Skip to main content

Advertisement

SpringerLink
Log in

Nonalcoholic Fatty Liver Disease Increases Risk for Gastroesophageal Reflux Symptoms

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Nonalcoholic fatty liver disease (NAFLD) is now recognized as a leading cause of liver dysfunction. Gastroesophageal reflux disease (GERD) is a common disorder causing symptoms that often impair patients’ quality of life. In recent years, the prevalence of both these diseases has increased, partially overlapping the rise of metabolic disorders.

Aims

We investigated whether a relation does exist between NAFLD and GERD symptoms.

Methods

Cross-sectional study among 206 outpatients diagnosed with NAFLD and 183 controls. We collected clinical and laboratory data, assessed severity and frequency of GERD symptoms and the esophageal endoscopic pattern.

Results

The prevalence of GERD symptoms was higher in NAFLD patients than controls (61.2 vs. 27.9 %, p < 0.001). We found a positive association between NAFLD and the experiencing of heartburn, regurgitation and belching. GERD symptoms were related to body mass index (BMI) and metabolic syndrome (MetS); a strong association persisted after adjustment for all the covariates (adjusted OR 3.49, 95 CI % 2.24–5.44, p < 0.001).

Conclusions

Our data show that the prevalence of GERD typical symptoms is higher in patients with NAFLD. GERD was associated with higher BMI and MetS, but not with age and diabetes type 2. NAFLD remained strongly associated with GERD, independently of a coexisting MetS status. Consistent with these findings, MetS can be considered a shared background, but cannot completely explain this correlation. We suggest NAFLD as an independent risk factor for GERD symptoms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013;58:593–608.

    Article  PubMed  Google Scholar 

  2. Tarantino G, Saldalamacchia G, Conca P, Arena A. Non-alcoholic fatty liver disease: further expression of the metabolic syndrome. J Gastroenterol Hepatol. 2007;22:293–303.

    Article  CAS  PubMed  Google Scholar 

  3. Kopec KL, Burns D. Nonalcoholic fatty liver disease: a review of the spectrum of disease, diagnosis, and therapy. Nutr Clin Pract. 2011;26:565–576.

    Article  PubMed  Google Scholar 

  4. Attar BM, Van Thiel DH. Current concepts and management approaches in nonalcoholic fatty liver disease. Sci World J. 2013;2013:481893.

    Article  Google Scholar 

  5. Obika M, Noguchi H. Diagnosis and evaluation of nonalcoholic fatty liver disease. Exp Diabetes Res. 2012;2012:145754.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Lipan MJ, Reidenberg JS, Laitman JT. Anatomy of reflux: a growing health problem affecting structures of the head and neck. Anat Rec B New Anat. 2006;289:261–270.

    Article  PubMed  Google Scholar 

  7. Wu P, Zhao XH, Ai ZS, et al. Dietary intake and risk for reflux esophagitis: a case-control study. Gastroenterol Res Pract. 2013;2013:691026.

    PubMed Central  PubMed  Google Scholar 

  8. Ronkainen J, Agréus L. Epidemiology of reflux symptoms and GORD. Best Pract Res Clin Gastroenterol. 2013;27:325–337.

    Article  PubMed  Google Scholar 

  9. El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2013. doi:10.1136/gutjnl-2012-304269.

    PubMed Central  Google Scholar 

  10. Camilleri M, Dubois D, Coulie B, et al. Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the US Upper Gastrointestinal Study. Clin Gastroenterol Hepatol. 2005;3:543–552.

    Article  PubMed  Google Scholar 

  11. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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) final report. Circulation. 2002;106:3143–3421.

    Google Scholar 

  12. Standards of Practice Committee, Lichtenstein DR, Cash BD, et al. Role of endoscopy in the management of GERD. Gastrointest Endosc. 2007;66(2):219–24.

    Google Scholar 

  13. Krishnan B, Babu S, Walker J, Walker AB, Pappachan JM. Gastrointestinal complications of diabetes mellitus. World J Diabetes. 2013;4:51–63.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Promberger R, Lenglinger J, Riedl O, et al. Gastro-oesophageal reflux disease in type 2 diabetics: symptom load and pathophysiologic aspects—a retro-pro study. BMC Gastroenterol. 2013;13:132.

    Article  PubMed Central  Google Scholar 

  15. Ayazi S, Hagen JA, Chan LS, et al. Obesity and gastroesophageal reflux: quantifying the association between body mass index, esophageal acid exposure, and lower esophageal sphincter status in a large series of patients with reflux symptoms. J Gastrointest Surg. 2009;13:1440–1447.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005;143:199–211.

    Article  PubMed  Google Scholar 

  17. El-Serag HB, Graham DY, Satia JA, Rabeneck L. Obesity is an independent risk factor for GERD symptoms and erosive esophagitis. Am J Gastroenterol. 2005;100:1243–1250.

