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New insights in the pathophysiology of chronic intermittent hypoxia-induced NASH: the role of gut–liver axis impairment
  1. Judith Aron-Wisnewsky1,2,3,
  2. Jean-Louis Pepin4,5
  1. 1Institute of Cardiometabolism and Nutrition (ICAN), Assistance Pitié-Salpêtrière Hospital, Paris, France
  2. 2Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, Paris, France
  3. 3INSERM, UMR_S U1166, Paris, France
  4. 4Institut national de la santé et de la recherche médicale (INSERM), U 1042, HP2 Laboratory (Hypoxia: Pathophysiology), University of Grenoble-Alpes, Grenoble, France
  5. 5Thorax and Vessels Division, Grenoble University Hospital, Grenoble, France
  1. Correspondence to Professor Jean-Louis Pepin, Institut national de la santé et de la recherche médicale (INSERM), U 1042, HP2 Laboratory (Hypoxia: Pathophysiology), University of Grenoble-Alpes, Grenoble F-38000, France; jpepin{at}

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Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition paralleling the growing epidemic of obesity and type-2 diabetes. This disease shows a continuous spectrum of severity ranging from simple steatosis to overt non-alcoholic steato-hepatitis (NASH) that can further progress towards cirrhosis and hepatocarcinoma.1 Although the complete physiopathology is not fully understood, many factors such as insulin resistance, inflammation, oxidative stress and lipotoxicity are involved in the onset of NAFLD.2 ,3 Obstructive sleep apnoea (OSA) is independently associated with the different components of the metabolic syndrome, particularly visceral obesity, hypertension, insulin resistance and abnormal lipid metabolism.4 The repetitive occurrence of partial or complete pharyngeal collapse during OSA induces chronic intermittent hypoxia (CIH) that subsequently results in low-grade inflammation, sympathetic overactivity and oxidative stress. Since OSA and NAFLD share common intermediary mechanisms, the presence of OSA, especially in the context of severe CIH, has been suggested as contributing to the pathogenesis and exacerbation of the severity of NAFLD.

Animal studies have demonstrated that in obesity, short-term or long-term exposure to CIH mimicking OSA induces NAFLD.5–7 Next, studies in human adults, using either non-invasive surrogate markers of liver injury or biopsies to diagnose NAFLD, have also demonstrated that CIH is involved in the development of NAFLD, independently of body mass index (BMI), and contributes to the deleterious progression into overt NASH.8–11 In contrast, other studies have shown that the absence of OSA seems to protect morbidly obese patients from developing NAFLD.12

In response to the currently emergent worldwide epidemic of childhood obesity, NAFLD has started to be more systematically investigated in children than previously.13 ,14 The prevalence of NAFLD reaches 10% in the paediatric population …

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