title: Nonalcoholic fatty liver disease, nocturnal hypoxia, and endothelial function in patients with sleep apnea.
abstract: BACKGROUND
  Nocturnal hypoxia, the hallmark of OSA, is a potential contributing factor for nonalcoholic fatty liver disease (NAFLD). NAFLD severity and its implication in OSA-related endothelial dysfunction have not been investigated in a large, unselected OSA population, including nonobese subjects.
  
  
  METHODS
  Noninvasive blood tests (SteatoTest, NashTest, and FibroTest) were used to evaluate steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis in a large cohort of patients with OSA. In the same group, endothelial function and its links with NAFLD severity were assessed.
  
  
  RESULTS
  Of the 226 subjects included who were referred for suspicion of OSA (men, 55%; median age, 56 years; median BMI, 34.2 kg/m2 [33% with BMI<30 kg/m2]), 61.5% exhibited moderate or severe steatosis. By multivariate analysis, independent factors for liver steatosis were, as expected, triglyceride levels (P<.0001) and insulin resistance (P=.0004) as well as nocturnal cumulative time spent<90% of oxygen saturation (CT90) (P=.01). Thirty-eight percent had borderline or possible NASH (N1 or N2 with NashTest). CT90 was significantly associated with borderline or possible NASH (P=.035) in univariate but not in multivariate analysis. The dose-response relationship between the severity of nocturnal hypoxia and liver injury was established only in morbid obesity and not in lean. Multivariate models showed that steatosis was independently associated with endothelial dysfunction after adjustment for confounders.
  
  
  CONCLUSIONS
  In a large, unselected OSA population, the severity of nocturnal hypoxia was independently associated with steatosis. Preexisting obesity exacerbated the effects of nocturnal hypoxemia. NAFLD is a potential mechanism of endothelial dysfunction in OSA.
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, QC, Canada; Université Joseph Fourier, INSERM U 1042, Laboratoire HP2, Hypoxie Physiopathologies, Pôle Locomotion, Rééducation et Physiologie, CHU de Grenoble, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Minville
authors.affiliation: Département d'Hépato Gastroentérologie, Pôle Digidune, CHU de Grenoble, France.
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Hilleret
authors.affiliation: Université Joseph Fourier, INSERM U 1042, Laboratoire HP2, Hypoxie Physiopathologies, Pôle Locomotion, Rééducation et Physiologie, CHU de Grenoble, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Tamisier
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Département Cœur et métabolisme, Centre de Nutrition Humaine, Hôpital Pitié-Salpétrière, Paris 75613, France; INSERM UMRS 872 team 7, Nutriomique, Université Pierre et Marie Curie-Paris 6, Centre de Recherche des Cordeliers, Paris 75006, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Aron-Wisnewsky
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Département Cœur et métabolisme, Centre de Nutrition Humaine, Hôpital Pitié-Salpétrière, Paris 75613, France; INSERM UMRS 872 team 7, Nutriomique, Université Pierre et Marie Curie-Paris 6, Centre de Recherche des Cordeliers, Paris 75006, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Clement
authors.affiliation: Laboratoire de Biochimie des Enzymes et des Protéines, CGD (Institut de Biologie et de Pathologie), CHU de Grenoble, France.
authors.forename: Candice
authors.initials: C
authors.lastname: Trocme
authors.affiliation: Université Joseph Fourier, INSERM U 1042, Laboratoire HP2, Hypoxie Physiopathologies, Pôle Locomotion, Rééducation et Physiologie, CHU de Grenoble, France. Electronic address: jpepin@chu-grenoble.fr.
authors.forename: Jean-Christian
authors.initials: JC
authors.lastname: Borel
authors.affiliation: Université Joseph Fourier, INSERM U 1042, Laboratoire HP2, Hypoxie Physiopathologies, Pôle Locomotion, Rééducation et Physiologie, CHU de Grenoble, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lévy
authors.affiliation: Département d'Hépato Gastroentérologie, Pôle Digidune, CHU de Grenoble, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zarski
authors.affiliation: Université Joseph Fourier, INSERM U 1042, Laboratoire HP2, Hypoxie Physiopathologies, Pôle Locomotion, Rééducation et Physiologie, CHU de Grenoble, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pépin
mesh_terms: D004730:Endothelium, Vascular / Q000503:physiopathology*; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D007333:Insulin Resistance; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D011446:Prospective Studies; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D014664:Vasodilation / Q000502:physiology*