doi:10.1111/j.1440-1746.2007.05249.

S P E C I A L R E P O RT

Asia-Pacific consensus on the management of

gastroesophageal reflux disease: Update
Kwong Ming Fock,* Nicholas J Talley,† Ronnie Fass,‡ Khean Lee Goh,§ Peter Katelaris,¶ Richard Hunt,**
Michio Hongo,†† Tiing Leong Ang,* Gerald Holtmann,‡‡ Sanjay Nandurkar,§§ San Ren Lin,¶¶
Benjamin CY Wong,*** Francis KL Chan,††† Abdul Aziz Rani,‡‡‡ Young-Tae Bak,§§§ Jose Sollano,¶¶¶
Lawrence KY Ho**** and Sathoporn Manatsathit††††
*Changi General Hospital, Singapore; †Mayo Clinic College of Medicine, Rochester, New York, USA; ‡University of Arizona Health Sciences
Center, Arizona, USA; §University of Malaya, Kuala Lumpur, Malaysia; ¶University of Sydney, Sydney, New South Wales, Australia; **McMaster
University Medical Center, Ontario, Canada; ††Tohoku University Hospital, Sendai, Japan; ‡‡Royal Adelaide Hospital, Adelaide, South Australia,
Australia; §§Monash University, Melbourne, Victoria, Australia; ¶¶The Third Hospital, Peking University, Beijing, China; ***Queen Mary Hospital,
Hong Kong; †††Prince of Wales Hospital, Hong Kong; ‡‡‡University of Indonesia, Indonesia; §§§Korea University College of Medicine, Seoul, Korea;
¶¶¶
University of Santo Tomas, Manila, Philippines; ****National University Hospital, Singapore; ††††Siriraj Hospital, Bangkok, Thailand

Key words Abstract

consensus, erosive esophagitis, non-erosive
reflux disease.
Accepted for publication 5 September 2007.
Correspondence
Professor Kwong Ming Fock, Division of
Gastroenterology, Department of Medicine,
Changi General Hospital, 2 Simei Street 3,
Singapore 529889. Email:
kwong_ming_fock@cgh.com.sg
Background and Aims: Since the publication of the Asia-Pacific GERD consensus in
2004, more data concerning the epidemiology and management of gastroesophageal reflux
disease (GERD) have emerged. An evidence based review and update was needed.
Methods: A multidisciplinary group developed consensus statements using the Delphi
approach. Relevant data were presented, and the quality of evidence, strength of recom-
mendation, and level of consensus were graded.
Results: GERD is increasing in frequency in Asia. Risk factors include older age, male
sex, race, family history, higher socioeconomic status, increased body mass index, and
smoking. Symptomatic response to a proton pump inhibitor (PPI) test is diagnostic in
patients with typical symptoms if alarm symptoms are absent. A negative pH study off
therapy excludes GERD if a PPI test fails. The role for narrow band imaging, capsule
endoscopy, and wireless pH monitoring has not yet been undefined. Diagnostic strategies
in Asia must consider coexistent gastric cancer and peptic ulcer. Weight loss and elevation
of head of bed improve reflux symptoms. PPIs are the most effective medical treatment.
On-demand therapy is appropriate for nonerosive reflux disease (NERD) patients. Patients
with chronic cough, laryngitis, and typical GERD symptoms should be offered twice daily
PPI therapy after excluding non-GERD etiologies. Fundoplication could be offered to
GERD patients when an experienced surgeon is available. Endoscopic treatment of GERD
should not be offered outside clinical trials.
Conclusions: Further studies are needed to clarify the role of newer diagnostic modalities
and endoscopic therapy. Diagnostic strategies for GERD in Asia must consider coexistent
gastric cancer and peptic ulcer. PPIs remain the cornerstone of therapy.

in epidemiology in Asia when compared to Western populations.

Introduction
Determination of the need for updated
guidelines
The first meeting of the Asia-Pacific consensus on the manage-
ment of gastroesophageal reflux disease (GERD) was initially held
in November 2002, and the full report subsequently published in
April 2004.1 The statements in the consensus were well received,
because there was a need for specific recommendations for the
management of GERD in the Asian context due to the differences
Notably, the prevalence of erosive esophagitis (ERD) and the
complications of GERD, including Barrett’s esophagus and
adenocarcinoma, were less common than in Western countries,
while non-erosive reflux disease (NERD) was more common in
Asia. In addition, the prevalence of Helicobacter pylori (H.pylori)
infection is higher in the Asia-Pacific region, making it crucial that
GERD be distinguished from H. pylori-related upper gastrointes-
tinal disorders, such as peptic ulcer disease and gastric cancer.
Since the consensus, more data concerning the epidemiology
of GERD in the Asia-Pacific region have emerged. In addition,

