Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese

• Published in: Journal of hepatology Vol. 56; no. 1; pp. 225 - 233
• Main Authors: Aron-Wisnewsky, Judith, Minville, Caroline, Tordjman, Joan, Lévy, Patrick, Bouillot, Jean-Luc, Basdevant, Arnaud, Bedossa, Pierre, Clément, Karine, Pépin, Jean-Louis
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01-01-2012; Elsevier
• Subjects: Adipose tissue; Adipose Tissue - metabolism; Adult; Bariatric Surgery; Biological and medical sciences; Chronic Disease; Cohort Studies; Fatty Liver - etiology; Fatty Liver - metabolism; Fatty Liver - pathology; Female; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Hypoxia - complications; Hypoxia - metabolism; Hypoxia - pathology; Insulin Resistance; Intermittent chronic hypoxia; Liver - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Metabolic diseases; Middle Aged; NAFLD; Non-alcoholic Fatty Liver Disease; Obesity; Obesity, Morbid - complications; Obesity, Morbid - metabolism; Obesity, Morbid - pathology; Obesity, Morbid - surgery; Other diseases. Semiology; Prospective Studies; Risk Factors; Sleep Apnea, Obstructive - complications; Sleep Apnea, Obstructive - metabolism; NAS; NAFLD; omental white adipose tissue; AHI; Adipose tissue; CPAP; subcutaneous white adipose tissue; oWAT; alanine aminotransferase; ALT; oxygen saturation; apnea/hypopnea index; SaO 2; interleukin-6; nonalcoholic steatohepatitis; SD; ODI; γ-glutamyl transferase; chronic intermittent hypoxia; OSA; homeostasis model assessment; BMI; obstructive sleep apnea; Obesity; AST; CIH; PaO 2; body mass index; partial pressure of oxygen in arterial blood; oxygen desaturation index; NASH; continuous positive airway pressure; Intermittent chronic hypoxia; IL-6; aspartate aminotransferase; HOMA-IR; nonalcoholic fatty liver disease; AT; GGT; scWAT; nonalcoholic fatty liver disease activity score; standard deviation; PaO2; SaO2; Oxygen; Nutrition disorder; Hepatic disease; Chronic; Non alcoholic steatohepatitis; Gastroenterology; Digestive diseases; Hypoxia; Nutritional status
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2011.04.022

Background & Aims Morbid obesity is frequently associated with low grade systemic inflammation, increased macrophage accumulation in adipose tissue (AT), obstructive sleep apnea (OSA), and nonalcoholic fatty liver disease (NAFLD). It has been suggested that chronic intermittent hypoxia (CIH) resulting from OSA could be an independent factor for early stage of NAFLD in addition to other well-recognized factors (dyslipidemia or insulin resistance). Moreover, macrophage accumulation in AT is associated with local hypoxia in fat tissue. We hypothesized that the association between CIH and morbid obesity could exert additional specific deleterious effects both in the liver and adipose tissues. Methods One hundred and one morbidly obese subjects were prospectively recruited and underwent bariatric surgery during which a liver needle biopsy as well as surgical subcutaneous and omental AT biopsies were obtained. Oxygen desaturation index (ODI) quantified the severity of nocturnal CIH. Results Histopathologic analysis of liver biopsies demonstrated that NAFLD lesions (ballooning of hepatocytes, lobular inflammation), NAFLD activity score (NAS), and fibrosis were significantly more severe in patients with the highest ODI tertile ( p values ⩽0.001 for all hepatic lesions). In multivariate analysis, after adjustment for age, obesity, and insulin resistance status, CIH remained independently associated with hepatic fibrosis, fibroinflammation, and NAS. By contrast, no association was found between CIH, macrophage accumulation, and adipocytes size in both subcutaneous and omental adipose tissue. Conclusions In morbidly obese patients, CIH was strongly associated with more severe liver injuries but did not worsen obesity induced macrophage accumulation in adipose tissue depots.