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BMJ No 7126 Volume 316
Editorial Saturday 17 January 1998
The management of H pyloriinfection
Helicobacter pyloriis the single most important pathogen in peptic ulcer disease since its eradication leads to cure.(1) As a result, a National Institutes of Health consensus meeting in 1994 recommended giving anti-H pyloritreatment to all patients with active peptic ulcer disease or a history of it and proved infection.(2) In 1996 the consensus meeting of the European Helicobacter Study Group in 1996 made similar recommendations and added bleeding peptic ulcers and low grade MALT lymphoma to the list.(3) Eradication for other indications remains more controversial. What therefore is the current best evidence on managing H pyloriinfection, and which is the best treatment?
Though the need for eradication in peptic ulcer disease is agreed, there is also evidence for eradicating H pyloriin patients with advanced and progressively worsening forms of gastritis such as intestinal metaplasia, glandular atrophy, and erosive or hypertrophic forms of gastritis, and after resection for early gastric cancer.(3) A recent prospective study, however, showed that the degree of intestinal metaplasia and atrophy remained unchanged despite successful eradication.(4) This finding should temper the belief that curing every infected patient will stop progression of presumed precancerous lesions. Long term follow up studies are still needed to show the effect of successful eradication on development of premalignant mucosal abnormalities, and the development of gastric malignancies. In the meantime management of H pyloriinfection implies diagnosis, therapy and monitoring of the clinical course after eventual cure of the infection.
Inevitably many cases of H pyloriinfection will be managed in primary care. Here the European consensus report suggests that urea breath testing is a reliable diagnostic test.(3) ELISA (enzyme linked immunosorbent assay) serological testing may be appropriate, but only if the test is validated locally. The sensitivity of the urea breath test is 90-95%, whereas desktop serological tests have sensitivities ranging from 63-97%.
Patients aged under 45 without alarm symptoms may be managed entirely in primary care. Continuing symptoms after eradication suggest another disease (such as gastroesophageal reflux disease). These patients should therefore be referred to a specialist. H pyloristatus should be assessed by histological examination and culture or rapid urease testing of gastric mucosal biopsy specimens from both the antrum and corpus. If persistent infection is found the resistance pattern of the H pyloristrain should guide further treatment.(5) Confirmation of H pylorieradication is also indicated in patients with complicated peptic ulcer disease, gastric ulcer, or low grade MALT lymphoma, preferably by biopsy.(3)
Many regimens have been devised for eradicating H pylori,and much debate remains over the best treatment.(6,7) Bismuth triple therapy (colloidal bismuth subcitrate, tetracycline, and metronidazole) was the first regimen to show eradication rates above 80%.(6,7) Since then many studies have shown consistent eradication rates of 87-89% in populations with unknown prevalences of imidazole resistance.(6,7) In patients infected with metronidazole resistant strains, however, efficacy drops to about 48%.(6,7)
In 1992 Hoskin et al showed that adding an acid suppressive drug (omeprazole) to bismuth triple therapy (quadruple therapy) was highly effective, even in a population with an assumed high prevalence of metronidazole resistant H pylori.(8) Recently two randomised trials have compared bismuth triple or quadruple therapy with dual therapy with a proton pump inhibitor and an antibiotic (omeprazole and amoxycillin).(9,10) In both cases the patients studied had peptic ulcer and were taking maintenance or on demand H2 receptor antagonists. H pyloriinfection and its eradication were confirmed by culture, histopathology, and urease testing of multiple gastric biopsy specimens. All patients were thoroughly instructed and highly motivated to comply. In the trial by Thijs et al H pylorieradication rates by intention to treat analysis were 69.8% for dual and 94.6% for triple therapy (P=0.001).(9) In that by de Boer et al they were 55.6% for dual and 92.5% for quadruple therapy (P<0.001).(10) Although dual therapy was better tolerated, both studies showed the superiority of bismuth triple and quadruple therapy over omeprazole and amoxycillin. These findings confirm those from an amalgamation of a large number of studies of omeprazole and amoxycillin, which showed mean eradication rates of 54-62%,(6,7) indicating that dual therapy can no longer be recommended. Nevertheless the very good results using bismuth triple and quadruple therapy in the two recent trials(9,10) could probably not be obtained routinely in primary care. The fact that most patients were also receiving H2 receptor antagonists may help explain why the results of triple therapy were as good as those of quadruple therapy.