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KM Fock et al.
there have been developments in terms of global definitions of
GERD and Barrett’s esophagus. Extra-esophageal symptoms such
as chronic cough and hoarseness are recognized. Newer imaging
modalities such as magnification chromoendoscopy, narrow band
imaging, capsule endoscopy, and wireless pH assessment have
been introduced. Data on the role of endoscopic management of
Barrett’s esophagus, including endoscopic mucosal resection have
emerged and three of the previously introduced endoscopic anti-
reflux procedures have already been withdrawn. A review of the
existing literature and the current guidelines from Canada2 and the
USA3 was conducted to determine whether there was a need for
updating the previous Asia-Pacific consensus guidelines. This
assessment revealed significant changes since the publication of
the previous guidelines. Thus there was a need for a comprehen-
sive, evidence-based review of GERD management in the Asia-
Pacific context.
Methods
Nature and extent of background preparation
The literature search included MEDLINE and manual searches of
bibliographies of key articles published in English from July 2002
to May 2006. MEDLINE search terms included ‘GERD’/GORD,
‘erosive esophagitis’, ‘nonerosive esophagitis’, ‘endoscopically
negative reflux disease’, and ‘Barrett’s esophagus’. Recently pub-
lished consensus statements were also reviewed.2–4 More than 500
articles were reviewed and clinically relevant issues categorized
under ‘epidemiology and definition’, ‘diagnosis’, and ‘treatment’
were identified for further discussion among the group prior to the
consensus meeting. For each topic heading, a list of publications
was identified for further review to guide the formulation of the
consensus statements. The classification system of the Canadian
Task Force on the Periodic Health Examination was used to cat-
egorize the quality of evidence and to classify the evidence-base
for formulating the consensus statements (Table 1).2
The members of the consensus group were selected from the
Asian-Pacific Association of Gastroenterology (APAGE), and are
experts in the area of GERD management and evidence-based
medicine. There were altogether 16 gastroenterologists from the
Asia-Pacific region, two gastroenterologists from the United
States, and one from Canada, with three non-voting members
(appendix).
Clinically relevant issues were identified by the group prior to
the consensus meeting and circulated according to a modified
Delphi process, which resulted in modifying statements according
to feedback. Consensus statements were formulated by the steer-
ing committee.
At the 2-day consensus meeting these statements were dis-
cussed at subgroup level, modified, and presented to the entire
consensus group. Keypad-based voting was carried out and the
entire process was recorded. The group evaluated each statement
and the strength of evidence and voted on the recommendations as
detailed in Table 1.
Journal of Gastroenterology and Hepatology 23 (2008) 8–22 © 2008 The Authors
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Asia-Pacific GERD consensus: Update
Table 1 Categorization of evidence, classification of recommenda-
tions, and voting schemata2
Quality of evidence
I Evidence obtained from at least one randomized controlled trial.
II-1 Evidence obtained from well-designed trials without
randomization.
II-2 Evidence obtained from well-designed cohort or case-control
analytic studies, preferably from more than one center or
research group.
II-3 Evidence obtained from comparisons between times or places
with or without the intervention, or dramatic results in
uncontrolled experiments.
III Opinion of respected authorities, based on clinical experience,
descriptive studies or reports of expert committees.
Classification of recommendations
A There is good evidence to support the procedure or treatment.
B There is fair evidence to support the procedure or treatment.
C There is poor evidence to support the procedure or treatment,
but recommendations may be made on other grounds.
D There is fair evidence that the procedure or treatment should
not be used.
E There is fair evidence that the procedure or treatment should
not be used.
Voting on the recommendations†
a Accept completely.
b Accept with some reservation.
c Accept with major reservation.
d Reject with reservation.
e Reject completely.
†
Statements were accepted when more than 50% of participants voted
a, b, or c.
Statements
Definition and epidemiology of GERD
Statement 1: GERD is defined as a disorder in which
gastric contents reflux recurrently into the esophagus,
causing troublesome symptoms and/or complications.
This statement is similar to the Montreal definition.4 Discussion on
the definition of GERD was straightforward. The term ‘trouble-
some’ was felt by the majority to be important and appropriate
because it connotes impairment of quality of life and encapsulates
the overwhelming opinion that for gastroesophageal reflux to be a
disease, it must affect the quality of life (QOL) of the patient.
Level of agreement: a: 81.2%; b: 12.5%; c: 0%; d: 6.2%; e: 0%
Statement 2: Typical symptoms of reflux are
heartburn (retrosternal burning sensation) and acid
regurgitation, which are commonly experienced by
Asian patients.
Heartburn, although a term that has no equivalent in any of the
Asian languages, is now thought to be increasingly understood by
Asian patients.5,6 Doctors may still have to describe in words in the
local vernacular language what heartburn means, i.e. ‘a burning
discomfort arising from the epigastrium and rising retrosternally’
9
Asia-Pacific GERD consensus: Update
to clarify the term. Asian patients more easily understand acid
regurgitation, meaning the experience of sour or acidic fluid in the
mouth.
Level of agreement: a: 81.2%; b: 12.5%; c: 6.2%; d: 0%, e: 0%
Statement 3: Patients may also present with other
symptoms such as chest pain, belching, nausea,
dysphagia, early satiety, and epigastric pain, with or
without typical reflux symptoms.
There was much discussion that Asian patients may not complain
of the cardinal symptoms of heartburn and acid regurgitation, but
instead complain of other upper gastrointestinal symptoms which
may in fact be more prominent. Non-cardiac chest pain, for
example, is a common condition among Asian patients7,8 and may
be a presenting feature of GERD. In general, it was agreed that
GERD symptoms among Asian patients are more protean, and
atypical symptoms may occur in the absence of heartburn and acid
regurgitation.
Level of agreement: a: 56.2%; b: 37.5%; c: 6.2%; d: 0%; e: 0%
Statement 4: NERD is defined as troublesome reflux
symptoms in the absence of esophageal mucosal
damage on endoscopy.
There is supportive evidence that these symptoms are acid-
mediated based on pH monitoring,9 response to acid suppression,
or a positive Bernstein test result. The group felt that in keeping
with the definition of GERD, the term ‘troublesome’ should also
be included in the definition of NERD and that typical reflux
symptoms should be present.
Level of agreement: a: 62.5%; b: 37.5%; c: 0%; d: 0%; e: 0%
Statement 5: Barrett’s esophagus is the presence of
columnar lined epithelium suspected at endoscopy
and proven by histology which requires the presence
of intestinal metaplasia.
It was felt strongly that the term Barrett’s esophagus has been
loosely used, giving rise to undue alarm and concern among
doctors and patients. The group emphasized the importance of
histological confirmation of columnar lined epithelium with intes-
tinal metaplasia in the definition of Barrett’s esophagus, in addi-
tion to endoscopic diagnosis. It was also highlighted that biopsies
to accurately reflect Barrett’s changes should be taken once ERD
has been adequately treated.
Level of agreement: a: 93.8%; b: 6.2%; c: 0%; d: 0%; e: 0%
Statement 6: We shall adopt the term ‘endoscopically
suspected esophageal metaplasia’ (ESEM) which
refers to endoscopic findings consistent with Barrett’s
esophagus that await histological confirmation.
This statement was rejected. The group debated the use of the term
‘endoscopically suspected esophageal metaplasia’ (ESEM), which
was suggested by the Montreal Consensus.4 Such a term was
necessary to prevent the loosely used term of ‘? Barrett’s esopha-
gus’. The group did not agree on the use of the acronym ‘ESEM’
as it was felt to be cumbersome, and the word ‘suspected’ was
10
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KM Fock et al.
thought to be inappropriate and not suitable for use in the Asian
context, where the prevalence of Barrett’s esophagus is low. An
alternative term, ‘columnar lined epithelium awaiting histology’,
was suggested.
Level of agreement: a: 18.8%; b: 9%; c: 18.8%; d: 31.2%; e:
31.2%
Statement 7: The term Barrett’s esophagus should not
be used without histological confirmation in
endoscopy reports.
The group felt that the term Barrett’s esophagus should not be used
indiscriminately unless there is histological proof; therefore, state-
ment 6, which was adopted by the Montreal Consensus,4 was
