Chronic Intermittent Hypoxia Is An Important Trigger For Non-Alcoholic Fatty Liver Disease

Abstract

Backgrounds and 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, 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 liver and adipose tissues. Methods: 101 morbidly obese subjects were prospectively recruited and underwent bariatric surgery during which a liver biopsy as well as subcutaneous and omental AT biopsies were obtained. Oxygen desaturation index (ODI) quantified the severity of nocturnal CIH. Results: Liver biopsies analysis demonstrated that NAFLD lesions (ballooning of hepatocytes, lobular inflammation), NAFLD activity score (NAS) and fibrosis were 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.