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Obstructive sleep apnea and liver injury in severely obese patients with nonalcoholic fatty liver disease

  • Sleep Breathing Physiology and Disorders • Original Article
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Abstract

Objectives

Obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) are common in subjects with severe obesity. It has been suggested that insulin resistance and systemic inflammation may play a role in the development of nonalcoholic steatohepatitis (NASH), but the mechanisms remain controversial. The aim of this study was to explore the influence of OSA on liver injury and its potential mechanisms in severely obese patients with NAFLD.

Methods

Severely obese patients requiring bariatric surgery were consecutively recruited between November 2017 and June 2018. Demographic, biochemical, liver ultrasound, and ambulatory polygraph data were collected.

Results

One hundred fifty-three subjects with liver ultrasound–verified NAFLD were classified into three groups according to the apnea-hypopnea index (AHI). The level of serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) tended to increase with more severe OSA (P = 0.024 and P = 0.004, respectively). In the unadjusted analysis, both ALT and GGT were positively correlated with AHI, oxygen desaturation index, percentage of total sleep time spent with oxyhemoglobin saturation below 90%, male sex, homeostasis model assessment of insulin resistance (HOMA-IR), and total cholesterol, while liver enzymes were negatively related to lowest oxygen saturation. In multiple regression analysis, AHI (odds ratio (OR) = 1.052, P = 0.044) and HOMA-IR (OR = 1.135, P = 0.001) were independent risk factors for an elevated ALT level. High-sensitivity C-reactive protein (hs-CRP) was positively associated with BMI and GGT (r = 0.349 and r = 0.164 (P < 0.05), respectively), and no correlation was found between hs-CRP and AHI or other parameters of hypoxia. hs-CRP and GGT remained significantly correlated after adjusting for confounding parameters (OR = 2.509, P = 0.013).

Conclusions

OSA may play a role in liver injury among severely obese individuals with NAFLD. Insulin resistance and systemic inflammation were possible contributing factors in this process.

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Abbreviations

AHI:

Apnea-hypopnea index

AI:

Apnea index

Alb:

Albumin

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

AST:

Aspartate transaminase

BMI:

Body mass index

CHO:

Cholesterol

DM:

Diabetes mellitus

GGT:

Gamma-glutamyl transpeptidase

HDL:

High-density lipoprotein

HI:

Hypopnea index

HOMA-IR:

Homeostasis model assessment of insulin resistance

HTN:

Hypertension

LDL:

Low-density lipoprotein

NAFLD:

Nonalcoholic fatty liver disease

ODI:

Oxygen desaturation index

OSA:

Obstructive sleep apnea

SpO2nadir:

Lowest oxygen saturation

T90:

Percent of total sleep time spent with oxyhemoglobin saturation below 90% time

TBIL:

Total bilirubin

TG:

Triglyceride

References

  1. Haglöw J, Miller CB, Bartlett DJ, Yee BJ, Openshaw HD, Grunstein RR (2018) Gender differences in obstructive sleep apnoea, insomnia and restless legs syndrome in adults—what do we know? A clinical update. Sleep Med Rev 38:28–38. https://doi.org/10.1016/j.smrv.2017.03.003

    Article  Google Scholar 

  2. Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, D’Agostino RB, Newman AB, Lebowitz MD, Pickering TG (2000) Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 283(14):1829–1836. https://doi.org/10.1001/JAMA.283.14.1829

    Article  CAS  PubMed  Google Scholar 

  3. Punjabi NM, Shahar E, Redline S, Gottlieb DJ, Givelber R, Resnick HE (2004) Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol 160(6):521–530. https://doi.org/10.1093/aje/kwh2614

    Article  PubMed  Google Scholar 

  4. Šiarnik P, Klobučníková K, Mucska I, Černá K, Kollár B, Turčáni P (2018) Obstructive sleep apnea and dyslipidemia. Vnitr Lek 64(10):934–938

