Helicobacter pylori eradication in patients with non-ulcer dyspepsia

Epidemiological and pathophysiological studies, as well as clinical trials, attempting to identify a relationship between Helicobacter pylori infection and non-ulcer dyspepsia (NUD), or a subset of NUD, have produced inconsistent and confusing results. While it is possible that H. pylori eradication may be beneficial for symptom relief in a small proportion of patients, routine H. pylori testing and treatment in documented NUD is not currently widely accepted. Despite the lack of convincing evidence, the European Helicobacter pylori Study Group, an Asian Pacific Consensus Meeting, the American Digestive Health Foundation and the American Gastroenterology Association have all recommended considering H. pylori eradication in patients with NUD on a patient-by-patient basis. Recently, large prospective, randomised, double-blind, controlled clinical trials applying highly effective antimicrobial therapy have been conducted with 12 months follow-up. Although these well-designed studies have reached differing conclusions, the results have been largely negative. H. pylori eradication therapy in NUD will fail to relieve symptoms in most patients in the long term.     

Helicobacter pylori clearance in the treatment of non-ulcer dyspepsia

One hundred and thirty north Nigerian patients with non-ulcer dyspepsia were treated with tripotassium dicitrato bismuthate and amoxycillin, or antacid. Symptoms resolved in 28 (33%) of bismuth and amoxycillin recipients completing the trial compared with 1 (4%) of the antacid recipients. Symptomatic improvement did not relate to clearance of Helicobacter pylori.     

There are some benefits for eradicating Helicobacter pylori in patients with non-ulcer dyspepsia

Background

: The relationship between Helicobacter pylori infection and non‐ulcer dyspepsia is not established.

Aim

: To determine whether eradication of H. pylori might be of benefit in non‐ulcer dyspepsia patients.

Methods

: We randomly assigned 129 H. pylori infected patients with severe epigastric pain, without gastro‐oesophageal reflux symptoms, to receive twice daily treatment with 300 mg of ranitidine, 1000 mg of amoxicillin, and 500 mg of clarithromycin for 7 days and 124 such patients to receive identical‐appearing placebos.

Results

: Treatment was successful (decrease of symptoms at 12 months) in 62% of patients in the active‐treatment group and in 60% of the placebo group (N.S.). At 12 months, the rate of eradication of H. pylori was 69% in the active‐treatment group and 18% in the placebo group (P < 0.001). Complete relief of symptoms occurred significantly more frequently in patients on the active treatment (43%) than in placebo‐treated patients (31%, P=0.048). Within the active‐treatment group, therapeutic success was significantly more frequent in the non‐infected patients (84% vs. 64%, P=0.04).

Conclusions

: Although eradicating H. pylori is not likely to relieve symptoms in the majority of patients with non‐ulcer dyspepsia, a small proportion of H. pylori‐infected patients may benefit from eradication treatment.

     

The role of Helicobacter pylori infection in non-ulcer dyspepsia

It is currently unclear whether Helicobacter pylori ( H. pylori ) infection plays a role in patients who fulfil the criteria for non-ulcer dyspepsia. This paper reviews evidence for H. pylori -induced changes in gastric emptying, gastrointestinal motility, gastric acid secretion, and gastric perception in patients with non-ulcer dyspepsia. Problems in study design and execution of non-ulcer dyspepsia treatment trials are discussed. The results of non-ulcer dyspepsia treatment trials which have been performed in H. pylori -positive patients are reviewed. To date none of them has convincingly shown that cure of the H. pylori infection leads to a sustained improvement in symptoms.     

Review article: symptom improvement through eradication of Helicobacter pylori in patients with non-ulcer dyspepsia

The aim of this article is to determine, by reviewing the literature, whether treatment of Helicobacter pylori infection in patients with non-ulcer dyspepsia affects symptoms. Ten publications were identified through a computerized and manual literature search, and the percentage of patients with symptom improvement after successful or unsuccessful eradication therapy for H. pylori infection was calculated. In the 10 studies, symptom improvement after treatment was found in 73% of the patients that became H. pylori -negative and 45% of the patients that remained H. pylori -positive. Symptom improvement was modified by various clinical features and methodological aspects. If eradication of H. pylori failed, symptoms only improved over a short period. Symptom improvement was more pronounced in dyspeptic patients in whom H. pylori was eradicated than in those in whom H. pylori infection persisted.     

