1) Helicobacter pylori infection is common and testing should be done for patients with dyspepsia, peptic ulcer history, or family history of gastric cancer. 2) The urea breath test is the best tool to detect active H. pylori infection. 3) Patients who test positive for H. pylori antibodies should undergo a urea breath test to confirm active infection before treatment.

1. Helicobacter Pylori
Challenges and Updates in 2020
Speaker : Chong Chern Hao
Moderator : Dr Jarrod Lee
gutCARE Digestive◦Liver◦Endoscopy Associates

2. Main objectives
• Epidemiology and Pathophysiology
• Risk factors
• Complication of HP infection
• Specialized diagnostic tests
• Treatment
• Common scenarios in clinical practice
2

3. Introduction
• Barry Mashall and Robin Warren first came across a recurrent gastric /duodenal
ulcer patient in 1982. First published Helicobacter Pylori infection in THE LANCET
1984
• 1985, Marshall drank a broth contained H Pylori bacteria , he did a pre and post
scope showing normal stomach later infected with H Pylori with new gastritis.
This was published in Medical Journal of Australia in 1985.
• Marshall and Robin were awarded Nobel Prize in physiology or medicine in 2005.
3

4. GLOBAL EPIDEMIOLOGY OF HP INFECTION
Zamani, M, Ebrahimtabar, F, Zamani, V, et al. Systematic review with
meta‐analysis: the worldwide prevalence of Helicobacter
pylori infection. Aliment Pharmacol Ther. 2018; 47: 868– 876.
Asia HP Prevalence : 58%
Risk factors: Poor household hygiene, high density population, bed
sharing in childhood, lack of running water

5. Complications of HP infection
5
1) Gastric Adenocarcinoma
2) Bleeding gastric and duodenal ulcer
3) Gastric MALT(mucosa-associated lymphoid tissue)
Lymphoma
4) Gastric Intestinal Metaplasia Changes
5) a/w squamous cell oesophageal cancer
6) a/w idiopathic thrombocytopenia purpura due to anti – CagA
ab cross react with platelet antigens

6. Intestinal Metaplasia - Clinical
Implications
Pangastritis (85%): HP infection
of stomach body causing
suppression of parietal cells and
acid production, leading to
atrophic changes and intestinal
metaplasia, increase risk of
stomach cancer
Antral-type gastritis ( 15%) :
decrease somatostatin and
increase gastrin secretion,
causing increase acid secretion,
increase risk of stomach and
duodenal ulcer.

7. Endoscopic Evaluation
7

8. Which Patients to Survey
8
AGA 2019 advised against routine use of endoscopic surveillance for patient with
gastric IM
Pool prevalence of GIM in 897,371 patients is 4.8%
3,5,10 years cumulative gastric cancer incidence : 0.4%, 1.1% , 1.6%
Patient with Gastric IM with specifically higher risk of gastric cancer include those:
> 45 Years old
1) Family history of gastric cancer
2) Extensive IM
3) Incomplete IM
Conditional, Very
Low Evidence

9. Common Clinical Scenarios
9
1) When Should I Test Patient for Helicobacter Pylori
infection for patient?
2) A Patient with history of dyspepsia found to have HP
positive, now his family came to ask about HP testing,
they are asymptomatic, should I do the test for them?
3) A Patient was seen in my clinic for reflux disease,
should I do HP testing for patient?
4) There are many HP treatment in guideline with different
durations, which one should I choose?
5) My Patient failed first line therapy, what should I do?

10. 1)When Should I Test Patient for Helicobacter
Pylori infection for patient?
Indication Evidence
Current/Past hx of peptic ulcer disease 1A
Uninvestigated Dyspepsia 1A
Reflux Symptoms 1C
Gastric MALT Lymphoma 1B
Family hx of gastric cancer 1B
Idiopathic thrombocytopenia 1B
Family hx of peptic ulcer disease 1B
Consider in family members residing in same
household as patients with proven HP infection
1B
El-Serag HB, Kao JY, Kanwal F, et al. Houston
Consensus Conference on Testing for Helicobacter
pylori Infection in the United States. Clin Gastroenterol
Hepatol. 2018;16(7):992-1002.e6.

