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Impact of long-term continuous positive airway pressure on liver fat in male obstructive sleep apnea patients with fatty liver

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Abstract

Obstructive sleep apnea (OSA) is an established factor in the pathogenesis and exacerbation of fatty liver disease. However, randomized controlled trials have failed to demonstrate decreases in liver fat content in OSA patients by continuous positive airway pressure (CPAP) performed for several months. The aim of this study is to investigate the impact of long-term CPAP therapy on liver fat content in OSA patients with fatty liver. Liver fat content in 61 male OSA patients was evaluated by computed tomography performed because of abdominal obesity before and after CPAP initiation. At baseline, there were 25 participants with fatty liver. Their apnea–hypopnea index and percent sleep time with oxygen saturation < 90% were greater than those in the 36 participants who did not have fatty liver (52.3 vs. 41.8/h and 30.4 vs. 14.8%, respectively). The average therapy duration was 31 months. In the analysis of the entire participant group, liver fat content did not change after CPAP therapy. In those without fatty liver, liver fat content increased accompanied by increases in BMI, whereas in the participants with fatty liver, liver fat content decreased despite stable BMI, abdominal fat distribution, and insulin resistance. In male OSA patients with abdominal obesity, decreases in liver fat content were observed after long-term CPAP therapy only when fatty liver was present at baseline. This implies that there are some conditions, such as OSA-related hypoxemia and others, which may exacerbate fatty liver and that fatty liver may improve with CPAP therapy.

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References

  1. Musso G, Cassader M, Olivetti C, Rosina F, Carbone G, Gambino R. Association of obstructive sleep apnoea with the presence and severity of non-alcoholic fatty liver disease. A systematic review and meta-analysis. Obes Rev. 2013;14:417–31.

    Article  CAS  PubMed  Google Scholar 

  2. Minville C, Hilleret MN, Tamisier R, Aron-Wisnewsky J, Clement K, Trocme C, Borel JC, Levy P, Zarski JP, Pepin JL. Nonalcoholic fatty liver disease, nocturnal hypoxia and endothelial function in sleep apnea patients. Chest. 2014;145:525–33.

    Article  PubMed  Google Scholar 

  3. Benotti P, Wood GC, Argyropoulos G, Pack A, Keenan BT, Gao X, Gerhard G, Still C. The impact of obstructive sleep apnea on nonalcoholic fatty liver disease in patients with severe obesity. Obesity. 2016;24:871–7.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Li J, Thorne LN, Punjabi NM, Sun CK, Schwartz AR, Smith PL, Marino RL, Rodriguez A, Hubbard WC, O’Donnell CP, Polotsky VY. Intermittent hypoxia induces hyperlipidemia in lean mice. Circ Res. 2005;97:698–706.

    Article  CAS  PubMed  Google Scholar 

  5. Li J, Grigoryev DN, Ye SQ, Thorne L, Schwartz AR, Smith PL, O’Donnell CP, Polotsky VY. Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. J Appl Physiol. 2005;99:1643–8.

    Article  CAS  PubMed  Google Scholar 

  6. Hoyos CM, Killick R, Yee BJ, Phillips CL, Grunstein RR, Liu PY. Cardiometabolic changes after continuous positive airway pressure for obstructive sleep apnoea: a randomised sham-controlled study. Thorax. 2012;67:1081–9.

    Article  PubMed  Google Scholar 

  7. Kritikou I, Basta M, Tappouni R, Pejovic S, Fernandez-Mendoza J, Nazir R, Shaffer M, Liao D, Bixler E, Chrousos G, Vgontzas AN. Sleep apnoea and visceral adiposity in middle-aged males and females. Eur Respir J. 2012;41:601–9.

    Article  PubMed  Google Scholar 

  8. Sivam S, Phillips CL, Trenell MI, Yee BJ, Liu PY, Wong KK, Grunstein RR. Effects of 8 weeks of continuous positive airway pressure on abdominal adiposity in obstructive sleep apnoea. Eur Respir J. 2012;40:913–8.

    Article  CAS  PubMed  Google Scholar 

  9. Jullian-Desayes I, Tamisier R, Zarski JP, Aron-Wisnewsky J, Launois-Rollinat SH, Trocme C, Levy P, Joyeux-Faure M, Pepin JL. Impact of effective versus sham continuous positive airway pressure on liver injury in obstructive sleep apnoea: data from randomized trials. Respirology. 2016;21:378–85.

