Helicobacter pylori is a common cause of peptic ulcer disease. It infects about half of the global population and transmission occurs through person-to-person contact or from infected instruments. Only 10-15% of infected individuals develop ulcers or other diseases. In Bangladesh, H. pylori infection rates are very high, ranging from 67-92% in studies. Treatment involves antibiotic regimens but resistance is a problem, with high rates of resistance to clarithromycin, metronidazole, and levofloxacin seen in Bangladesh. Management of peptic ulcers involves testing and treating H. pylori, endoscopic treatment for bleeding ulcers, and maintenance therapy to prevent

1. Helicobacter pylori associated
Peptic ulcer disease
DR. S. M. ALI HASAN
MD RESIDENT (PHASE-B), GASTROENTEROLOGY, BSMMU

2. Helicobacter pylori (Hp)
Microbiology
 Small, curved, microaerophilic, Gram
negative, spiral shaped bacteria.
 Produce large amount of urease which
hydrolyses urea to produce ammonia
(alkaline) and CO2.
 H. pylori is typically acquired during
childhood and causes lifelong infection
thereafter.
 Transmission: person to person through
direct, gastro-oral, fecal-oral or oral-oral
route. Iatrogenic from infected instruments.

3. Diseases caused by Hp
 Mostly asymptomatic chronic infection.
 10%-15% develop
 Chronic active gastritis,
 PUD,
 gastric adenocarcinoma,
 MALT lymphoma.
 May be associated with
 ITP, IDA.

4. Helicobacter pylori (Hp)
Epidemiology
 Worldwide, chronic H. pylori infection is highly prevalent: about half of the
global human population is thought to be infected.
 Prevalence of infection ranged from 7% to 87%, depending on the
methods of diagnosis and the population.
 In industrialized nations H. pylori colonization is much less frequent than in
previous years, and is still declining.

5. Bangladesh perspectives
 A cross-sectional study was conducted among randomly selected
households from a peri-urban community in Dhaka, Bangladesh to get an
idea about H. pylori status in the lower socioeconomic area.
 A total of 287 subjects were screened by stool antigen test, of them, 92.7%
were positive for stool antigen test.
 Of 259 stool antigen positive samples, 59.1% (n = 153) were H. pylori
culture positive.
[Nahar S et al. 2018. Epidemiology of H. pylori in Bangladesh]

6.  In a study conducted in 1995, 92% of the Bangladeshi population was
found to be H. pylori positive by ELISA.
[Ahmad et al., 1997, Bardhan, 1997]
 67% of the children of a lower socioeconomic area was found to be H.
pylori positive detected by urea breath test.
[Mahalanabis et al., 1996]
 Reinfection of H. pylori was 5.02% per year in the H. pylori eradicated
patients using urea breath test.
[Ahmad et al., 2007]
Bangladesh perspectives

7.  H. pylori showed high rates of resistance to
 Clarithromycin - 39.3% and
 Metronidazole - 94.6%.
 Levofloxacin - 66.1%
 The resistance rate of levofloxacin was significantly higher in patients living
in Dhaka city compared to those living in the village (p = 0.049).
 However, amoxicillin and tetracycline resistance rates were very low.
 Resistance to clarithromycin, metronidazole, and levofloxacin were high in
Bangladesh, which suggests that triple therapy based on these drugs may
not be useful as first-line therapies in Bangladesh.
Aftab et al. – H. pylori antibiotic susceptibility in Bangladesh J Infect Dev Ctries 2016;
Bangladesh perspectives

8.  PPI-amoxycillin-metronidazole was used for 14 days as anti-H. pylori
regimen.
 The eradication rate was 89% and 64% for metronidazole susceptible and
resistant strains, respectively.
 negative RUT tests 4 weeks after treatment with triple therapy.
Hasan et al. 2014, J Enam Med Col Vol 4 No 1
[BSMMU, June 2008 to May 2009]
Bangladesh perspectives

9. Peptic Ulcer Disease (PUD)
Definition
 Peptic ulcers are localized defects of the GI mucosa extending to at least
the depth of the muscularis mucosa.
 Through the endoscope, an ulcer is identified as a mucosal break with
considerable depth.
 The arbitrary criterion (used in most clinical trials) is that an ulcer has a
diameter of 5 mm or larger, and lesions smaller than 5 mm are called
erosions.

10. Etiology
 The majority of PUD is caused by
 H. pylori infection (about 90% of DUs, and up to 80% of GUs) or
 nonsteroidal anti inflammatory drugs (NSAIDs) including aspirin.

11. Etiology
non-Hp, non-NSAID causes (Peptic)
 The most common causes of an apparently non-H. pylori, non-NSAID ulcer are
still H. pylori or NSAIDs.
 Acid hypersecretion, with hormonal- or mediator-induced ulcers
 gastrin
 gastrinoma in Zollinger-Ellison syndrome and MEN1
 antral G-cell hyperfunction (controversial independent of H. pylori)
 histamine
 systemic mastocytosis
 basophilia associated with myeloproliferative diseases
 rebound acid secretion after withdrawal of PPI therapy

12. H. pylori associated PUD
 H. pylori was identified as the major etiological agent for PUD in 1982 by
Warren and Marshall.
 This discovery revolutionized our understanding of the pathogenesis and
management of PUD and other GI disorders.
 Their work was recognized with the award of the Nobel Prize for Medicine
or Physiology in 2005.