11. 11
1)When Should I Test Patient for Helicobacter
Pylori infection for patient with dyspepsia?
• Uninvestigated dyspepsia may have underlying H pylori related
peptic ulcer disease, estimated NNT 8 to achieve 1 symptomatic
response.
• Test and treat strategy has been proposed in American college
of gastroenterology, Canadian and Kyoto guidelines
• HP eradication may not resolve the clinical problem, but
successful eradication will reduce significantly long term risk of
peptic ulcer or gastric cancer
Mass Eradication of Helicobacter pylorito Prevent Gastric
Cancer: Theoretical and Practical Considerations.Lee YC,
Chiang TH, Liou JM, Chen HH, Wu MS, Graham DY
Gut Liver. 2016 Jan; 10(1):12-26.

12. Common Clinical Scenarios
12
1) When Should I Test Patient for Helicobacter Pylori
infection for patient?
2) A Patient with history of dyspepsia found to have HP
positive, now his family came to ask about HP testing,
they are asymptomatic, should I do the test for them?
3) A Patient was seen in my clinic for reflux disease,
should I do HP testing for patient?
4) Is Helicobacter Pylori re-infection common?
5) There are many HP treatment in guideline with different
durations, which one should I choose?
6) My Patient failed first line therapy, what should I do?

13. 13
A Patient with history of dyspepsia found to
have HP positive, now his family came to ask
about HP testing, they are asymptomatic,
should I do the test for them?
• 1st degree relatives of those with symptomatic H pylori disease
are usually raised in the same environment as the affected
patient
• H pylori is primarily acquired in childhood and transmitted within
famiies, 1st degree relatives are at increase risk of similar
disease outcome, leading to recommendation of test and treat
strategy.
• This is particularly important in countries with higher gastric
cancer prevalence, such as Japan, Korea, China and Taiwan.
Increased prevalence of precancerous changes in relatives of
gastric cancer patients: critical role of H. pylori.El-Omar EM,
Oien K, Murray LS, El-Nujumi A, Wirz A, Gillen D, Williams C,
Fullarton G, McColl KE
Gastroenterology. 2000 Jan; 118(1):22-30.

14. Common Clinical Scenarios
14
1) When Should I Test Patient for Helicobacter Pylori
infection for patient?
2) A Patient with history of dyspepsia found to have HP
positive, now his family came to ask about HP testing,
they are asymptomatic, should I do the test for them?
3) A Patient was seen in my clinic for reflux disease,
should I do HP testing for patient?
4) There are many HP treatment in guideline with different
durations, which one should I choose?
5) My Patient failed first line therapy, what should I do?

15. 15
A Patient was seen in my clinic for reflux
disease, should I do HP testing for patient?
• GERD is typically a manifestation of robust acid secretion and
abnormal oesophagogastric antireflux barrier.
• High acid output sometimes can be associated with antral type
HP gastritis.
• Unfortunately, Studies shows that treatment of HP in patient
with GERD does not alter the symptoms.
• Thus test is only recommended if patient has concomitant
dyspeptic symptoms, or those who are high risk of HP related
disease.
Raghunath A, Hungin AP, Wooff D, et al. Prevalence
of Helicobacter pylori in patients with gastro-oesophageal
reflux disease: systematic review. BMJ 2003;326:737
Moayyedi P, Bardhan C, Young L, et al. Helicobacter
pylori eradication does not exacerbate reflux symptoms in
gastroesophageal reflux disease. Gastroenterology 2001