    Article  PubMed  Google Scholar 

  10. Kohler M, Stradling JR. Does continuous positive airway pressure therapy improve non-alcoholic fatty liver disease? Respirology. 2016;21:209–10.

    Article  PubMed  Google Scholar 

  11. Chen LD, Lin L, Zhang LJ, Zeng HX, Wu QY, Hu MF, Xie JJ, Liu JN. Effect of continuous positive airway pressure on liver enzymes in obstructive sleep apnea: a meta-analysis. Clin Respir J. 2016. https://doi.org/10.1111/crj.12554.

    Google Scholar 

  12. Kodama Y, Ng CS, Wu TT, Ayers GD, Curley SA, Abdalla EK, Vauthey JN, Charnsangavej C. Comparison of CT methods for determining the fat content of the liver. Am J Roentgenol. 2007;188:1307–12.

    Article  Google Scholar 

  13. Poynard T, Ratziu V, Naveau S, Thabut D, Charlotte F, Messous D, Capron D, Abella A, Massard J, Ngo Y, Munteanu M, Mercadier A, Manns M, Albrecht J. The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis. Comp Hepatol. 2005;4:10.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Shpirer I, Copel L, Broide E, Elizur A. Continuous positive airway pressure improves sleep apnea associated fatty liver. Lung. 2010;188:301–7.

    Article  PubMed  Google Scholar 

  15. Tiniakos DG, Vos MB, Brunt EM. Nonalcoholic fatty liver disease: Pathology and pathogenesis. Ann Rev Pathol Mech Dis. 2010;5:145–71.

    Article  CAS  Google Scholar 

  16. Hashimoto E, Tokushige K. Prevalence, gender, ethnic variations, and prognosis of NASH. J Gastroenterol. 2011;46:63–9.

    Article  PubMed  Google Scholar 

  17. Toyama Y, Tanizawa K, Kubo T, Chihara Y, Harada Y, Murase K, Azuma M, Hamada S, Hitomi T, Handa T, Oga T, Chiba T, Mishima M, Chin K. Impact of obstructive sleep apnea on liver fat accumulation according to sex and visceral obesity. PLoS One. 2015;10:e0129513.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Examination Committee of Criteria for ‘Obesity Disease’ in Japan, Japan Society for the Study of Obesity, Matsuzawa Y, Nakamura T, Takahashi M, Ryo M, Inoue S, Ikeda Y, Ohno M, Sakata T, Fukagawa K, Saitoh Y, Sato Y, Shirai K, Miyazaki S, Tokunaga K, Yamanouchi K, Takahashi M, Shibasaki T, Nagai M. New criteria for ‘obesity disease’ in Japan. Circ J. 2002; 66:987–92.

    Article  Google Scholar 

  19. Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AHB, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161–7.

    Article  CAS  PubMed  Google Scholar 

  20. Yoshizumi T, Nakamura T, Yamane M, Waliul Islam AHM, Menju M, Yamasaki K, Arai T, Kotani K, Funahashi T, Yamashita S, Matsuzawa Y. Abdominal fat: standardized technique for measurement at CT. Radiology. 1999;211:283–6.

    Article  CAS  PubMed  Google Scholar 

  21. Harada Y, Oga T, Chihara Y, Azuma M, Murase K, Toyama Y, Aihara K, Tanizawa K, Yoshimura C, Hitomi T, Handa T, Tsuboi T, Mishima M, Chin K. Differences in associations between visceral fat accumulation and obstructive sleep apnea by sex. Ann Am Thorac Soc. 2014;11:383–9.

    Article  PubMed  Google Scholar 

  22. Iber C, Ancoli-Israel S, Chesson A, Quan SF, for the American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events: Rules, terminology, and technical specifications. Westchester: American Academy of Sleep Medicine; 2007.

    Google Scholar 

  23. Punjabi NM, Newman AB, Young TB, Resnick HE, Sanders MH. Sleep-disordered breathing and cardiovascular disease: an outcome-based definition of hypopneas. Am J Respir Crit Care Med. 2008;177:1150–5.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Chihara Y, Chin K, Aritake K, Harada Y, Toyama Y, Murase K, Yoshimura C, Hitomi T, Oga T, Mishima M, Urade Y. A urine biomarker for severe obstructive sleep apnoea patients: lipocalin-type prostaglandin D synthase. Eur Respir J. 2013;42:1563–74.

