helicobacter pylori and peptic ulcer disease. r.j.l.f.loffeld md phd department of internal medicine...

Helicobacter pylori and peptic ulcer disease.

R.J.L.F.Loffeld MD PhD

Department of Internal Medicine

Zaans Medical Centre

Zaandam

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


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.


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.


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<0.01Lane et al Lancet 1988


Duodenal ulcer: healing and relapse rates

healing relapse

Martin 1981 Cim/TDB 60/66 85/39

vanTrappen 1981 Cim/TDB - 30/10

Kang 1982 Cim/TDB - 75/76

Bianchi Porro 1984 Ran/TDB - 71/41

Lee 1985 Ran/TDB 81/90 89/62

Bismuth preparation is more effective in preventing relapse.


H.pylori and duodenal ulcer disease

n H.pylori +

Marshall 1985 70 90%

Price 1985 21 80%

Booth 1986 32 78%

O’Connor 1987 66 93%

Coghlan 1987 66 93%

Rauws 1988 36 100%

Goodwin 1988 107 93%


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.


Diagnosis:

Invasive methods (require endoscopy): HE stain, modified Giemsa stain, immunoperoxidase stain, Gram’s stain, culture with microbial resistance,CLO-testLeucocyte strip test.

Non-invasive methods: serology (ELISA), 13C or 14C urea breath test, stool antigen test.


• 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.


• 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.


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.


Study n follow-up DU relapse H.pylori + H.pylori -

Coghlan 1987 39 12 22/29 76% 1/10 10%Lambert 1987 45 6 25/33 76% 0/12 0%Marshall 1988 70 12 38/47 81% 5/23 22%Smith 1988 36 18 20/29 69% 0/7 0%Borody 1988 21 12-25 3/3 100% 0/18 0%Borody 1989 58 9-37 3/4 75% 0/54 0%Rauws 1990 38 12 17/21 81% 0/17 0%Blum 1990 192 6 73/179 41% 1/13 8%George 1990 62 12 - 48% 0/62 0%Grigorjev 1990 90 12 41/50 82% 0/40 0%Carride 1990 129 12-36 12/59 20% 0/70 0%Patchett 1990 51 12 5/18 28% 0/33 0%Lamouliatte 1991 44 12 15/18 83% 1/26 4% Graham 1991 100 9 - 95% - 0%Collins 1991 60 24 11/19 58% 0/41 0%Logan 1991 20 9 12/17 71% 0/3 0%Fiocca 1991 144 6 55/114 48% 3/30 10%Unge 1992 233 6 - 45% - 16%Sobala 1992 71 12 25/44 57% 1/17 6%Coelho 1992 48 18 10/19 53% 0/19 0%Bayerdörfer 1992 53 12 19/31 61% 0/22 0%Labenz 1992 48 12 14/19 74% 1/29 3%Hentschel 1993 104 12 46/52 89% 1/52 2%


Duodenal ulcer treated with anti-H.pylori therapy: seven year follow-up

DU n=100: 78 available for follow-up

63 endoscopic follow-up: 5-7.6 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


Definite cure of H.pylori associated peptic ulcer. But what about the

complications?


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


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.


Peptic ulcer n=173: anti-H.pylori treatment

follow-up 3 years, free of infection 106, still infected 69

Bleeding: pre-eradication: 0.056 per patient per year

post-eradication: 0.003 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


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 1993 DU/GU 4-26 29% 0%

Rokkas 1995 DU 4-14 25% 0%

Labenz 1994 DU/GU 6-33 37% 0%

Jaspersen 1995 GU 6 40% 3%


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;330:382-386.


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;330:382-386.


“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;330:428-429.


“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.


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;22:529-37.


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


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.


Ontdekkers bacterie krijgen Nobelprijs GeneeskundeANP

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.

helicobacter pylori and peptic ulcer disease. r.j.l.f.loffeld md phd department of internal medicine...

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