Treatment of Helicobacter pylori infection
BMJ 2008; 337 doi: https://doi.org/10.1136/bmj.a1454 (Published 15 September 2008) Cite this as: BMJ 2008;337:a1454All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
Other modalities of treatment are now being considered for H. Pylori,
other than
antibiotics,PPis or bismuth. Recent meta- analyses have shown an
association
between the use of probiotics and modest increases in eradication rates of
H.
Pylori. Improvement in healing rates have also been seen by reducing the
gastric
mucus layer with pronase and N- acetyl cysteine, exposing H.Pylori, thus
increasing the effects of triple therapy (1).
(1) Graham D, Shiotani A. New concepts of resistance in the treatment
of
Helicobacter pylori infections. Nat Clin Pract Gastroenterol Hepatol
2008;5;321-
331.
Competing interests:
None declared
Competing interests: No competing interests
The authors advise that re-testing after eradication should be with
the urea breath test or stool antigen test. Although they do not
specifically state who needs re-testing the implication in the review is
that it should be offered routinely.
This is in contradiction to the recent NICE guidelines on dyspepsia
which suggest that for dyspepsia not needing referral, which comprise the
majority of patients that I see, re-testing is not required, even if
dyspepsia remains, unless there is a strong clinical need.
Competing interests:
None declared
Competing interests: No competing interests
Fuccio et al quote an annual re-infection rate of 3.4% in
industrialised countries, but a minority of patients seem to get frequent
relapses with re-infection. I suspect these patients are being re-infected
by an intimate partner.
Over the years I have had several patients who have a good clinical
response to Eradication Therapy, only to repeatedly relapse (demonstrated
both clinically and by Carbon urea breath-testing), with further short-
term improvement after further treatment.
These patients are often sharing a bed with a Helicobacter-positive
person (as least some of whom will describe dyspeptic symptoms on direct
questioning).
In patients who frequently re-infect a case can be made for “contact-
tracing”, testing intimate partners, and if found positive prescribing
simultaneous Eradication Therapy.
Fuccio L, Laterza L, Zagari RM, Cennamo V, Grilli D, Bazzoli F.
Treatment of Helicobacter pylori infection. BMJ 2008;337:a1454
Competing interests:
None declared
Competing interests: No competing interests
Have a look at this article in
The Economist. Quote:
"Martin Blaser, a microbiologist at the New York University School of Medicine, and his team have already linked the bug's disappearance with increased levels of obesity and with the rise of cancer of the oesophagus. Last month they added asthma to the list by publishing a study showing that children who had not been infected by H. pylori were more likely to suffer from the condition than those who had.
It is a mistake, according to Dr Blaser, to think of H. pylori as just another pathogen. He reckons that it is better perceived as a symbiont that is sometimes helpful and sometimes harmful."
Competing interests:
None declared
Competing interests: No competing interests
Among the benefits of treating H.pylori infection(1), mention must
also be made of remission of iron deficiency anaemia previously refractory
to oral iron, and unassociated with either coelic disease or chronic blood
loss when the latter has been ruled out by upper gastrointestinal
endoscopy and by colonoscopy in both males and females, and, in addition,
by gynaecological evaluation in female subjects(2). Where the confounding
effect of menstrual blood loss does not apply, as in a study exclusively
confined to males(where coeliac disease had been ruled out and also
chronic blood loss in regions of the gastrointestinal tract accesible to
upper gastrointestinal endoscopy and to colonoscopy), fourteen iron
deficient subjects in whom H.pylori gastritis was the sole abnormality
were documented as having anaemia refractory to oral iron(3). Following
eradication of H.pylori using triple therapy all 14 subjects acheived
normal haemoglobin levels. Oral iron was then discontinued and, on 18-53
months follow-up, eleven of the original fourteen still maintained their
normal haemoglobin levels. Three, however, still required chronic
replacement therapy to maintain normal haemoglobin levels(3). The
rationale for H.pylori eradication in refractory iron deficiency(where
neither coeliac disease or chronic blood loss is an issue)is that H.pylori
infection gives rise to an increase in intragastric pH(4) and this, in
turn, impairs absorption of oral iron be it dietary or pharmacological.
