clinical aspects of Helicobacter pylori eradication therapy in peptic ulcer disease

Background and aims : Although the role of H. pylori in peptic ulcer disease is no longer in dispute, certain aspects of eradication therapy in this condition have yet to be settled. Uncertainties still surround the relationship between Helicobacter pylori status and ulcer healing, the efficacy of eradication therapy in alleviating acute symptoms and healing ulcers, and the prognosis after eradication with respect to recurrence of symptoms, ulcers and complications. The present literature review, encompassing studies published up to October 1995, specifically addresses these issues.
Results : Pooled data show that eradication therapy heals 90% of duodenal ulcers and 85% of gastric ulcers, while individual studies repeatedly confirm that it is more effective at healing ulcers than conventional treatment with anti-secretory drugs. Recent reports indicate that triple therapy regimens for 1 week, provided they include an anti-secretory drug, are sufficient to achieve high rates of healing and rapid symptom relief. A detailed analysis of the data, particularly those from studies reporting healing rates in relation to H. pylori status after eradication therapy, provides strong evidence that eradication of H. pylori produces ulcer healing. Follow-up studies show that ulcer recurrence and complications are rare after eradication treatment in patients with either gastric or duodenal ulcer disease. However, while ulcer symptoms are infrequent during follow-up, a proportion of patients appear to develop gastrooesophageal reflux after eradication.
Conclusions : H. pylori eradication is highly effective in promoting ulcer healing and preventing subsequent ulcer recurrence. These beneficial effects of eradication therapy are observed in patients with either gastric or duodenal ulcers which are associated with H. pylori infection.     

Antral gastrin cell hyperfunction and Helicobacter pylori infection

Background : Antral gastrin cell hyperfunction (AGCH), is a rare cause of duodenal ulcer associated with non-tumour hypergastrinaemia and acid hypersecretion.
Aim : To investigate the role of Helicobacter pylori in AGCH.
Patients : Twelve AGCH patients and eight H. pylori -positive non-hypergastrinaemic duodenal ulcer patients were compared.
Methods : Basal and peak acid outputs, gastrin-stimulation (meal and bombesin) tests, and immunohistochemistry for antral G and D cells were performed. One year after H. pylori eradication, six AGCH patients were again investigated with the same tests.
Results : Significantly more basal, and stimulated gastrin and acid secretion, were found in AGCH compared to the H. pylori -positive duodenal ulcer patients ( P <0.01). G cell counts were significantly higher in AGCH than in duodenal ulcer patients (118.8, range 58–192.4, vs. 86.1, range 49–184; P <0.05), and the resulting G/D cell ratio was also higher in AGCH patients (4.2, range 2.6–5.6, vs. 3.3, range 1.9–4.3; P <0.05). H. pylori was present in the gastric mucosa of all 12 AGCH patients. Cure of infection in six AGCH individuals resulted in marked a decrease of gastrin levels associated with a significant (23.7%; P <0.05) decrease of G cell count and an increase (12%; P <0.05) of D cell count.
Conclusions : The results indicate that AGCH may result from H. pylori overstimulation of gastrin cell function in patients with some presently undefined, familial predisposition and that an imbalance of the G/D cell ratio may have a role in the genesis of hypergastrinaemia.     

Effects of lansoprazole plus amoxycillin on the cure of Helicobacter pylori infection in Japanese peptic ulcer patients

Aim : The effect of lansoprazole plus amoxycillin on curing Helicobacter pylori infection and peptic ulcer recurrence was evaluated.
Method : The study group was composed of 68 patients with gastric ulcers and 51 with duodenal ulcers, all were H. pylori -positive. The participants were assigned at random to the lansoprazole alone group (lansoprazole 30 mg o.m. for 6 or 8 weeks) or the lansoprazole plus amoxycillin group (lansoprazole alone regimen plus amoxycillin at 500 mg q.d.s. concomitantly for the first 2 weeks). Healed patients were not given maintenance treatment with acid secretion inhibitors. The cure rate for H. pylori infection and the ulcer recurrence rate after 1 year were investigated.
Result : The cure rate for H. pylori infection was 4.2% in patients receiving lansoprazole alone and 38.5% in patients receiving lansoprazole plus amoxycillin ( P < 0.01) for gastric ulcers, and 0% in patients receiving lansoprazole alone and 61.9% in patients receiving lansoprazole plus amoxycillin ( P <0.001) for duodenal ulcers. The recurrence rate was 42.3% in patients receiving lansoprazole alone and 28.6% in patients receiving lansoprazole plus amoxycillin for gastric ulcers, and 66.7% for patients receiving lansoprazole alone and 11.1% for patients receiving lansoprazole plus amoxycillin ( P <0.001) for duodenal ulcers. None of the patients with gastric or duodenal ulcers cured of H. pylori infection had a recurrence.
Conclusion : Concomitant use of lansoprazole and amoxycillin increased the curative effects on H. pylori infection. However, the cure rates with this regimen remained inadequate.     

