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