13. Why only some people infected with H. pylori
develop peptic ulcer disease
 Only about 10% - 20% of infected people ever develop a peptic ulcer.
 It depends on
 the virulence of the infecting H. pylori strain (cag-PAI, VacA)
 host genetic susceptibility,
 the host immune response, and
 environmental cofactors

14. Natural history of H. pylori associated ulcers
 H. pylori-associated ulcers have been observed to relapse without eradication
– over a 12-month period, (Bardhan, 1988)
 26% of patients did not experience further symptoms after documented DU healing,
whereas
 33% experienced one recurrence,
 24% had two episodes, and
 17% had three or more episodes
 Treatment of H. pylori infection markedly reduces recurrences and alters
natural history. The symptomatic benefit is greatest for DU
(Koivisto et al., 2008).
 Eradication of H. pylori is more effective at preventing recurrent bleeding from
peptic ulcer.

15. DiagnosisandManagement
ACG and Canadian Association of Gastroenterology (CAG) guideline algorithm for the management of undiagnosed PUD
Am J Gastroenterol 2017

17. False negative:
 Anti-secretory therapy e.g PPI, Bismuth; Antibiotic.
 These drugs should stop at least 4 weeks before testing.
Test for successful Hp eradication:
 All individual treated for Hp (European guideline).
 All infected individual with PUD, MALT lymphoma, early gastric cancer and
dyspepsia should be confirmed for successful eradication (US guideline).
 Test should be perform at least 4 weeks after completion of eradication therapy
and 1-2 week after stoppage of PPI.
The American Journal of GASTROENTEROLOGY, 2017

18. Management
Evidence-based clinical practice guidelines for H. pylori associated peptic
ulcer disease
 Japanese society of Gastroenterology, 2015
 American College of Gastroenterology, 2017
 The Maastricht V/Florence Consensus Report, 2018

19. H. pylori eradication therapy
Initial treatment
 Eradication therapy in H. pylori-positive patients with an active gastric or
duodenal ulcer is performed as initial treatment, because successful
eradication of H. pylori accelerates gastric or duodenal ulcer healing.
 After H. pylori eradication therapy, additional treatment for ulcer healing is
recommended.
 Eradication of H. pylori is recommended as a preventive care for the
recurrence of peptic ulcer.
Ulcer recurrence after eradication
 Ulcers recur after eradication in only 0–2 % of cases
Japanese society of Gastroenterology, 2015

20. First-lineeradicationtherapy
The American Journal of GASTROENTEROLOGY, 2017

21. 2nd-line therapy/Salvage regimen
The American Journal of GASTROENTEROLOGY, 2017

22. Management of Helicobacter pylori infection—the
Maastricht V/Florence Consensus Report, 2018
 A test-and-treat strategy is appropriate for uninvestigated dyspepsia. This
approach is subject to regional H. pylori prevalence and cost-benefit
considerations. It is not applicable to patients with alarm symptoms or older
patients.
 An endoscopy-based strategy should be considered in patients with dyspeptic
symptoms, particularly in low prevalence H. pylori populations.
 Urea breath test (UBT) is the most investigated and best recommended non-
invasive test in the context of a ‘test-and-treat strategy’.
 Stool antigen test (SAT) can also be used.

23.  In clinical practice when there is an indication for endoscopy, and there is
no contraindication for biopsy, the rapid urease test (RUT) is
recommended as a first-line diagnostic test.
 In the case of a positive test, it allows immediate treatment. One biopsy
should be taken from the corpus and one from the antrum. RUT is not
recommended as a test for H. pylori eradication assessment after
treatment.
Maastricht V/Florence Consensus Report, 2018

24.  Factors to be considered before choice of antibiotic regimen
 Previous antibiotic exposure
 Local antibiotic resistance
 Penicillin allergy
 After a first failure, if an endoscopy is carried out, culture and standard
antimicrobial susceptibility testing (AST) are recommended to tailor the
treatment, except if a bismuth-based quadruple therapy is considered.
 UBT is the best option for confirmation of H. pylori eradication and
monoclonal SAT is an alternative. It should be performed at least 4 weeks
after completion of therapy.
Maastricht V/Florence Consensus Report, 2018

25.  In areas of low clarithromycin resistance (<15%), clarithromycin based triple
therapy is recommended as first-line empirical treatment. Bismuth-containing
quadruple therapy is an alternative.
 Clarithromycin-containing triple therapy without prior susceptibility testing
should be abandoned when the clarithromycin resistance rate in the region is
more than 15%.
 In patients with penicillin allergy, in areas of low clarithromycin resistance, for
a first-line treatment, a PPI-clarithromycin-metronidazole combination may
be prescribed, and in areas of high clarithromycin resistance, BQT should be
preferred.
Maastricht V/Florence Consensus Report, 2018