    PubMed  Google Scholar 

  5. Young T, Palta M, Dempsey J, Peppard PE, Nieto FJ, Hla KM (2009) Burden of sleep apnea: rationale, design, and major findings of the Wisconsin Sleep Cohort Study. WMJ 108(5):246–249

    PubMed  PubMed Central  Google Scholar 

  6. Al Lawati NM, Patel SR, Ayas NT (2009) Epidemiology, risk factors, and consequences of obstructive sleep apnea and short sleep duration. Prog Cardiovasc Dis 51(4):285–293. https://doi.org/10.1016/j.pcad.2008.08.001

    Article  PubMed  Google Scholar 

  7. Shah N, Roux F (2009) The relationship of obesity and obstructive sleep apnea. Clin Chest Med 30(3):455–465. https://doi.org/10.1016/j.ccm.2009.05.012

    Article  PubMed  Google Scholar 

  8. Young T, Shahar E, Nieto FJ, Redline S, Newman AB, Gottlieb DJ, Walsleben JA, Finn L, Enright P, Samet JM (2002) Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study. Arch Intern Med 162(8):893–900. https://doi.org/10.1001/archinte.162.8.893

    Article  PubMed  Google Scholar 

  9. Kotronen A, Yki-Järvinen H (2008) Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol 28(1):2738. https://doi.org/10.1161/ATVBAHA.107.147538

    Article  CAS  Google Scholar 

  10. Minville C, Hilleret MN, Tamisier R, Aron-Wisnewsky J, Clement K, Trocme C, Borel JC, Lévy P, Zarski JP, Pépin JL (2014) Nonalcoholic fatty liver disease, nocturnal hypoxia, and endothelial function in patients with sleep apnea. Chest 145(3):525–533. https://doi.org/10.1378/chest.13-0938

    Article  PubMed  Google Scholar 

  11. Lin QC, Chen LD, Chen GP, Zhao JM, Chen X, Huang JF, Wu LH (2015) Association between nocturnal hypoxia and liver injury in the setting of nonalcoholic fatty liver disease. Sleep Breath 19(1):273–280. https://doi.org/10.1007/s11325-014-1008-7

    Article  PubMed  Google Scholar 

  12. Benotti P, Craig Wood G, Argyropoulos G, Pack A, Keenan BT, Gao X, Gerhard G, Still C (2016) The impact of obstructive sleep apnea on nonalcoholic fatty liver disease in patients with severe obesity. Obesity 24 (4):871–877. https://doi.org/10.1002/oby.21409

  13. 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(10):918–921. https://doi.org/10.1097/01.mcg.0000225692.62121.55

  14. Jouët P, Sabaté JM, Maillard D, Msika S, Mechler C, Ledoux S, Harnois F, Coffin B (2007) Relationship between Obstructive Sleep Apnea and Liver Abnormalities in Morbidly Obese Patients: A Prospective Study. Obesity Surgery 17 (4):478–485

  15. Sivam S, Phillips CL, Trenell MI, Yee BJ, Liu PY, Wong KK, Grunstein RR (2012) Effects of 8 weeks of continuous positive airway pressure on abdominal adiposity inobstructive sleep apnoea. Eur Respir J 40(4):913–918. https://doi.org/10.1183/09031936.00177011

    Article  CAS  PubMed  Google Scholar 

  16. Jullian-Desayes I, Tamisier R, Zarski JP, Aron-Wisnewsky J, Launois-Rollinat SH, Trocme C, Levy P, Joyeux-Faure M, Pepin JL (2016) Impact of effective versus sham continuous positive airway pressure on liver injury in obstructive sleep apnoea: data from randomized trials. Respirology 21(2):378–385. https://doi.org/10.1111/resp.12672

  17. Day CP, Saksena S (2002) Non-alcoholic steatohepatitis: definitions and pathogenesis. J Gastroenterol Hepatol 17(Suppl 3):S377–S384.https://doi.org/10.1046/j.1440-1746.17.s3.31.x