Recurrent symptoms and gastro-oesophageal reflux disease in patients with duodenal ulcer treated for Helicobacter pylori infection

BACKGROUND: Eradication of Helicobacter pylori has been shown to prevent relapse of endoscopically detected duodenal ulcers. There is controversy regarding symptom improvement after therapy. Some studies have suggested that a substantial number of patients remain symptomatic after eradication therapy. Other studies suggest that gastro-oesophageal reflux disease (GERD) may develop as a result of H. pylori eradication. AIM: To determine the relationship between symptoms and H. pylori eradication and to determine whether H. pylori eradication results in symptoms or endoscopic findings of GERD. METHODS: Two hundred and forty-two patients with endoscopically documented duodenal ulcer disease and evidence of H. pylori infection by rapid urease testing and histology were studied in four randomized, placebo-controlled, double-blind trials of H. pylori eradication therapy. All patients underwent symptom assessment and endoscopy with biopsy before therapy and 1 and 6 months after completing therapy. The rapid urease test and histology were used to determine H. pylori status. Interviewers were blinded to H. pylori status after eradication and were unaware of the endoscopic findings (interviews were performed prior to repeat endoscopy). RESULTS: The presence of epigastric pain was significantly associated with persistent H. pylori infection 1 month after therapy (odds ratio 2.3, 95% CI: 1.02-5.2; P=0.041), as was nausea (OR 7.1, 95% CI: 0.93-55.6; P=0.029). The presence of epigastric pain was significantly associated with ulcer relapse at 6 months (OR 7.5, 95% CI: 3.6-15.7; P < 0.001) as was nausea (OR 5.1, 95% CI: 1.7-16.0; P=0.002). Heartburn was not associated with eradication of H. pylori or ulcer relapse. New onset reflux symptoms were reported by 17% (17 of 101 patients) at 6 months and were not significantly different in patients with (15%) and without (22%) persistent H. pylori infection (P=0.47). Erosive oesophagitis was present at endoscopy in one of the 17 cases that developed new heartburn. CONCLUSIONS: One month after completion of therapy, the presence of epigastric pain or nausea is associated with persistent infection and these symptoms at 6 months are suggestive of duodenal ulcer relapse. The incidence of GERD is not increased in patients who have eradication of H. pylori.     

Triple therapy for Helicobacter pylori eradication is more effective than long-term maintenance antisecretory treatment in the prevention of recurrence of duodenal ulcer: a prospective long-term follow-up study