Standard treatment for Helicobacter pylori infection is suboptimal in non-ulcer dyspepsia compared with duodenal ulcer in Chinese

BACKGROUND: Recent studies suggest that the Helicobacter pylori eradication rate in patients with non-ulcer dyspepsia is lower when compared to patients with peptic ulcer diseases. AIM: The aim of this study was to study the efficacy of triple therapy for H. pylori infection in patients with duodenal ulcer vs. patients with non-ulcer dyspepsia. METHODS: A total of 582 Chinese patients with proven H. pylori infection were recruited to receive: omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg all given twice daily for 7 days (OCA regime). Endoscopy with rapid urease test, histology and culture were performed before treatment. Post-treatment H. pylori status was determined by (13)C-urea breath test. Metronidazole, clarithromycin and amoxicillin resistance was defined as minimum inhibitory concentration (MIC) of >8 microg/mL, >1 microg/mL and >1 microg/mL, respectively. RESULTS: A significantly higher (intention-to-treat/per-protocol) eradication rate was found in patients with duodenal ulcer than those with non-ulcer dyspepsia (91/94% vs. 84/88% respectively, P = 0.011 and P = 0.016). Clarithromycin resistance rate was higher in patients with non-ulcer dyspepsia than those with duodenal ulcer (14% vs. 6%, P = 0.015). Clarithromycin resistance (40% vs. 5%, P < 0.001, OR 12, 95% CI: 5.7-24.3) and the diagnosis of non-ulcer dyspepsia (91% vs. 84%, P = 0.011, OR 2.0, 95% CI: 1.2-3.3) significantly affected the success of H. pylori eradication. CONCLUSION: Clarithromycin resistance accounts for the significantly lower and suboptimal H. pylori eradication rate of OCA regimen in Chinese patients with non-ulcer dyspepsia compared to those with duodenal ulcer.     

A randomized comparison of four omeprazole-based triple therapy regimens for the eradication of Helicobacter pylori in patients with non-ulcer dyspepsia

BACKGROUND: Helicobacter pylori eradication rates in France after therapy with omeprazole, amoxicillin and clarithromycin are among the lowest in Europe. This study evaluated alternative eradication regimens. METHODS: Helicobacter pylori-positive patients (n=323) with non-ulcer dyspepsia were randomized to receive one of four 1-week regimens consisting of omeprazole, 20 mg b.d., plus either: amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d. (OAC); bacampicillin, 1200 mg b.d., and clarithromycin, 500 mg b.d. (OBC); clarithromycin, 250 mg b.d., and metronidazole, 500 mg b.d. (OCM); or amoxicillin, 1000 mg b.d, and azithromycin, 500 mg on day 1 and 250 mg on days 2-5 (OAAz). Eradication was confirmed by urea breath test 4-6 weeks after treatment. Susceptibility testing was performed in the case of eradication failure. RESULTS: The eradication rate with OAAz was 38% (95% CI, 25.6-49.4) on intention-to-treat analysis, which was lower (P < 0.05) than with the other regimens [OCM, 61% (50.0-72.8); OBC, 65% (54.0-76.5); OAC, 72% (61.8-81.8)]. Of the strains isolated following treatment failure with OAC, OBC or OCM, 84% were clarithromycin resistant. CONCLUSIONS: OAC remains the reference treatment for H. pylori eradication in France, although bacampicillin offers a useful alternative to amoxicillin. Susceptibility testing should be considered after unsuccessful eradication therapy.     

Patterns of gastritis and the effect of eradicating Helicobacter pylori on gastro-oesophageal reflux disease in Western patients with non-ulcer dyspepsia

Summary

Background

The effect of Helicobacter pylori eradication on the development of gastro‐oesophageal reflux disease is controversial.

Aim

To determine the incidence of symptoms of reflux disease and of erosive oesophagitis, and the relationship to changes in histological gastritis, in patients with non‐ulcer dyspepsia over 12 months.

Methods

Six hundred and ninety‐three patients in two similar randomized placebo controlled trials of H. pylori eradication in non‐ulcer dyspepsia were studied. Symptoms were assessed using the validated Gastrointestinal Symptom Rating Scale during a 1‐week run‐in period, at 6 months and 12 months. Endoscopy was performed at baseline to exclude patients with pathology and at 3 months and 12 months to determine if oesophagitis was present. Gastric biopsies were scored using the modified Sydney Classification.

