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The association of insomnia with gastroesophageal reflux symptoms in biopsy-proven nonalcoholic fatty liver disease

  • Original Article—LIVER, PANCREAS, AND BILIARY TRACT
  • Published:
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Abstract

Background

It is suggested that nonalcoholic fatty liver disease (NAFLD), including nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), can be associated with insomnia and gastro-esophageal reflux disease (GERD). The relationship between GERD and insomnia in subjects with biopsy-proven NAFLD was investigated.

Methods

This study enrolled 123 patients with biopsy-proven NAFLD. Insomnia was assessed by the Athens Insomnia Scale (AIS), a self-assessment psychometric instrument designed to quantify sleep difficulty based on ICD-10 criteria; AIS scores ≥ 6 were considered positive for insomnia. GERD symptoms were evaluated using a frequency scale for the symptoms of GERD (FSSG); FSSG scores ≥ 8 were considered positive. Logistic regression models were used to evaluate the association of insomnia with GERD, after adjusting for potential confounders. Thirteen patients with GERD were treated with the proton pump inhibitor rabeprazole (RPZ; 10 mg/day), for 12 weeks.

Results

Of the 123 patients, 76 (62 %) were female and 87 (71 %) were obese, with 34 (28 %) having AIS scores ≥ 6 and 31 (25 %) having FSSG scores ≥ 8. Liver biopsy revealed that 40 patients (33 %) had NAFL and 83 (67 %) had NASH. FSSG and AIS scores were similar in the two groups. HOMA-IR, FSSG scores and γGT (GGT) concentrations were significantly higher in insomniacs than in non-insomniacs. Logistic regression analysis demonstrated that FSSG score and GGT concentration were independently associated with insomnia. RPZ treatment resulted in significantly reductions in both AIS and FSSG scores.

Conclusions

Nearly 30 % of patients with biopsy-proven NAFLD had insomnia, which was related to GGT and GERD and could be relieved by RPZ treatment.

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Abbreviations

BMI:

Body mass index

GERD:

Gastro-esophageal reflux disease

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

References

  1. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221–31.

    Article  CAS  PubMed  Google Scholar 

  2. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Non-alcoholic steatohepatitis. Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434–8.

    CAS  PubMed  Google Scholar 

  3. David K, Kowdley KV, Unalp A, Kanwal F, Brunt EM, Schwimmer JB. Quality of life in adults with nonalcoholic fatty liver disease: baseline data from the nonalcoholic steatohepatitis clinical research network. Hepatology. 2009;49:1904–12.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Kim CW, Yun KE, Jung HS, Chang Y, Choi ES, Kwon MJ, et al. Sleep duration and quality in relation to non-alcoholic fatty liver disease in middle-aged workers and their spouses. J Hepatol. 2013;59(2):351–7.

    Article  PubMed  Google Scholar 

  5. Hsieh SD, Muto T, Murase T, Tsuji H, Arase Y. Association of short sleep duration with obesity, diabetes, fatty liver and behavioral factors in Japanese men. Intern Med. 2011;50:2499–502.

    Article  PubMed  Google Scholar 

  6. Dew MA, Hoch CC, Buysse DJ, Monk TH, Begley AE, Houck PR, et al. Healthy older adults’ sleep predicts all-cause mortality at 4 to 19 years of follow-up. Psychosom Med. 2003;65:63–73.

    Article  PubMed  Google Scholar 

  7. Fujikawa Y, Tominaga K, Fujii H, Machida H, Okazaki H, Yamagami H, et al. High prevalence of gastroesophageal reflux symptoms in patients with non-alcoholic fatty liver disease associated with serum levels of triglyceride and cholesterol but not simple visceral obesity. Digestion. 2012;86:228–37.

    Article  CAS  PubMed  Google Scholar 

  8. Miele L, Cammarota G, Vero V, Racco S, Cefalo C, Marrone G, et al. Non-alcoholic fatty liver disease is associated with high prevalence of gastro-oesophageal reflux symptoms. Dig Liver Dis. 2012;44:1032–6.

    Article  PubMed  Google Scholar 

  9. Kusano M, Kouzu T, Kawano T, Ohara S. Nationwide epidemiological study on gastroesophageal reflux disease and sleep disorders in the Japanese population. J Gastroenterol. 2008;43:833–41.