BACKGROUND: The effectiveness of Helicobacter pylori eradication treatment and long term acid suppression maintenance in the natural course of duodenal ulcer has not been directly compared. AIM: To compare in a prospective randomized study the effectiveness of H. pylori eradication on the prevention of recurrence of duodenal ulcer with long-term maintenance acid suppression therapy. METHODS: One hundred and fourteen duodenal ulcer patients were randomized to the treatment over a 12-month period. Fifty-seven of them received triple therapy consisting of 1 g sucralfate q.d.s. for 28 days, 300 mg metronidazole q.d.s. for 14 days and 250 mg clarithromycin q.d.s. for 14 days. Another 57 received 20 mg omeprazole q.d.s. for 12 months. An upper endoscopy was performed before treatment, at 6 weeks, and 2, 6 and 12 months after the first endoscopy. Side-effects were self-recorded and clinical follow-ups were arranged for up to 4.25 years. RESULTS: The ulcer healing rate was 90.2% (95% confidence interval (95% CI): 79-97%) in the omeprazole group at 6 weeks as compared to 83.3% (95% CI: 70-93%) in the triple therapy group (P = 0.38). There was a higher success rate of pain control in the omeprazole group. Side-effects were more frequently reported and compliance was poorer in the triple therapy group during the first 4 weeks. During follow-up, more relapses were seen in the omeprazole group (9.8%, 95% CI: 3-21%) than the triple therapy group (4.2%, 95% CI: 1-13%) at 1 year (P = 0.44). All relapses were due to the persistence of H. pylori infection. At the 1 year follow-up, none of the patients who were H. pylori negative had an endoscopic relapse compared to 7 out of 56 patients who remained H. pylori positive (12.5%, 95% CI: 5-24%, P = 0.018). After a mean follow-up of 4.07 years, none of those who remained H. pylori negative had an ulcer relapse while the 11 out of 41 who remained H. pylori positive had an ulcer relapse (26.8%, 95% CI 14-43, P = 0. 0005). CONCLUSIONS: Both regimens were highly effective in healing ulcers. The eradication of H. pylori infection was associated with more side-effects and poor compliance but was more effective than the maintenance therapy in reducing the recurrence of duodenal ulcers. For the prevention of ulcer recurrence, testing of H. pylori status after triple therapy is more important than maintenance therapy.     

Mucosal interleukin-1β production and acid secretion in enlarged fold gastritis

Background : We have previously shown that eradication of Helicobacter pylori increases acid secretion in H. pylori -associated enlarged fold gastritis.
Aim : To investigate whether locally produced interleukin-1β is possibly involved in the inhibition of acid secretion in H. pylori gastritis.
Methods : IL-1β release from the gastric body mucosa was determined by short-term culture of biopsy specimens in 13 patients with enlarged fold gastritis (all H. pylori -positive), five H. pylori -positive and 10 H. pylori -negative patients without enlarged folds. The acid-inhibitory effect of locally produced IL-1β was examined by [¹⁴C]-aminopyrine uptake assay using isolated rabbit gastric glands.
Results : IL-1β release was significantly greater in patients with enlarged fold gastritis, significantly correlated with both basal and tetragastrin-stimulated acid outputs in the H. pylori -positive patients ( r  = −0.591 and r  = −0.641, respectively; P  < 0.01), and significantly decreased with concomitant increases in acid secretions after eradication of H. pylori . [¹⁴C]-aminopyrine uptake was inhibited by IL-1β in a dose-dependent manner.
Conclusions : Increased production of IL-1β caused by H. pylori infection is possibly involved in the inhibition of acid secretion in enlarged fold gastritis.     

Systematic review: the effect of Helicobacter pylori and its eradication on gastro-oesophageal reflux disease in patients with duodenal ulcers or reflux oesophagitis

BACKGROUND: The effect of Helicobacter pylori in provoking or protecting against gastro-oesophageal reflux disease is unclear and studies have given conflicting results. Recent guidelines recommend H. pylori eradication in patients on long-term proton pump inhibitors. AIM: To ascertain the effect of H. pylori eradication on gastro-oesophageal reflux disease outcomes (reflux oesophagitis and heartburn) in patients with duodenal ulcer disease, and to ascertain the effect of H. pylori infection on reflux oesophagitis concerning heartburn, pH, severity, healing and relapse rates. METHODS: A systematic review of electronic databases was undertaken to September 2003. Experts in the field, pharmaceutical companies and journals were contacted about unpublished trials. Studies were reviewed according to predefined eligibility and quality criteria. Twenty-seven studies/trials were included in the systematic review. RESULTS: Study variation rather than therapy-influenced results in relation to the presence or absence of oesophagitis in patients with duodenal ulcer who underwent H. pylori eradication at 6-48 months follow-up. In patients with reflux oesophagitis no obvious differences were discovered in heartburn scores, 24-h pH values, healing and relapse rates between H. pylori-positive and -negative cases. CONCLUSION: There is no evidence to indicate that H. pylori eradication in duodenal ulcer disease provokes reflux oesophagitis or worsens heartburn; (ii) there are insufficient data to draw firm conclusions about the impact of H. pylori in patients with reflux oesophagitis.     