Results

Patients without predominant heartburn, oesophagitis or ulcers at endoscopy were randomized to active (n = 297, omeprazole, amoxicillin and clarithromycin) treatment or to placebo/omeprazole (n = 306) for 1 week. The eradication rate was 82% in the active treatment group. Antrum‐predominant gastritis (55%) was more frequently found than corpus‐predominant gastritis (6%). In patients with antrum‐predominant gastritis, heartburn and regurgitation scores improved significantly 12 months after eradication. Erosive oesophagitis developed in 15/232 patients in the eradication group (7%) compared with 2/227 (2%) in the control group, but there was no significant difference when adjusted for oesophagitis present at baseline.

Conclusions

Antrum‐predominant gastritis is the most common pattern of gastritis seen in non‐ulcer dyspepsia in Western populations. Heartburn and regurgitation improve after eradication therapy or placebo in patients with non‐ulcer dyspepsia; the development of oesophagitis is uncommon.

     

The effect of Helicobacter pylori eradication therapy on gastric antral myoelectrical activity and gastric emptying in patients with non-ulcer dyspepsia

BACKGROUND: Dysmotility of the gastroduodenal region and delayed gastric emptying have been considered to play roles in non-ulcer dyspepsia (NUD). Helicobacter pylori-induced inflammation of the gastric mucosa may affect gastric motility. AIM: To evaluate the effects of H. pylori eradication therapy on gastrointestinal motility and symptoms in NUD patients. METHODS: : Forty-six NUD patients were examined for gastric emptying, antral myoelectrical activity, H. pylori infection, and symptom scores. In H. pylori-positive NUD patients, gastric emptying, antral myoelectrical activity, and symptom scores were also analysed 2 months after cure of H. pylori infection. RESULTS: Sixty-seven per cent of NUD patients were H. pylori-positive. Both abnormal gastric emptying and antral myoelectrical activity were observed in NUD patients. H. pylori-positive NUD patients were divided into three groups according to their gastric emptying: the delayed group, the normal group, and the rapid group. In the delayed and rapid gastric emptying groups, the emptying and symptom scores were improved significantly by eradication. There was no improvement in symptom scores in the normal gastric emptying NUD group by the eradication therapy. CONCLUSIONS: Disturbed gastric emptying and antral myoelectrical activity play roles in NUD. H. pylori-induced disturbed gastric emptying may cause some NUD symptoms. Gastric emptying and symptom scores are improved by H. pylori eradication therapy in NUD patients with disturbed gastric emptying; H. pylori eradication therapy is effective in H. pylori-positive NUD patients with disturbed gastric emptying.     

Randomized controlled comparison of nitroimidazoles for the eradication of Helicobacter pylori and relief of ulcer-associated and non-ulcer dyspepsia

BACKGROUND: A combination of omeprazole, clarithromycin and either metronidazole or tinidazole is commonly used for Helicobacter pylori eradication. Metronidazole is considerably cheaper than tinidazole but the two have not previously been compared in a randomized trial. METHODS: One hundred and twenty dyspeptic H. pylori-positive patients with endoscopically defined peptic ulcer [DU (n = 65), GU (n = 12)] or non-ulcer dyspepsia (NUD, n = 43) were randomized to receive a 1-week course of twice daily omeprazole 20 mg, clarithromycin 250 mg and either metronidazole 400 mg (OCM) or tinidazole 500 mg (OCT) in a double-blind fashion. Eradication of H. pylori, safety and side-effects of treatment, dyspeptic symptom score and consumption of antisecretory drugs were assessed at 6 weeks and 1 year after treatment. RESULTS: H. pylori eradication was successfully achieved in 57/60 (95%, ITT analysis) of patients receiving OCT and 58/60 (97%, ITT analysis) receiving OCM. Both regimens had similar side-effect profiles, which accounted for only one patient withdrawal. All patients remained uninfected (as assessed by 14C-urea breath test) at 1-year follow-up, but major symptom improvements and decreased antisecretory drug use were only seen in patients with DU (P<0.0001). CONCLUSIONS: Treatment with OCM is as effective as the more expensive OCT at eradicating H. pylori. H. pylori eradication results in long-term relief of dyspeptic symptoms and reduced antisecretory consumption only in patients with DU, and not in those with NUD.     

