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Journal of Gastroenterology

, Volume 49, Issue 7, pp 1163–1174 | Cite as

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

  • Hiroyoshi Taketani
  • Yoshio SumidaEmail author
  • Saiyu Tanaka
  • Kento Imajo
  • Masato Yoneda
  • Hideyuki Hyogo
  • Masafumi Ono
  • Hideki Fujii
  • Yuichiro Eguchi
  • Kazuyuki Kanemasa
  • Kazuaki Chayama
  • Yoshito Itoh
  • Toshikazu Yoshikawa
  • Toshiji Saibara
  • Kazuma Fujimoto
  • Atsushi Nakajima
  • Japan Study Group of NAFLD (JSG-NAFLD)
Original Article—LIVER, PANCREAS, AND BILIARY TRACT

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.

Keywords

GERD Insomnia Nonalcoholic fatty liver disease Proton-pump inhibitor 

Abbreviations

BMI

Body mass index

GERD

Gastro-esophageal reflux disease

NAFLD

Nonalcoholic fatty liver disease

NASH

Nonalcoholic steatohepatitis

Notes

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.

References

  1. 1.
    Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221–31.PubMedCrossRefGoogle Scholar
  2. 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.PubMedGoogle Scholar
  3. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 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.PubMedCrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 14.
    Orr WC. Review article: sleep-related gastro-oesophageal reflux as a distinct clinical entity. Aliment Pharmacol Ther. 2010;31:47–56.PubMedCrossRefGoogle Scholar
  15. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 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.PubMedGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 27.
    Soldatos CR, Dikeos DG, Paparrigopoulos TJ. The diagnostic validity of the Athens Insomnia Scale. J Psychosom Res. 2003;55:263–7.PubMedCrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedGoogle Scholar
  33. 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. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.PubMedGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 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.PubMedCrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.CrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 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.PubMedCrossRefGoogle Scholar
  46. 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.PubMedCrossRefGoogle Scholar
  47. 47.
    Lee DH, Jacobs DR Jr. Serum gamma-glutamyltransferase: new insights about an old enzyme. J Epidemiol Community Health. 2009;63:884–6.PubMedCrossRefGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 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.PubMedCrossRefGoogle Scholar
  50. 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.PubMedCrossRefGoogle Scholar
  51. 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.PubMedCrossRefGoogle Scholar
  52. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Hiroyoshi Taketani
    • 1
  • Yoshio Sumida
    • 2
    Email author
  • Saiyu Tanaka
    • 1
  • Kento Imajo
    • 3
  • Masato Yoneda
    • 3
  • Hideyuki Hyogo
    • 4
  • Masafumi Ono
    • 5
  • Hideki Fujii
    • 6
  • Yuichiro Eguchi
    • 7
  • Kazuyuki Kanemasa
    • 1
  • Kazuaki Chayama
    • 4
  • Yoshito Itoh
    • 2
  • Toshikazu Yoshikawa
    • 2
  • Toshiji Saibara
    • 5
  • Kazuma Fujimoto
    • 7
  • Atsushi Nakajima
    • 3
  • Japan Study Group of NAFLD (JSG-NAFLD)
  1. 1.Center for Digestive and Liver DiseasesNara City HospitalNaraJapan
  2. 2.Department of Gastroenterology and HepatologyKyoto Prefectural University of MedicineKyotoJapan
  3. 3.Division of GastroenterologyYokohama City University Graduate School of MedicineYokohamaJapan
  4. 4.Department of Medicine and Molecular Science, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan
  5. 5.Department of Gastroenterology and HepatologyKochi Medical SchoolKochiJapan
  6. 6.Department of Hepatology, Graduate School of MedicineOsaka City UniversityOsakaJapan
  7. 7.Department of Internal Medicine, Saga Medical SchoolSaga UniversitySagaJapan

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