1. Helicobacter pylori and peptic ulcer disease.
R.J.L.F.Loffeld MD PhD
Department of Internal Medicine
Zaans Medical Centre
Zaandam

2. Helicobacter pylori and peptic ulcer disease.

3. Helicobacter pylori and peptic ulcer disease.
History of spiral organisms in the human stomach
1893 Bizzozero
1896 Salomon
1906 Krienitz
1940 Freedberg and Barron
1975 Steer
1979 Warren
1981 Rollason
1981/1982 Marshall and Warren
1982 successful culture: Campylobacter pyloridis
1987 Campylobacter pylori
1989 New genus: Helicobacter pylori

4. Helicobacter pylori and peptic ulcer disease.
The description of H.pylori was a major breakthrough in Gastroenterology.
The recognition of H.pylori as a major pathogen changed the common beliefs about peptic ulcer disease.
Infection with H.pylori is the major cause of peptic ulcer disease!
Peptic ulcer disease is a “simple” infectious disease.
Schwarz’s dictum: NO ACID NO ULCER
has become: NO H.pylori NO ULCER.

5. Helicobacter pylori and peptic ulcer disease.
Characteristics of peptic ulcer disease:
High prevalence in the population, high morbidity.
Adequate therapy available (acid suppressive therapy), high success rate in acute therapy.
High recurrence rate, once high number of operations.
Introduction acid suppressive maintenance therapy.
Chronic recurrent disease.

6. Helicobacter pylori and peptic ulcer disease.
4-years analysis of the evolution of healed duodenal ulcers.
Double blind trial: cimetidine, ranitidine, pirenzepin, sucralfate, CBS, placebo
follow-up: 4 years endpoint: relapse DU
n=562 after follow-up n=436
relapse CIM RAN Piren SUC CBS Placebo
6 months 46% 43% 30% 38% 19%# 29%
1 year 69% 74% 59% 63% 37%# 64%
2 years 89% 90% 86% 87% 88% 93%
3 years 92% 90% 89% 93% 93% 93%
4 years 92% 92% 89% 96% 95% 98%
# p<0.01
Lane et al Lancet 1988

7. Helicobacter pylori and peptic ulcer disease.
Duodenal ulcer: healing and relapse rates
healing relapse
Martin Cim/TDB 60/ /39
vanTrappen Cim/TDB /10
Kang Cim/TDB /76
Bianchi Porro Ran/TDB /41
Lee Ran/TDB 81/ /62
Bismuth preparation is more effective in preventing relapse.

8. Helicobacter pylori and peptic ulcer disease.
H.pylori and duodenal ulcer disease
n H.pylori +
Marshall %
Price %
Booth %
O’Connor %
Coghlan %
Rauws %
Goodwin %

9. Helicobacter pylori and peptic ulcer disease.
Known facts about ulcer disease:
The stomach is sterile
Ulcers were caused by lifestyle, diet, alcohol, drugs, genetically determined.
Initial work on H.pylori and peptic ulcer disease was refuted because the results were outside the current paradigm.

10. Helicobacter pylori and peptic ulcer disease.
Diagnosis:
Invasive methods (require endoscopy): HE stain, modified Giemsa stain, immunoperoxidase stain, Gram’s stain, culture with microbial resistance, CLO-test Leucocyte strip test.
Non-invasive methods: serology (ELISA), C or 14C urea breath test, stool antigen test.

11. Helicobacter pylori and peptic ulcer disease.

12. Helicobacter pylori and peptic ulcer disease.

13. Helicobacter pylori and peptic ulcer disease.

14. Helicobacter pylori and peptic ulcer disease.
H.pylori exerts several effects on gastric acid production
Increase in basal gastrin levels.
Increase in basal acid output.
Increase in intra-gastric acidity.
Increase in peak acid output.
All effects are reversed after successful eradication of H.pylori.