西沙必利治疗非溃疡性消化不良

目的：观察西沙必利治疗非溃疡性消化不良的疗效。方法：非溃疡性消化不良病人８０例，随机单盲分为治疗组４０例，男性１７例，女性２３例，年龄４７．０±ｓ２．０ａ，给予西沙必利５～１０ｍｇ，ｔｉｄ，餐前３０ｍｉｎｐｏ。另４０例为对照组，男性１９例，女性２１例，年龄４１±５ａ给安慰剂谷维素２０ｍｇ加复合维生素Ｂ２片，ｔｉｄ，亦餐前３０ｍｉｎ加，２组皆服药４ｗｋ为一个疗程。结果：总有效率治疗组是８８％，对照组是２５％（Ｐ＜０．０１）。结论：西沙必利是治疗非溃疡性消化不良较满意的药物。     

Cure of Helicobacter pylori infection does not improve symptoms in non-ulcer dyspepsia patients-a double-blind placebo-controlled study

BACKGROUND: It remains controversial whether the cure of H. pylori infection improves NUD symptoms. AIM: To conduct a double-blind placebo-controlled single centre study with concealed allocation to investigate this question. PATIENTS AND METHODS: Ninety NUD patients with H. pylori infection were randomly assigned to either the treatment group (50 patients) or placebo group (40 patients). The treatment group received omeprazole, amoxycillin, clarithromycin and the placebo group received omeprazole and placebos for 7 days. Symptoms were assessed every week for up to 12 weeks after completion of medication by a symptom questionnaire. Alteration of histological parameters for gastritis was also evaluated. RESULTS: The infection was cured in 41 out of 48 patients in the treatment group and none in the placebo group. There was no significant difference in the mean symptom scores at any assessment point up to 12 weeks between the treatment and placebo groups. Regarding histological parameters, activity and inflammation, not atrophy or intestinal metaplasia, were significantly improved in the treatment group. CONCLUSION: Although histological parameters were significantly improved in the treatment group, there was no significant improvement in symptoms of NUD in the treatment group compared to placebo.     

Helicobacter pylori and nonulcer dyspepsia

Although up to 50% of patients diagnosed with nonulcer dyspepsia (NUD) have Helicobacter pylori infection and underlying chronic gastritis, it remains controversial whether any causal relationship exists. The results of worldwide epidemiological studies have been unconvincing. No clear-cut link has been documented between H. pylori and any specific symptom profile or pathophysiological mechanism in NUD. In the randomized controlled trials, methodological weaknesses may explain in part the conflicting results, but even in the well-conducted trials controversy persists. Although meta-analyses have attempted to resolve the issue, inherent methodological difficulties with meta-analysis remain a problem. Moreover, even the methodologically sound meta-analyses have reported conflicting results. In addition, predictors of treatment response remain obscure, and there continue to be theoretical concerns about the treatment of H. pylori infection in all patients with NUD. Hence, the management of these patients is challenging, but eradication of H. pylori infection may be beneficial in a small subgroup of cases with NUD that cannot be identified before treatment.     

Helicobacter pylori and uninvestigated dyspepsia

Although dyspepsia is a very common disorder, the incidence of Helicobacter pylori infection in Western medical clinics is very low (20–35%). In cases where H. pylori is detected, elimination of it may be cost-effective in the long term, but even eradication is not a guarantee for long-term relief. Further studies to determine the connection between H. pylori and dyspepsia need to be completed before H. pylori eradication becomes the treatment of choice for that minority of patients. The majority of dyspeptic patients are not as simple to diagnose, and may need several empirical trials of therapy, or more specific diagnostic assessment.     

Clinical and pathological implications of IgG antibody responses to Helicobacter pylori and its virulence factors in non-ulcer dyspepsia

AIM: To determine whether pre-treatment antibody response to Helicobacter pylori virulence factors predicts eradication success and symptom relief 12 months after triple therapy in non-ulcer dyspepsia. METHODS: H. pylori-positive patients with non-ulcer dyspepsia received 1-week omeprazole-based triple therapy, or omeprazole plus placebos. Symptoms were assessed using a validated Likert scale. Gastric biopsies taken before and 12 months after treatment were used for histological examination. Pre-treatment blood samples were used for the detection of anti-H. pylori immunoglobulin G (IgG) antibodies, and specific IgG antibodies to 19.5-, 26.5-, 30-, 35-, 89- (VacA) and 116-kDa (CagA) antigens of H. pylori. RESULTS: IgG antibodies to the six antigens were detected in 62%, 96%, 88%, 47%, 54% and 78% of patients, respectively. The presence of antibody to 19.5-, 26.5- or 30-kDa antigen was associated with an increased anti-H. pylori IgG absorbance index. IgG absorbance indices were greater in those with H. pylori eradication (vs. persistent infection). The prevalence of antibodies to the six antigens was not significantly different between those with symptom relief vs. those without. The 19.5-kDa antigen (P = 0.018) and VacA (P = 0.001) were independent risk factors for body gastritis. CONCLUSIONS: An increased pre-treatment anti-H. pylori IgG absorbance index may be a useful predictor of the success of eradication therapy. Although the 19.5-kDa antigen and VacA were associated with body gastritis, none of the six antigens tested predicted symptom relief after triple therapy.     