    Article  CAS  PubMed  Google Scholar 

  25. Murase K, Hitomi T, Hamada S, Azuma M, Toyama Y, Harada Y, Tanizawa K, Handa T, Yoshimura C, Oga T, Mishima M, Chin K. The additive impact of periodic limb movements during sleep on inflammation in obstructive sleep apnea patients. Ann Am Thorac Soc. 2014;11:375–82.

    Article  PubMed  Google Scholar 

  26. Aron-Wisnewsky J, Clement K, Pepin JL. Nonalcoholic fatty liver disease and obstructive sleep apnea. Metabolism. 2016;65:1124–35.

    Article  CAS  PubMed  Google Scholar 

  27. Hang LW, Chen CF, Wang CB, Wu TN, Liang WM, Chou TC. The association between continuous positive airway pressure therapy and liver disease development in obstructive sleep apnea/hypopnea syndrome patients: a nationwide population-based cohort study in Taiwan. Sleep Breath. 2016. https://doi.org/10.1007/s11325-016-1439-4.

    PubMed  Google Scholar 

  28. Tachikawa R, Ikeda K, Minami T, Matsumoto T, Hamada S, Murase K, Tanizawa K, Inouchi M, Oga T, Akamizu T, Mishima M, Chin K. Changes in energy metabolism after continuous positive airway pressure for obstructive sleep apnea. Am J Respir Crit Care Med. 2016;194:729–38.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Respiratory Medicine, Osaka Kaisei Hospital, 1-6-10 Miyahara, Yodogawa-Ku, Osaka, 532-0003, Japan

    Yoshiro Toyama

  2. Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Shogoin 54, Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Kimihiko Murase, Kiminobu Tanizawa, Toru Oga & Kazuo Chin

  3. Department of Respiratory Medicine, Osaka Saiseikai Nakatsu Hospital, 2-10-39 Shibata, Kita-Ku, Osaka, 530-0012, Japan

    Masanori Azuma

  4. Department of Respiratory Medicine, Hikone Municipal Hospital, 1882, Yasaka-cho, Hikone, 522-8539, Japan

    Satoshi Hamada

  5. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1, Minatojimaminamimachi, Chuo-ku, Kobe, 650-0047, Japan

    Ryo Tachikawa

  6. Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Shogoin 54, Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Tomohiro Handa & Toyohiro Hirai

  7. Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Shogoin 54, Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Takeshi Kubo

  8. Department of Clinical Laboratory, Graduate School of Medicine, Kyoto University, Shogoin 54, Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Takefumi Hitomi

Authors
  1. Yoshiro Toyama
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  2. Kimihiko Murase
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  3. Masanori Azuma
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  4. Satoshi Hamada
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  5. Ryo Tachikawa
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  6. Kiminobu Tanizawa
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  7. Tomohiro Handa
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  8. Takeshi Kubo
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  9. Takefumi Hitomi
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  10. Toru Oga
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  11. Toyohiro Hirai
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  12. Kazuo Chin
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Corresponding author

Correspondence to Kazuo Chin.

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Conflict of interest

Kimihiko Murase, Kiminobu Tanizawa, Toru Oga, and Kazuo Chin belong to the Department of Respiratory Care and Sleep Control Medicine which is funded by endowments from Philips-Respironics, Teijin Pharma, Fukuda Denshi, and Fukuda Lifetec Keiji to Kyoto University. Other authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

Kyoto University Graduate School and Faculty of Medicine Ethics Committee (IRB approval number: E-1307). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

This study was supported by Grants (26293198 and 17H04182) from the Japanese Ministry of Education, Culture, Sports, Science and Technology, the Intractable Respiratory Diseases and Pulmonary Hypertension Research Group, the Ministry of Health, Labor and Welfare, Japan, and Health, Labor and Welfare Sciences Research Grants, Research on Region Medical, the Ministry of Health, Labor and Welfare, Japan and the Japan Vascular Disease Research Foundation. The Department of Respiratory Care and Sleep Control Medicine is funded by endowments from Philips-Respironics, Teijin Pharma, Fukuda Denshi and Fukuda Lifetec Keiji to Kyoto University. The sponsor had no role in the design or conduct of this research.

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Informed consent was obtained from all individual participants included in the study.

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Toyama, Y., Murase, K., Azuma, M. et al. Impact of long-term continuous positive airway pressure on liver fat in male obstructive sleep apnea patients with fatty liver. Sleep Biol. Rhythms 16, 117–124 (2018). https://doi.org/10.1007/s41105-017-0133-7

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  • DOI: https://doi.org/10.1007/s41105-017-0133-7

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