Dr Mark Cottrill explains how the revised guidelines on H. pylori will ensure that dyspeptic patients receive the best available management based on current evidence
New information and knowledge about Helicobacter pylori has emerged at an amazing pace over the last decade. As evidence-based guidelines are only valid at a certain point in time, it is appropriate that revisions should be made in the light of new research. The Primary Care Society for Gastroenterology (PCSG) has thus updated the guidelines for the management of H. pylori infection.
In the developed world, and probably globally, H. pylori infection is disappearing rapidly. Its disappearance is independent of eradication of the bacterium.
It is estimated that a child born in the 1990s will never be exposed to the infection. Consequently, the incidence of H. pylori-associated peptic ulcer has decreased remarkably, while the incidence of non-drug-induced, non-H. pylori ulcers has increased.
The guidelines for H. pylori management that emerged from the National Institutes of Health in the US in 1996 were followed by the European Guidelines (Maastricht) the following year. The latter, based more on consensus than hard evidence, supported a 'test and treat' strategy in primary care, and recommended eradication of the bacterium to many more patient groups.
The concept of 'test and treat' was attractive to primary care physicians. A patient suspected of having peptic ulcer disease could be tested for H. pylori in the surgery and, if positive, could be offered eradication therapy. If successful, this would cure the patient's ulcer disease and possibly reduce his or her risk of developing gastric cancer.
In theory this management strategy would reduce the referral rate for endoscopy. However, it only works when the local incidence of peptic ulcer disease is high.
In reality, the vast majority of dyspeptic paients who test positive for H. pylori do not have ulcer disease and do not respond well to eradication therapy. Such patients may also develop reflux symptoms post eradication. The net result is potentially an increase in endoscopy referrals – hence the need for updated guidelines.
Another issue that needed addressing was the availability and accuracy of non-invasive testing. In the recent past, serology testing was not widely available and breath testing was only available in certain centres. Now serology is widely available (but not always validated) and breath tests are available on an FP10 prescription. The PCSG needed to address the question of the choice of test.
Finally, the PCSG has examined the wide range of treatment regimens used for H. pylori eradication. Historically there has been considerable variation in the antibiotics employed, duration of therapy and timing of doses. Uniformity of treatment strategies that are evidence based is clearly desirable.
Wide media coverage of the discovery of H. pylori and the multitude of national and local guidelines have added to the confusion surrounding the management of dyspepsia. In the absence of reliable near-patient tests, and sometimes prompted by demands from patients, GPs have treated H. pylori infection empirically, while supporters of a 'test and treat' strategy have been disappointed by the results.
The old PCSG guidelines advocated near-patient testing but, if this proved positive, recommendedáreferral for endoscopy. This was in conflict with many local guidelines that supported a 'test and treat' strategy. The revised guidelines give an option of 'test and treat' or 'test and endoscope' (see Figure 1, below). This remains an area of debate and even recent studies have produced conflicting results.
|Figure 1: Extract from the PCSG's ‘Decision Points in the Management of H. pylori Infection in Primary Care’*|
|* The full guideline is contained in the European Journal of General Practice 1999; 5: 98-104. The project group was led by Dr Greg Rubin, UK, Dr Villy Meineche-Schmick, Denmark, and Dr Niek de Wit, Netherlands, for the European Society for Primary Care Gastroenterology|
The new guidelines, however, do support a strategy of testing only patients with chronic symptoms. This is a logical progression since most H. pylori-positive dyspeptic patients will not benefit symptomatically from eradication treatment.
There is total agreement that all patients with proven peptic ulcer disease who are on maintenance therapy or present with a relapse should be offered eradication therapy. The evidence for this is undisputed.
The conflict arises in patients who have H. pylori, non-ulcer dyspepsia (i.e. are H. pylori positive but have had a normal gastroscopy). Recent well-conducted multicentre studies have shown that successful eradication in this group of patients is no better at controlling symptoms than non-eradication.
The debate centres on the supposition that eradication may, however, reduce the chance of developing an ulcer in the future, reduce the risk of developing gastric cancer, and even reduce the incidence of H. pylori infection in the community.
Balanced against this is evidence that eradication may lead to an increase in reflux symptoms (and complications) and that proton pump inhibitor (PPI) drugs seem to work better in the presence of the bacterium.