  18. Dalmas E, Rouault C, Abdennour M, Rovere C, Rizkalla S, Bar-Hen A, Nahon JL, Bouillot JL, Guerre-Millo M, Clément K, Poitou C (2011) Variations in circulating inflammatory factors are related to changes in calorie and carbohydrate intakes early in the course of surgery-induced weight reduction. Am J Clin Nutr 94(2):450–458. https://doi.org/10.3945/ajcn.111.013771

    Article  CAS  PubMed  Google Scholar 

  19. Osawa H, Mori Y (1996) Sonographic diagnosis of fatty liver using a histogram technique that compares liver and renal cortical echo amplitudes. J Clin Ultrasound 24(1):25–29. https://doi.org/10.1002/(SICI)1097-0096(199601)24:1<25::AID-JCU>3.0.CO;2-N

    Article  CAS  PubMed  Google Scholar 

  20. Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, Mullen KD, Cooper JN, Sheridan MJ (2002) The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 123(3):745–750. https://doi.org/10.1053/gast.2002.35354

    Article  PubMed  Google Scholar 

  21. Berry RB, Budhiraja R, Gottlieb DJ, Gozal D, Iber C, Kapur VK, Marcus CL, Mehra R, Parthasarathy S, Quan SF, Redline S, Strohl KP, Davidson Ward SL, Tangredi MM (2012) Rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events. Deliberations of the sleep apnea definitions task force of the American Academy of Sleep Medicine. J Clin Sleep Med 8(5):597–619. https://doi.org/10.5664/jcsm.2172

    Article  PubMed  PubMed Central  Google Scholar 

  22. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419. https://doi.org/10.1007/bf00280883

    Article  CAS  PubMed  Google Scholar 

  23. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of the 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). JAMA (285):2486–2497. https://doi.org/10.1001/jama.285.19.2486

  24. Türkay C, Ozol D, Kasapoğlu B, Kirbas I, Yıldırım Z, Yiğitoğlu R (2012) Influence of obstructive sleep apnea on fatty liver disease: role of chronic intermittent hypoxia. Respir Care 57(2):244–249. https://doi.org/10.4187/respcare.01184

    Article  PubMed  Google Scholar 

  25. Daltro C, Cotrim HP, Alves E, de Freitas LA, Araújo L, Boente L, Leal R, Portugal T (2010) Nonalcoholic fatty liver disease associated with obstructive sleep apnea: just a coincidence? Obes Surg 20(11):1536–1543. https://doi.org/10.1007/s11695-010-0212-1

    Article  PubMed  Google Scholar 

  26. Tanné F, Gagnadoux F, Chazouillères O, Fleury B, Wendum D, Lasnier E, Lebeau B, Poupon R, Serfaty L (2005) Chronic liver injury during obstructive sleep apnea. Hepatology 41(6):1290–1296. https://doi.org/10.1002/hep.20725

    Article  PubMed  Google Scholar 

  27. Sundaram SS, Sokol RJ, Capocelli KE, Pan Z, Sullivan JS, Robbins Ket Halbower AC (2014) Obstructive sleep apnea and hypoxemia are associated with advanced liver histology in pediatric nonalcoholic fatty liver disease. J Pediatr 164(4):699–706 e1. https://doi.org/10.1016/j.jpeds.2013.10.072

    Article  CAS  PubMed  Google Scholar 

  28. Polotsky VY, Patil SP, Savransky V, Laffan A, Fonti S, Frame LA, Steele KE, Schweizter MA, Clark JM, Torbenson MS, Schwartz AR (2009) Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity. Am J Respir Crit Care Med 179(3):228–234. https://doi.org/10.1164/rccm.200804-608OC

