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Unformatted text preview: Controversy The case for Helicobacter pylori eradication in India:
sensationalism, skepticism and scientific salesmanship
Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029 W ith tenacity and a prepared mind” the duo
“ challenged prevailing dogmas”, said a press
release from the Nobel Assembly at Karolinska Institute
in Stockholm, Sweden announcing that the 2005 Nobel
p rize in Physiology or Medicine had been awarded to
R obin Warren and Barry Marshall for their discovery
t hat a bacterium named H elicobacter pylori c auses
m ost peptic ulcers. 1,2 I t is somewhat discomforting
t hat this J ournal h as commissioned a debate on the
n eed for treating H . pylori i nfection at a time when
t riumph of the ulcer-bug theory formed ‘news of
t he week’ for many journals and even the lay press.
It thus appears unjust to wield, or at least an inopportune
t ime for wielding, a coroner ’s s calpel to exhume the
o dyssey. W hy are we still reluctant to embrace this
c oncept? Was it an unbridled sensationalism for over
a d ecade that has spurred a rebound vociferous
I n the year 2006, a debate on the proficiency of
H . p ylori e radication would be classified as an “unfair
d uel”. Not the David vs. Goliath kind where the
u nderdog wins but a duel where the result is not
m erely a writing on the wall but is deeply etched and
engraved. Nevertheless, it provides a good opportunity
t o place on record the evidence that has led to the
a cceptance of H . pylori e radication as treatment for
p eptic ulcer disease. In pursuit of this objective, this
a rticle will focus on four central concepts: i) Is there
i rrefutable evidence that H . pylori c auses peptic ulcer
a nd gastric cancer? ii) Does eradication of H . pylori
i nfection alter the natural history of these diseases?
i ii) Has the beneficial effect been exaggerated? and,
i v) What are the diseases in which benefit of H .
p ylori e radication remains unproven?
“ E vidence that H . pylori c auses
p eptic ulcer and gastric cancer P eptic ulcer
H. pylori infection has a strong association with chronic
a ctive gastritis and duodenal ulcer (DU). Ingestion
o f H . pylori h as been shown to produce acute antral
g astritis.3,4,5 H . pylori i nfection can be detected in
9 0% of patients with DU and 70% of those with
g astric ulcers. 6 A c ritique published in 1991 deter- mined that there was strong association between H .
p ylori a nd DU, but that evidence for biological gra dient and temporality and supportive experimental
e vidence was insufficient. 7 S ince then, plenty of new
e vidence has become available.
S ipponen e t al s howed that 11% of individuals
w ith H . pylori i nfection developed DU over a 10 year follow up, in contrast to fewer than 1% of non infected individuals.8 Cullen et al studied 407 subjects
a nd showed that DU developed in 15% of H . pyloriseropositive individuals as compared to 3% of
s eronegative individuals.9 I n a Scandinavian followup study over 10 years, 13% of patients with H .
p ylori g astritis developed peptic ulcer. 10
K och’s first postulate states that the organism
m ust always be found in the diseased animals and
n ot in healthy ones. Only 15%-20% of H . pylori
i nfected persons develop peptic ulcer disease. How ever, the role of indigenous biota in human diseases
i s often complex. For instance, C andida albicans
a nd B acteroides s pp. are normally present in humans
a nd yet can at times cause life-threatening disease. 11
K och’s second postulate states that ‘the organ ism must be isolated from diseased animals and grown
i n pure culture away from the animal’. This postu late was fulfilled by Marshall who succeeded in
c ulturing H . pylori, after 34 failures. 12
K och’s third postulate requires that ‘the organism
i solated in pure culture must initiate and reproduce
t he disease when re-inoculated into susceptible
a nimals,’ and the fourth states that ‘the organism
s hould be re-isolated from the experimentally infected
a nimals’. Ohkusa e t al e xperimentally inoculated
M ongolian gerbils with three strains of H . pylori; a ll
three strains induced gastric ulceration and two strains,
in addition, induced gastric metaplasia in the duodenum
a nd duodenitis.13 Two gerbils developed superficial
d uodenal ulceration; this occurred on a background
o f gastric metaplasia, a s in humans.
