Helicobacter pylori and peptic ulcer disease.

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Helicobacter pylori and peptic ulcer disease.

• R.J.L.F.Loffeld MD PhD
• Department of Internal Medicine
• Zaans Medical Centre
• Zaandam

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Helicobacter pylori and peptic ulcer disease.
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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
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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.
Schwarzs dictum NO ACID
NO ULCER has become NO
H.pylori NO ULCER.
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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.
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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 n562 after follow-up n436 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 plt0.01 Lane et
al Lancet 1988
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Helicobacter pylori and peptic ulcer disease.
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.
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Helicobacter pylori and peptic ulcer disease.
H.pylori and duodenal ulcer disease n
H.pylori Marshall 1985 70 90 Price 1985
21 80 Booth 1986 32 78 OConnor 1987
66 93 Coghlan 1987 66 93 Rauws 1988
36 100 Goodwin 1988 107 93
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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.
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Helicobacter pylori and peptic ulcer disease.
Diagnosis Invasive methods (require endoscopy)
HE stain, modified Giemsa stain,
immunoperoxidase stain, Grams stain,
culture with microbial resistance, CLO-
test Leucocyte strip test. Non-invasive
methods serology (ELISA), 13C or
14C urea breath test, stool antigen test.
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Helicobacter pylori and peptic ulcer disease.
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Helicobacter pylori and peptic ulcer disease.
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Helicobacter pylori and peptic ulcer disease.
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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.

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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.

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Helicobacter pylori and peptic ulcer disease.
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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.
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Helicobacter pylori and peptic ulcer disease.
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
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Helicobacter pylori and peptic ulcer disease.
Duodenal ulcer treated with anti-H.pylori
therapy seven year follow-up DU n100 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
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Helicobacter pylori and peptic ulcer disease.
Definite cure of H.pylori associated peptic
ulcer. But what about the complications?
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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.
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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.
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Helicobacter pylori and peptic ulcer disease.
Peptic ulcer n173 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
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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 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
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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 1994330382-386.
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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 1994330382-386.
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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 1994330428-429.

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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 199433153-54.
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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.
200522529-37.
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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
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Helicobacter pylori and peptic ulcer disease.
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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.
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Helicobacter pylori and peptic ulcer disease.
Ontdekkers bacterie krijgen Nobelprijs
GeneeskundeANPSTOCKHOLM - 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.

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Helicobacter pylori and peptic ulcer disease.

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