Accordingly, eradication of H.pylori should enhance bioavailability of
oral iron in its pharmacological formulation, hence the favourable
haematological responses documented in the foregoing studies(2)(3), and
also in its dietary form, hence the sustained haematological improvement
even after discontinuation of pharamacological formulations of oral
iron(3)
References
(1) Fuccio L., Laterza L., Zagari RM et al
Treatment of Helicobacter pylori infection
British Medical Journal 2008:337:a1454
(2)Hershko C., Hoffbrand AV., Keret D et al
Role of autoimmune gastritis, Helicobacter pylori and celiac disease in
refractory or unexplained iron deficiency anemia
Haematologica 2005:90:585-95
(3)Hershko C., Ianculovich M., Souroujon M
A hematologist's view of unexplained iron deficiency anemia in males:
Impact of Helicobacter pylori eradication
Blood Cells Molecules and Diseases 2007:38:45-53
(4)Annibale B., Capurso G., Lahner E et al
Concomitant alterations in intragastric pH and ascorbic acid concentration
in patients with Helicobacter pylori gastritis and associated iron
deficiency anaemia
Competing interests:
None declared
Competing interests: No competing interests
The comprehensive review by Fuccio et al[1] outlines some of the
benefits of H. pylori eradication therapy with different regimens and some
of their pitfalls. However two groups of patients frequently seen by
haematologists that particularly benefit from eradication therapy were not
mentioned. Those with gastric marginal zone B-cell lymphoma of mucosa-
associated lymphoid tissue (gastric MALT lymphoma), and chronic immune
thrombocytopenic purpura (ITP).
Evidence of H. pylori infection in patients with gastric MALT
lymphoma is found in at least 90% of patients, and eradication therapy is
part of initial therapy. 50% of those without detectable evidence of
infection have a genetic translocation, t(11;18)(q21;q21),[2] and tend to
respond poorly to eradication therapy alone, warranting earlier
chemotherapeutic consideration.[3] However, those without evidence of
infection or this translocation may still respond to eradication therapy
alone, particularly if disease is localised.[3]
Both children and adults with chronic ITP that have detectable H.
pylori respond well to eradication therapy with sustained platelet counts
without other therapies. Studies mainly originate from Japan, where H.
pylori rates are higher compared to the UK[1]. However, a small randomised
controlled trial of 36 patients with platelet counts of greater than
20x10[9]/L treated with eradication therapy (amoxicillin 750 mg bd,
clarithromycin 200 mg bd, and lansoprazole 30 mg bd for 1 week) confirmed
the benefit seen in previously reported series, with 46% achieving
sustained platelet responses of greater than 70x10[9]/L.[4] This is
consistent with a larger subsequent series from Iran, where 136 patients
with a platelet count of greater than 30x10[9]/L received eradication
therapy (amoxicillin 1g bd, clarithromycin 500 mg bd and omeprazole 20mg
bd for 2 weeks), and 48% achieved a platelet count of greater than
100x10[9]/L at 24 weeks, sustained at 48 weeks in 96%.[5] Therefore,
H.pylori testing and eradication therapy should be undertaken earlier in
the management of ITP to potentially avoid the short and long term side
effects of frequent courses of corticosteroids.
References
[1] Fuccio L, Laterza L, Zagari RM, Cennamo V, Grilli D, Bazzoli F.
Treatment of Helicobacter pylori infection. BMJ 2008;337:a1454
[2] Ye H, Liu H, Raderer M, Chott A, Ruskone-Fourmestraux A,
Wotherspoon A, Dyer MJS, Chuang SS, Dogan A, Isaacson PG, Du MQ. High
incidence of t(11;18)(q21;q21) in Helicobacter pylori-negative gastric
MALT-lymphoma. Blood 2003;101:2547–50.