15. Helicobacter pylori and peptic ulcer disease.
H.pylori induced effects are related to distribution of gastritis
H.pylori associated antral gastritis induces increased acid secretion.
H.pylori associated corpus gastritis induces reduced or even absent acid secretion.
Pangastritis induces no overall change in acid production.

16. Helicobacter pylori and peptic ulcer disease.

17. Helicobacter pylori and peptic ulcer disease.
H.pylori: Virulence factors with potential predictive value for specific pathologies include the presence of the cag-pathogenicity island, specific vacuolating cytotoxin A (vacA) genotypes, protein induced by contact with epithelium (iceA) alleles, and blood group antigen-binding adhesion (babA2) genes.

18. Helicobacter pylori and peptic ulcer disease.
Study n follow-up DU relapse
H.pylori + H.pylori -
Coghlan /29 76% 1/10 10%
Lambert /33 76% 0/12 0%
Marshall /47 81% 5/23 22%
Smith /29 69% 0/7 0%
Borody /3 100% 0/18 0%
Borody /4 75% 0/54 0%
Rauws /21 81% 0/17 0%
Blum / % 1/13 8%
George % 0/62 0%
Grigorjev /50 82% 0/40 0%
Carride /59 20% 0/70 0%
Patchett /18 28% 0/33 0%
Lamouliatte /18 83% 1/26 4%
Graham % - 0%
Collins /19 58% 0/41 0%
Logan /17 71% 0/3 0%
Fiocca / % 3/30 10%
Unge % %
Sobala /44 57% 1/17 6%
Coelho /19 53% 0/19 0%
Bayerdörfer /31 61% 0/22 0%
Labenz /19 74% 1/29 3%
Hentschel /52 89% 1/52 2%

19. Helicobacter pylori and peptic ulcer disease.
Duodenal ulcer treated with anti-H.pylori therapy: seven year follow-up
DU n=100: 78 available for follow-up
63 endoscopic follow-up: years
DU relapse current relapse proven relapse clinical relapse
H.pylori + 5(20%) 9(35%) 11(42%)
H.pylori - 1(3%) 3(8%) 8(22%)
Annual rate of reinfection: 1.2% (CI 0-4.8%)
3 out of 35 H.pylori - became H.pylori + in 248 post eradication years.
Forbes et al. Lancet 1994

20. Helicobacter pylori and peptic ulcer disease.
Definite cure of H.pylori associated peptic ulcer. But what about the complications?

21. Helicobacter pylori and peptic ulcer disease.
In case of a complicated bleeding peptic ulcer the recurrence will present with the same complication in 50% of cases.

22. Helicobacter pylori and peptic ulcer disease.
Althought there has been improval in the survival rate of patients with peptic ulcer disease the mortality rate of bleeding still is 10%.
Despite all endoscopic techniques.

23. Helicobacter pylori and peptic ulcer disease.
Peptic ulcer n=173: anti-H.pylori treatment
follow-up 3 years, free of infection 106, still infected 69
Bleeding: pre-eradication: per patient per year
post-eradication: per patient per year
- 94%
“maintenance of ulcer remission following successful eradication of H.pylori significantly reduced ulcer complications”
Powel et al. Quaterly J Med 1994

24. Helicobacter pylori and peptic ulcer disease.
Rebleeding of gastric or duodenal ulcer depends on H.pylori status after treatment.
Recurrent bleeding
author ulcer site follow-up H.pylori + H.pylori -
Graham DU/GU % 0%
Rokkas DU % 0%
Labenz DU/GU % 0%
Jaspersen GU % 3%

25. Helicobacter pylori and peptic ulcer disease.
Jensen D. M., Cheng S., Kovacs T., Randall G., Jensen M. E., Reedy T., Frankl H., Machicado G., Smith J., Silpa M., Van Deventer G. A controlled study of ranitidine for the prevention of recurrent hemorhage from duodenal ulcer N Engl J Med 1994;330:

26. Helicobacter pylori and peptic ulcer disease.
For patients whose duodenal ulcers heal after severe hemorrhage, long-term maintenance therapy with ranitidine is safe and reduces the risk of recurrent bleeding.
Jensen DM, Cheng S, Kovacs T, Randall G, Jensen ME, Reedy T, Frankl H, Machicado G, Smith J, Silpa M, Van Deventer G. A controlled study of ranitidine for the prevention of recurrent hemorhage from duodenal ulcer N Engl J Med 1994;330:

27. Helicobacter pylori and peptic ulcer disease.
“Despite the lack of data, some physicians may nevertheless choose to use antimicrobial agents to treat patients who have bled from a peptic ulcer and who are infected with H.pylori. If so, it is my opinion that until studies prove that the eradication of H.pylori prevents recurrent bleeding, such patients, especially those who would tolerate recurrent bleeding poorly (among them the elderly and those with other medical illnesses) should also receive long-term maintenance therapy with antisecretory agents.
Prevention of upper gastrointestinal bleeding.
Peterson W. L. N Engl J Med 1994;330:

28. Helicobacter pylori and peptic ulcer disease.
“Peterson argues that large, prospective, randomized trials are needed to compare maintenance therapy consisting of antisecretory agents with anti-H. pylori therapy. The result of such studies is already known, even before they are conducted. If a duodenal ulcer does not recur after successful eradication, how can rebleeding occur?
Ranitidine and recurrent hemorrhage from duodenal ulcer.
Loffeld R.J.L.F., van der Putten A.B.M.M. New Engl J Med 1994;331:53-54.

29. Helicobacter pylori and peptic ulcer disease.
Because H. pylori treatment is very effective, it is unclear whether testing to confirm eradication is worthwhile.
A Markov cost-effectiveness model was developed to compare testing vs. non-testing of H. pylori eradication in peptic ulcer haemorrhage. Testing for H. pylori eradication costs less than the strategy of not confirming eradication. Testing remained the superior strategy when varying the model regarding age, the initial success of eradication, various test and retreatment strategies, and the rate and costs of recurrent bleeding.
Conclusions: Patients with H. pylori-associated peptic ulcer bleeding should be tested to confirm eradiation of H. pylori after completion of antibiotic treatment.
H. Pohl H, Finlayson SR, Sonnenberg A, Robertson DJ. Helicobacter pylori-associated ulcer bleeding: should we test for eradication after treatment? Aliment Pharmacol Ther. 2005;22:

30. Helicobacter pylori and peptic ulcer disease.
Certain indications for H.pylori eradication therapy:
Peptic ulcer disease
Mucosa-associated tissue lymphoma
Atrophic gastritis
Post-gastric cancer resection
Patients who are first degree relatives of gastric cancer patients
Patients’ wishes
Debatable indications for H.pylori eradication therapy:
Non-ulcer dyspepsia / functional dyspepsia
Gastro-oesophageal reflux disease
Prevention of gastric cancer.
Maastricht consensus report 2000

31. Helicobacter pylori and peptic ulcer disease.

32. Helicobacter pylori and peptic ulcer disease.
Conclusions:
H.pylori is a major pathogen in gastric and duodenal diseases.
H.pylori associated peptic ulcer disease can be definitely cured via anti-H.pylori therapy.
Peptic ulcer complication like bleeding can be prevented by successful eradication of H.pylori.

33. Helicobacter pylori and peptic ulcer disease.
Ontdekkers bacterie krijgen Nobelprijs Geneeskunde ANP STOCKHOLM - De Australische medici Barry J. Marshall en J. Robin Warren hebben de Nobelprijs 2005 voor Geneeskunde gewonnen. Ze krijgen die voor de ontdekking van de bacterie Helicobacter pylori en de betekenis daarvan bij de aan-doeningen gastritis en bij andere aandoeningen van de spijsvertering-organen.

34. Helicobacter pylori and peptic ulcer disease.