    Article  PubMed  Google Scholar 

  18. Ierardi E, Rosania R, Zotti M, et al. Metabolic syndrome and gastro-esophageal reflux: a link towards a growing interest in developed countries. World J Gastrointest Pathophysiol. 2010;1:91–96.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Lee YC, Yen AM, Tai JJ, et al. The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease. Gut. 2009;58:174–181.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Festi D, Scaioli E, Baldi F, et al. Body weight, lifestyle, dietary habits and gastroesophageal reflux disease. World J Gastroenterol. 2009;15:1690–1701.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Jung HS, Choi MG, Baeg MK, et al. Obesity is associated with increasing esophageal acid exposure in Korean patients with gastroesophageal reflux disease symptoms. J Neurogastroenterol Motil. 2013;19:338–343.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Hajar N, Castell DO, Ghomrawi H, Rackett R, Hila A. Impedance pH confirms the relationship between GERD and BMI. Dig Dis Sci. 2012;57:1875–1879.

    Article  PubMed  Google Scholar 

  23. Fox M, Barr C, Nolan S, Lomer M, Anggiansah A, Wong T. The effects of dietary fat and calorie density on esophageal acid exposure and reflux symptoms. Clin Gastroenterol Hepatol. 2007;5:439–444.

    Article  PubMed  Google Scholar 

  24. Wu JC, Mui LM, Cheung CM, Chan Y, Sung JJ. Obesity is associated with increased transient lower esophageal sphincter relaxation. Gastroenterology. 2007;132:883–889.

    Article  PubMed  Google Scholar 

  25. Shapiro M, Green C, Bautista JM, et al. Assessment of dietary nutrients that influence perception of intra-oesophageal acid reflux events in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2007;25:93–101.

    Article  CAS  PubMed  Google Scholar 

  26. Lacy BE, Carter J, Weiss JE, et al. The effects of intraduodenal nutrient infusion on serum CCK, LES pressure, and gastroesophageal reflux. Neurogastroenterol Motil. 2011;23(7):631–e256.

    Google Scholar 

  27. Holloway RH, Lyrenas E, Ireland A, Dent J. Effect of intraduodenal fat on lower oesophageal sphincter function and gastro-oesophageal reflux. Gut. 1997;40:449–453.

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Altomare A, Ma J, Guarino MP, et al. Platelet-activating factor and distinct chemokines are elevated in mucosal biopsies of erosive compared with non-erosive reflux disease patients and controls. Neurogastroenterol Motil. 2012;24(10):943–e463.

    Google Scholar 

  29. Souza RF, Huo X, Mittal V, et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology. 2009;137:1776–1784.

    Article  CAS  PubMed  Google Scholar 

  30. Mönkemüller K, Wex T, Kuester D, et al. Interleukin-1beta and interleukin-8 expression correlate with the histomorphological changes in esophageal mucosa of patients with erosive and non-erosive reflux disease. Digestion. 2009;79:186–195.

    Article  PubMed  Google Scholar 

  31. Rieder F, Cheng L, Harnett KM, et al. Gastroesophageal reflux disease-associated esophagitis induces endogenous cytokine production leading to motor abnormalities. Gastroenterology. 2007;132:154–165.

    Article  CAS  PubMed  Google Scholar 

  32. Yoshida N, Uchiyama K, Kuroda M, et al. Interleukin-8 expression in the esophageal mucosa of patients with gastroesophageal reflux disease. Scand J Gastroenterol. 2004;39:816–822.

    Article  CAS  PubMed  Google Scholar 

  33. Isomoto H, Saenko VA, Kanazawa Y, et al. Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease. Am J Gastroenterol. 2004;99:589–597.

    Article  CAS  PubMed  Google Scholar 

  34. Ma J, Altomare A, de la Monte S, et al. HCl-induced inflammatory mediators in esophageal mucosa increase migration and production of H2O2 by peripheral blood leukocytes. Am J Physiol Gastrointest Liver Physiol. 2010;299:G791–G798.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Tutuian R, Castell DO. Review article: complete gastro-oesophageal reflux monitoring—combined pH and impedance. Aliment Pharmacol Ther. 2006;24:27–37.

    Article  PubMed  Google Scholar 

  36. McGown C, Birerdinc A, Younossi ZM. Adipose tissue as an endocrine organ. Clin Liver Dis. 2014;18:41–58.

    Article  PubMed  Google Scholar 

  37. Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci. 2013;9:191–200.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Kwon H, Pessin JE. Adipokines mediate inflammation and insulin resistance. Front Endocrinol. 2013;4:71.

    Article  Google Scholar 

  39. Haase J, Weyer U, Immig K, et al. Local proliferation of macrophages in adipose tissue during obesity-induced inflammation. Diabetologia. 2013. doi:10.1007/s00125-013-3139-y.

  40. Blüher M. Adipose tissue dysfunction contributes to obesity related metabolic diseases. Best Pract Res Clin Endocrinol Metab. 2013;27:163–177.

    Article  PubMed  Google Scholar 

  41. Harwood HJ Jr. The adipocyte as an endocrine organ in the regulation of metabolic homeostasis. Neuropharmacology. 2012;63:57–75.

    Article  CAS  PubMed  Google Scholar 

  42. Braunersreuther V, Viviani GL, Mach F, Montecucco F. Role of cytokines and chemokines in non-alcoholic fatty liver disease. World J Gastroenterol. 2012;18:727–735.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Jarrar MH, Baranova A, Collantes R, et al. Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2008;27:412–421.