    Article  PubMed  Google Scholar 

  10. Jansson C, Nordenstedt H, Wallander MA, Johansson S, Johnsen R, Hveem K, Lagergren J. A population-based study showing an association between gastroesophageal reflux disease and sleep problems. Clin Gastroenterol Hepatol. 2009;7:960–5.

    Article  PubMed  Google Scholar 

  11. Fujiwara Y, Kohata Y, Kaji M, Nebiki H, Yamasaki T, Sasaki E, et al. Sleep dysfunction in Japanese patients with gastroesophageal reflux disease: prevalence, risk factors, and efficacy of rabeprazole. Digestion. 2010;81:135–41.

    Article  CAS  PubMed  Google Scholar 

  12. Johnson DA. Gastroesophageal reflux disease and sleep disorders: a wake-up call for physicians and their patients. Rev Gastroenterol Disord. 2005;5(Suppl 2):S3–11.

    PubMed  Google Scholar 

  13. Mody R, Bolge SC, Kannan H, Fass R. Effects of gastroesophageal reflux disease on sleep and outcomes. Clin Gastroenterol Hepatol. 2009;7:953–9.

    Article  PubMed  Google Scholar 

  14. Orr WC. Review article: sleep-related gastro-oesophageal reflux as a distinct clinical entity. Aliment Pharmacol Ther. 2010;31:47–56.

    Article  CAS  PubMed  Google Scholar 

  15. Yamamichi N, Mochizuki S, Asada-Hirayama I, Mikami-Matsuda R, Shimamoto T, Konno-Shimizu M, et al. Lifestyle factors affecting gastroesophageal reflux disease symptoms: a cross-sectional study of healthy 19864 adults using FSSG scores. BMC Med. 2012;10:45.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Orr WC, Goodrich S, Robert J. The effect of acid suppression on sleep patterns and sleep-related gastro-oesophageal reflux. Aliment Pharmacol Ther. 2005;21:103–8.

    Article  CAS  PubMed  Google Scholar 

  17. Fujiwara Y, Kohata Y, Kaji M, Nebiki H, Yamasaki T, Sasaki E, et al. Sleep dysfunction in Japanese patients with gastroesophageal reflux disease: prevalence, risk factors, and efficacy of rabeprazole. Digestion. 2010;81:135–41.

    Article  CAS  PubMed  Google Scholar 

  18. Examination Committee of Criteria for ‘Obesity Disease’ in Japan; Japan Society for the Study of Obesity. New criteria for ‘obesity disease’ in Japan. Circ J. 2002;66:987–92.

    Article  Google Scholar 

  19. Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus. Report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus. J Jpn diabetes Soc. 2010;53:450–67.

    Google Scholar 

  20. Ogihara T, Kikuchi K, Matsuoka H, Fujita T, Higaki J, Horiuchi M, et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009). Hypertens Res. 2009;32:3–107.

    Article  CAS  PubMed  Google Scholar 

  21. Kusano M, Shimoyama Y, Sugimoto S, Kawamura O, Maeda M, Minashi K, Kuribayashi S, Higuchi T, Zai H, Ino K, Horikoshi T, Sugiyama T, Toki M, Ohwada T, Mori M. Development and evaluation of FSSG: frequency scale for the symptoms of GERD. J Gastroenterol. 2004;39:888–91.

    Article  PubMed  Google Scholar 

  22. Yasaka S, Murakami K, Abe T, Anan J, Mizukami K, Tanahashi J, Okimoto T, Kodama M, Kudo Y, Kawasaki H, Fujioka T. Evaluation of esophageal function in patients with gastroesophageal reflux disease using transnasal endoscopy. J Gastroenterol Hepatol. 2009;24:1677–82.

    Article  PubMed  Google Scholar 

  23. Miyamoto M, Haruma K, Takeuchi K, Kuwabara M. Frequency scale for symptoms of gastroesophageal reflux disease predicts the need for addition of prokinetics to proton pump inhibitor therapy. J Gastroenterol Hepatol. 2008;23:746–51.

    Article  CAS  PubMed  Google Scholar 

  24. Furuta T, Shimatani T, Sugimoto M, Ishihara S, Fujiwara Y, Kusano M, et al. Investigation of pretreatment prediction of proton pump inhibitor (PPI)-resistant patients with gastroesophageal reflux disease and the dose escalation challenge of PPIs-TORNADO study: a multicenter prospective study by the Acid-Related Symptom Research Group in Japan. J Gastroenterol. 2011;46:1273–83.

