Risk of obstructive sleep apnea with daytime sleepiness is associated with liver damage in non-morbidly obese patients with nonalcoholic fatty liver disease

PLoS One. 2014 Apr 24;9(4):e96349. doi: 10.1371/journal.pone.0096349. eCollection 2014.

Abstract

Background: A high prevalence of obstructive sleep apnea syndrome (OSAS) has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD), but few studies have evaluated OSAS in non-morbidly obese NAFLD patients.

Aims: To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage.

Methods: We considered 159 consecutive patients with histological NAFLD and body mass index (BMI) <35 Kg/m2, and 80 controls without ultrasonographic steatosis matched for age, sex, and BMI. OSAS risk was determined by positivity for Berlin questionnaire (BQ), and daytime sleepiness by the Sleepness Epworth Scale (ESS). Liver damage was evaluated according to the NAFLD activity score.

Results: In NAFLD patients, BQ alone was positive in 39 (25%), ESS in 8 (5%), and both in 13 (8%, OSAS with sleepines); p = ns vs. controls without steatosis. In NAFLD patients at risk for OSAS with (but not in those without) sleepiness, we observed a higher prevalence of nonalcoholic steatohepatitis (NASH; 11/13, 85% vs. 72/146, 49%; p = 0.018), and of clinically significant fibrosis (stage>1; 9/13, 69% vs. 39/146, 27%; p = 0.003). At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7-51, p = 0.005 and OR 14.0, 95% c.i. 3.5-70, p = 0.0002, respectively).

Conclusions: A proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Female
  • Humans
  • Liver / pathology*
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / pathology
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / complications*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Obesity / complications*
  • Obesity / pathology
  • Risk Factors
  • Sleep Apnea, Obstructive / etiology*
  • Sleep Stages
  • Young Adult

Grants and funding

The work was supported by the “Centro Universitario per lo Studio e la Cura delle Malattie Metaboliche del Fegato”, Università degli Studi di Milano, and by the “Associazione Malattie Metaboliche del Fegato ONLUS” (academic and non-profit organizations for the study and care of metabolic liver diseases). NM was partially supported by a European Regional Development Fund – Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123). There is no conflict of interest to disclose relevant to this manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.