T he next step is a biologically and conceptually
s atisfying pathogenetic mechanism for production of
D U by H . pylori i nfection; this, however, is yet to
b e attained. It has been proposed that the outcome
o f H . pylori i nfection may depend on the gastric Copyright © 2006 by Indian Society of Gastroenterology 20 Indian Journal of Gastroenterology 2006 Vol 25 January - February Ahuja H. pylori eradication in India: the case for a cid secretory ability of the infected individual; thus,
p ersons with naturally high acid secretion are prone
t o develop antrum-predominant gastritis and are at
i ncreased risk of DU, whereas those with low acid
s ecretion develop colonization of gastric body with
H . p ylori, l eading to multifocal atrophic gastritis and
p ossibly gastric cancer. 14 G astric cancer
G astric carcinogenesis is a multi-step process, the
k ey steps being chronic superficial gastritis, chronic
a trophic gastritis leading to achlorhydria, intestinal
metaplasia and dysplasia. An epidemiological association
b etween H . pylori a nd gastric cancer was initially
e stablished in three prospective case-control studies
a nd a cohort study, followed by a meta-analysis. 1518 Watanabe e t al s tudied gastric histology in Mon golian gerbils that had been experimentally infected
w ith H . pylori .20 A t 26 weeks post-inoculation, all
i nfected animals showed severe active chronic gas tritis, ulcers and intestinal metaplasia. By 62 weeks,
a denocarcinoma had developed in the pyloric region
o f 37% of the infected gerbils, fulfilling Koch’s pos tulates for the relationship of H . pylori a nd gastric
c ancer. Further, in a follow up of 1526 Japanese
p atients, gastric cancer developed in 3% of H . py lori-infected patients but in none of the uninfected
H . p ylori i s also an important factor for gastric
M ALT l ymphomas, although it is difficult to prove
a n association because of a low incidence of this
A few befuddling questions remain. Why do only
1 % and 15% of infected people develop gastric can cer and peptic ulcer, respectively? W hy is H . pylori
i nfection most prevalent among the elderly whereas
p eptic ulcer is a disease of the young? Why has the
i ncidence of DU gone up in the last century, w hile
t he prevalence of H . pylori w as on the downslide?
A ttempts have been made to answer these ques tions. H . pylori h as been a part of the gastric biota
s ince antiquity. T he ultra-low biological activity of
i ts lipopolysaccharide and expression of Lewis anti gens facilitate its persistence in human hosts. Changes
i n modern life are however gradually eliminating it
f rom being only a commensal. Peptic ulcer disease
w as uncommon when H . pylori c olonization was
n early universal. The incidence of peptic ulcer started
r ising, as in the last century, as the colonization rate
o f H . pylori b egan to decline. This increase in inci dence of peptic ulcer could be related to changes in gastric microecology related to improved nutrition,
c hanges in nature of H . pylori c olonization, and in
i mmune response to the organism related to older
a ge at the time of acquisition of infection. Also,
d ifferences in response of individual hosts, in strains
o f H . pylori, in environmental factors, and in age of
t he patient at the time of acquisition of the infection
m ay determine the variable response to infection.
