Helicobacter Pylori treatment and Management plans. Latest guidelines and evidence Acorn Gastroenterology

1. 《Latest Update on Helicobacter Pylori
Infection and Treatment》
Dr Chong Chern Hao
Gastroenterologist

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

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.

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.
Fock KM . H Pylori Current status in Singapore. 1997
Asia HP Prevalence : 58%
Sg HP prevalence : 31% (Chinese 34.3/Indian 33.6/Malay 13.7)
Risk factors: Poor household hygiene, high density population, bed
sharing in childhood, lack of running water

5. Complications of HP
infection
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. H Pylori Associated Gastritis - 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

8. Who requires GC Surveillance?
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%
Academic of Medicine SG ( July 2022 Guideline)
Patient with Gastric IM with specifically higher risk of gastric
cancer include those:
> 50 Years old w 3 or more risks
1) Chinese
2) Male
3) 1st Degree Family history of gastric cancer
4) History of HP infection
5) Heavy Smoker
6) Pernicious Anaemia

9. Common Clinical Scenarios
1) 1) When Should I order Helicobacter Pylori test for patient?
2) 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) 3) A Patient was seen in my clinic for reflux disease, should I do HP testing
for patient?
4) 4) There are many HP treatment in guideline with different durations,
which one should I choose?
5) 5) My Patient failed first line therapy, what should I do?

10. 1)When Should I order Helicobacter Pylori test 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. 1) Why Should I Test/Treat 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
1) 1) When Should I Test Patient for Helicobacter Pylori infection for patient?
2) 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) 3) A Patient was seen in my clinic for reflux disease, should I do HP testing
for patient?
4) 4) There are many HP treatment in guideline with different durations,
which one should I choose?
5) 5) My Patient failed first line therapy, what should I do?

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
1) 1) When Should I Test Patient for Helicobacter Pylori infection for patient?
2) 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) 3) A Patient was seen in my clinic for reflux disease, is there a benefit
test/treat HP for this patient?
4) 4) There are many HP treatment in guideline with different durations,
which one should I choose?
5) 5) My Patient failed first line therapy, what should I do?

15. A Patient was seen in my clinic for reflux disease, is there a
benefit test/treat for this patient?
• GERD is typically a manifestation of robust acid secretion and abnormal oesophagogastric anti reflux
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
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, abx > 4 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
Test Advantages Disadvantages
Serology (IgG Antibody) Accessible, least expensive Does not differentiate current/past
infection, cannot confirm eradication
Stool Antigen test (Sent out test to
SGH)
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 (SGH) Specificity, test for Abx Sensitivity in
failed therapy
Not widely available, variable
sensitivity, result takes weeks
Histology Provides information such as
intestinal metaplasia, atrophic
gastritis
Requires endoscopy, Variable Sn/Sp
due to inter observer variability
Rapid Urease based tests Good sn/sp, rapid, inexpensive Requires discontinuation of
antibiotics, PPI.

18. Common Clinical Scenarios
1) 1) When Should I Test Patient for Helicobacter Pylori infection for patient?
2) 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) 3) A Patient was seen in my clinic for reflux disease, is there a benefit
test/treat HP for this patient?
4) 4) There are many HP treatment in guideline with different durations,
which one should I choose?
5) 5) My Patient failed first line therapy, what should I do?

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

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

21. Treatment Strategies
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
Gastric Acid Suppresion is one of the key to improve eradication rate

23. Vonoprazan
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 for
H Pylori Treatment

25. Second Line Treatment
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

27. 3rd and 4th Line therapy
Consider Referral for endoscopic evaluation and culture
Options : High Dose Dual Therapy – Rabeprazole 20mg QDS, Amoxicillin 750mg QDS x 14 days
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
*Levofloxacin (250mg daily) + PPI (double
dose daily) + nitazoxanide (500mg twice
daily) + doxycycline (100mg daily)

30. Other Practical Scenarios
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
• 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
1) 2) Urea Breath Test is the best tool to look for active Helicobacter pylori infection
1) 3) Patient with HP Serology positive should be referred for UBT confirmation prior to treatment
1) 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
2) 5) Bismuth based quad therapy is the first line treatment for patients with penicillin allergy
1) 6) Consider to refer when :
- - Red Flags
- - Failure to response to first line therapy
- - Persistent Symptoms
- - High risk for gastric cancer

32. Thank You