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 1

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. Gastroesofageal Reflux Disease A major public health concern
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

5. GERD is a condition which develops when the reflux of gastric content causes troublesome symptoms or complications
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
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 prevalence of GERD-symptoms
Date of publication
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 prevalence of GERD-symptoms from 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. Age-adjusted incidence rates in the U.S.
Esophageal cancer
Age-adjusted incidence rates in the U.S.
Everhart JE & Constance ER. Gastroenterology 2009

12. Limitations of reflux symptom-based epidemiological studies
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 severity in 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. Prevalence of Barrett’s esophagus in the general population
ESEM: endoscopically suspected esophageal metaplasia
SIM: Specialized intestinal metaplasia

21. Prevalence of Barrett’s esophagus in individuals with or
without symptoms of GERD in the general population

22. Proportion of individuals with Barrett’s oesophagus who
do not have symptoms of GERD in the general population
ESEM SIM
Kalixanda
ESEM SIM
Loiano Monghidoro
ESEM SIM
SILC

23. Large-scale endoscopic surveys in the general population
True prevalence of GERD
Kalixanda
Loiano Monghidoro
SILC
Subjects n.
1000
1033
1029
GERD symptoms
28.1%
25.9%
4.7%
NO GERD symptoms
Esophagitis
12.1%
8.6%
6.1%
Barrett - SIM
1.9%
0.8%
N/A
True prevalence
42.1%
35.3% --

24. Screening for Barrett’s Esophagus
Screening all patients with GERD for Barrett’s esophagus is NOT recommended
(week recommendation, moderate-quality evidence)
In patients with GERD and multiple risk factors for 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-quality evidence)
AGA Guidelines, Gastroenterology 2011

25. The incidence of esophageal cancer and high-grade dysplasia in Barrett’s esophagus A Systematic Review and Meta-analysis
Pooled estimate
Per 100 person-years
Person-years
Cancer
0.39
1 in 256
Cancer and
high-grade dysplasia
0.77
1 in 130
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
Risk factors
Protective factors
Hiatus Hernia
Overweight / Obesity
Age
Gender
Genetic
Cigarette smoking
Alcohol consumption
Drugs intake
Helicobacter pylori
Physical activity

28. Hiatus hernia and GERD in endoscopic-based population studies
Hiatus Hernia is significantly associated with an increased risk of:
Frequent reflux symptoms
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
Hampel et al. Ann Intern Med 2005
El-Serag H. Dig Dis Sci 2008
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. a negative association
H.pylori and GERD:
a negative association
GERD symptoms
Barrett’s esophagus
Fischbach et al. Helicobacter 2012
Esophageal adenocarcinoma
A possible association between GERD and HP infection has been a matter of study and debate in recent years.
It is presently accepted that a negative association at least in some geographical areas is present between HP and GERD symptoms, and this has been shown also for Barrett’s esophagus and esophageal adenocarcinoma.
A negative association could imply the presence of HP infection being a protective factor for the development of gastroesophageal reflux disease.
Zhou et al. Clin Oncol 2008
Raghunath et al. BMJ 2003

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

35. Before chemoprevention After chemoprevention
Prevalence of gastric and oesophageal lesions before and after mass eradication of H. pylori in Shangai
Before chemoprevention
After chemoprevention
Subjects n.
1762
841
Atrophic gastritis
1056 (59.9%)
115 (13.7%)
Peptic ulcer
193 (11.0%)
30 (3.6%)
Reflux oesophagitis
241 (13.7%)
230 (27.3%)
Lee et al. GUT 2013

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

37. Negative linear association between prevalence of esophagitis and prevalence of H. pylori in the general population
Pearson’s correlation coefficient, r =
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. Conclusions
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.

40. Prevalence of esophagitis in the general population