Prof. Rocco Maurizio ZagariUniversità di Bologna
Epidemiologia della malattia da reflusso
gastro-esofageo: una prospettiva globale
Ferrara 27 Settembre 2014Camera di Commercio, Largo Castello
Ferrara 27 Settembre 2014Camera di Commercio, Largo Castello
Gastro-esophageal reflux disease (GERD)
GERD is a DISEASE which develops when the reflux of
gastric content causes troublesome symptoms or
complications
GERD is a DISEASE which develops when the reflux of
gastric content causes troublesome symptoms or
complications
The Montreal Definition and Classification of Gastroesophageal Reflux Disease, AJG 2006
GERD is a condition which develops when the reflux of gastric content causes troublesome symptoms or complications
GERD is a condition which develops when the reflux of gastric content causes troublesome symptoms or complications
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
The Montreal Definition and Classification of Gastroesophageal Reflux Disease, AJG 2006
GERD is a condition which develops when the reflux of gastric content causes troublesome symptoms or complications
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
Population-based studies of the incidence of GERD-symptoms
El-Serag et al. GUT 2014
Worldwide prevalence of GERD-symptoms
El-Serag et al. GUT 2014
Worldwide time-trend prevalenceof GERD-symptoms
Date of publicationDate of publication
Pre
vale
nc
eP
reva
len
ce
Bazzoli F, DDW 2012
Poisson regression analysis of trends in the prevalence of GERD worldwide
El-Serag et al. GUT 2014
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
Everhart JE & Constance ER. Gastroenterology 2009
Esophageal cancerAge-adjusted incidence rates in the U.S.
• 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.
Limitations of reflux symptom-based epidemiological studies
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 studyZagari 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
Endoscopic studies in the general population
Large-scale endoscopic surveys in the general population
25,9%
4,7%
28,1%
0%
10%
20%
30%
40%
Kalixanda LoianoMonghidoro
SILC
Prevalence of symptom-defined GERD
Prevalence of different types of endoscopic findings in the general population
%
Dent J et al. Clin Gastroenterol Hepatol 2012
Prevalence of esophagitis by severityin the general population
Prevalence of esophagitis in individuals with or without symptoms of GERD in the general population
66,6%52,5%
90,9%
0%
20%
40%
60%
80%
100%
Kalixanda Loiano Monghidoro SILC
No GERDs GERDs
Proportion of individuals with esophagitis who do not have symptoms of GERD in the general population
Diagnostic Features of Barrett’s Esophagus
Spechler SJ. NEJM 2014
ESEM: endoscopically suspected esophageal metaplasiaSIM: Specialized intestinal metaplasia
10,3%
3,6%
1,8%1,6% 1,3%
0%
2%
4%
6%
8%
10%
12%
Kalixanda Loiano Monghidoro SILC
Prevalence of Barrett’s esophagus in the general population
0%
4%
8%
12%
16%
Kalixanda Loiano Monghidoro SILC
ESEM GERDs ESEM No GERDs SIM GERDs SIM No GERDs
Prevalence of Barrett’s esophagus in individuals with or without symptoms of GERD in the general population
ESEM SIMKalixanda
ESEM SIMKalixanda
ESEM SIMLoiano Monghidoro
ESEM SIMLoiano Monghidoro
ESEM SIMSILC
ESEM SIMSILC
Proportion of individuals with Barrett’s oesophagus who do not have symptoms of GERD in the general population
True prevalence of GERD
KalixandaLoiano
MonghidoroSILC
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% --
Large-scale endoscopic surveys in the general population
Screening for Barrett’s Esophagus
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
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
Screening all patients with GERD for Barrett’s esophagus is NOT recommended
Screening all patients with GERD for Barrett’s esophagus is NOT recommended
(strong recommendation, low-quality evidence)(strong recommendation, low-quality evidence)
AGA Guidelines, Gastroenterology 2011
(week recommendation, moderate-quality evidence)(week recommendation, moderate-quality evidence)
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 dysplasia0.77 1 in 130
Yousef et al Am J Epidemiol 2008
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
Risk and protective factors for GERD
• Hiatus Hernia• Overweight / Obesity• Age• Gender • Genetic • Cigarette smoking• Alcohol consumption• Drugs intake
• Helicobacter pylori • Physical activity
Risk factors Protective factors
Hiatus hernia and GERD in Hiatus hernia and GERD in endoscopic-based population studiesendoscopic-based population studies
Hiatus Hernia is significantly associated with an increased risk of:
Ronkainen et al. Scand J Gastroenterol 2005Ronkainen et al. Gastroenterology 2005
Zagari et al. GUT 2008
• Frequent reflux symptoms
• Esophagitis
• Barrett’s esophagus
23,9%
43,0%
0,7%0%
10%
20%
30%
40%
50%
Kalixanda LoianoMonghidoro
SILC
Prevalence of Hiatus hernia in the general population
Jacobson BC et al, NEJM 2006
BMI and the risk of GERD symptoms
El-Serag H. Dig Dis Sci 2008
GERD symptoms Esophagitis
Esophageal AdenocarcinomaBarrett Esophagus
Hampel et al. Ann Intern Med 2005 El-Serag H. Dig Dis Sci 2008
Kamat et al. Ann Thorac Surg 2009
Obesity and GERD: a positive association
Wang et al, Lancet 2011
Past and projected prevalence of overweight(BMI ≥25 kg/m2)
Esophageal adenocarcinomaEsophageal adenocarcinoma
GERD symptoms
H.pylori and GERD:a negative association
Fischbach et al. Helicobacter 2012
Zhou et al. Clin Oncol 2008Raghunath et al. BMJ 2003
Barrett’s esophagusBarrett’s esophagus
Helicobacter pylori and GERD
Ghoshal et al. JNM 2010
Before
chemopreventionAfter
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
Prevalence of gastric and oesophageal lesions before
and after mass eradication of H. pylori in Shangai
Prevalence of gastric and oesophageal lesions before
and after mass eradication of H. pylori in Shangai
Worldwide prevalence of H.pylori infection
Bauer et al. Ulcers 2011
Negative linear association between prevalence of esophagitis and prevalence of H. pylori in the general
population
Negative linear association between prevalence of esophagitis and prevalence of H. pylori in the general
populationPearson’s correlation coefficient, r = - 0.99Pearson’s correlation coefficient, r = - 0.99
Zagari RM, Unpublished 2014Zagari RM, Unpublished 2014
Time trend of H. pylori infection prevalence
Malaysia
China
India
USA
0%
10%
20%
30%
40%
50%
60%
70%
1988-1991 1992-1995 1996-1999 2000-2003
Eastern Europe
Western Europe
Goh et al. APT 2008Grad et al. Am J Epidemiol 2011
Miendje Deyi et al. Epidemiol Infect 2011
• 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.
ConclusionsConclusionsConclusionsConclusions
15,5%
11,8%
6,4%
0%
5%
10%
15%
20%
Kalixanda LoianoMonghidoro
SILC
Prevalence of esophagitisin the general population