rejected, while statement 7 was accepted.
Level of agreement: a: 62.5%; b: 12.5%; c: 18.8%; d: 6.2%; e:
0%
Statement 8: Standardized definitions of
prevalence/incidence of GERD need to be
implemented to allow cross-comparisons of
epidemiological studies in the region.
Different definitions have been used in published data all over the
world including in Asia, with a frequency of GERD symptoms
ranging from once a week to even once a year. To allow meaning-
ful comparisons within the region, a standardized definition should
be determined and followed.
Level of agreement: a: 81.2%; b: 18.8%; c: 0%; d: 0%; e: 0%
Statement 9: Putative risk factors for GERD in the
Asia-Pacific region include older age, male sex, race,
family history, higher socioeconomic status, increased
body mass index (BMI), and smoking.
Data based on several Asian studies indicate the above to be risk
factors for GERD. Community or population-based studies iden-
tified older age and male sex as risk factors for GERD
symptoms.10–12 Endoscopy-based studies have also identified age
and male sex as risk factors for ERD.13,14 Alcohol was reported as
a risk factor in two studies,13,15 smoking in one study,15 BMI in
more than 25 studies, and hiatus hernia in one study.13 Three
reports from South-East Asia identified Indian race as being a risk
factor for GERD.13,14,16 One study identified Indian race as a risk
factor for Barrett’s esophagus.14
Level of agreement: a: 31.2%; b: 50%; c: 18.8%; d: 0%; e: 0%
Level of evidence: II-2, 3
Statement 10: Weight gain increases the risk of GERD
and weight loss decreases the risk of GERD.
There have been no direct studies addressing this issue. In a study
from Singapore, a temporal increase in reflux esophagitis occurred
at the same time as an increase in obesity in the same population.17
Level of agreement: a: 31.2%; b: 43.8%; c: 12.5%; d: 12.5%; e:
0%
Level of evidence: II-2
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Statement 11: GERD is increasing in frequency in Asia.
Prevalence studies of GERD symptoms and reflux esophagitis
have shown generally higher figures compared to previously pub-
lished studies throughout Asia.18,19 Time trend studies have shown
both an increase in symptoms of GERD20 in the community, as
well as an increase in the prevalence of esophagitis.21–26
Level of agreement: a: 87.5%; b: 6.2%; c: 6.2%; d: 0%; e: 0%
Level of evidence: II-2, 3
Statement 12: Barrett’s esophagus and
adenocarcinoma of the esophagus, although lower
than in the Western populations, is increasing in Asia.
The prevalence of Barrett’s esophagus is generally low in Asian
patients and ranges from 0.9% to 2%.13,27,28 An isolated study,
however, showed prevalence rates of up to 6% of patients endo-
scoped,14 which was at variance with other studies from the same
region. This needs confirmation from other studies from the same
geographic area.
A study based at the Singapore Cancer Registry has shown a
significant decrease in squamous cell carcinoma of the esophagus
over 34 years and a numerical, but not statistically significant,
increase in adenocarcinoma of the esophagus.17
Level of agreement: a: 37.5%; b: 25%; c: 31.2%; d: 6.2%; e:
0%
Level of evidence: II-2
Statement 13: There is an overlap of reflux symptoms,
irritable bowel syndrome (IBS), and functional
dyspepsia.
Data from a Hong Kong study has shown a marked overlap of
GERD symptoms with dyspepsia.29 There is current interest in the
overlap of GERD and IBS as part of a spectrum of functional
gastrointestinal disorders.30 A study from Singapore, looking at
gastrointestinal symptoms in the community, found an association
between frequent heartburn and IBS symptoms (using univariate
analysis).16 Further work in Asia needs to be carried out to eluci-
date this association.
Level of agreement: a: 81.2%, b: 18.8%; c: 0%; d: 0%; e: 0%
Level of evidence: III
Diagnosis of GERD
Statement 14: Heartburn and regurgitation (or both)
that occurs after meals are symptoms highly specific
for GERD.
Although the Montreal Global Consensus reported a high level of
agreement on this issue, it was noted that the definition of heart-
burn and the specificity of the term for GERD had been studied
mostly in Caucasian populations, whereas the symptom ‘heart-
burn’ carries different meanings to different ethnic groups in Asia.4
The lack of published data on the specificity and sensitivity of
heartburn as a predictor of GERD in the Asia-Pacific region was
recognized. Thus, we do not know if heartburn is a definite marker
of GERD in Asia. The term heartburn must be further described
and tested regionally.
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Asia-Pacific GERD consensus: Update
Similarly, the definition of regurgitation, as the perception of
refluxed gastric contents into the mouth or hypopharynx, has yet to
be validated in Asian populations. Despite this, there was broad
agreement that both symptoms were characteristic of GERD,
although there was some reservation about the degree of
specificity.
Level of agreement: a: 43.8%; b: 43.8%; c: 12.5%; d: 0%;
e: 0%
Statement 15: GERD symptoms do not predict the
severity of esophagitis.
Although there is some correlation between the severity of symp-
toms and the presence and grade of esophagitis, this is not suffi-
ciently close to be predictive in individual patients.5,31 A longer
duration of symptoms, with increased frequency and occurrence at
night, as well as in the daytime, are characteristics that are more
likely to be associated with esophagitis. This correlation has been
established in Caucasian GERD patients; about 30–40% of
patients are found to have ERD, with the remainder having NERD.
In Asian populations, the ratio of ERD to NERD is much lower
and the correlation and predictive value of symptoms with erosive
disease in this setting has not been tested sufficiently.
Level of agreement: a: 62.5%; b: 37.5%; c: 0%; d: 0%; e: 0%
Level of evidence: II-2
Statement 16: Patients with alarm symptoms should
undergo endoscopy.
The sensitivity and specificity of alarm symptoms (including dys-
phagia, weight loss, and anemia) varies depending on definitions,
duration of symptoms, and the cohort studied. A clinical diagnosis
made by a physician in a patient with alarm symptoms is very
specific (range, 97–98%), but lacks sensitivity.32
Prompt endoscopy in patients with alarm symptoms results in a
significant yield of cancer (approximately 4% in one series) and of
serious benign disease such as peptic ulcer, stricture, and severe
esophagitis (13%).33 There are no published regional data on the
correlation between alarm symptoms and peptic stricture and
esophagitis largely because stricture is rare in the Asia-Pacific
region.
In the Asia-Pacific region, patients with alarm features are
likely to have gastric rather than esophageal cancer due to the
higher prevalence of peptic ulcer disease and gastric cancer in the
region. Nevertheless, alarm features have low predictive value and
suggest advanced, rather than early, malignancy.34
There was much discussion about the need for prompt endos-
copy in patients with alarm symptoms, even if this does not lead to
earlier diagnosis of curable cancers. In clinical practice, any
patient expectation and anxiety is a major driver because any
perceived delay in the diagnosis of cancer will lead to patient
dissatisfaction.
Level of agreement: a: 81.2%; b: 18.8%; c: 0%; d: 0%; e: 0%
Level of evidence: II-2
Statement 17: Patients with GERD symptoms for
ⱖ5 years but no alarm features should undergo
endoscopy to exclude Barrett’s esophagus.
This statement was rejected. Although this practice has support in
11
Asia-Pacific GERD consensus: Update
some published guidelines,3 there are no randomized trials to
support this statement. The statement is irrelevant to Asia at
present as there is a very low prevalence of Barrett’s esophagus in
the region and adenocarcinoma of the esophagus is very rare.
Given the overlap of upper gastrointestinal symptoms and the
greater prevalence of peptic ulcer and gastric cancer in the region,
the indication for endoscopy is more often to exclude gastric
cancer or peptic ulcer than Barrett’s esophagus or esophageal
adenocarcinoma. In this context, the groups felt that there is a need
to perform endoscopy if upper gut symptoms, including reflux
symptoms, are persistent or relapse frequently.
Level of agreement: a: 0%; b: 0%; c: 25%; d: 37.5%; e: 37.5
Level of evidence: III
Statement 18: Patients with Barrett’s esophagus are
more likely to have GERD symptoms longer than
patients without Barrett’s esophagus.
Based on published data from Caucasian cohorts, this statement
was accepted as correct in that context.35 However, data from
Asia are mostly cross-sectional studies that examine the preva-
lence of GERD and the correlation between symptom severity
and endoscopic findings. There are no local data on symptom
duration and presence of Barrett’s esophagus. Moreover,
although the prevalence of Barrett’s esophagus in Asia may
increase with changing demography over time, currently this is