    Article  CAS  PubMed  Google Scholar 

  25. Sakamoto Y, Inamori M, Iwasaki T, Lida H, Endo H, Hosono K, et al. Relationship between upper gastrointestinal symptoms and diet therapy: examination using frequency scale for the symptoms of gastroesophageal reflux disease. Hepatogastroenterology. 2010;57:1635–8.

    PubMed  Google Scholar 

  26. Soldatos CR, Dikeos DG, Paparrigopoulos TJ. Athens Insomnia Scale: validation of an instrument based on ICD-10 criteria. J Psychosom Res. 2000;48:555–60.

    Article  CAS  PubMed  Google Scholar 

  27. Soldatos CR, Dikeos DG, Paparrigopoulos TJ. The diagnostic validity of the Athens Insomnia Scale. J Psychosom Res. 2003;55:263–7.

    Article  PubMed  Google Scholar 

  28. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver diseases: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116:1413–9.

    Article  CAS  PubMed  Google Scholar 

  29. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Nonalcoholic Steatohepatitis Clinical Research Network, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.

    Article  PubMed  Google Scholar 

  30. 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. 1999;94:2467–74.

    Article  CAS  PubMed  Google Scholar 

  31. Doi Y, Minowa M, Uchiyama M, Okawa M, Kim K, Shibui K, Kamei Y. Psychometric assessment of subjective sleep quality using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) in psychiatric disordered and control subjects. Psychiatry Res. 2000;97:165–72.

    Article  CAS  PubMed  Google Scholar 

  32. Kim K, Uchiyama M, Okawa M, Liu X, Ogihara R. An epidemiological study of insomnia among the Japanese general population. Sleep. 2000;23:41–7.

    CAS  PubMed  Google Scholar 

  33. Yoshioka E, Saijo Y, Kita T, Satoh H, Kawaharada M, Kishi R. Effect of the interaction between employment level and psychosocial work environment on insomnia in male Japanese public service workers. Int J Behav Med. 2012. doi:10.1007/s12529-012-9230-9.

  34. Yoshioka E, Saijo Y, Kita T, Satoh H, Kawaharada M, Fukui T, Kishi R. Gender differences in insomnia and the role of paid work and family responsibilities. Soc Psychiatry Psychiatr Epidemiol. 2012;47:651–62.

    Article  PubMed  Google Scholar 

  35. Monterrosa-Castro A, Marrugo-Flórez M, Romero-Pérez I, Chedraui P, Fernández-Alonso AM, Pérez-López FR. Prevalence of insomnia and related factors in a large mid-aged female Colombian sample. Maturitas. 2013;74:346–51.

    Article  PubMed  Google Scholar 

  36. Blümel JE, Cano A, Mezones-Holguín E, Barón G, Bencosme A, Benítez Z, et al. A multinational study of sleep disorders during female mid-life. Maturitas. 2012;72:359–66.

    Article  PubMed  Google Scholar 

  37. Yoshioka E, Saijo Y, Fukui T, Kawaharada M, Kishi R. Association between duration of daily visual display terminal work and insomnia among local government clerks in Japan. Am J Ind Med. 2008;51:148–56.

    Article  PubMed  Google Scholar 

  38. Utsugi M, Saijo Y, Yoshioka E, Horikawa N, Sato T, Gong Y, Kishi R. Relationships of occupational stress to insomnia and short sleep in Japanese workers. Sleep. 2005;28:728–35.

    PubMed  Google Scholar 

  39. Nishitani N, Sakakibara H. Job stress factors, stress response, and social support in association with insomnia of Japanese male workers. Ind Health. 2010;48:178–84.

    Article  PubMed  Google Scholar 

  40. Kozaki T, Miura N, Takahashi M, Yasukouchi A. Effect of reduced illumination on insomnia in office workers. J Occup Health. 2012;54:331–5.

    Article  PubMed  Google Scholar 

  41. Spiegel K, Tasali E, Penev P, Van Cauter E. Brief communication: sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med. 2004;141:846–50.

    Article  PubMed  Google Scholar 

  42. Spiegel K, Leproult R, L’hermite-Baleriaux M, Copinschi G, Penev PD, Van Cauter E. Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin. J Clin Endocrinol Metab. 2004;89:5762–71.