E radication of H . pylori i nfection and
n atural history of peptic ulcer disease
T he most persuasive argument in support of a patho genic role for H . pylori i n peptic ulcer disease re lates to a dramatic decrease of spontaneous relapse
r ate of DU after successful eradication of infection
w ith this organism. 23 H opkins e t al r eviewed 14
s tudies on DU and eight on gastric ulcer and found
t hat ulcer recurrence was significantly less common
a mong patients with cured H . pylori i nfection (6%
v s. 67% for DU, 4% vs. 59% for gastric ulcers). 24
T his reduction is sustained for at least seven years
f ollowing H . pylori e radication. Eradication of H .
p ylori a lso reduces the rate of recurrence of ulcer
h emorrhage more effectively than does long-term
m aintenance treatment with either ranitidine or
o meprazole. 25
T he overwhelming reduction in ulcer recurrence
r ates after H . pylori e radication has made this a
s tandard treatment for patients with peptic ulcer
d isease. However, epidemiological differences may
r estrict a simple extrapolation of these data from
d eveloped countries to developing countries. Due to
a h igh frequency of infection, overcrowding and
l ower standards of hygiene, the H . pylori r e-infec tion rate after treatment may be higher in the latter
countries. This, combined with lower eradication rates,
m ay partially nullify the long-term benefits of H .
p ylori e radication on the natural history of peptic
u lcer disease in developing countries. 26
H owever, does this mean that we stop attempts
a t eradicating H . pylori i nfection, or should we de vise more effective strategies to treat this infection
a nd prevent re-infection? For instance, if drug resis tance were frequent among patients with tuberculo sis and treatment delivered poor results, would we
l ook for alternative etiologies for such patients or
r ather develop more effective treatment strategies?
H as the beneficial effect
b een exaggerated?
T he arguments that H . pylori m ay not be the primary
c ause of DU are as follows: prevalence of H . pylori negative DU is increasing; early cases of DU are Indian Journal of Gastroenterology 2006 Vol 25 January - February 21 Ahuja
m ore often H . pylori n egative than chronic cases of
D U; colonization of gastric metaplasia in duodenum
w ith H . pylori i s infrequent; and rate of recurrence
of H. pylori infection is higher in developing countries.
O ne needs to recognize that H . pylori, t hough
a n important cause of peptic ulcer, is not the only
c ause. Laine’s meta-analysis showed that the 20%
r ecurrence rate of peptic ulcers after successful
e radication of H . pylori i nfection may be because
n on-H. pylori , non-NSAID induced ulcers are more
c ommon than previously believed.27 T hus, ulcers in
p atients with H . pylori i nfection are not always H .
p ylori i nduced, since we are currently unable to
d ifferentiate virulent and c ommensal H . pylori .
P resence of H . pylori a nywhere does not imply
t hat it should be treated instantaneously. Blaser has
s trongly argued that H . pylori f orms normal biota of
t he human stomach and infection with it should be
treated selectively. He believes that H. pylori infection
i s b eneficial a nd p rotects h umans a gainst
g astroesophageal reflux disease and cardia cancer.28
H ence, elimination of H . pylori i nfection is needed
o nly in defined settings, as discussed above. The
i ssue would become clearer when we have accurate
a nd convenient tests to discriminate between virulent
a nd non-virulent H . pylori, s omewhat akin to the
s ituation with E ntamoeba dispar a nd E . histolytica .29
D isease associations where benefit of
H . p ylori e radication is still unproven G astr oesophageal reflux disease (GERD)
T he issues that require examination are: (i) Is there
a n epidemiological association between GERD and
H . p ylori? ( ii) How does eradication of H . pylori
i nfection affect GERD in patients with DU or reflux
e sophagitis, and in the healthy population? and, (iii)
D oes one need to eradicate H . pylori i nfection if
l ong-term proton pump inhibitor (PPI) therapy is
p lanned for GERD treatment?
I t is not merely the presence of H . pylori b ut
i ts density and distribution in the stomach that
determine gastric acid secretion, and hence the impact
o f this infection on GERD. Thus, antral colonization
w ith H . pylori i s associated with increased gastric
a cid secretion and increased propensity to develop
G ERD. On the other hand, colonization of the gastric
c orpus is associated with reduced gastric secretion
a nd may protect against GERD. Thus, both a direct
a nd an inverse association between H . pylori a nd
G ERD are theoretically plausible. Raghunath e t al
e xamined 20 studies and obtained a pooled odds ratio
o f 0.60 (95% CI 0.47-0.78) for the presence of H . H. pylori eradication in India: the case for
p ylori i n patients with GERD, 30 s uggesting that H .
p ylori i nfection protected against GERD.