not a major issue and not the focus of strategies to reduce mor-
bidity and mortality from upper gut disease in the region. It was
noted that in populations where Barrett’s esophagus is more
common, definitive evidence of benefit for any screening
program is still lacking.
Level of agreement: a: 0%; b: 18.8%; c: 62.5%; d: 18.8%; e:
0%
Level of evidence: II-2
Statement 19: Every patient with GERD symptoms
should undergo endoscopy once in a lifetime.
This statement was rejected as a strategy aimed at detecting Bar-
rett’s esophagus in order to enter such patients into a surveillance
program. The major reason to evaluate patients with chronic symp-
toms of GERD is to detect Barrett’s esophagus. The highest yield
of Barrett’s esophagus would be expected in white men with
chronic symptoms of GERD.36 However, the specific criteria to
select patients to screen for Barrett’s are not yet defined and it is
recognized that there are asymptomatic individuals with Barrett’s
esophagus. Even within the Western population, this a strategy of
screening for Barrett’s esophagus is not uniformly accepted.37
Such a strategy is irrelevant to Asia at this time because of the low
prevalence of Barrett’s esophagus18,19 and adenocarcinoma of the
esophagus. A recent direct comparative study also found a signifi-
cantly lower prevalence of esophagitis (6% vs 27%) and columnar-
lined esophagus (1% vs 4%) in Asians compared to Western
patients.38 In the region, the major driver for endoscopy is the
diagnosis or exclusion of gastric cancer or peptic ulcer. There was
considerable discussion as to whether endoscopy should be per-
formed at least once in patients with chronic upper gut symptoms,
recognizing the imprecision of clinical diagnosis between GERD
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KM Fock et al.
and peptic ulcer and the ability of endoscopy to provide or exclude
a diagnosis and aid in tailoring therapy. In one study, 18% of
H. pylori-related peptic ulcers were misdiagnosed as GERD based
on symptoms alone.39 The value to the patient of the reassurance of
a negative test was discussed but could not be quantified. As fear
of gastric cancer is a major concern, endoscopy performed early
rather than later had much support. As empiric use of proton pump
inhibitors (PPIs) is common prior to endoscopy, the increased risk
of a false negative H. pylori biopsy test was noted with the require-
ment to cease PPI prior to testing. Comments were made about the
relatively low cost and widespread availability of endoscopy in
many parts of the region, with endoscopic approaches favoured
over a non-invasive test and treat approach in this context (despite
the lack of cost-benefit data). Marked regional disparities in avail-
ability of health care resources were also noted, suggesting that
such strategies need to be tailored to the needs and resources of
individual countries.
Level of agreement: a: 0%; b: 12.5%; c: 6.2%; d: 50%; e:
31.2%
Level of evidence: III
Statement 20: Symptomatic response to a trial of PPI
is sufficient for a presumptive diagnosis of GERD in a
patient with typical symptoms, in the absence of
alarm symptoms in the primary care setting.
Although a symptomatic response to an empirical trial of PPI
therapy has long been used to support a diagnosis of GERD in
patients with typical symptoms, a meta-analysis revealed that the
combined sensitivity and specificity of this is only modest.40 More-
over, the strategy is influenced by the pretest probability of GERD,
which may be higher in published studies than in the Asian
context. Given also the overlap of GERD with the symptoms of
peptic ulcer, the response of ulcer symptoms to PPI therapy, and
the higher prevalence of ulcer in the region, such a strategy needs
to be validated locally. Nonetheless, there was support for an
empirical trial of PPI in those with typical symptoms, particularly
in the primary care setting.
Level of agreement: a: 31.2%; b: 68.8%; c: 0%; d: 0%; e: 0%
Level of evidence: I
Statement 21: A negative ambulatory pH study off
therapy helps to exclude GERD if a PPI test fails.
While there was agreement on this statement, with reservation, it
was recognized that ambulatory pH testing is not widely available
in Asia and is rarely done outside of major centers. Furthermore,
there are few robust data on the test characteristics in Asian
populations.
For diagnostic purposes, the need to have patients off PPIs
when performing pH studies was stressed. The likelihood of a
positive test while on PPIs is low; the main role of the test with the
patient on PPIs is for the assessment of the adequacy of acid
suppression in patients with GERD who are not responding to
therapy.
Level of agreement: a: 31.2%; b: 50%; c: 18.8%; d: 0%; e: 0%
Level of evidence: II-3
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KM Fock et al.
Statement 22: There is currently no established role
for the use of narrow band imaging (NBI), capsule
endoscopy, and wireless pH monitoring in the routine
management of GERD in the Asia-Pacific region.
There was agreement that these newer diagnostic modalities require
validation as research tools and for clinical practice. It was recog-
nized that they are not appropriate for routine clinical use in the
region at present as the impact on diagnosis and management and
the cost effectiveness of these new tests remains to be determined.
Specifically, NBI was considered a potentially valuable tool in
diagnosing GERD, in particular in patients with Barrett’s esopha-
gus, but limited data is available. Wireless pH monitoring has been
shown to increase the diagnostic yield of GERD by 20%41 in
Caucasian cohorts, but has yet to be shown to be useful in the
region, may not be cost effective, and conveys a small risk.
Capsule endoscopy of the esophagus was considered irrelevant to
the needs of the Asia-Pacific region, where the need to visualize
and biopsy the stomach was considered paramount.
Level of agreement: a: 6.6%; b: 20%; c: 46.7%; d: 26.7%; e:
0%
Level of evidence: II-3
Statement 23: GERD is rarely the sole cause of chronic
cough, chronic laryngitis, or asthma.
There was agreement that there is an association between GERD
and chronic cough, laryngitis, and asthma demonstrated in popu-
lation studies. However, it was noted that while GERD may be an
aggravating factor, the etiology of these conditions appears multi-
factorial. The modest results from intervention trials suggest
GERD is rarely the sole cause. Furthermore, it was agreed that
in the absence of typical reflux symptoms, GERD was rarely
implicated.
Level of agreement: a: 21.4%; b: 71.4%; c: 0%; d: 7.1%; e: 0%
Level of evidence: I
Statement 24: Ambulatory pH study is required in
diagnosis of supra-esophageal symptoms of GERD.
This statement was rejected. The group felt that there was insuf-
ficient data, particularly of the role of dual probe measurement, to
determine the role of pH studies in these conditions. A positive pH
study provides useful supportive evidence of association, but is not
a gold standard. A sustained PPI test is preferred to ambulatory pH
monitoring in clinical practice.
Level of agreement: a: 0%; b: 14.3%; c: 21.4%; d: 57.1%; e:
7.1%
Level of evidence: II-3
Statement 25: GERD may have a role in triggering
apneic episodes in patients with obstructive sleep
apnea.
This statement was rejected. An increased prevalence of GERD in
patients with sleep apnea has been reported,42 but causation has not
been established. This is an area of considerable research interest
but the issue is unresolved currently. Some recent studies have not
found an association.43,44
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Asia-Pacific GERD consensus: Update
Level of agreement: a: 0%; b: 14.3%; c: 21.4%; d: 64.3%; e:
0%
Level of evidence: III
Statement 26: Diagnostic strategies in the Asia-Pacific
region must take into account the coexistence of
GERD with other common conditions such as gastric
cancer and peptic ulcer.
There was unanimity on this issue. The group acknowledged that
in some Asian countries, the prevalence of GERD may be increas-
ing, but that the morbidity and mortality associated with this at
present is much less than the burden of peptic ulcer disease and
gastric cancer, which remain major health issues in much of the
region. Indeed, gastric cancer still accounts for nearly one million
deaths worldwide annually, with much of this occurring in the
region. The difficulty of designing management strategies in a
large diverse region, where the prevalence and spectrum of GERD,
peptic ulcer, and gastric cancer vary considerably, was also
acknowledged, as was the vastly different availability and provi-
sion of health care. Diagnostic pathways must be tailored to local
prevalence of disease and the most cost-effective use of investiga-
tions and therapy.
It was agreed that a strategy for managing upper gut symptoms
must recognize that symptoms of GERD, peptic ulcer disease, and
functional dyspepsia frequently overlap, causing difficulty in dis-
tinguishing these conditions clinically. This is compounded by the
imprecision of commonly used terminology to describe reflux in