16. Approach to Dyspepsia
16
Alarm features? NSAIDS?
> 40, history of GERD?
YES No
OGD to look for
1) Peptic Ulcer
2) Gastric Cancer
3) Barrett’s oesophagus
Non invasive test for HP
infection ( stop PPI 2 weeks)
- UBT
- Stool Antigen Test
- HP serology
Treat if positive, confirm
eradication 4-6 weeks later w
UBT
Trial of PPI x 2-4 weeks
Symptoms persistent
Treat based on findings

17. Helicobacter Pylori Tests
17
Test Advantages Disadvantages
Serology Accesible, least expensive Does not differentiate
current/past infection, cannot
confirm eradication
Stool Antigen test High negative/positive PPV
Use for confirmation
eradication/active infection
Stool sample required,
discontinuation of abx, PPI
Urea Breath Test High negative/positive PPV
Use for confirmation
eradication/active infection
Need resources/trained
personnel
Discontinuation of abx, PPI
Endoscopic
Culture Specificity, test for abx sn Not widely available, variable
sensitivity
Histology Good sn/sp
Provides information such as
intestinal metaplasia, atrophic
gastritis
Requires endoscopy, higher
cost, inter observer variability
Rapid Urease based tests Good sn/sp, rapid,
inexpensive
Requires discontinuation of
antibiotics, PPI.

18. Treatment of Helicobacter Pylori infections
18
Special considerations:
1) Antibiotics previously used by patient
2) Drug allergy
3) Antibiotic Resistance Rate
4) Local guidelines

19. H Pylori Antibiotic resistance in
ASEAN
19
Asian Pac J Cancer May 2018
Antibiotic
resistance profile
China 2019
Clarithromycin 31%
Metronidazole 78%
Levofloxacin 56%
Amoxicillin 9%
Tetrcycline 15%

20. Common Clinical Scenarios
20
1) When Should I Test Patient for Helicobacter Pylori
infection for patient?
2) A Patient with history of dyspepsia found to have HP
positive, now his family came to ask about HP testing,
they are asymptomatic, should I do the test for them?
3) A Patient was seen in my clinic for reflux disease,
should I do HP testing for patient?
4) There are many HP treatment in guideline with different
durations, which one should I choose?
5) My Patient failed first line therapy, what should I do?

21. Treatment Strategies
21
First LIne Duration Eradication
No Penicillin
allergy
1) Amoxicillin 1g BD, Clarithromycin 500mg BD, PPI
BD
2) Amoxicillin 1g BD, Clarithromycin 500mg BD, PPI
BD, Metronidazole 400mg TDS
3) Bismuth subcitrate 240mg BD/subsalicylate 525mg
QDS, metronidazole 400mg TDS, Tetracycline 500
QDS, PPI BD
4) Amoxicillin 1g BD, clarithromycin 500mg BD,
Bismuth and PPI BD
10-14D 70-85%
70-85%
75-90%
Singapore Data Amoxicillin 1g BD, Clarithromycin 500mg BD, PPI BD 7 Days
10 Days
14 Days
76.9%
88.3%
92%
Penicillin Allergy Bismuth subcitrate 240mg BD/subsalicylate 525mg
QDS, metronidazole 400mg TDS, Tetracycline 500 QDS,
PPI BD
14D 75-90%
Helicobacter Pylori Treatment Strategies
in Singapore. Ang TL 2019 Dec

22. pH and Bacteria Survival
22

23. Vonoprazan
23
First in class Potassium Competitive Acid Blocker
Provides greater acid suppression compared to
conventional PPI
Useful in GERD, Peptic Ulcer Disease and
Helicobacter Pylori Eradication

24. Vonoprazan Vs Conventional PPI
24

25. Second Line Treatment
25
Regime Duration (Days) Eradication Rate
Levofloxacin 500mg OD +PPI
(high dose) + Amoxicillin 1g BD
7
10
69%
84%
Bismuth Based Quad Therapy 7
10
14
76%
77%
82%
Repeat Initial Clarithromycin
Based Triple therapy
7-14 34-58% (due to
clarithromycin resistance)
Metronidazole based triple
therapy ( PPI + Amoxicillin)
7 84-91% (Small Cohort
Japanese Study)
Singapore Real World Data
Bismuth Based Quad Therapy
Levo+Amox+PPI
14
14
82.4%
90.9%
ALWAYS CHECK COMPLIANCE!!