Disturbed bowel habits in patients with non-ulcer dyspepsia

BACKGROUND; Emerging medications for non-ulcer-dyspepsia, such as the serotonin-receptor modulators, also affect bowel habits by altering colonic transit. If drugs that alter colonic function were to prove useful in non-ulcer dyspepsia, knowledge of baseline bowel habit disturbances would be potentially critical. AIM: To estimate the rate of non-ulcer dyspepsia patients with clinically relevant constipation or diarrhoea potentially precluding use of motility agents. METHODS: Consecutive patients with non-ulcer dyspepsia (n = 79), gastro-oesophageal reflux disease (n = 135) and organic upper gastrointestinal disease (upper gastrointestinal disease; n = 36) completed a validated symptom questionnaire evaluating predominant bowel habits in the last year. RESULTS: Prevalence of constipation was higher in non-ulcer dyspepsia (34%) than in gastro-oesophageal reflux disease (P = 0.01) and organic upper gastrointestinal disease (P = 0.01), prevalence of alternating diarrhoea/constipation (24%) and diarrhoea (22%) was similar, while prevalence of normal bowel habits was significantly less in non-ulcer dyspepsia (20%; P = 0.01 vs. gastro-oesophageal reflux disease and P < 0.01 vs. organic upper gastrointestinal disease). Constipation was particularly frequent in ulcer-like and dysmotility-like non-ulcer dyspepsia, while prevalence of diarrhoea was lowest in dysmotility-like non-ulcer dyspepsia. A normal bowel habit was equally uncommon in male (21%) and female non-ulcer dyspepsia patients (20%). CONCLUSIONS: Only one of five non-ulcer dyspepsia patients had normal bowel habits based on clinical symptoms; constipation is particularly prevalent. Patients with functional dyspepsia who are prescribed motility altering drugs should be evaluated by taking a thorough bowel habit history.     

Double vs. single dose of pantoprazole in combination with clarithromycin and amoxycillin for 7 days, in eradication of Helicobacter pylori in patients with non-ulcer dyspepsia

BACKGROUND: The necessity of increasing intragastric pH during eradication treatment in Helicobacter pylori infected patients is well established. However, the optimal dose of the proton pump inhibitors used in eradication regimen is still a subject of debate. AIMS: To compare the efficacy and tolerability of a double vs. a single daily dose of pantoprazole in a 7-day triple therapy in eradicating H. pylori. METHODS: In this regional, multicentre, comparative, randomized and double-blind study, H. pylori-positive patients with non-ulcer dyspepsia were treated for 7 days with clarithromycin 500 mg b.d. and amoxycillin 1000 mg b.d. and either a double (2 x 40 mg, Group 2PCA) or a single (40 mg, Group 1PCA) daily dose of pantoprazole. H. pylori infection was assessed at entry and at the end (day 38) of the study by histology and culture, or in some cases by 13C-urea breath test. RESULTS: From 203 patients recruited, 192 patients (96 in Group 2PCA and 96 in Group 1PCA) formed the intention-to-treat population. Twenty-six of them judged as major protocol violators were excluded from the per protocol analysis. H. pylori eradication rate was 75% in Group 2PCA and 56% in Group 1PCA in intention-to-treat analysis, and 80% in Group 2PCA and 59% in Group 1PCA in per protocol analysis (P < 0.05). The primary resistance to clarithromycin was 10.5%. The eradication rates for the clarithromycin susceptible strains were 86% for Group 2PCA and 71% for Group 1PCA in per protocol analysis (P < 0.05). Both regimens led to similar improvement of clinical symptoms and were equally well tolerated. CONCLUSION: A double (2 x 40 mg) daily dose of pantoprazole in a 7-day triple therapy is more effective than a single (40 mg) dose of this drug in eradication of H. pylori.