the region and the not infrequent co-occurrence of these condi-
tions. Furthermore, the role of testing for and treating H. pylori
infection as a risk reduction strategy was recognized. Although
relief of symptoms is an initial goal, cure of peptic ulcer disease
and reduction of gastric cancer risk are attainable outcomes in
individual patients.
Level of agreement: a: 100%; b: 0%; c: 0%; d: 0%; e: 0%
Level of evidence: III
Statement 27: H. pylori testing should be considered
in new patients presenting with GERD symptoms in
regions with a high prevalence of gastric cancer or
peptic ulcer disease.
This statement was discussed extensively by the group. Differ-
ences in approach by representatives from different countries
reflected, in part, the regional differences in the prevalence of
GERD and H. pylori infection and the impact of the latter on ulcer
and cancer rates.
As discussed in the preceding statement, it was agreed that
symptoms were an imprecise way of distinguishing between upper
gastrointestinal conditions in Asia and that GERD may coexist
with other conditions. It was acknowledged that at present, peptic
ulcer and gastric cancer have greater impact than GERD on mor-
bidity and mortality in the region. It was also acknowledged that
there is evidence that benefits are gained by testing and treating
H. pylori infection in the context of reducing symptoms, curing
ulcer disease, and reducing the risk of gastric cancer.45
It was agreed that H. pylori does not cause or prevent reflux
disease and that eradication of this organism does not appreciably
13
Asia-Pacific GERD consensus: Update
increase the risk of GERD occurring.46 It was also accepted that
long-term PPI therapy for GERD increases the risk of progression
of gastric atrophy and intestinal metaplasia in those infected with
H. pylori. Although this data is intermediary only with respect to
cancer risk, it was accepted that it is reasonable to offer eradication
therapy prior to long-term PPI therapy in this setting in agreement
with other international guidelines.47 The decision to test for and
treat H. pylori infection in the context of reflux must be individu-
alized based on patient factors including comorbidity, age, gastric
histology, family history, and informed choice. Distinction must be
made between treating symptoms and potentially reducing risks.
Further research to clarify the risks and benefits of such an
approach is required.
Lastly it was recognized that PPI therapy reduces the accuracy
of diagnostic tests for H. pylori infection, so that if testing were to
be done it should occur either before PPI therapy has commenced
or after a period off therapy to maximize the accuracy of the test.
Level of agreement: a: 21.4%, b: 21.4%; c: 50%; d: 7.1%;
e: 0%
Level of evidence: III
Management of GERD
Statement 28: Weight loss and elevation of head of
bed could improve symptoms in GERD patient. There
is insufficient data to support other lifestyle
modification recommendations.
Lifestyle modifications are commonly used as first line of therapy
in patients presenting with GERD-related symptoms. They include
weight loss, smoking cessation, avoidance of postprandial recum-
bency for a period of at least 3 h, elevation of the head of the bed,
avoidance of tight-fitting garments, and avoidance of large heavy
meals as well as food and drink that exacerbate GERD symptoms
(e.g. spicy foods, fatty meals, peppermint, chocolate, onions, citrus
juices, and carbonated beverages).3 In spite of the introduction of
potent antireflux treatments, enthusiasm about lifestyle modifica-
tions among health care providers remains very high. However, for
many patients lifestyle modifications are difficult to follow, too
restrictive, and may adversely affect their quality of life. In a recent
systematic review that evaluated the value of the different lifestyle
modifications in GERD, the authors demonstrated that only weight
loss and elevation of the head of the bed are effective in improving
GERD-related parameters.48 Elevation of the head of the bed and
left lateral decubitus positioning improved the overall time
pH < 4.0, and weight loss improved pH profiles and GERD-related
symptoms. There was no evidence that lifestyle interventions such
as dietary measures and tobacco or alcohol cessation were effec-
tive in reducing esophageal acid exposure or ameliorating GERD
symptoms.48,49
There is still a paucity of information regarding a variety of
lifestyle modifications that are commonly practiced (e.g. avoid-
ance of coffee and caffeine, chocolate, spicy foods, citrus, carbon-
ated beverages, fatty foods, and mint).11,50–56 Future studies may
prove that these interventions are also effective in GERD and thus
have a therapeutic value.
Level of agreement: a: 28.6%; b: 50%; c: 21.4%; d: 0%; e: 0%
Level of evidence: II-2
Grade of recommendation: B
14
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KM Fock et al.
Statement 29: PPIs are the most effective treatment
for patients with ERD and NERD.
There was general agreement regarding this statement, but one of
the participants felt that the statement should be qualified in terms
of both medical and surgical treatment. Furthermore, it should
be mentioned that surgery is effective in a subset of GERD
patients.
PPIs are the most efficacious medical intervention for GERD.
Studies have shown repeatedly and consistently that PPIs are supe-
rior to histamine 2 receptor antagonists (H2RAs) in healing the
esophageal mucosa and relieving GERD-related symptoms of
patients with ERD.57–59 In a meta-analysis, the authors demon-
strated that after 12 weeks of treatment, healing rates were 83.6%
with PPIs, 51.9% with H2RAs, 39.2% with sucralfate, and 28.2%
with placebo.60 In addition, treatment with PPIs resulted in healing
rates of esophageal inflammation and relief of heartburn symp-
toms that were two-fold higher than what was observed in patients
receiving H2RAs. Similarly, PPIs demonstrate superiority in
relieving heartburn symptoms in patients with NERD when com-
pared to H2RAs.61–63 Even when ‘soft’ clinical endpoints were
used, such as average heartburn severity score or days without
heartburn, PPIs were significantly better than H2RAs.
The superiority of PPIs over H2RAs in ERD is not limited to
acute therapy, but has also been demonstrated in maintenance
studies over as long as 11 years.64 Similar comparative trials in
NERD are not available.
The symptoms response rate to once daily PPI in randomized,
placebo controlled trials has been shown to be significantly higher
in patients with ERD, as compared to those with NERD. In one
meta-analysis, pooled response rates at 4 weeks were significantly
higher for patients with ERD as compared to those with NERD
(56% vs 37%, P < 0.0001).63
Level of agreement: a: 92.9%; b: 0%; c: 0%; d: 0%; e: 7.1%
Level of evidence: I
Grade of recommendation: A
Statement 30: H2RAs and antacids are useful in
treating episodic heartburn.
H2RAs and antacids are commonly used for episodic heartburn,
primarily for postprandial heartburn. The perception of heartburn
serves as a trigger for medication use, and the expectation is an
immediate symptom relief that PPIs are unlikely to provide. The
onset of action of antacids on esophageal acid concentration is
30 min after dosing and inhibition persists for 1 h.65 However,
studies reported that meaningful heartburn relief can already be
achieved 19 min after consumption.66 In contrast, H2RAs have
been shown to provide symptom relief within 30 min of dosing
that can last up to 12 h.67 When consumed 30 min prior to a meal,
H2RAs are effective in completely or partially preventing post-
prandial heartburn.68 There is some evidence to suggest that simul-
taneous consumption of both an H2RA and an antacid provides
better control of esophageal acid exposure and heartburn symp-
toms, when compared to the clinical effect of each one of these
products alone.65 On-demand treatment with H2RAs has been
shown to be safe and effective in GERD patients. In one study,
ranitidine 75 mg daily was consumed on demand (up to
three times daily) as compared to placebo in patients with
Journal of Gastroenterology and Hepatology 23 (2008) 8–22 © 2008 The Authors
KM Fock et al.
uninvestigated GERD.69 The authors demonstrated that 38–41% of
those receiving H2RAs reported relief of at least 75% of heartburn
episodes during the study period as compared to 28% on placebo.
Level of agreement: a: 50%; b: 50%; c: 0%; d: 0%; e: 0%
Level of evidence: I
Grade of recommendation: A
Statement 31: The use of prokinetic agents either as
monotherapy or adjunctive therapy to PPIs may have
a role in the treatment of GERD in Asia.
Several recent studies have demonstrated the value of prokinetic
agents in GERD management. Itopride, a dopamine D2 antagonist
with antiacetylcholinesterase effect, has been recently evaluated in
patients with an abnormal pH test and mild ERD. After 30 days of
treatment in an open label study design, itopride significantly
reduced the extent of esophageal acid exposure and improved
GERD-related symptoms as compared to baseline values.70
