Prof. Rocco Maurizio Zagari Università di Bologna

1. Ferrara 27 Settembre 2014 Camera di Commercio, Largo Castello Epidemiologia della malattia da reflusso gastro-esofageo: una prospettiva globale Prof. Rocco Maurizio Zagari Università di Bologna

2. Gastro-esophageal reflux disease (GERD) GERD is a DISEASE which develops when the reflux of gastric content causes troublesome symptoms or complications

3. GERD is a condition which develops when the reflux of gastric content causes troublesome symptoms or complications The Montreal Definition and Classification of Gastroesophageal Reflux Disease, AJG 2006

4. A global chronic disease Costly, with a significant negative impact on quality of life Associated with esophageal adenocarcinoma Epidemiology of GERD: not an easy task Few well designed epidemiological studies in the general population Gastroesofageal Reflux DiseaseA major public health concern

5. In population-based studies, GERD is defined by heartburn and/or regurgitation – occurring at least 2 days per week, if mild, or at least 1 day per week, if moderate / severe GERD is a condition which develops when the reflux of gastric content causes troublesome symptoms or complications The Montreal Definition and Classification of Gastroesophageal Reflux Disease, AJG 2006

6. Population-based studies of the incidence of GERD-symptoms El-Serag et al. GUT 2014

7. Worldwide prevalence of GERD-symptoms El-Serag et al. GUT 2014

8. Worldwide time-trend prevalenceof GERD-symptoms Prevalence Date ofpublication Bazzoli F, DDW 2012

9. Poisson regression analysis of trends in the prevalence of GERD worldwide El-Serag et al. GUT 2014

10. Changes in prevalenceofGERD-symptomsfrom 1995-7 to 2006-9 by sex in Norway The prevalence of at least weekly GERD-symptoms increased by 47% (from 11.6% to 17.1%) Ness-Jensen et al. GUT 2011

11. Esophageal cancer Age-adjusted incidence rates in the U.S. Everhart JE & Constance ER. Gastroenterology 2009

12. Limitations of refluxsymptom-basedepidemiologicalstudies • Estimates based on symptom surveys alone may under-diagnose • true GERD prevalence. • Only endoscopy can identify asymptomatic subjects with reflux • esophagitis or Barrett’s esophagus. • Reflux symptom-based and endoscopic diagnoses of GERD • provide complementary information for epidemiological research. • Very few large-scale endoscopic studies in the general population • have been carried out so far.

13. Endoscopic studies in the general population High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: the Swedish Kalixanda study. Ronkajnen et al, Scand J Gastroenterol 2005 Gastro-oesophageal reflux symptoms, oesophagitis and Barrett’s oesophagus in the general population: the Italian Loiano–Monghidoro study Zagari et al, GUT 2008 Epidemiology of symptom-defined gastroesophageal reflux disease and reflux esophagitis: the Chinese SILC study. Zou et al, Scand J Gastroenterol 2011

14. Large-scale endoscopic surveys in the general population Prevalence of symptom-defined GERD

15. Prevalence of different types of endoscopic findings in the general population %

16. Prevalence of esophagitis by severityin the general population Dent J et al. Clin Gastroenterol Hepatol 2012

17. Prevalence of esophagitis in individuals with or without symptoms of GERD in the general population

18. Proportion of individuals with esophagitis who do not have symptoms of GERD in the general population

19. Diagnostic Features of Barrett’s Esophagus Spechler SJ. NEJM 2014

20. PrevalenceofBarrett’s esophagus in the generalpopulation ESEM: endoscopically suspected esophageal metaplasia SIM: Specialized intestinal metaplasia

21. PrevalenceofBarrett’s esophagus in individualswith or withoutsymptomsof GERD in the generalpopulation

22. ProportionofindividualswithBarrett’s oesophaguswho do nothavesymptomsof GERD in the generalpopulation ESEM SIM Kalixanda ESEM SIM LoianoMonghidoro ESEM SIM SILC

23. Large-scale endoscopic surveys in the general population True prevalence of GERD

24. Screening for Barrett’s Esophagus Screening all patients with GERD for Barrett’s esophagus is NOT recommended (week recommendation, moderate-qualityevidence) In patients with GERD and multiple risk factorsfor Barrett’s esophagus and esophageal adenocarcinoma screening for Barrett’s esophagus is suggested: Risk factors: Age > 50 years, male sex, white race, obesity and smoking (strong recommendation, low-qualityevidence) AGA Guidelines, Gastroenterology 2011

25. The incidence of esophageal cancer and high-grade dysplasia in Barrett’s esophagusA Systematic Review and Meta-analysis Yousef et al Am J Epidemiol 2008

26. Surveillance of Barrett’s esophagus • Endoscopic surveillance should be performed in patients with Barrett’s esophagus with the following surveillance intervals: • Barrett’s esophagus: 3 – 5 years • Low-grade dysplasia: 6 –12 months • High-grade dysplasia in absence of eradication therapy: 3 months • (weak recommendation, low-quality evidence) AGA – Guidelines 2011 Spechler SJ. NEJM 2014

27. Risk and protective factors for GERD Riskfactors Protectivefactors • Hiatus Hernia • Overweight / Obesity • Age • Gender • Genetic • Cigarette smoking • Alcohol consumption • Drugs intake • Helicobacter pylori • Physical activity

28. Hiatushernia and GERD in endoscopic-basedpopulationstudies Hiatus Hernia is significantly associated with an increased risk of: • Frequentrefluxsymptoms • Esophagitis • Barrett’s esophagus Ronkainen et al. Scand J Gastroenterol 2005 Ronkainen et al. Gastroenterology 2005 Zagari et al. GUT 2008

29. Prevalence of Hiatus hernia in the general population

30. BMI and the risk of GERD symptoms Jacobson BC et al, NEJM 2006

31. Obesity and GERD: a positive association GERD symptoms Esophagitis El-Serag H. Dig Dis Sci 2008 Hampel et al. Ann Intern Med 2005 Barrett Esophagus Esophageal Adenocarcinoma Kamat et al. Ann Thorac Surg 2009 El-Serag H. Dig Dis Sci 2008

32. Past and projected prevalence of overweight (BMI ≥25 kg/m2) Wang et al, Lancet 2011

33. H.pylori and GERD: a negative association GERD symptoms Barrett’s esophagus Fischbach et al. Helicobacter 2012 Esophageal adenocarcinoma Zhou et al. Clin Oncol 2008 Raghunath et al. BMJ 2003

34. Helicobacter pylori and GERD Ghoshal et al. JNM 2010

35. Prevalenceofgastric and oesophageallesionsbefore and after mass eradicationofH. pylori in Shangai Lee et al. GUT 2013

36. Worldwide prevalence of H.pylori infection Bauer et al. Ulcers 2011

37. Negative linear association between prevalence of esophagitisand prevalence of H. pylori in the general population Pearson’s correlation coefficient, r = - 0.99 Zagari RM, Unpublished 2014

38. Time trend of H. pylori infection prevalence Eastern Europe Western Europe Goh et al. APT 2008 Grad et al. Am J Epidemiol 2011 Miendje Deyi et al. Epidemiol Infect 2011

39. In USA and Europe GERD seems to be an “endemic disease” with a prevalence of about 30-40% in the general population. The prevalence of GERD is still increasing in western countries and it is now clearly rising also in Asia A substantial proportion of subjects with esophagitis or Barrett’s esophagus are free of GERD symptoms. The changing epidemiology of GERD correlates with changing epidemiology of the most important associated factors, such as obesity and Helicobacter pylori. Conclusions

40. Prevalence of esophagitisin the general population