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

. 2014 ; 9 (4) : e96349. [epub] 20140424

Language English Country United States Media electronic-ecollection

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/pmid24763757

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.

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Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, et al. (2001) Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 50: 1844–1850. PubMed

Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F (2013) The burden of liver disease in Europe: A review of available epidemiological data. J Hepatol 58: 593–608. PubMed

Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, et al. (2002) Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 123: 134–140. PubMed

Dongiovanni P, Anstee QM, Valenti L (2013) Genetic Predisposition in NAFLD and NASH: Impact on Severity of Liver Disease and Response to Treatment. Curr Pharm Des. PubMed PMC

Musso G, Gambino R, Cassader M, Pagano G (2012) Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 43: 617–649. PubMed

Simon S, Collop N (2012) Latest advances in sleep medicine: obstructive sleep apnea. Chest 142: 1645–1651. PubMed

Musso G, Cassader M, Olivetti C, Rosina F, Carbone G, et al. (2013) Association of obstructive sleep apnoea with the presence and severity of non-alcoholic fatty liver disease. A systematic review and meta-analysis. Obes Rev 14: 417–431. PubMed

Aurora RN, Punjabi NM (2013) Obstructive sleep apnoea and type 2 diabetes mellitus: a bidirectional association. Lancet Respir Med 1: 329–338. PubMed

Garvey JF, Taylor CT, McNicholas WT (2009) Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation. Eur Respir J 33: 1195–1205. PubMed

Day CP (2006) From fat to inflammation. Gastroenterology 130: 207–210. PubMed

Savransky V, Nanayakkara A, Vivero A, Li J, Bevans S, et al. (2007) Chronic intermittent hypoxia predisposes to liver injury. Hepatology 45: 1007–1013. PubMed

Li J, Grigoryev DN, Ye SQ, Thorne L, Schwartz AR, et al. (2005) Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. J Appl Physiol 99: 1643–1648. PubMed

Drager LF, Li J, Reinke C, Bevans-Fonti S, Jun JC, et al. (2011) Intermittent hypoxia exacerbates metabolic effects of diet-induced obesity. Obesity (Silver Spring) 19: 2167–2174. PubMed PMC

Tanne F, Gagnadoux F, Chazouilleres O, Fleury B, Wendum D, et al. (2005) Chronic liver injury during obstructive sleep apnea. Hepatology 41: 1290–1296. PubMed

Tatsumi K, Saibara T (2005) Effects of obstructive sleep apnea syndrome on hepatic steatosis and nonalcoholic steatohepatitis. Hepatol Res 33: 100–104. PubMed

Turkay C, Ozol D, Kasapoglu B, Kirbas I, Yildirim Z, et al. (2012) Influence of obstructive sleep apnea on fatty liver disease: role of chronic intermittent hypoxia. Respir Care 57: 244–249. PubMed

Singh H, Pollock R, Uhanova J, Kryger M, Hawkins K, et al. (2005) Symptoms of obstructive sleep apnea in patients with nonalcoholic fatty liver disease. Dig Dis Sci 50: 2338–2343. PubMed

Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP (1999) Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med 131: 485–491. PubMed

Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14: 540–545. PubMed

Johns MW (2000) Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the epworth sleepiness scale: failure of the MSLT as a gold standard. J Sleep Res 9: 5–11. PubMed

Hiestand DM, Britz P, Goldman M, Phillips B (2006) Prevalence of symptoms and risk of sleep apnea in the US population: Results from the national sleep foundation sleep in America 2005 poll. Chest 130: 780–786. PubMed

Gus M, Goncalves SC, Martinez D, de Abreu Silva EO, Moreira LB, et al. (2008) Risk for Obstructive Sleep Apnea by Berlin Questionnaire, but not daytime sleepiness, is associated with resistant hypertension: a case-control study. Am J Hypertens 21: 832–835. PubMed

Valenti L, Al-Serri A, Daly AK, Galmozzi E, Rametta R, et al. (2010) Homozygosity for the PNPLA3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 51: 1209–1217. PubMed

Mishra P, Younossi ZM (2007) Abdominal ultrasound for diagnosis of nonalcoholic fatty liver disease (NAFLD). Am J Gastroenterol 102: 2716–2717. PubMed

Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, et al. (2000) Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 23: 57–63. PubMed

Supplement 1. American Diabetes Association: clinical practice recommendations 2000. Diabetes Care 23 Suppl 1S1–116. PubMed

Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106: 3143–3421. PubMed

Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, et al. (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41: 1313–1321. PubMed

Rosselli M, MacNaughtan J, Jalan R, Pinzani M (2013) Beyond scoring: a modern interpretation of disease progression in chronic liver disease. Gut 62: 1234–1241. PubMed

Kallwitz ER, Herdegen J, Madura J, Jakate S, Cotler SJ (2007) Liver enzymes and histology in obese patients with obstructive sleep apnea. J Clin Gastroenterol 41: 918–921. PubMed

Mishra P, Nugent C, Afendy A, Bai C, Bhatia P, et al. (2008) Apnoeic-hypopnoeic episodes during obstructive sleep apnoea are associated with histological nonalcoholic steatohepatitis. Liver Int 28: 1080–1086. PubMed

Aron-Wisnewsky J, Minville C, Tordjman J, Levy P, Bouillot JL, et al. (2012) Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese. J Hepatol 56: 225–233. PubMed

Newton JL, Jones DE, Henderson E, Kane L, Wilton K, et al. (2008) Fatigue in non-alcoholic fatty liver disease (NAFLD) is significant and associates with inactivity and excessive daytime sleepiness but not with liver disease severity or insulin resistance. Gut 57: 807–813. PubMed

Newton JL (2010) Systemic symptoms in non-alcoholic fatty liver disease. Dig Dis 28: 214–219. PubMed

Bersagliere A, Raduazzo ID, Nardi M, Schiff S, Gatta A, et al. (2012) Induced hyperammonemia may compromise the ability to generate restful sleep in patients with cirrhosis. Hepatology 55: 869–878. PubMed

Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, et al. (2000) Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 132: 112–117. PubMed

Fracanzani AL, Valenti L, Bugianesi E, Andreoletti M, Colli A, et al. (2008) The risk of severe liver disease in NAFLD with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology 48: 792–798. PubMed

Chin K, Nakamura T, Takahashi K, Sumi K, Ogawa Y, et al. (2003) Effects of obstructive sleep apnea syndrome on serum aminotransferase levels in obese patients. Am J Med 114: 370–376. PubMed

Kohler M, Pepperell JC, Davies RJ, Stradling JR (2009) Continuous positive airway pressure and liver enzymes in obstructive sleep apnoea: data from a randomized controlled trial. Respiration 78: 141–146. PubMed

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