Mosapride, a newly developed 5-HT4 agonist, has been shown to
increase the rate of complete esophageal bolus transit and
enhances esophageal bolus transit in normal controls.71 In one
study from India, 68 patients suffering from heartburn twice a
week were randomized to either pantoprazole 40 mg twice daily or
pantoprazole 40 mg twice daily plus mosapride 5 mg thrice daily
for a period of 8 weeks.72 The authors found that the PPI +
mosapride regimen provided significantly better symptom control
in patients with ERD as compared to the PPI alone. There was no
difference between the two therapeutic arms in ERD healing rates
or symptomatic response of subjects with NERD.
Further studies using the new prokinetic agents are needed, but
those that are currently available demonstrate some efficacy as sole
therapy or in combination with a PPI in subsets of patients with
GERD.
Level of agreement: a: 7.1%; b: 28.6%; c: 28.6%; d: 35.7%;
e: 0%
Level of evidence: II-3
Grade of recommendation: C
Statement 32: NERD patients will require a minimum
of 4 weeks of initial continuous therapy with a PPI.
Almost all therapeutic trials in NERD patients have lasted only 4
weeks.63,73,74 The studies were designed with the assumption that 4
weeks are sufficient to assess symptom improvement as opposed
to esophageal mucosal healing, which requires more than 4 weeks
of PPI therapy. This arbitrary time frame is unlikely to provide the
full symptomatic response rate of patients with NERD undergoing
PPI treatment. In a systematic review of the literature, the authors
noted a trend in increased therapeutic gain for NERD patients
throughout the 4 weeks, suggesting that a 4-week follow-up evalu-
ation alone may be insufficient to show the full therapeutic gain in
this patient population.63 Consequently, we stated that a minimum
of 4 weeks of initial continuous (daily) therapy with a PPI once
daily is needed in NERD patients. However, we realize that some
of the NERD patients will require more than 4 weeks of treatment
to achieve satisfactory symptom control. Maintenance treatment in
NERD patients is discussed below.
Level of agreement: a: 7.1%; b: 42.9%; c: 42.9%; d: 7.1%;
e: 0%
Journal of Gastroenterology and Hepatology 23 (2008) 8–22 © 2008 The Authors
Journal compilation © 2008 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Asia-Pacific GERD consensus: Update
Level of evidence: III
Grade of recommendation: C
Statement 33: ERD patients will require a minimum of
4–8 weeks of initial continuous therapy with a PPI.
Therapeutic studies in patients with ERD have almost always
lasted 8 weeks. Healing rates in those receiving PPI once daily for
8 weeks ranged from 85–96%, regardless of the PPI that was used
and the underlying severity or ERD.75–78 However, patients with
severe grades of ERD demonstrated higher PPI failure rates as
compared to those with mild to moderate disease after 8 weeks of
treatment.76 In one study, patients were randomized to either ome-
prazole 20 mg once daily versus esomeprazole 40 mg once daily.79
The failure rate in those with Los Angeles grade A was 9.6% and
6.6%; grade B, 28.7% and 10.6%; grade C, 29.6% and 12.8%; and
grade D 26.2% and 20%, respectively. Patients with lower grades
of ERD are likely to heal earlier, and thus 4 weeks of treatment
could be sufficient. This is particularly important in the Asian
context where generally patients are less likely to develop severe
ERD, specifically Los Angeles grades C and D, as compared to
their Western counterparts.19
The rate of symptom resolution in patients with ERD is com-
monly 5–15% lower when compared to esophageal mucosal
healing rate after 8 weeks of treatment.75–79 This clearly suggests
that a small portion of the patients with ERD will continue to
report GERD-related symptoms despite complete esophageal
mucosal healing.
In a meta-analysis of 43 therapeutic trials in ERD, the authors
reported an overall 65% healing rate of esophageal mucosa after 4
weeks, 80% after 8 weeks, and 84% after 12 weeks of treatment
with PPI once daily.60 PPIs provided a healing rate of 11.7% per
week and complete heartburn relief at a rate of 11.5% per week.
The meta-analysis demonstrated that 12 weeks of treatment with
PPI once a day provided only a modest increase in the healing rate
as compared to 8 weeks of treatment in patients with ERD.
Level of agreement: a: 50%; b: 42.9%; c: 7.1%; d: 0%; e: 0%
Level of evidence: III
Grade of recommendation: C
Statement 34: On-demand therapy is an appropriate
ongoing management strategy in NERD patients.
Several alternative therapeutic strategies have been proposed for
patients with NERD. The one that has been studied the most is
on-demand therapy defined as PPI consumption (up to once daily)
when needed and for the duration desired. This patient-driven
therapeutic strategy has been shown to be clinically efficacious
and cost effective. On-demand therapy is attractive to patients
because it provides their input into their own management,
addresses concerns about chronic ingestion of PPIs, and offers
personal cost savings. Studies have also demonstrated that patients
are commonly consuming PPIs in an on-demand fashion despite
instructions to take their medications on a daily basis.80 Many
studies have assessed the value of on-demand PPI therapy as a
maintenance strategy in patients with NERD.81–87 These studies
commonly followed a similar design. Patients who responded to
an acute treatment (4 weeks) with a daily PPI were then random-
ized to either placebo or PPI for a period of 6 months. Commonly
15
Asia-Pacific GERD consensus: Update
used clinical endpoints included GERD symptom–load, days and
nights without heartburn, discontinuation due to insufficient
control of heartburn, and daily antacids consumption. All studies
have shown that on-demand PPI therapy was superior to placebo in
controlling GERD-related symptoms, antacids consumption, and
patients’ satisfaction with therapy. Several cost effectiveness
analyses have demonstrated that on-demand treatment with a PPI
is cost effective compared with other therapeutic strategies for
GERD (e.g. lifestyle therapy and antacids, H2RA therapy, step-up,
step-down, as well as others).48,88,89 It must be clarified that
although the term ‘on-demand’ is used, it does not mean that
patients take PPI whenever they like. The pharmacology of PPIs is
such that to maximize gastric acid suppression, PPI should be
taken 30–60 min before the first meal of the day and continued for
5–14 days on a daily basis when restarted.
Level of agreement: a: 100%; b: 0%; c: 0%; d: 0%; e: 0%
Level of evidence: I
Grade of recommendation: A
Statement 35: For GERD patients who want to
discontinue maintenance treatment, fundoplication
could be offered when an experienced surgeon is
available.
Antireflux surgery is an effective therapeutic strategy for a subset
of patients with GERD.90,91 Long-term maintenance studies com-
paring medical therapy for GERD with antireflux surgery have
demonstrated either similar clinical efficacy or significantly better
control of GERD symptoms postsurgery.92–94 Patients’ satisfaction
with antireflux surgery has been reported to be exceptionally
high.95,96 However, several recent publications have tempered the
enthusiasm for antireflux surgery. Long-term follow-up of patients
who underwent antireflux surgery (up to 13 years post-surgery)
demonstrated a high rate of symptoms relapse requiring continu-
ing antireflux medications.89–91 This phenomenon can be seen soon
after surgery and appears to increase in prevalence over the years,
affecting up to 62% of patients more than 10 years post-
surgery.95–97 This is also compounded by a postoperative mortality
of up to 0.8% and a variety of complications after antireflux
surgery, such as dysphagia, postvagotomy symptoms, gas-bloat
syndrome, and others.98–100 Furthermore, a surgeon’s experience in
performing antireflux surgery is highly predictive of clinical
success.99 In addition, several cost-effectiveness analyses have
concluded that medical therapy is significantly less costly than
antireflux surgery.101 Thus, only in GERD patients who wish to
discontinue maintenance of medical treatment is surgery by a fully
trained and highly experienced surgeon recommended.
Level of agreement: a: 42.9%; b: 57.1%; c: 0%; d: 0%; e: 0%
Level of evidence: I
Grade of recommendation: A
Statement 36: Antireflux surgery does not reduce the
risk of development of malignancy in Barrett’s
esophagus.
Several studies have reported that antireflux surgery significantly
reduced or completely eliminated the risk for neoplastic progres-
16
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KM Fock et al.
sion in patients with Barrett’s esophagus.102–104 Some have even
suggested that antireflux surgery provides a superior protection
against neoplastic progression in patients with Barrett’s esophagus
when compared with medical treatment for GERD.104 However, a
recent meta-analysis105 revealed that the cancer incidence rate after
antireflux surgery was 3.8 cancers/1000 patient years, compared
with 5.3 in the medial group (P = NS). Multivariate analysis con-
