Digestive Diseases and Sciences

, Volume 50, Issue 12, pp 2338–2343 | Cite as

Symptoms of Obstructive Sleep Apnea in Patients with Nonalcoholic Fatty Liver Disease

  • Harminder Singh
  • Richard Pollock
  • Julia Uhanova
  • Meir Kryger
  • Kim Hawkins
  • Gerald Y. Minuk


Nonalcoholic fatty liver disease (NAFLD) is a term often used to describe two related conditions: a relatively benign, nonalcoholic fatty liver (NAFL) and potentially aggressive, nonalcoholic steatohepatitis (NASH). Both conditions (NAFL and NASH) occur in the setting of peripheral insulin resistance. Recently, obstructive sleep apnea (OSA) has been proposed as an independent risk factor for insulin resistance. To date, few studies have documented the prevalence of OSA or symptoms of OSA (SOSA) in NAFLD patients. The objectives of this study were (1) to document the prevalence of SOSA in patients with NAFLD and (2) to determine whether prevalence rates for SOSA differ in NAFL versus NASH patients. One hundred ninety biochemically defined NAFLD patients (116 NAFL and 74 NASH), of whom 50 (18 NAFL and 32 NASH) had undergone liver biopsy, completed a Modified Berlin Sleep Apnea Questionnaire for SOSA. Risk factors for NAFLD were also documented in NAFL and NASH patients. Eighty-seven of the 190 (46%) NAFLD patients met questionnaire criteria for SOSA. The prevalence of SOSA was similar in both biochemically (45% versus 49%, respectively; P= 0.66) and histologically (39% versus 63%, respectively; P= 0.11) defined NAFL and NASH patients. Other risk factors for NAFLD such as body mass index, plasma cholesterol and triglyceride levels, and prevalence of diabetes were also similar in the two groups. Approximately one-half of NAFLD patients, whether NAFL or NASH, have SOSA. Further studies are required to determine whether a causal link exists between NAFLD and OSA.