[3] Raderer M, Streubel B, Wöhrer S, Häfner M, Chott A. Successful
antibiotic treatment of Helicobacter pylori negative gastric mucosa
associated lymphoid tissue lymphomas. Gut 2006;55:616-618.
[4] Suzuki T, Matsushima M, Masui A, Watanabe K, Takagi A, Ogawa Y,
Shirai T, Mine T. Effect of Helicobacter pylori eradication in patients
with chronic idiopathic thrombocytopenic purpura-a randomized controlled
trial. Am J Gastroenterol 2005;100(6):1265-70.
[5] Rostami N, Keshtkar-Jahromi M, Rahnavardi M, Keshtkar-Jahromi M,
Esfahani FS. Effect of eradication of Helicobacter pylori on platelet
recovery in patients with chronic idiopathic thrombocytopenic purpura: a
controlled trial. Am J Hematol 2008;83(5):376-81.
Competing interests:
None declared
Competing interests: No competing interests
Who and how to test for successful helicobacter eradication?
Dear Sirs,
The authors give an excellent account on the management of helicobacter
pylori infection. However there are a few points in their strategy for the
confirmation of eradication therapy success. Firstly, they do not suggest
who should have confirmatory testing for success of therapy. I agree and
so would most patients that the best tests are the non-invasive methods
including urea breath testing. It may be difficult for many health
economies to justify blanket testing all patients after therapy and it may
be more reasonable to test only those who, for instance, are still
symptomatic, those with a familial gastric cancer risk or those with a
history of recurrent peptic ulceration. Certainly in the UK, the national
guidelines for the management of dyspepsia in primary care do not advocate
universal post eradication testing (1).
Secondly, it is not recommended by the authors to use “rapid urease
tests” instead of histological confirmation of helicobacter infection when
an endoscopic biopsy is performed. It is not clear whether the urease
tests being referred to are the more established agar gel based ones such
as CLOtest, Pyloritek or Hpfast, which have been previously referred to as
“rapid urease tests” which when read at 4 hours post procedure give
sensitivities and specificities of around 90% and 99% respectively (2).
More recently other tests have been developed around a urea membrane
system which allows reading within one hour of biopsy (Pyloritec,
Helicocheck) which give sensitivities and specificities of 89-98% and 89-
93% respectively (3-4). Indeed there is evidence that urease testing
however rapid is more accurate than relying on histological analysis of
antral biopsies (5). I believe therefore, that urease tests should not be
discounted in the endoscopic assessment of helicobacter eradication
therapy.
1. Dyspepsia: managing dyspepsia in primary care. Clinical guideline
CG17 August 2004
National Institute for Clinical Excellence (NICE)
2. Prospective comparison of commercially available rapid urease
tests for the diagnosis of Helicobacter pylori. Laine L; Lewin D; Naritoku
W; Estrada R; Cohen H. Gastrointest Endosc 1996 Nov;44(5):523-6.
3. Evaluation of a new reagent strip rapid urease test for detection
of Helicobacter pylori infection. Yousfi MM; el-Zimaity HM; Genta RM;
Graham DY. Gastrointest Endosc 1996 Nov;44(5):519-22.
4. Prospective evaluation of a new urea-membrane test for the
detection of Helicobacter pylori in gastric antral tissue. Young EL;
Sharma TK; Cutler AF. Gastrointest Endosc 1996 Nov;44(5):527-31.
5. A prospective evaluation of new rapid urease tests before and
after eradication treatment of Helicobacter pylori, in comparison with
histology, culture and 13C-urea breath test. Nishikawa K; Sugiyama T; Kato
M; Ishizuka J; Kagaya H; Hokari K; Asaka M. Gastrointest Endosc 2000
Feb;51(2):164-8.
Competing interests:
None declared
Competing interests: No competing interests