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Non-ulcer dyspepsia (NUD) is a term used when patients have symptoms thought to be arising from the upper gastrointestinal tract but investigations, including endoscopy, show no clear underlying cause. It is a very common condition and one for which there is no particularly effective treatment.
The aetiology of NUD is largely unknown and presumed to be heterogeneous. The prevalence of H pylori infection is slightly higher in NUD patients than in asymptomatic controls,1 2 raising the possibility of the infection being the cause of symptoms in a subgroup of such patients.
Several well designed studies have now examined the effect ofH pylorieradication therapy versus placebo on symptom resolution inH pylori positive patients with NUD. Some of these studies have shown a clear statistically significant benefit of active treatment3-6while others have shown no significant difference.7-10Symptomatic benefit has been most apparent in the studies conducted in single centres or within a single country and least apparent in multicentre multinational studies. Symptomatic response is a difficult outcome to assess and reliable measurement is likely to be a particular problem when recruiting patients of different languages and cultural backgrounds. Consequently, the multicentre multinational studies may have lacked the sensitivity required to detect a beneficial response.
A meta-analysis of all valid randomised studies examining the effect ofH pylori treatment in NUD has recently been published.11 This indicates a 9% benefit of active treatment over placebo (95% confidence interval 4–14%) (p=0.0002). This magnitude of benefit is such that most of the individual studies will have had insufficient power to detect it.
A key clinical question is whether this relatively small therapeutic benefit justifies prescribing H pylori eradication therapy. In addressing this, it is useful to compare the symptomatic benefit achieved withH pylori eradication therapy with that of other medical treatments for NUD. The only other treatment shown to be clearly effective over placebo is acid inhibition with proton pump inhibitors. In 1998, Talley et al, in a study involving 1262 NUD patients, found that omeprazole 20 mg/day had 10% superiority over placebo with respect to symptomatic response.12 The benefit was similar inH pylori positive and negative subjects. In a recent paper by Blum et al involving 792 NUD patients, omeprazole 20 mg/day produced 17% benefit over placebo in H pylori positive patients but no significant benefit in H pylori negative patients.13 The magnitude of benefit achieved byH pylori eradication therapy in NUD is therefore not dissimilar to that achieved with the only other medical treatment for the condition.
One major advantage of H pylori eradication therapy is that the symptomatic benefit achieved is sustained following a single one week course of treatment. This contrasts with the benefit with proton pump inhibitor therapy which depends on maintaining long term therapy. This makes H pylorieradication a cost effective treatment for NUD, as concluded by the most recent systematic review and economic evaluation.11
In summary, current evidence indicates thatH pylorieradication therapy for NUD is of similar clinical efficacy to other available treatment and is cost effective.
There are several additional reasons for supporting eradication ofH pylori in patients with NUD. The first is that a significant proportion of such patients go on to develop actual peptic ulcer disease which is prevented by eradicating the infection. Between 4% and 21% of NUD patients have an ulcer detected within 12 months.7 9 10 14 15 The second reason is that the infection has been proved to be an important aetiological factor for gastric cancer and lymphoma.16 Eradicating the infection is likely to reduce the risk of this cancer. The third reason is concern about adverse interactions between the infection and subsequent proton pump inhibitor therapy. A substantial proportion of NUD patients are likely to receive proton pump inhibitors which results in accelerated development of moderate and severe atrophic gastritis in the presence but not the absence of H pyloriinfection.17 18 It is also much simpler to eradicateH pylori prior to commencing proton pump inhibitor therapy as the latter makes determination ofH pylori status very difficult.
Reluctance to eradicate H pylori in NUD patients has arisen from the study by Labenz et al, reporting an increased incidence of oesophagitis in duodenal ulcer patients following eradication therapy.19 However, subsequent studies do not support this.20 21 In addition, the Labenz study refers to duodenal ulcer and not NUD patients. Concern has also been expressed that eradicating the infection might increase the incidence of gastro-oesophageal junction cancer. However, this is based entirely on epidemiological association without evidence of causality.
In conclusion, eradicating H pyloriinfection has similar clinical efficacy to any other available medical treatment for NUD and is cost effective. It has the additional benefits of reducing the risk of developing actual ulcer disease and non-cardia gastric cancer, and removing concerns about adverse interactions between infection and subsequent proton pump inhibitor therapy. Taking all these benefits together makes eradicatingH pylori infection worthwhile in patients with NUD.
Reasons for eradicating H pylori in NUD
Meta-analysis confirms symptomatic benefit from H pylori treatment
Magnitude of benefit equivalent to any other effective treatment for NUD
H pylori treatment for NUD shown to be cost effective
Eradicating H pylori removes increased risk of ulcer disease and risk factor of gastric cancer
Prevents progression to atrophic gastritis with subsequent proton pump inhibitor treatment
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