Nonalcoholic fatty liver disease, nocturnal hypoxia, and endothelial function in patients with sleep apnea

Chest. 2014 Mar 1;145(3):525-533. doi: 10.1378/chest.13-0938.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endothelium, Vascular / physiopathology*
  • Fatty Liver / etiology*
  • Fatty Liver / metabolism
  • Fatty Liver / physiopathology
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoxia / complications*
  • Hypoxia / metabolism
  • Hypoxia / physiopathology
  • Insulin Resistance
  • Liver Function Tests
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Prospective Studies
  • Sleep Apnea, Obstructive / complications*
  • Sleep Apnea, Obstructive / metabolism
  • Sleep Apnea, Obstructive / physiopathology
  • Vasodilation / physiology*