Finally, recent studies suggest that the strains of the bacterium in non-ulcer dyspepsia may be more resistant to eradication therapy. It is understandable therefore that many specialists and GPs are losing interest in the 'test and treat' strategy. At endoscopy, the trend is not to test for the bacterium at all when the examination is otherwise normal.
The revised guidelines address the issue of which test to use (Figure 2, below). Serology is supported if the test is validated, while urea breath testing is recommended where available. The problem with serology is the accuracy of the test, but now that breath testing is effectively available to all GPs this should be the non-invasive test of choice.
|Figure 2: Extract from the PCSG's ‘Decision Points in the Management of H. pylori Infection in Primary Care’|
The guidelines confirm that breath testing should be used after eradication where patients remain symptomatic. The evidence for this is undisputed.
Finally, the guidelines recommend first-line eradication therapy comprising a PPI in 'standard' dose twice daily with amoxycillin 1g and clarithromycin 500mg twice daily for one week.
Evidence from clinical trials has shown this regimen to be the most effective on an 'intention to treat' basis. Logically, but perhaps confusingly, the guidelines support the substitution of metronidazole for amoxycillin where metronidazole resistance is known to be low. In reality, few primary care physicians are aware of local resistance rates for metronidazole.
Correctly the guidelines do not support a second-line regimen since patients who remain positive for the infection require endoscopy, biopsy and culture (ideally).
Current evidence for second-line treatment favours a metronidazole regimen such as quadruple therapy with bismuth, PPI and tetracycline. If this is the case then it is recommended that a patient is not exposed to metronidazole in first-line therapy.
The revised guidelines have simplified the management of H. pylori-related disease in primary care (Table 1). By identifying patient groups who may benefit from treatment and recommending who to treat or investigate, the primary care physician is better equipped to manage his or her dyspeptic patients.
There remain some unanswered questions, especially in the management of H. pylori-positive non-ulcer dyspepsia, and further studies may help to provide answers. By standardising first-line eradication therapy, the guidelines should ensure that GPs are less confused about the wide range of regimens used in the past.
|Table 1: Summary of the revised PCSG guidelines|
|Patients over 45 or with 'alarm' symptoms should be referred for endoscopy|
|Patients under 45 with dyspepsia should not be tested at first presentation|
|Patients under 45 with relapsing dyspepsia who test positive should be offered either gastroscopy or eradication treatment ('test and treat' or 'test and investigate')|
|Patients with non-ulcer dyspepsia (previous normal gastroscopy) should not be tested routinely|
|Patients with a past history of a duodenal ulcer should be treated without prior testing|
|Patients with a past history of gastric ulcer should be tested before treatment|
|Patients with recurrent dyspepsia after eradication therapy should be breath tested|
|Breath testing is the most reliable non-invasive test|
Recommended first-line therapy regimen is:
All given twice daily for one week
|Consider substituting metronidazole for amoxycillin where resistance is known to be low|
Logically, the provision of simple, evidence-based guidelines containing clear information for GPs should improve patient care.
The primary care physician will be able to advise when a non-invasive test is appropriate and necessary. Such testing should be restricted to patients in a younger age group without 'alarm symptoms' who have continuing symptoms. The value lies in the negative test where referral for endoscopy becomes unnecessary.
Patients who test positive should be offered gastroscopy (test and endoscope). If treatment is offered without gastroscopy (test and treat) patients should be advised that eradication might not improve their symptoms.
All patients with proven ulcer disease, whether on maintenance therapy or suffering a relapse of symptoms, should be offered therapy. First-line therapy should be standardised, while second-line therapy should be at the recommendation of the specialist after endoscopy, biopsy and culture.
By following these guidelines, GPs can be assured that their patients are receiving the best available management based on current evidence.
|The main value of near-patient testing in a young age group is in the negative test when endoscopy is then probably inappropriate.|
|All patients known to have ulcer disease who are either on maintenance therapy or suffering a recurrence of symptoms should be treated (testing known gastric ulcer patients).|
The value of treating patients with a normal endoscopy who are H. pylori positive is uncertain:
If you don't want to treat H.pylori (in non-ulcer dyspepsia, reflux) – don't test.
- GPs can obtain a free copy of the revised and updated version of the PCSG's Decision Points in the Management of Helicobacter pylori in Primary Care from Laura Tipple, c/o Shire Hall Communications, 3 Olaf Street, London, W11 4BE (tel 020 7229 9922). The full guideline is contained in the European Journal of General Practice 1999; 5: 98-104.