Editorials

# Who benefits from Helicobacter pylori eradication?

BMJ 2006; 332 (Published 26 January 2006) Cite this as: BMJ 2006;332:187
1. Brendan C Delaney, professor of primary care (b.c.delaney{at}bham.ac.uk)
1. University of Birmingham, Edgbaston, Birmingham B15 2TT

Mainly patients with endoscopically proved peptic ulcer or functional dyspepsia

Dyspepsia has most recently been defined as predominant epigastric pain present for at least four weeks, with or without heartburn.1 By implication gastro-oesophageal reflux disease (GORD) refers to predominant heartburn. These definitions work reasonably well when peptic ulcer has been excluded by endoscopy, but they fail to be sufficiently predictive in uninvestigated patients.2 Thus the guideline on dyspepsia produced by the National Institute for Health and Clinical Excellence (NICE) in 2004 recommended a common pathway for investigating and treating previously uninvestigated patients who had both heartburn and epigastric pain.3 Patients who have had endoscopy can be categorised according to the cause found—peptic ulcer, oesophagitis, or no obvious cause (functional dyspepsia or functional heartburn).

Eradication of Helicobacter pylori is most effective in preventing the recurrence of duodenal ulcer: the number needed to treat (NNT) for preventing one recurrence of ulceration at one year is 2.4 It now seems naive to have expected such effectiveness of eradication in other conditions related to dyspepsia, but undue optimism has led to several underpowered randomised controlled trials, particularly on functional dyspepsia, being conducted. After peptic ulcer and oesophagitis have been excluded by endoscopy, the NNT of eradication in functional dyspepsia is 15 (95% confidence interval 10 to 31).5 Nothing else is any more effective in this condition, so a reduction in the incidence of recurrent symptoms from 70% to 63% has been considered both as “insignificant’” from a clinical perspective and of great value.6

Because dyspepsia is a common recurrent and relapsing problem, small therapeutic benefits may often be cost effective as they reduce long term expense. It is important not to raise expectations of cure when treating functional dyspepsia. We also now know that eradicating H pylori does not increase the risk of GORD, as some early observational studies had suggested.7

For primary care the most important reasons for considering H pylori eradication are to manage uninvestigated dyspepsia in people aged under 55 and to provide long term benefit in asymptomatic patients detected through screening.8 A recent meta-analysis of individual patient data pooled the health economic information essential to deciding on a strategy for managing this high cost condition. H pylori eradication in the strategy known as test and treat is marginally less effective than management based on endoscopy but is still cost effective because the excess cost of endoscopy is not offset by sufficient benefit.9

In contrast the CADET-Hp study found that test and treat was more effective than placebo plus a proton pump inhibitor in preventing recurrence of dyspeptic symptoms in patients positive for H pylori who consulted Canadian general practitioners with dyspepsia (NNT 8 (95% confidence interval 50 to 4).2 The cost effectiveness of this strategy compared with that of empirical treatment with a proton pump inhibitor is the subject of the MRC-CUBE randomised trial (http://pcpoh.bham.ac.uk/primarycare/research/cube/index.htm), due to report in 2006, and an issue on which the 2004 NICE guideline was in equipoise.

If we should pursue H pylori eradication with enthusiasm in patients with peptic ulcer, with hope in those with functional dyspepsia, and as a means of avoiding costly investigations in uninvestigated dyspeptic patients, what place do screening and eradication have in asymptomatic patients in the community? In the absence of very large, long term trials to determine the impact of screening on the subsequent development of distal gastric adenocarcinoma, the outcomes of interest are dyspeptic symptoms and consultations for dyspepsia. In the Leeds HELP study, eradication of H pylori reduced the prevalence of dyspeptic symptoms two years after screening, with an NNT of 20 (10 to 100) compared with no screening, but did not find a significant difference in cost.10

In this issue (p 199), Lane and colleagues confirm this beneficial effect on symptoms in a comparatively affluent population in North Bristol, using an accurate H pylori test and an effective eradication regimen. In addition they show that consultations for dyspepsia were significantly decreased by screening, with an NNT of 30 to avoid one patient consulting.11 Notably, only 15% of those screened, aged 20-59, were positive for H pylori. At this low prevalence it is essential to use accurate tests—either the 13C urea breath test, which can be prescribed, or the stool antigen test—where they are available locally. Serology for H pylori is much less sensitive: half of all positive results on serology tests will be false positives.

The eradication regimen chosen by Lane and colleagues was quite expensive and was marketed by one of the study funders. Other regimens, such as those recommended by NICE, are similarly effective and cost less than a third of the £83.40 ($146; €) quoted in this study. It is difficult to estimate the cost effectiveness of screening in practice on the basis of this study, but it would probably be in the region of £1500-£2000 per successful treatment, based on a cost difference of £50 for testing and eradication and a response rate of 3% compared with no screening. In contrast, the CADET-Hp study found that a test and treat strategy reduced the cost per successful treatment by$C387 (£188; $333; €) (-$C1707 to \$C607).12

Lane and colleagues provide further evidence that eradicating H pylori is beneficial. But their study does not greatly change the evidence base of the 2004 NICE guideline which recommended H pylori eradication as first choice in endoscopically proved peptic ulcer and functional dyspepsia and as a treatment option in uninvestigated dyspepsia.

Research p 199

## Footnotes

• Competing interests Competing interests: BCD has received speaker's honorariums from AstraZeneca, Wyeth, Reckitt-Benkiser, and Takeda, and ad hoc payments for consultancy from AstraZeneca, Wyeth, and Merck.

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