26. Second Line Treatment for
Penicillin Allergy
26

27. 3rd and 4th Line therapy
27
Consider Referral for endoscopic evaluation and culture
Options : High Dose Dual Therapy – Rabeprazole 20mg QDS, Amoxicillin 750mg QDS
Medicine (Baltimore). Xue et Al 2019 Feb

28. Rifabutin containing Therapy
28
Antibiotic commonly used for tuberculosis and mycobacterium avium
complex
Not widely available, need special approval to prescribed for HP treatment
Rifabutin-Based Triple Therapy (RHB-105) for Helicobacter pylori Eradication. 2020 May
5]. Graham et al. Ann Intern Med.
Rifabutin-based High-Dose Proton-Pump Inhibitor and Amoxicillin Triple Regimen as the
Rescue Treatment for Helicobacter Pylori. Hyun et al 2014
Regime Eradication
ERADICARE Hp2 2020 Rifabutin 150mg OD/Amoxicillin
1g TDS/Omeprazole 40mg TDS
83.8%
Vs Amoxicillin 1g
TDS/Omeprazole 40mg TDS 14
days
57.7%
Hyun et al Helicobacter 2014 Lansoprazole 30mg
BD+Amoxicillin 1g TDS +Rifabutin
150mg BD
78.1%
Lansoprazole 60mg BD,
Amoxicillin 1g TDS+Rifabutin
150mg BD
96.3%

29. Helicobacter Pylori Treatment
29
Triple Therapy Quad Therapy
High Dose
Dual/Levofloxacin
containing agent
Non Penicillin
Allergy
Quad
Therapy
Levofloxacin
Containing
Therapy
Rifabutin
Containing
Therapy
Penicillin
Allergy
Consider Gastric Biopsy for
Culture and Sensitivity
Use high dose PPI
Consider role of
Vonoprazan

30. Other Practical Scenarios
30
1) Can I use Serology to look for active HP infection?
Serology Testing not suitable to detect active HP infection, it measures
exposure.
A confirmatory UBT test should be done for patient if serology positive
2) How long Should antibiotic and PPI be stopped before UBT?
4 weeks
3) My Patient concerns he may have gastric pain once PPI stopped upon
treatment completion while waiting for UBT 4 weeks later, are there any
medication he can take without affecting the result?
- Yes , H2 blockers and antacids may be utilized without affecting accuracy
of UBT
4) My Patient asked if he can get HP reinfection again in future
- Based on studies, the reinfection rate ranges from 1.7%-3.3%
- Risk of reinfection – younger age, infection of close contacts, dental plaque
and low income
Once successful eradication, we recommend against further HP testing
unless patient develop new symptoms/recurrent symptoms years later.

31. Summary
31
1) Helicobacter Pylori Infection is common, patient with
recurrent/persistent dyspepsia, history of peptic ulcer disease, family of
gastric cancer should be tested for Helicobacter Pylori Infection
2) Urea Breath Test is the best tool to look for active Helicobacter pylori
infection
3) Patient with HP Serology positive should be referred for UBT
confirmation prior to treatment
4) Eventhough local clarithromycin resistance rate reported as 17%, our
local triple therapy regime 14 days sensitivity still achieve > 90%
eradication rate, thus still consider being used as first line treatment
5) Bismuth based quad therapy is the first line treatment for patients
with penicillin allergy
6) Consider to refer when :
- Red Flags
- Failure to response to first line therapy
- Persistent Symptoms
- High risk for gastric cancer

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