Gastroesophageal Reflux Disease (GERD) is a common disorder that has undergone many paradigm changes in the last 15 years. We discuss the current paradigms in the pathophysiology, diagnosis and management of GERD.

1. GERD: Current Paradigms
Dr Jarrod Lee
Gastroenterologist &
Advanced Endoscopist
Peer to Peer Workshop
Rosso Bianco
2 Aug 2018

2. Scope
• Pathophysiology
• Clinical spectrum
• Natural history
• Diagnosis
• Medical treatment

3. What Causes GERD?
• Transient relaxation of lower esophageal sphincter (LES) exposes
esophagus to stomach acid and contents
• Factors that increase exposure
• Increased intra-abdominal pressure: pregnancy, obesity
• Descreased esophageal or gastric motility
• Hiatal hernia
• Increased esohageal sensitivity predisposes to more severe symptoms
or tissue damage
• NOT due to increased acid production

4. Pathophysiology

5. • Increased prevalence in pregnancy: 30-50% of pregnant women
complain of heartburn
• Predictors of heartburn: gestational age, parity, presence of heartburn
before pregnancy
• Diagnosis and treatment should be based on symptoms
• Usually resolves after delivery
• Limited treatment data: small trials, no RCTs
For Healthcare Professionals Only

6. What causes Heartburn in Pregnancy?
Hormonal Changes
• Increased of circulating
progesterone relaxes the LES,
allowing food and acid to flow back
up into the esophagus
Increase in intra-abdominal pressure
• Growing fetus pushes up on the
stomach and increase pressure on
the abdominal

7. GERD Clinical
Spectrum
7

8. Natural History: Traditional Paradigm
• Progression along spectrum over time
• NERD is a mild form of GERD
• Focus on Erosive Esophagitis
• Most well designed GERD studies focus on mucosal healing and symptom
improvement in Erosive Esophagitis
NERD
Erosive
Esophagitis
Barrett’s
Esophagus

9. NERD: Where is the Evidence?
• Most community based patients have NERD
• Few progress to Erosive Esophagitis
• 10-15% over 5-20 years
• Only mild Erosive Esophagitis (Grade A)
• No Barrett’s Esophagus or Cancer
• Lower symptom response to PPIs
• Increased number of treatment failures
• Relapse back to NERD after treatment

10. Epidemiology: East vs West
• GERD Incidence:
• West: 10-20%
• Asia: 5%
• Singapore: 10%
• NERD percentage
• West: 50-70%
• Asia: 60-90%
10
NERD
EE

12. GERD Natural History

13. How is GERD diagnosed?
• No gold standard!!
• Presumptive diagnosis can be made with typical symptoms:
• Heartburn, acid regurgitation
• Frequency: at least weekly
• If presumptive diagnosis made, can proceed to an empirical trial of PPI
• Good Sensitivity 75-85%: 4-8 weeks of PPI will control symptoms in 75-85%
• Poor Specificity 25-65%: may be positive in other acid disorders; specificity with
placebo 40% !!

14. What is the
Role of
Endoscopy?
I’m worried
and concerned
Symptoms
bother me!
My whole life is
affected
Heartburn
disturbs my
sleep
I cannot eat or
drink what I like
I cannot bend
over or exercise

15. Endoscopy in Uncomplicated GERD
• Good specificity but poor sensitivity < 30%
• Only 10% sensitivity in Asia
• Problem with patients on treatment
• NO ROLE FOR DIAGNOSIS!!
• Used for:
• Evaluate treatment failures and atypical symptoms
• Evaluate alarm symptoms: dysphagia, LOW, persistent vomiting, bleeding, anemia
• Screen for Barrett’s Esophagus if at risk: males > 50 yrs with chronic GERD

16. OGD in
GERD

17. Narrow Band Imaging
Improves visualization of squamo-columnar junction

18. NBI in GERD
Endoscopy Finding Conventional
Endoscopy
Advanced
Imaging
Micro-erosions 0% 52.8%
Increased vascularity at junction 0% 91.7%

19. NBI in NERD
Using a composite of: increased vascularity & absence of round pit pattern
• Sensitivity 86.1%
• Specificity 83.3%
Advanced Imaging NERD Controls P
Micro erosions 52.8% 23.3% < 0.001
Increase vascularity 91.7% 36.7% < 0.001
Round pit pattern 5.6% 70% < 0.001

20. • Increased number, dilatation, tortuosity of intrapapillary capillary loops (IPCLs)
• Micro-erosions, increased vascularity
• Absence of round pit pattern

21. Treatment Paradigms

22. Lifestyle Measures
• Eat smaller meals
• Avoid eating late at night (2-3 hours before sleep)
• Elevation of head of the bed or sleep in left lateral position
• Lose weight, stop smoking
• Dietary modifications may improve symptoms or reduce complications,
but evidence is very weak
• Some foods may lower LES tone (carminatives)
• Other foods may irritate inflamed esophageal mucosa (citrus)
• Patients may report improvement when avoiding particular substances