    Article  PubMed  Google Scholar 

  29. Ota T, Takamura T, Kurita S, Matsuzawa N, Kita Y, Uno M, Akahori H, Misu H, Sakurai M, Zen Y, Nakanuma Y, Kaneko S (2007) Insulin resistance accelerates a dietary rat model of nonalcoholic steatohepatitis. Gastroenterology 132(1):282–293. https://doi.org/10.1053/j.gastro.2006.10.014

    Article  PubMed  Google Scholar 

  30. Wang T, Zhou YT, Chen XN, Zhu AX (2014) Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1alpha expression. Braz J Med Biol Res 47(9):738–745. https://doi.org/10.1590/1414-431x20142910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yang D, Liu Z, Yang H, Luo Q (2013) Effects of continuous positive airway pressure on glycemic control and insulin resistance in patients with obstructive sleep apnea: a meta-analysis. Sleep Breath 17(1):33–38. https://doi.org/10.1007/s11325-012-0680-8

    Article  PubMed  Google Scholar 

  32. Choi J, Joseph L, Pilote L (2013) Obesity and C-reactive protein in various populations: a systematic review and meta-analysis. Obes Rev 14(3):232–244. https://doi.org/10.1111/obr.12003

    Article  CAS  PubMed  Google Scholar 

  33. Poitou C, Coussieu C, Rouault C, Coupaye M, Cancello R, Bedel JF, Gouillon M, Bouillot JL, Oppert JM, Basdevant A, Clément K (2006) Serum amyloid A: a marker of adiposity-induced low-grade inflammation but not of metabolic status. Obesity (Silver Spring) 14(2):309–318. https://doi.org/10.1038/oby.2006.40

    Article  CAS  Google Scholar 

  34. Zimmermann E, Anty R, Tordjman J, Verrijken A, Gual P et al (2011) C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients. J Hepatol 55(3):660–665. https://doi.org/10.1016/j.jhep.2010.12.017

  35. Bhatt SP, Guleria R, Vikram NK, Gupta AK (2019) Non-alcoholic fatty liver disease is an independent risk factor for inflammation in obstructive sleep apnea syndrome in obese Asian Indians. Sleep Breath 23(1):171–178. https://doi.org/10.1007/s11325-018-1678-7

    Article  PubMed  Google Scholar 

  36. Hernaez R, Lazo M, Bonekamp S, Kamel I, Brancati FL, Guallar E, Clark JM (2011) Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology 54(3):1082–1090. https://doi.org/10.1002/hep.24452

    Article  PubMed  Google Scholar 

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Funding

This work was supported by research grants from the Precision Medicine Project (2016YFC0903602) and the National Key Research and Development Project (2016YFC1304500) from the Ministry of Science and Technology of China.

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Author notes

  1. Li Zhang and Xiaolei Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Pulmonary and Critical Care Medicine, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China

    Li Zhang, Xiaolei Zhang & Chen Wang

  2. Center for Respiratory Diseases, China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Beijing, 100029, China

    Li Zhang, Xiaolei Zhang, Yiming Li, Teng Han & Chen Wang

  3. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Xiaolei Zhang & Chen Wang

  4. The Graduate School of Peking Union Medical College, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Xiaolei Zhang & Chen Wang

  5. Capital Medical University, Beijing, China

    Xiaolei Zhang & Chen Wang

  6. Peking University Health Science Center, Beijing, China

    Xiaolei Zhang & Chen Wang

  7. Department of General Surgery, China-Japan Friendship Hospital, Beijing, 100029, China

    Hua Meng

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  1. Li Zhang
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Correspondence to Chen Wang.

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Zhang, L., Zhang, X., Meng, H. et al. Obstructive sleep apnea and liver injury in severely obese patients with nonalcoholic fatty liver disease. Sleep Breath 24, 1515–1521 (2020). https://doi.org/10.1007/s11325-020-02018-z

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  • DOI: https://doi.org/10.1007/s11325-020-02018-z

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