26.  In areas of high (>15%) clarithromycin resistance, bismuth quadruple or
non-bismuth quadruple, concomitant (PPI, amoxicillin, clarithromycin and a
nitroimidazole) therapies are recommended.
 In areas of high dual clarithromycin and metronidazole resistance, bismuth
quadruple therapy (BQT) is the recommended first-line treatment
 The treatment duration of bismuth or non bismuth quadruple
(concomitant) therapy should be extended to 14 days, unless 10 day
therapies are proven effective locally.
Maastricht V/Florence Consensus Report, 2018

27.  After failure of PPI-clarithromycin-amoxicillin triple therapy, a bismuth-
containing quadruple therapy or a fluoroquinolone-containing triple or
quadruple therapy are recommended as a second-line treatment.
 After failure of bismuth-containing quadruple therapy, a fluoroquinolone-
containing triple or quadruple therapy may be recommended.
Maastricht V/Florence Consensus Report, 2018

28.  After failure of a non-bismuth quadruple therapy, either a bismuth
quadruple therapy or a fluoroquinolone-containing triple or quadruple
therapy are recommended.
 After failure of second-line treatment, culture with susceptibility testing or
molecular determination of genotype resistance is recommended in order
to guide treatment.
Maastricht V/Florence Consensus Report, 2018

29.  After failure of the first-line treatment (triple or non-bismuth quadruple)
and second-line treatment (fluoroquinolone-containing therapy), it is
recommended to use the bismuth-based quadruple therapy
 After failure of first-line treatment with bismuth quadruple and second-line
treatment (fluoroquinolone-containing therapy), it is recommended to use
a clarithromycin-based triple or quadruple therapy. A combination of
bismuth with different antibiotics may be another option.
 In cases of high quinolone resistance, the combination of bismuth with
other antibiotics, or rifabutin, may be an option.
Maastricht V/Florence Consensus Report, 2018

30. © 2020 UpToDate, Inc.
Initial approach to antibiotic treatment for Helicobacter pylori infection

31. Approach to antibiotic treatment in patients with persistent Helicobacter
pylori infection
© 2020 UpToDate, Inc.

32. Non-eradication therapy
Initial therapy
 PPIs are recommended is the first-line drug for the initial non-eradication
treatment of peptic ulcers
 If PPIs cannot be prescribed, H2RAs are recommended
 If PPIs cannot be prescribed, drugs such as pirenzepine, sucralfate, and
misoprostol are recommended.
Japanese society of Gastroenterology, 2015

33. Maintenance therapy
 Indication of non eradication maintenance therapy
 Giant ulcer (>2cm) and old age or multiple comorbidities
 Failure to eradicate H. pylori infection
 Continued NSAID use
 Frequently recurrent ulcer (>2/year)
 Non-H. pylori non-NSAID ulcer
 In non-eradication therapy for gastric ulcers, maintenance treatment is
effective for the prevention of ulcer recurrence in healed peptic ulcers, and this
treatment is recommended.
 In non-eradication therapy (maintenance treatment) for peptic ulcers, PPI,
H2RA and sucralfate are recommended.
Japanese society of Gastroenterology, 2015

34. Bleeding gastric and duodenal ulcers
Endoscopic therapy
 Endoscopic therapy for peptic ulcer bleeding is superior to
pharmacotherapy alone with regard to initial hemostasis and re-bleeding.
 Endoscopic therapy decreases the need for surgery and mortality versus
pharmacotherapy alone.
 Active bleeding and ulcer with non-bleeding visible vessel is a good
indication for endoscopic hemostasis
Japanese society of Gastroenterology, 2015

35.  Second-look endoscopy is recommended to confirm recurrent bleeding of
high-risk patients.
 predictors of re-bleeding –
 hemodynamic instability and comorbid illness,
 active bleeding at endoscopy, large ulcer size, posterior duodenal ulcer, and
lesser gastric curvature ulcer.
 Medication with antacid agents is strongly recommended after endoscopic
treatment for hemorrhagic peptic ulcers.
 H. pylori eradication therapy is strongly recommended in the H. pylori-
infected patients with hemorrhagic peptic ulcers cured by conservative
treatment.
Japanese society of Gastroenterology, 2015

36.  Endoscopic balloon dilation is recommended for maintenance therapy with
stenosis of peptic ulcer alternative to surgery.
Japanese society of Gastroenterology, 2015

37. Surgical treatment
 Over recent decades, the development of potent antisecretory agents
(especially PPI) and the discovery of H. pylori have essentially eliminated the
need for elective surgery.
 PUD now only infrequently requires operative intervention.
 Indications for surgical treatment are
 peptic ulcer perforation
 bleeding cannot be easily controlled by endoscopy
 a stenosis caused by a chronic peptic ulcer.
 Eradication is recommended if the patient is positive for H. pylori after the
surgery for peptic ulcer
Japanese society of Gastroenterology, 2015

38. Japanese society of Gastroenterology, 2015

39. Japanese society of Gastroenterology, 2015