    Article  CAS  PubMed  Google Scholar 

  44. García-Galiano D, Sánchez-Garrido MA, Espejo I, et al. IL-6 and IGF-1 are independent prognostic factors of liver steatosis and non-alcoholic steatohepatitis in morbidly obese patients. Obes Surg. 2007;17:493–503.

    Article  PubMed  Google Scholar 

  45. Karbownik-Lewinska M, Szosland J, et al. Direct contribution of obesity to oxidative damage to macromolecules. Neuro Endocrinol Lett. 2012;33:453–461.

    CAS  PubMed  Google Scholar 

  46. Palmieri VO, Grattagliano I, Portincasa P, Palasciano G. Systemic oxidative alterations are associated with visceral adiposity and liver steatosis in patients with metabolic syndrome. J Nutr. 2006;136:3022–3026.

    CAS  PubMed  Google Scholar 

  47. Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114:1752–1761.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Kim YJ, Kim EH, Hahm KB. Oxidative stress in inflammation-based gastrointestinal tract diseases: challenges and opportunities. J Gastroenterol Hepatol. 2012;27:1004–1010.

    Article  CAS  PubMed  Google Scholar 

  49. Erbil Y, Türkoglu U, Barbaros U, et al. Oxidative damage in an experimentally induced gastric and gastroduodenal reflux model. Surg Innov. 2005;12:219–225.

    Article  PubMed  Google Scholar 

  50. Wetscher GJ, Hinder RA, Bagchi D, et al. Reflux esophagitis in humans is mediated by oxygen-derived free radicals. Am J Surg. 1995;170(6):552–556; discussion 556–557.

    Google Scholar 

  51. Farhadi A, Fields J, Banan A, Keshavarzian A. Reactive oxygen species: are they involved in the pathogenesis of GERD, Barrett’s esophagus, and the latter’s progression toward esophageal cancer? Am J Gastroenterol. 2002;97:22–26.

    Article  CAS  PubMed  Google Scholar 

  52. Oh TY, Lee JS, Ahn BO, et al. Oxidative damages are critical in pathogenesis of reflux esophagitis: implication of antioxidants in its treatment. Free Radic Biol Med. 2001;30:905–915.

    Article  CAS  PubMed  Google Scholar 

  53. Basaranoglu M, Basaranoglu G, Sentürk H. From fatty liver to fibrosis: a tale of “second hit”. World J Gastroenterol. 2013;19:1158–1165.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury: present concepts. J Gastroenterol Hepatol. 2011;26:173–179.

    Article  CAS  PubMed  Google Scholar 

  55. Seki S, Kitada T, Sakaguchi H, et al. Clinicopathological significance of oxidative cellular damage in non-alcoholic fatty liver diseases. Hepatol Res. 2005;33:132–134.

    Article  CAS  PubMed  Google Scholar 

  56. Chalasani N, Deeg MA, Crabb DW. Systemic levels of lipid peroxidation and its metabolic and dietary correlates in patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2004;99:1497–1502.

    Article  CAS  PubMed  Google Scholar 

  57. Van de Wier B, Balk JM, Haenen GR, et al. Elevated citrate levels in non-alcoholic fatty liver disease: the potential of citrate to promote radical production. FEBS Lett. 2013;587:2461–2466.

    Article  PubMed  Google Scholar 

  58. Duseja A, Chawla YK. Obesity and NAFLD: the role of bacteria and microbiota. Clin Liver Dis. 2014;18:59–71.

    Article  PubMed  Google Scholar 

  59. Miele L, Cammarota G, Vero V, et al. Non-alcoholic fatty liver disease is associated with high prevalence of gastro-oesophageal reflux symptoms. Dig Liver Dis. 2012;44:1032–1036.

    Article  PubMed  Google Scholar 

  60. Fujikawa Y, Tominaga K, Fujii 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;86:228–237.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Section of Gastroenterology, Department of Medical and Pediatric Sciences, Institute of Internal Medicine “A. Francaviglia”, University of Catania, “G. Rodolico” Hospital, Bldg. 4 - I Floor, Room 17, Via S. Sofia, 78, 95123, Catania, Italy

    Roberto Catanzaro, Federica Calabrese, Sergio Occhipinti, Maria Grazia Anzalone, Angelo Italia & Michele Milazzo

  2. ReGenera Research Group for Aging Intervention, Piazza Firenze, 12, 20154, Milan, Italy

    Francesco Marotta

Authors
  1. Roberto Catanzaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Federica Calabrese
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sergio Occhipinti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Grazia Anzalone
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Angelo Italia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michele Milazzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Francesco Marotta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roberto Catanzaro.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Catanzaro, R., Calabrese, F., Occhipinti, S. et al. Nonalcoholic Fatty Liver Disease Increases Risk for Gastroesophageal Reflux Symptoms. Dig Dis Sci 59, 1939–1945 (2014). https://doi.org/10.1007/s10620-014-3113-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-014-3113-7

Keywords

Search

Navigation