trolling for subject’s age, country of origin, and length of Barrett’s
esophagus did not alter these findings.
Level of agreement: a: 85.7%; b: 14.3%; c: 0%; d: 0%; e: 0%
Level of evidence: I
Grade of recommendation: A
Statement 37: Endoscopic treatment of GERD should
not be offered outside well-designed clinical trials.
Various endoscopic techniques to treat GERD have been intro-
duced in the last few years.106 They include endoscopic suture/
plication, radiofrequency energy, and submucosal bulking. The
clinical efficacy of the different endoscopic techniques has been
suggested to be due to augmentation of the lower esophageal
sphincter basal pressure, reduction in the rate of transient lower
esophageal sphincter relaxations, and decrease in proximal migra-
tion of acid reflux events.107,108 While initial studies reported good
safety profiles, high patient satisfaction rate with the clinical
outcome, and good feasibility, further studies have reported severe
complications and lack of durability with some of the techniques
and improvement in subjective clinical parameters only when
compared with sham intervention.109 Several of the endoscopic
techniques have been removed from the market due to devastating
complications or marginal efficacy.110,111 Others are scarcely used
due to the potential for severe complications or lack of long-term
clinical efficacy.112–115 Presently, the future of the first generation of
endoscopic techniques for GERD remains unclear. This is despite
a recent celebrated publication demonstrating the clinical efficacy,
in both objective and subjective parameters (e.g. GERD symp-
toms, PPI use, and esophageal acid exposure) of the endoscopic
full-thickness plication technique.116 Consequently, we believe that
until better endoscopic techniques to treat GERD are introduced,
the use of any of the currently available endoscopic techniques
outside well-designed clinical trials should be discouraged. Pres-
ently, the first generation of endoscopic techniques for GERD is
not ready for prime time.
Level of agreement: a: 78.6%; b: 14.3%; c: 7.1%; d: 0%; e: 0%
Level of evidence: I
Grade of recommendation: A
Statement 38: Patients with chronic cough and
laryngitis and typical GERD symptoms should be
offered twice daily PPI therapy after exclusion of
non-GERD etiologies.
GERD is the third (21%) most common cause for chronic cough,
preceded by postnasal drip (41%), and asthma (24%).117 However,
26% of the patients with chronic cough will have more than a
single underlying mechanism for their symptoms.117 Conse-
quently, patients with chronic cough should be evaluated by ear,
nose and throat (ENT) or pulmonary physicians prior to referral to
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KM Fock et al.
a gastroenterologist for further workup or initiating antireflux
treatment.118 While most patients (up to 75%) with GERD-related
chronic cough lack typical GERD symptoms, such as heartburn
and acid regurgitation, the presence of these symptoms is highly
predictive of a response to antireflux treatment.118–120 Numerous
open label and several randomized, placebo-controlled trials have
demonstrated a significant efficacy of PPI treatment in improving
GERD-related chronic coughing as well as GERD symptoms if
present.121–125 However, other studies using double-dose PPI over a
period of 2–4 months have been unable to demonstrate its superi-
ority over placebo.126–130 The disappointing results of these small
sample size studies was recently supported by a larger, placebo-
controlled, randomized trial that included 145 patients, who
received either esomeprazole 40 mg twice daily or placebo for a
period of 4 months.131 The authors demonstrated that double-dose
PPI was not better than placebo in all clinical endpoints, including
relief of symptoms, symptom-free patients, and mean percentage
of symptom-free days. Furthermore, two recent meta-analyses of
randomized, placebo-controlled trials concluded that PPI therapy
offers only modest but non-significant clinical benefits over
placebo in patients with suspected GERD-related chronic cough
and laryngitis.132,133 These studies suggest that many of the sus-
pected GERD-related chronic cough patients are unlikely to have
GERD as the underlying cause for their symptoms. The current
diagnostic criteria for posterior laryngitis are neither specific nor
sensitive for GERD, leading to inappropriate referrals to gastro-
enterologists of large numbers of patients with chronic cough that
is not due to GERD.
Regardless, and until improved diagnostic criteria for posterior
laryngitis are introduced, a subset of chronic cough patients will
respond effectively to antireflux treatment. Recently, Park et al.
demonstrated that double-dose PPI is superior to once-daily PPI in
controlling chronic cough symptoms.134 Furthermore, the authors
also documented that higher levels of clinical response were
achieved at 4 months as compared with 2 months of treatment.
Thus, aggressive acid suppression with twice-daily PPI for at least
4 months is warranted for the treatment of GERD-related chronic
cough.97
Level of agreement: a: 92.9%; b: 7.1%; c: 0%; d: 0%; e: 0%
Level of evidence: I
Grade of recommendation: B
Management algorithm
Alarm features
The management of GERD in the Asia-Pacific region was consid-
ered, after reviewing the previous Asia-Pacific algorithm1 as well
as management algorithms from the Western countries.2–4,135–138
There was a consensus that in the setting of uninvestigated typical
reflux symptoms, patients should be stratified based on the pres-
ence or absence of alarm features (Table 2). Patients with progres-
sive dysphagia or other alarm symptoms or signs should be
promptly referred for endoscopy (Fig. 1). Although the positive
predictive value of these alarm features is probably relatively
low,139 it was concluded that best practice will require clinicians to
pay close attention to any alarm features, until convincing evi-
dence to the contrary arises.
Journal of Gastroenterology and Hepatology 23 (2008) 8–22 © 2008 The Authors
Journal compilation © 2008 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Asia-Pacific GERD consensus: Update
Table 2 Alarm features (‘red flags’)
Progressive dysphagia
Odynophagia
Weight loss (unintentional)
Anemia (new onset)
Hematemesis and/or Melena
Family history of gastric and/or esophageal cancer
Chronic non-steroidal anti-inflammatory drug use
Age >40 years in areas of a high prevalence of gastric cancer
Establishing H. pylori status
At esophagogastroduodenoscopy (EGD), it was recommended
that H. pylori testing be routinely undertaken regardless of the
findings in the esophagus (in the absence of any obvious malig-
nancy) (Fig. 1). The rational for undertaking H. pylori testing is as
follows:
• Based on systematic reviews of the literature, there remains a
lack of evidence that H. pylori eradication has any substantial
role in inducing reflux disease.135
• In Asia, peptic ulcer disease secondary to H. pylori infection
may be clinically misdiagnosed as reflux disease, and ulcer
disease may come and go and be missed at initial endoscopy.39
Treatment of H. pylori infection in this setting may lead to relief
of reflux-type symptoms.
• Long-term acid suppression therapy with PPIs in patients
infected with H. pylori can be associated with acceleration of
atrophic gastritis.140–142 Even though there remains some contro-
versy about the clinical significance of developing atrophic gas-
tritis in the setting of acid suppression therapy, it was considered
sensible to offer eradication to all patients who may end up
receiving long-term acid suppression therapy in the Asia-Pacific
region.
• A convincing relationship between H. pylori infection and
gastric cancer has been identified, although the benefits of
H. pylori eradication has yet to be proven.143,144 The exact risk-
to-benefit ratio of offering eradication therapy to all patients
with reflux disease who test positive for H. pylori infection at
endoscopy is not established in the Asia-Pacific region, but is
probably cost-effective.145,146 The consensus of the assembled
experts was to offer eradication therapy in this setting based on
all the available evidence, unless convincing data to the contrary
arise in the future.
Empiric acid suppression
In patients without any alarm features, it was considered reason-
able to provide a 4-week course of PPI therapy (full dose PPI
treatment should be offered and taken before the first meal of the
day). A meta-analysis has shown that a 1-week trial of PPI has only
modest specificity for the diagnosis of reflux disease.40 Further-
more, most patients have NERD in Asia. Data suggest that a short
course of PPI of only 1-week duration had inadequate predictive
value for defining any benefit or lack of benefit at the end of
4 weeks of treatment.147
The pragmatic viewpoint emerged that patients should be
assessed at 2–4 weeks to determine their symptomatic benefit on
PPI therapy. If symptoms resolve or improve substantially, it was
17
Asia-Pacific GERD consensus: Update KM Fock et al.

