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


OBJECTIVE
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.
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milano, Italy.
Edoardo Alessandro
EA
Pulixi
Department of Biomedical and Clinical Sciences "L. Sacco", Division of Medicine and Pathophysiology, Università degli Studi di Milano, Ospedale Luigi Sacco, Milano, Italy.
Eleonora
E
Tobaldini
Department of Health Sciences, Università degli Studi di Milano, Division of Medicine and Gastroenterology and Liver Unit, Ospedale San Paolo, Milano, Italy.
Pier Maria
PM
Battezzati
Department of Health Sciences, Università degli Studi di Milano, Division of Medicine and Gastroenterology and Liver Unit, Ospedale San Paolo, Milano, Italy.
Paola
P
D'Ingianna
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milano, Italy.
Vittorio
V
Borroni
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milano, Italy.
Anna Ludovica
AL
Fracanzani
Pathology, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milano, Italy.
Marco
M
Maggioni
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milano, Italy.
Serena
S
Pelusi
Department of Biomedical and Clinical Sciences "L. Sacco", Division of Medicine and Pathophysiology, Università degli Studi di Milano, Ospedale Luigi Sacco, Milano, Italy.
Mara
M
Bulgheroni
Department of Health Sciences, Università degli Studi di Milano, Division of Medicine and Gastroenterology and Liver Unit, Ospedale San Paolo, Milano, Italy.
Massimo
M
Zuin
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milano, Italy.
Silvia
S
Fargion
Department of Biomedical and Clinical Sciences "L. Sacco", Division of Medicine and Pathophysiology, Università degli Studi di Milano, Ospedale Luigi Sacco, Milano, Italy; International Clinical Research Center, St. Anne University Hospital, Brno, Czech Republic.
Nicola
N
Montano
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milano, Italy.
Luca
L
Valenti
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000150:complications / Q000473:pathology; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000473:pathology; D009765:Obesity / Q000150:complications* / Q000473:pathology; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000209:etiology*; D012894:Sleep Stages; D055815:Young Adult