E vidence for this protective role is three-fold:
t heoretical plausibility, negative epidemiological
a ssociation, and cagA strains having an even greater
n egative association. To p rove the protective role of
H . p ylori f or GERD, w e need to (i) determine the
e ffect of H . pylori e radication on GERD outcomes
( reflux esophagitis and heartburn) in patients with
DU, and (ii) determine the effect of H. pylori infection
o n reflux esophagitis. Data are available from 13
trials in patients with DU, which estimated proportion
o f patients newly developing reflux esophagitis
f ollowing H . pylori eradication therapy. 31 T hese s how
t hat H . pylori e radication status had no effect on
r ates of persistence of pre-existing GERD or fresh
d evelopment of GERD. This is not surprising because
p atients with DU have high acid secretion, which
d ecreases following H . pylori e radication. It follows
t hat the likelihood of their developing GERD should
d ecrease, not increase, after H . pylori e radication.
T he next issue is the effect of H . pylori i nfection
and eradication in patients with GERD. A prospective,
d ouble-blind study failed to find any difference in
t he severity of GERD between patients with and
w ithout H . pylori i nfection . 32 T hree randomized
c ontrolled trials have looked at the effect of H . pylori
e radication in patients with reflux esophagitis and
f ound no worsening of symptoms or of acid
reflux. 33,34,35 Moayyaedi et al concluded that treatment
of H . pylori g astritis in healthy population did not
l ead to symptoms of GERD over a 2-year period. 36
H ence, negative epidemiological association between
H . p ylori i nfection and GERD is not supported by
clinical data, and H. pylori eradication does not induce
o r worsen GERD, either in patients with DU or pre existing GERD or in the healthy population.
T he last issue is whether patients receiving longterm PPI therapy for the treatment of GERD require
p rior H . pylori e radication. Administration of PPI to
H . p ylori -infected subjects induces a corpuspredominant gastritis, a recognized risk factor for
g astric cancer; yet we do not know whether such
c orpus atrophic gastritis progresses with time. Also,
e radication of H . pylori i nfection may reduce the
efficacy of PPI in controlling GERD since PPI therapy
h as been shown to be much more potent in H . pyloripositive subjects. However, since eradication of H .
p ylori i nfection does not worsen GERD in patients
w ith both DU and GERD, it i s unlikely to harm
p atients with GERD alone. Thus, treatment may be
u sed in patients who are candidates for long-term 22 Indian Journal of Gastroenterology 2006 Vol 25 January - February Ahuja H. pylori eradication in India: the case for P PI therapy, though there is no conclusive proof yet
i n favor of this approach. F unctional dyspepsia
S everal clinical trials have studied the role of H .
p ylori i nfection in non-ulcer dyspepsia (NUD).
H owever, six well-designed large studies reached
c ontradictory conclusions, 37-42 s uggesting that
f unctional dyspepsia was a heterogeneous disorder.
S imilarly, five meta-analyses on the subject have
s hown conflicting results. 43-48 I nterestingly, Laine
e t al 44 c oncluded that symptom relief after H . pylori
eradication therapy was no better than with a placebo,
w hereas a Cochrane systematic review showed a
9 % (95% CI 4-14) relative risk reduction after H .
p ylori e radication.49
This lack of consistency suggests that eradication
of H . pylori i nfection may be useful in a small subset
o f patients with NUD. However, this argument may
n ot be applicable globally. In particular, there are no
I ndian data to either support or refute a role for
e radication of H . pylori i nfection in patients with
N UD. Thus, it appears impractical to provide H .
p ylori e radication therapy to a huge number of H .
p ylori -infected persons with NUD till further data
o n the predictors of response to such treatment are
I t is evident that H . pylori i nfection has a causal link
w ith peptic ulcer and gastric cancer and that its
s uccessful eradication dramatically reduces the risk
o f ulcer recurrence. Therefore, an attempt at eradi cation of this infection should be the first-line ap proach for all patients with H. pylori-associated peptic
u lcer disease.