The latest development in treatment has been the use of proton pump inhibitor triple therapy (a proton pump inhibitor and two antibiotics, usually clarithromycin and amoxycillin or metronidazole), with success rates of around 90%.(5)(11) Compliance should be at least as good as with other regimens because of twice daily dosing and fewer side effects.(12) The impact on efficacy of resistance to antibiotics such as metronidazole and clarithromycin is uncertain.
The Maastricht consensus report recommended proton pump triple therapy on the grounds that it was simple, well tolerated, easy to comply with, and cost effective and achieved an efficacy of over 80% on a rigorous intention to treat analysis.
Since H pyloriinfection rarely recurs after successful eradication,(13) no ulcer relapse is to be expected. We therefore suggest discontinuing acid suppressive therapy after eradication in uncomplicated ulcer disease if the patient has become asymptomatic. If, however, treatment fails the susceptibility of the H pyloristrain should determine the regimen of choice for retreatment.(5)
E A J Rauws
Staff member
R W M van der Hulst
Staff member
Department of Gastroenterology,
Academic Medical Centre,
1105
AZ Amsterdam,
The Netherlands
References
1 Hopkins R J, Girardi L S, Turney E A. Relationship between
Helicobacter pylori eradication and reduced duodenal and gastric ulcer
recurrence: A review. Gastroenterology 1996;110:1244-52.
2 NIH Consensus Conference. Helicobacter pylori in peptic ulcer
disease. JAMA 1994;272:65-9.
3 The European Helicobacter Study Group. Current European
concepts in the management of Helicobacter pylori infection. The
Maastricht consensus report. Gut 1997;41:8-13.
4 Van der Hulst R W M, van der Ende A, Dekker F, ten Kate F J W,
Weel J F L, Keller J J, et al. Effect of Helicobacter pylori eradication
on gastritis in relation to cagA: a prospective one year follow up
study. Gastroenterology 1997;113:25-30.
5 Van der Hulst R W M, Weel J F L, van der Ende A, ten Kate F J W,
Dankert J, Tygat G N J. Therapeutic options after failed H pylori
eradication therapy. Am J Gastroenterol 1996;91:2333-7.
6 Van der Hulst R W M, Keller J J, Rauws E A J, Tytgat G N J. Treatment
of Helicobacter pylori infection: Review of the world literature.
Helicobacter 1996;1:6-19.
7 Penston J G. Review article: Helicobacter pylori
eradication-understandable caution but no excuse for inertia.
Aliment Pharmacol Ther 1994;8:369-89.
8 Hosking S W, Ling T K W, Yung MY, Cheng A, Chung S C, Leung J W, et
al. Randomised controlled trial of short term treatment to eradicate
Helicobacter pylori in patients with duodenal ulcer. BMJ
1992;305:502-4.
9 Thijs J C, van Zwet A A, Moolenaar W, Wolfhagen M J, ten Bokkel
Huinink J. Triple therapy versus amoxicillin plus omeprazole for
treatment of Helicobacter pylori infection: a multicenter, prospective,
randomised, controlled study of efficacy and side effects. Am J
Gastroenterol 1996;91:93-7.
10 De Boer W A, Driessen W M, Jansz A R, Tytgat G N J. Quadruple
therapy compared with dual therapy for eradication of Helicobacter
pylori in ulcer patients: results of randomised prospective single
center study. Eur J Gastroenterol Hepatol
1995;7:1189-94.
11 Bazzoli F, Zagari R M, Fossi S, Pozzato P, Alampi G, Roda A, et
al. Short term low dose triple therapy for the eradication of
Helicobacter pylori. Eur J Gastroenterol Hepatol
1994;6:773-7.
12 Axon A T R, Moayyedi P. Omeprazole in combination with
antibiotics. Scand J Gastroenterol 1996;31(suppl
215):82-9.
13 Van der Hulst R W M, Rauws E A J, Koycu B, Keller J J, ten
Kate F J W, Dankert J, et al. Helicobacter pylori reinfection is
virtually absent after successful eradication. J Infect
Dis 1997;176:196-200.
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