    Article  CAS  PubMed  Google Scholar 

  43. Donga E, Van Dijk M, Van Dijk JG, Biermasz NR, Lammers GJ, van Kralingen KW, et al. A single night of partial sleep deprivation induces insulin resistance in multiple metabolic pathways. J Clin Endocrinol. 2010;95:2963–8.

    Article  CAS  Google Scholar 

  44. Bajaj JS, Bajaj S, Dua KS, Jaradeh S, Rittmann T, Hofmann C, Shaker R. Influence of sleep stages on esophago-upper esophageal sphincter contractile reflex and secondary esophageal peristalsis. Gastroenterology. 2006;130:17–25.

    Article  PubMed  Google Scholar 

  45. Schey R, Dickman R, Parthasarathy S, Quan SF, Wendel C, Merchant J, et al. Sleep deprivation is hyperalgesic in patients with gastroesophageal reflux disease. Gastroenterology. 2007;133:1787–95.

    Article  PubMed  Google Scholar 

  46. Johnson DA, Orr WC, Crawley JA, Traxler B, McCullough J, Brown KA, Roth T. Effect of esomeprazole on nighttime heartburn and sleep quality in patients with GERD: a randomized, placebo-controlled trial. Am J Gastroenterol. 2005;100:1914–22.

    Article  CAS  PubMed  Google Scholar 

  47. Lee DH, Jacobs DR Jr. Serum gamma-glutamyltransferase: new insights about an old enzyme. J Epidemiol Community Health. 2009;63:884–6.

    Article  PubMed  Google Scholar 

  48. Gulec M, Ozkol H, Selvi Y, Tuluce Y, Aydin A, Besiroglu L, Ozdemir PG. Oxidative stress in patients with primary insomnia. Prog Neuropsychopharmacol Biol Psychiatry. 2012;37:247–51.

    Article  CAS  PubMed  Google Scholar 

  49. Irie M, Sohda T, Iwata K, Kunimoto H, Fukunaga A, Kuno S, et al. Levels of the oxidative stress marker γ-glutamyltranspeptidase at different stages of nonalcoholic fatty liver disease. J Int Med Res. 2012;40:924–33.

    Article  CAS  PubMed  Google Scholar 

  50. Kozakova M, Palombo C, Eng MP, Dekker J, Flyvbjerg A, Mitrakou A, et al. Fatty liver index, gamma-glutamyltransferase, and early carotid plaques. Hepatology. 2012;55:1406–15.

    Article  CAS  PubMed  Google Scholar 

  51. Barceló A, Barbé F, de la Peña M, Vila M, Pérez G, Piérola J, et al. Antioxidant status in patients with sleep apnoea and impact of continuous positive airway pressure treatment. Eur Respir J. 2006;27:756–60.

    Article  PubMed  Google Scholar 

  52. 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 

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Conflict of interest

Yuichiro Eguchi received a research grant from Bristol-Myers Squibb. Yoshito Itoh received commercial research funds from Dainippon Sumitomo Pharma Co., Ltd.

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Authors and Affiliations

  1. Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan

    Hiroyoshi Taketani, Saiyu Tanaka & Kazuyuki Kanemasa

  2. Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, 602-8566, Japan

    Yoshio Sumida, Yoshito Itoh & Toshikazu Yoshikawa

  3. Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Kento Imajo, Masato Yoneda & Atsushi Nakajima

  4. Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

    Hideyuki Hyogo & Kazuaki Chayama

  5. Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan

    Masafumi Ono & Toshiji Saibara

  6. Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Hideki Fujii

  7. Department of Internal Medicine, Saga Medical School, Saga University, Saga, Japan

    Yuichiro Eguchi & Kazuma Fujimoto

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  1. Hiroyoshi Taketani
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Japan Study Group of NAFLD (JSG-NAFLD)

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Correspondence to Yoshio Sumida.

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Taketani, H., Sumida, Y., Tanaka, S. et al. The association of insomnia with gastroesophageal reflux symptoms in biopsy-proven nonalcoholic fatty liver disease. J Gastroenterol 49, 1163–1174 (2014). https://doi.org/10.1007/s00535-013-0871-5

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  • DOI: https://doi.org/10.1007/s00535-013-0871-5

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