I t is quite apparent that much of the skepticism
a bout the bug-ulcer relationship was spurred by the
i nitial sensationalism, the exaggerated attention that
H . p ylori r eceived soon after its discovery, and the
u nsubstantiated early revelry for claims of curing
t he disease. It is however now time to shed this
s kepticism and move on to embrace the scientific
evidence supporting the relationship. Perhaps, George
B ernard Shaw’s words sum it all well: “All great
t ruths begin as blasphemies.”
1. Enserink M. Physiology or medicine. Triumph of the ulcerbug theory. Science 2005;310:34-5.
2. Kuehn BM. Nobels honor research on ulcer microbe, “green”
drug production method. JAMA 2005;294:2289-90.
3. Marshall BJ, Armstrong JA, McGechie DB, Glancy RJ. Attempt to fulfill Koch’s postulates for pyloric
Campylobacter. Med J Aust 1985;142:436-9.
4. Morris A, Nicholson G. Ingestion of Campylobacter pyloridis
c auses gastritis and raised fasting gastric pH. A m J
5. Graham Y, Alpert LC, Smith JL, Yoshimura HH. Iatrogenic
Campylobacter pylori infection as a cause of epidemic achlorhydria. Am J Gastroenterol 1988;83:974-80.
6. Malaty HM, Nyren O. Epidemiology of Helicobacter pylori
infection. Helicobacter 2003;8(Suppl 1):8-12.
7. Rabeneck L, Ransohoff DF. Is Helicobacter pylori a cause
of duodenal ulcer? A methodologic critique of current evidence. Am J Med 1991;91:566-72.
8. Sipponen P, Varis K, Fraki O, Korri UM, Seppala K,
Siurala M. Cumulative 10-year risk of symptomatic duodenal and gastric ulcer in patients with or without chronic
gastritis. A clinical follow-up study of 454 outpatients.
Scand J Gastroenterol 1990;25:966-73.
9. Cullen DJE, Collins BJ, Christiansen KJ, Epis J, Warren
JR, Cullen KJ. Long term risk of peptic ulcer disease in
people with Helicobacter pylori infection: a community
based study (Abstract). Gut 1993;34(Suppl 1):F284
10. Niemela S, Karttunen T, Kerola T. Helicobacter pyloriassociated gastritis. Evolution of histologic changes over 10
years. Scand J Gastroenterol 1995;30:542-9.
11. Blaser MJ. Helicobacters are indigenous to the human stomach: duodenal ulceration is due to changes in gastric
microecology in the modern era. Gut 1998;43:721-7.
12. Fukuda Y, Shimoyama T, Shimoyama T, Marshall BJ. Ksai,
Kobayashi and Koch’s postulates in the history of Helicobacter
pylori. In: Marshall BJ, Ed. Helicobacter Pioneers. Blackwell
Science, Victoria. 2002: p. 15-24.
13. Ohkusa T, Okayasu I, Miwa H, Ohtaka K, Endo S, Sato N.
Helicobacter pylori infection induces duodenitis and superficial duodenal ulcer in Mongolian gerbils. Gut 2003;52:797803.
14. Graham DY. Helicobacter pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: a model. Gastroenterology 1997;113:1983-91.
15. Parsonnet J, Friedman GD, Vandersteen DP, Chang Y,
Vogelman JH, Orentreich N, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N E ngl J Med
16. Nomura A, Stemmermann GN, Chyou P-H, Kato I, PerezPerez GI, Blaser MJ. Helicobacter pylori infection and
gastric carcinoma among Japanese Americans in Hawaii. N
Engl J Med 1991;325:1132-6.
