; Female; Obesity; Hyaluronic Acid; Insulin Resistance; Child; Fibrosis; Hypoxia; Nonalcoholic fatty liver disease; Sleep apnea; Steatosis; C-Reactive Protein; Child; Fatty Liver; Female; Humans; Hyaluronic Acid; Interleukin-6; Keratin-18; Liver; Male; Non-alcoholic Fatty Liver Disease; Obesity; Polysomnography; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha; Insulin Resistance; Pulmonary and Respiratory Medicine; Critical Care and Intensive Care Medicine

Rationale: Obstructive sleep apnea syndrome (OSAS) and nonalcoholic fatty liver disease (NAFLD) are frequently encountered in obese children. Whether OSAS intermittent hypoxia associated with injury pediatric NAFLD is unknown.Objectives: To assess the relationship of NAFLD.Methods: Sixty-five consecutive children biopsy-proven (age, mean ± SD, 11.7 2.1 yr; 58% boys; body mass index z score, 1.93 0.61) underwent a clinical-biochemical assessment standard polysomnography. Insulin sensitivity, circulating proinflammatory cytokines, markers hepatocyte apoptosis (cytokeratin-18 fragments), hepatic fibrogenesis (hyaluronic acid) were measured. Liver inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3, CD163, surface leukocytes, T cells, activated macrophage/Kupffer respectively. defined an apnea/hypopnea (AHI) greater than or equal to 1 event/h, severe AHI 5 events/h.Measurements Main Results: Fifty-five percent had steatohepatitis (NASH), 34% significant (stage F ≥ 2) fibrosis. affected 60% NAFLD; presence severity NASH (odds ratio, 4.89; 95% confidence interval, 3.08–5.98; P = 0.0001), fibrosis 5.91; 3.23–7.42; activity score (β, 0.347; 0.029), independently index, abdominal adiposity, metabolic syndrome, insulin resistance. This held also nonobese NAFLD. The duration hemoglobin desaturation (SaO2 < 90%) correlated increased intrahepatic leukocytes macrophages/Kupffer cells fibrogenesis.Conclusions: In NAFLD, biochemical, immunohistochemical, histological features impact hypoxemia correction on warrants evaluation future trials.