ALGORITHM

Uninvestigated typical reflux symptoms

ALARM FEATURES PRESENT ALARM FEATURES ABSENT

PPI therapy 4 weeks and

review at 2 to 4 weeks

Symptoms Symptoms
persist respond
REFER
for EGD Stop PPI at
and least 1 week
H. pylori Test
Trial of stopping
PPI

Relapse

Frequent relapses, or On-demand Restart

alarm features therapy PPI

Figure 1 Management of uninvestigated typical reflux symptoms. EGD, esophagogastroduodenoscopy; H. pylori, helicobacter pylori; PPI, proton
pump inhibitor.

recommended that therapy be ceased. This is based on good evi-
dence that 20–30% of patients with NERD have sustained remis-
sion following induction of symptom relief by acid suppression
therapy.135 In Asia, very few patients have severe reflux esophagitis
(Los Angeles grade C or D) where acid suppression should not be
stopped.135
If the patient does relapse and return, it was recommended that
PPI therapy in full dose be restarted, and then, based on clinical
judgement, stepped down to on-demand treatment.135 On-demand
therapy has been shown to be superior to placebo in the manage-
ment of NERD.148 If symptoms persist, stopping PPI therapy and
referring for prompt endoscopy was recommended.
Referral for endoscopy
In those who frequently relapse or subsequently develop alarm
features, a prompt endoscopy is recommended. It was agreed that
it is important to stop acid suppression therapy for at least 1 week
(and preferably longer) prior to the procedure, to maximize the
chances of identifying any evidence of reflux esophagitis, and to
reduce the false negative rate of testing for H. pylori infection135,149
(Fig. 1).
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Appendix List of participants
Australia: Professor Peter Katelaris, Professor Gerald Holtmann,
Professor Sanjay Nandurkar; Canada: Professor Richard Hunt;
China: Professor San Ren Lin, Professor Benjamin CY Wong,
Professor Francis KL Chan; Indonesia: Professor Abdul Aziz Rani;
Japan: Professor Michio Hongo; Korea: Professor Young-Tae Bak;
Malaysia: Professor Khean Lee Goh; Philippines: Professor Jose
Sollano; Singapore: Professor Kwong Ming Fock, Professor
Lawrence KY Ho, Dr Tiing Leong Ang; Thailand: Professor
Sathoporn Manatsathit; United States: Professor Ronnie Fass, Pro-
fessor Nicholas J Talley.
Journal of Gastroenterology and Hepatology 23 (2008) 8–22 © 2008 The Authors