17. Forman D, Newell DG, Fullerton F, Yarnell JW, Stacey
AR, Wald N, et al. Association between infection with
Helicobacter pylori and risk of gastric cancer: evidence from
a prospective investigation. Br Med J 1991;302:1302-5.
18. The Eurogast Study Group. An international association
between Helicobacter pylori infection and gastric cancer.
19. Huang J-Q, Sridhar S, Chen Y, Hunt RH. Meta-analysis of
the relationship between Helicobacter pylori seropositivity
and gastric cancer. Gastroenterology 1998;114:1169-79.
20. Watanabe T, Tada M, Nagai H, Sasaki S, Nakao M.
H elicobacter pylori i nfection induces gastric cancer in
Mongolian gerbils. Gastroenterology 1998;115:642-8. Indian Journal of Gastroenterology 2006 Vol 25 January - February 23 Ahuja
21. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi
S, Yamakido M, et al. Helicobacter pylori infection and the
development of gastric cancer. N Engl J Med 2001;345:7849.
22. Andersen LP, Nielsen H. Peptic ulcer: an infectious disease? Ann Med 1993;25:563-8.
23. Penston JG. Helicobacter pylori eradication: understandable
caution but no excuse for inertia. Aliment Pharmacol Therap
24. Hopkins RJ, Girardi LS, Turney EA. Relationship between
Helicobacter pylori eradication and reduced duodenal and
g astric ulcer recurrence: a review. G astroenterology
25. Gisbert JP, Khorrami S, Carballo F, Calvet X, Gene E,
Dominguez-Munoz JE. H. pylori eradication therapy vs.
antisecretory non-eradication therapy (with or without longterm maintenance antisecretory therapy) for the prevention
of recurrent bleeding from peptic ulcer. Cochrane Database
Syst Rev 2004;(2):CD004062.
26. Ahuja V, Sharma MP. High recurrence rate of Helicobacter
pylori infection in developing countries. Gastroenterology
27. Laine L, Hopkins RJ, Girardi LS. Has the impact of
Helicobacter pylori therapy on ulcer recurrence in the United
States been overstated? A meta-analysis of rigorously designed trials. Am J Gastroenterol 1998;93:1409-15.
28. Blaser MJ. An endangered species in the stomach. Sci Am
29. Ahuja V. Gazing through the crystal ball: Helicobacter pylori.
Trop Gastroenterol 2004;25:57-9.
30. Raghunath A, Hungin AP, Wooff D, Childs S. Prevalence
of Helicobacter pylori in patients with gastro-oesophageal
reflux disease: systematic review. Br Med J 2003;326:737.
31. Raghunath AS, Hungin AP, Wooff D, Childs S. Systematic
review: the effect of Helicobacter pylori and its eradication
on gastro-oesophageal reflux disease in patients with duodenal ulcers or reflux oesophagitis. Aliment Pharmacol Ther
32. Fallone CA, Barkun AN, Mayrand S, Wakil G, Friedman G,
Szilagyi A, et al. There is no difference in the disease
severity of gastro-oesophageal reflux disease between patients infected and not infected with H. pylori . Aliment
Pharmacol Ther 2004;20:761-8.
33. Moayyedi P, Bardhan C, Young L, Dixon MF, Brown L,
Axon AT. Helicobacter pylori eradication does not exacerbate reflux symptoms in gastroesophageal reflux disease.
34. Schwizer W, Thumshirn M, Dent J, Guldenschuh I, Menne
D, Cathomas G, et al. Helicobacter pylori and symptomatic
relapse of gastro-oesophageal reflux disease: a randomised
controlled trial. Lancet 2001;357:1738-42.
