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.

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

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

has become:

NO H.pylori

NO ULCER

NO ULCER.

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.

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

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.

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%

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.

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),
13
C or 14C urea breath test,
stool antigen test.

Helicobacter pylori and peptic ulcer disease.

Helicobacter pylori and peptic ulcer disease.

Helicobacter pylori and peptic ulcer disease.

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.

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.

Helicobacter pylori and peptic ulcer disease.

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.

Helicobacter pylori and peptic ulcer disease.

Study

follow-up

Coghlan 1987
Lambert 1987
Marshall 1988
Smith 1988
Borody 1988
Borody 1989
Rauws 1990
Blum 1990
George 1990
Grigorjev 1990
Carride 1990
Patchett 1990
Lamouliatte 1991
Graham 1991
Collins 1991
Logan 1991
Fiocca 1991
Unge 1992
Sobala 1992
Coelho 1992
Bayerdrfer 1992
Labenz 1992

39
45
70
36
21
58
38
192
62
90
129
51
44
100
60
20
144
233
71
48
53
48

12
6
12
18
12-25
9-37
12
6
12
12
12-36
12
12
9
24
9
6
6
12
18
12
12

DU relapse
H.pylori +
22/29
76%
25/33
76%
38/47
81%
20/29
69%
3/3
100%
3/4
75%
17/21
81%
73/179 41%
48%
41/50
82%
12/59
20%
5/18
28%
15/18
83%
95%
11/19
58%
12/17
71%
55/114 48%
45%
25/44
57%
10/19
53%
19/31
61%
14/19
74%

H.pylori -

1/10
0/12
5/23
0/7
0/18
0/54
0/17
1/13
0/62
0/40
0/70
0/33
1/26
0/41
0/3
3/30
1/17
0/19
0/22
1/29

10%
0%
22%
0%
0%
0%
0%
8%
0%
0%
0%
0%
4%
0%
0%
0%
10%
16%
6%
0%
0%
3%

Helicobacter pylori and peptic ulcer disease.

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

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

Helicobacter pylori and peptic ulcer disease.

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

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.

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.

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: 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

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%

40%

3%

Jaspersen 1995 GU

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;330:382386.

Helicobacter pylori and peptic ulcer disease.

For patients whose duodenal ulcers heal after severe hemorrhage, longterm 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.

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;330:428-429.

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.

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 pyloriassociated ulcer bleeding: should we test for eradication after treatment?
Aliment Pharmacol Ther. 2005;22:529-37.

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

Helicobacter pylori and peptic ulcer disease.

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 antiH.pylori therapy.
Peptic ulcer complication like bleeding can be prevented by successful
eradication of H.pylori.

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 aandoeningen gastritis en bij andere
aandoeningen van de spijsverteringorganen.

Helicobacter pylori and peptic ulcer disease.