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Current views on Helicobacter pylori eradication therapy   Back Bookmark and Share

Author : Byrne MF, Murray FE

The spiral, urease producing organism, H. pylori, has been shown over the last decade to play a critical role in peptic ulcer disease. The management of peptic ulcers and dyspepsia has been changed with this discovery. This is a review of the role of H. pylori in dyspepsia in general and an update on the appropriate treatment and indications for H. pylori eradication. 

H. pylori and dyspepsia

The evidence linking H. pylori infection with duodenal ulceration is overwhelmingly convincing. Several studies1 have shown a high prevalence (up to 95%) of H. pylori infection in patients with duodenal ulceration, but the exact pathogenesis is still open to debate. Most importantly, many studies have demonstrated that eradication of gastroduodenal H. pylori infection prevents relapse of duodenal ulceration.2

The association of H. pylori with non-NSAID gastric ulceration is also very strong. H. pylori is present in about 80% of cases of gastric ulceration1 and eradication treatment reduces risk of relapse to about 10% per year compared to 50% in untreated patients. 

Several studies support an association between H. pylori infection and gastric carcinoma.3 Indeed, the WHO has classified H. pylori as a definite carcinogen. The link with gastric lymphoma or MALToma is stronger, and indeed there have been several reports of regression of low grade lymphoma following eradication of H. pylori infection.4

The role of H. pylori in NSAID related ulcers is highly contentious. Up to 25% of ulcer patients taking NSAIDs are H. pylori positive and the usefulness of H. pylori eradication in the NSAID group as a whole is not defined, although a recent small study suggests that H. pylori eradication may reduce the incidence of NSAID associated gastroduodenal ulcers.5

The relationship between H. pylori and non-ulcer dyspepsia (NUD) (defined as chronic or intermittent upper abdominal symptoms for which no organic cause can be found) is equivocal. Excess acid secretion or disordered motility may be responsible for the symptoms of NUD in some patients, but although H. pylori infection is more common in patients with NUD than in the control population, the association is far from clear. The results of clinical trials evaluating the role of H. pylori eradication in treatment of NUD are conflicting, although there may be a trend to long term benefit in a subgroup of NUD patients. 

Asymptomatic screening

There is debate as to whether screening and treatment of H. pylori infection in non-ulcer patients in prevention of gastric carcinoma is to be recommended. Less than 1% of the population will develop gastric cancer in a population in which roughly 40% of people are infected with H. pylori. The counsel of perfection is that cancer prevention trials are undertaken. 

Eradication therapy in selected patients in the community

The management of uncomplicated dyspepsia in patients under 45 years in general practice remains controversial, with competing regimens based on either empirical therapy with ulcer healing drugs, early endoscopy or a H. pylori eradication therapy. A recent study from London suggests that H. pylori positive patients under 45 years with uncomplicated dyspepsia and no alarm features or history of NSAID or aspirin use may be managed satisfactorily with H. pylori eradication therapy.6 Such a strategy has been reported as resulting in reduced need for endoscopy and subsequent ulcer healing drug prescribing. Results of long term studies in this area are not yet available. 

Indications for treatment

Two bodies, the Scottish Intercollegiate Guidelines Network (SIGN)7 and the European Helicobacter Pylori Study Group (EHPSG),8 have recently published guidelines concerning indications for treatment of H. pylori and have suggested acceptable regimens to be used (Table1). The EHPSG consensus is that all patients with a diagnosis of peptic ulcer (duodenal or gastric) past or present, bleeding duodenal ulcer, low grade MALT lymphoma, gastritis with severe macroscopic or microscopic abnormalities, and those following resection of early gastric carcinoma should receive H. pylori eradication therapy. The European guidelines also advise H. pylori eradication therapy in patients with H. pylori associated NUD after full investigation - based on potential long term benefits of H. pylori eradication (possible decreased risk of peptic ulcer disease and gastric carcinoma) and also on cost analyses modelling indicating the cost-effectiveness of H. pylori eradication in NUD. The actual role played by H. pylori in the presenting symptoms of an NUD patient remains unclear. 

Table 1. Recommendations for H.pylori eradication in different clinical conditions (after EHPSG 1997)
 

Disease
Recommendation (overall evaluation)
Scientific evidence
DU/GU (active or not)
1
A
MALToma
1
B
Gastritis with severe abnormalities
1
B
Post early gastric cancer resection
1
B
Functional dyspepsia
2
C
Family history of gastric cancer
2
C
GORD treated by long term -
2
B
NSAID therapy
2
C
Post surgery for PUD
2
B
Asymptomatic subjects
3
C
Extra alimentary tract disease
3
C
proton pump inhibitor
 
 
1. Strongly recommended
 A. Unequivocal
 
2. Advisable
B. Supportive
3. Uncertain
C. Equivocal

Eradication therapies

Several different H. pylori eradication regimens have been evaluated in recent years with variable success and level of patient tolerance/compliance. Eradication is defined as the presence of negative tests for H. pylori 4 weeks or longer after the end of therapy. The drug regimen should be easy to take, effective and well tolerated. Mono and dual therapies have been tried with variable and generally unsatisfactory rates of eradication and are generally no longer recommended. Triple therapies have been shown to be most effective. 

Classical H. pylori triple therapy, namely a two week course of colloidal bismuth subcitrate (CBS), metronidazole and amoxycillin or tetracycline, is the most studied regimen9 and gives eradication rates of up to 95%. However, adverse side effects are common, including nausea and metallic taste and thus there has been a considerable problem with compliance. 

More recent data support the use of a low dose, one-week triple thera

   
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