obstructive sleep apnea nonalcoholic fatty liver disease nonalcoholic fatty liver nonalcoholic steatohepatitis fatty liver hepatitis obesity epidemiology 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Wanless IR, Lentz JS: Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 12:1106–1110, 1990PubMedGoogle Scholar
  2. 2.
    Andersen T, Christoffersen P, Gluud C: The liver in consecutive patients with morbid obesity: A clinical, morphological, and biochemical study. Int J Obes 8:107–115, 1984PubMedGoogle Scholar
  3. 3.
    Younossi ZM, Diehl AM, Ong JP: Nonalcoholic fatty liver disease: an agenda for clinical research. Hepatology 35:746–752, 2002CrossRefPubMedGoogle Scholar
  4. 4.
    Day CP: Pathogenesis of steatohepatitis. Best Pract Res Clin Gastroenterol 16:663–678, 2002CrossRefPubMedGoogle Scholar
  5. 5.
    Gami AS, Caples SM, Somers VK: Obesity and obstructive sleep apnea. Endocrinol Metab Clin North Am 32:869–894, 2003CrossRefPubMedGoogle Scholar
  6. 6.
    Fogarty P: Obstructive sleep apnea. The clinical consequences. Aust Fam Phys 25:170–174, 1996Google Scholar
  7. 7.
    Jordan AS, White DP, Fogel RB: Recent advances in understanding the pathogenesis of obstructive sleep apnea. Curr Opin Pulm Med 9:459–464, 2003PubMedGoogle Scholar
  8. 8.
    Lavie L, Vishnevsky A, Lavie P: Evidence for lipid peroxidation in obstructive sleep apnea. Sleep 27:123–128, 2004PubMedGoogle Scholar
  9. 9.
    Saibara T, Nozaki Y, Nemoto Y, Ono M, Onishi S: NASH and Pickwickian syndrome. Lancet 359:980, 2002CrossRefPubMedGoogle Scholar
  10. 10.
    Chin K, Nakamura T, Takahashi K, Sumi K, Ogawa Y, Masuzaki H, Muro S, Hattori N, Matsumoto H, Niimi A, Chiba T, Nakao K, Mishima M, Ohi M, Nakamura T: Effects of obstructive sleep apnea syndrome on serum aminotransferase levels in obese patients. Am J Med 114:370–376, 2003CrossRefPubMedGoogle Scholar
  11. 11.
    Carpagnano GE, Kharitonov SA, Resta O, Foschino-Barbaro MP, Gramiccioni E, Barnes PJ: Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnea patients. Chest 122:1162–1167, 2002CrossRefPubMedGoogle Scholar
  12. 12.
    Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR: Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94:2467–2474, 1999CrossRefPubMedGoogle Scholar
  13. 13.
    Ancoli-Israel S, Kripke DF, Klauber MR, Mason WJ, Fell R, Kaplan O: Sleep-disordered breathing in community-dwelling elderly. Sleep 14:486–495, 1991PubMedGoogle Scholar
  14. 14.
    Vgontzas AN, Tan TL, Bixler EO, Martin LF, Shubert D, Kales A: Sleep apnea and sleep disruption in obese patients. Arch Intern Med 154:1705–1711, 1994CrossRefPubMedGoogle Scholar
  15. 15.
    Resta O, Foschino-Barbaro MP, Legari G, Talamo S, Bonfitto P, Palumbo A, Minenna A, Giorgino R, De Pergola G: Sleep-related breathing disorders, loud snoring and excessive daytime sleepiness in obese subjects. Int J Obes Relat Metab Disord 25:669–675, 2001CrossRefPubMedGoogle Scholar
  16. 16.
    Richman RM, Elliott LM, Burns CM, Bearpark HM, Steinbeck KS, Caterson ID: The prevalence of obstructive sleep apnoea in an obese female population. Int J Obes Relat Metab Disord 18:173–177, 1994PubMedGoogle Scholar
  17. 17.
    Tassone F, Lanfranco F, Gianotti L, Pivetti S, Navone F, Rossetto R, Grottoli S, Gai V, Ghigo E, Maccario M: Obstructive sleep apnoea syndrome impairs insulin sensitivity independently of anthropometric variables. Clin Endocrinol (Oxf) 59:374–379, 2003CrossRefGoogle Scholar
  18. 18.
    Ip MS, Lam B, Ng MM, Lam WK, Tsang KW, Lam KS: Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 165:670–676, 2002PubMedGoogle Scholar
  19. 19.
    de la Eva RC, Baur LA, Donaghue KC, Waters KA: Metabolic correlates with obstructive sleep apnea in obese subjects. J Pediatr 140:654–659, 2002PubMedGoogle Scholar
  20. 20.
    Meslier N, Gagnadoux F, Giraud P, Person C, Ouksel H, Urban T, Racineux JL: Impaired glucose-insulin metabolism in males with obstructive sleep apnoea syndrome. Eur Respir J 22:156–160, 2003CrossRefPubMedGoogle Scholar
  21. 21.
    Tiihonen M, Partinen M, Narvanen S: The severity of obstructive sleep apnoea is associated with insulin resistance. J Sleep Res 2:56–61, 1993PubMedGoogle Scholar
  22. 22.
    Harsch IA, Schahin SP, Radespiel–Troger M, Weintz O, Jahreiss H, Fuchs FS, Wiest GH, Hahn EG, Lohmann T, Konturek PC, Ficker JH: Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. Am J Respir Crit Care Med 169:156–162, 2004PubMedGoogle Scholar
  23. 23.
    Brooks B, Cistulli PA, Borkman M, Ross G, McGhee S, Grunstein RR, Sullivan CE, Yue DK: Obstructive sleep apnea in obese noninsulin-dependent diabetic patients: effect of continuous positive airway pressure treatment on insulin responsiveness. J Clin Endocrinol Metab 79:1681–1685, 1994CrossRefPubMedGoogle Scholar
  24. 24.
    Somers VK, Dyken ME, Clary MP, Abboud FM: Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 96:1897–1904, 1995PubMedCrossRefGoogle Scholar
  25. 25.
    Clark RW, Boudoulas H, Schaal SF, Schmidt HS: Adrenergic hyperactivity and cardiac abnormality in primary disorders of sleep. Neurology 30:113–119, 1980PubMedGoogle Scholar
  26. 26.
    Loredo JS, Ziegler MG, Ancoli-Israel S, Clausen JL, Dimsdale JE: Relationship of arousals from sleep to sympathetic nervous system activity and BP in obstructive sleep apnea. Chest 116:655–659, 1999PubMedGoogle Scholar
  27. 27.
    Tiihonen M, Partinen M, Narvanen S: The severity of obstructive sleep apnoea is associated with insulin resistance. J Sleep Res 2:56–61, 1993PubMedCrossRefGoogle Scholar
  28. 28.
    Bratel T, Wennlund A, Carlstrom K: Pituitary reactivity, androgens and catecholamines in obstructive sleep apnoea. Effects of continuous positive airway pressure treatment (CPAP). Respir Med 93:1–7, 1999PubMedGoogle Scholar
  29. 29.
    Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL: Sleep-disordered breathing and insulin resistance in middle-aged and overweight men. Am J Respir Crit Care Med 165:677–682, 2002PubMedGoogle Scholar
  30. 30.
    Gianotti L, Pivetti S, Lanfranco F, Tassone F, Navone F, Vittori E, Rossetto R, Gauna C, Destefanis S, Grottoli S, De Giorgi R, Gai V, Ghigo E, Maccario M: Concomitant impairment of growth hormone secretion and peripheral sensitivity in obese patients with obstructive sleep apnea syndrome. J Clin Endocrinol Metab 87:5052–5057, 2002CrossRefPubMedGoogle Scholar
  31. 31.
    Cheng N, Cai W, Jiang M, Wu S: Effect of hypoxia on blood glucose, hormones, and insulin receptor functions in newborn calves. Pediatr Res 41:852–856, 1997PubMedGoogle Scholar
  32. 32.
    Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP: Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med 131:485–491, 1999PubMedGoogle Scholar
  33. 33.
    Calhoun DA, Nishizaka MK, Zaman MA, Harding SM: Aldosterone excretion among subjects with resistant hypertension and symptoms of sleep apnea. Chest 125:112–117, 2004CrossRefPubMedGoogle Scholar
  34. 34.
    Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA: Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 107:1103–1109, 1994PubMedGoogle Scholar
  35. 35.
    Sanyal AJ: AGA technical review on nonalcoholic fatty liver disease. Gastroenterology 123:1705–1725, 2002CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Harminder Singh
    • 1
  • Richard Pollock
    • 1
  • Julia Uhanova
    • 1
  • Meir Kryger
    • 2
  • Kim Hawkins
    • 1
  • Gerald Y. Minuk
    • 1
    • 3
  1. 1.The Sections of HepatologyDepartment of Medicine University of ManitobaWinnipegCanada
  2. 2.The Sections of Chest MedicineDepartment of Medicine University of ManitobaWinnipegCanada
  3. 3.University of Manitoba, Liver Diseases Unit, John Buhler Research CenterWinnipegCanada

Personalised recommendations