35. Tefera S, Hatlebakk JG, Berstad AE, Berstad A. Eradication
of Helicobacter pylori does not increase acid reflux in patients with mild to moderate reflux oesophagitis. Scand J
36. Moayyedi P, Feltbower R, Brown J, Mason S, Mason J,
Nathan J, et al. Effect of population screening and treatment for Helicobacter pylori on dyspepsia and quality of H. pylori eradication in India: the case for
life in the community: a randomised controlled trial. Leeds
HELP Study Group. Lancet 2000;355:1665-9.
37. McQuaid KR. Eradication of Helicobacter pylori in nonulcer
d yspepsia: how much analysis do we need? J C lin
38. Talley NJ, Vakil N, Ballard ED II, Fennerty MB. Absence
of benefit of eradicating Helicobacter pylori in patients with
nonulcer dyspepsia. N Engl J Med 1999;341:1106-11.
39. Talley NJ, Janssens J, Lauritsen K, Racz I, Bolling-Sternevald
E. Eradication of Helicobacter pylori in functional dyspepsia: randomised double blind placebo controlled trial with
1 2 months’ follow up. The Optimal Regimen Cures
Helicobacter Induced Dyspepsia (ORCHID) Study Group.
Br Med J 1999;318:833-7.
40. Blum AL, Talley NJ, O’Morain C, van Zanten SV, Labenz
J, Stolte M, et al. Lack of effect of treating Helicobacter
p ylori i nfection in patients with nonulcer dyspepsia.
Omeprazole plus Clarithromycin and Amoxicillin Effect One
Year after Treatment (OCAY) Study Group. N Engl J Med
41. McColl K, Murray L, El-Omar E, Dickson A, El-Nujumi A,
W irz A, e t al. S ymptomatic benefit from eradicating
H elicobacter pylori i nfection in patients with nonulcer
dyspepsia. N Engl J Med 1998;339:1869-74.
42. Bruley Des Varannes S, Flejou JF, Colin R, Zaim M, Meunier
A, Bidaut-Mazel C. There are some benefits from eradicating Helicobacter pylori in patients with non-ulcer dyspepsia. Aliment Pharmacol Ther 2001;15:1177-85.
43. Danesh J, Lawrence M, Murphy M, Roberts S, Collins R.
S ystematic review of the epidemiological evidence on
Helicobacter pylori infection and nonulcer or uninvestigated
dyspepsia. Arch Intern Med 2000;160:1192-8.
44. Laine L, Schoenfeld P, Fennerty MB. Therapy for Helicobacter
pylori in patients with nonulcer dyspepsia. A meta-analysis
of randomized, controlled trials. Ann Intern Med 2001;134:3619.
45. Laheij RJ, Jansen JB, van de Lisdonk EH, Severens JL,
Verbeek AL. Review article: symptom improvement through
eradication of Helicobacter pylori in patients with non-ulcer
dyspepsia. Aliment Pharmacol Ther 1996;10:843-50.
46. Laheij RJ, van Rossum LG, Verbeek AL, Jansen JB.
Helicobacter pylori infection treatment of nonulcer dyspepsia: an analysis of meta-analyses. J C lin Gastroenterol
47. Moayyedi P, Soo S, Deeks J, Forman D, Mason J, Innes
M, et al. Systematic review and economic evaluation of
H elicobacter pylori e radication treatment for non-ulcer
d yspepsia. Dyspepsia Review Group. B r Med J
48. Jaakkimainen RL, Boyle E, Tudiver F. Is Helicobacter pylori associated with non-ulcer dyspepsia and will eradication improve symptoms? A meta-analysis. B r Med J
49. Moayyedi P, Soo S, Deeks J, Delaney B, Harris A, Innes
M, et al. Eradication of Helicobacter pylori for non-ulcer
dyspepsia. Cochrane Database Syst Rev 2005;(1):CD002096.
Correspondence to: Dr Ahuja, Associate Professor. Fax: (11)
2658 8663. E-mail: [email protected] 24 Indian Journal of Gastroenterology 2006 Vol 25 January - February ...
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