23. The Acid Pocket

24. The Acid Pocket and Hiatal Hernia

25. Alginate (Barrier)
Antacids
• Alginates are natural polymers extracted from brown algae (kelp)
• In acidic environment, form a viscous gel-raft that floats; bicarbonate
neutralizes acid
• Alginate raft refluxes into esophagus before gastric contents
• Provides a physical barrier to prevent reflux of gastric contents
• Coats the esophagus with rafts, which acts as protective layer

26. Alginate Antacids in
Pregnancy
• Recommended 1st line drug
• Safe and effective: 90% response in
pregnant women
• Rapid relief: 90% within 20 minutes
• Lasts up to 4H
• Best used ‘on demand’
0
20
40
60
80
100
120
0 <10 10-<20 20-<30 30-<60 >60
Time (min)
Cumulativepercentageof
patientswithonsetofsymptom
relief
B. Patient Assessment
0
10
20
30
40
50
60
Very Good Good Acceptable Poor V Poor
Efficacy Rating
Patientsreportingefficacy
ofproduct(%)

27. Control of
Acid
Secretion
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28. H2 Receptor
Antagonists
• Competitively histamine binding on gastric parietal cells
• Helps heal erosive esophagitis and improve symptoms
• Use limited by tachyphylaxis; best used ‘on demand’
• Safe in pregnancy

29. Proton Pump
Inhibitors
(PPIs)
• First-line agents for patients with erosive disease or with typical symptoms
• Irreversibly inhibit parietal cell proton pump
• More potent acid suppressors than H2RAs, no tachyphylaxis
• Safe in pregnancy

30. PPI therapy in GERD
• NOT a definite solution
– Symptoms will recur once PPI
stopped
– Reduces acidity but not
frequency or volume of reflux
• Efficacy in Erosive Esophagitis
– Mucosal healing: 85-95%
– Symptomatic response: 75-85%
• Reasons for PPI failure
– Compliance
– Concomitant functional
disorder, e.g. IBS, FD
– Wrong diagnosis
– NERD

31. PPI Failures
31

32. Ambulatory 24H pH Impedance Monitoring
• ‘Gold’ standard for GERD
diagnosis
• Documents ALL reflux; improves
GERD diagnosis in up to 90%
• Correlates symptoms with reflux
event
• Can differentiate NERD subtypes

33. NERD
Subtypes

34. Lyon Consensus for GERD Diagnosis 2018

35. Potassium Competitive
Acid Blocker (PCAB)
• New acid suppressant drug
• Fast and profound acid suppression
• Reversibly inhibits parietal cell proton pump
• Dosing independent of meal times
• Compared to PPI: longer half life in blood, more stable in acidic
environment, and can inhibit new proton pumps that are synthesized

36. 24 hours gastric pH4 HTR (Study V-E: Vonoprazan 20mg and Esomeprazole 20mg administered)
Vonoprazan 20 mg group (n=10)
Esomeprazole 20 mg group (n=10)
100
0
day 1 of administration day 7 of administration
80
60
40
20 23.9
61.2
71.4
85.8
pH4HTR
Average value ±standard deviation
pH4 HTR: pH≧4 Holding Time Ratio (Holding time ratio is greater than pH 4)
Difference between both
drugs (%) [95% CI]
47.5 [35.5, 59.4] Difference between both
drugs (%) [95% CI]
24.6 [16.2, 33.1]
Sakurai Y, et al: Aliment Pharmacol Ther. 2015; 42 (6): 719-730
(%)
Target and method: In a randomized, open-label 2-period crossover study of 20 adult Japanese males with CYP2C19 genotype EM
(including hetero EM, homo EM), once daily dose of Vonoprazan 20mg and Esomeprazole 20mg (Study V-E, n=10), Vonoprazan
20mg and Rabeprazole 10mg (Study V-R, n=10) was administered for 7 days.

37. Difference between both
drugs (%) [95% CI]
58.2 [43.6, 72.9]
Difference between both
drugs (%) [95% CI]
28.8 [17.2, 40.4]
24 hours gastric pH4 HTR (Study V-R: Vonoprazan 20mg and Rabeprazole 10mg administered)
Vonoprazan 20 mg group (n=7)
Rabeprazole 10 mg group (n=7)
Average value ±standard deviation
pH4 HTR: pH≧4 Holding Time Ratio (Holding time ratio is greater than pH 4)
100
(%)
0
day 1 of administration day 7 of administration
80
60
40
20
pH4HTR
26.3
65.1
93.8
84.2
Target and method: In a randomized, open-label 2-period crossover study of 20 adult Japanese males with CYP2C19 genotype EM
(including hetero EM, homo EM), once daily dose of Vonoprazan 20mg and Esomeprazole 20mg (Study V-E, n=10), Vonoprazan
20mg and Rabeprazole 10mg (Study V-R, n=10) was administered for 7 days.
Sakurai Y, et al: Aliment Pharmacol Ther. 2015; 42 (6): 719-730. More figures

39. Take Home Message
• GERD paradigms have evolved
considerably in the past 20 years.
• Treatment algorithm has become
more sophisticated.
• Refer PPI refractory GERD patients to
a Gastroenterology service with
motility capability.
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