Esomeprazole: a review of its use in the management of gastric acid-related diseases in adults

Esomeprazole (Nexium); S-omeprazole) is a single optical isomer proton-pump inhibitor (PPI) approved for the management of reflux oesophagitis, the symptomatic treatment of gastro-oesophageal reflux disease (GORD), the prevention and healing of NSAID-associated gastric ulcer disease (and the prevention of NSAID-associated duodenal ulcers in the UK), the treatment of Helicobacter pylori infection and associated duodenal ulcer disease (and prevention of relapse of H. pylori-associated peptic ulcers in the UK), and the treatment of Zollinger-Ellison syndrome (and other hypersecretory syndromes in the US).Once-daily oral esomeprazole 40 mg demonstrates greater antisecretory activity than other PPIs. Overall, in well designed clinical studies of 4 weeks' to 6 months' duration in patients with GORD, esomeprazole had similar or better efficacy than other agents. In patients requiring ongoing treatment with NSAIDs, co-therapy with once-daily esomeprazole 20 or 40 mg achieved relief of gastrointestinal symptoms or prevented ulcer occurrence, more effectively than placebo. Esomeprazole was also better than ranitidine 150 mg twice daily in healing NSAID-associated gastric ulcers. In addition, the drug has demonstrated efficacy as part of a triple-therapy regimen for the eradication of H. pylori infection, the healing of H. pylori associated duodenal ulcers and the prevention of relapse of gastric ulcers. Esomeprazole also effectively treated patients with Zollinger-Ellison syndrome. Esomeprazole is generally well tolerated with an adverse-event profile similar to that of other PPIs. Thus, the efficacy and tolerability of esomeprazole for the management of GORD and H. pylori eradication remains undisputed, and the data support its use for the first-line treatment of NSAID-associated gastric ulcer disease and Zollinger-Ellison syndrome.     

Effect of Helicobacter pylori eradication on duodenal ulcer scar in patients with no clinical history of duodenal ulcer

BACKGROUND: Helicobacter pylori eradication has become the standard treatment for duodenal ulcer. However, there is no relevant evidence for antibacterial treatment of the white scar stage of duodenal ulcer (duodenal ulcer scar) in patients with no past history of duodenal ulcer. AIM: To investigate whether H. pylori eradication could decrease duodenal ulcer recurrence in patients with duodenal ulcer scar and no past history of duodenal ulcer. PATIENTS AND METHODS: We prospectively enrolled 66 patients with duodenal ulcer scar: 53 were H. pylori-positive and 13 were H. pylori-negative. H. pylori-positive patients were randomly assigned into two groups (two-to-one allocation): 36 patients were assigned to the treatment group and 17 to the follow-up group. Thirteen H. pylori-negative patients were followed up according to the study protocol. Follow-up endoscopy was performed to evaluate ulcer scar changes and H. pylori status 6 weeks after anti-H. pylori treatment and then every 6 months for up to 30 months. RESULTS: Active duodenal ulcer recurrence was identified in seven of 23 H. pylori-positive/non-cured patients (30%). There was no duodenal ulcer recurrence in 43 H. pylori-negative/cured patients (0%), which was significantly different in terms of duodenal ulcer recurrence (P=0.001). CONCLUSIONS: H. pylori eradication is effective at preventing active duodenal ulcer recurrence in patients with duodenal ulcer scar and no past history of duodenal ulcer.     

Pharmacological study on the pathological changes of the gastric mucosa in Helicobacter pylori-infected Mongolian gerbils]

Helicobacter pylori (H. pylori) infection has been recognized to be a causal factor of gastritis, ulcers and gastric cancer in man. Using Mongolian gerbils (M. gerbils), which are suitable for an H. pylori infection animal model, we examined 1) how H. pylori infection, indomethacin and their combination affects the healing of gastric ulcers and whether or not such factors provoke a relapse of healed acetic acid ulcers; and 2) whether or not eradication of the bacteria with drugs at specified times after infection prevents the development of mucosal changes, including gastric adenocarcinoma. 1) H. pylori infection significantly delayed ulcer healing 4 weeks following infection. Indomethacin treatment showed a tendency to delay ulcer healing. Ulcer healing in H. pylori-infected M. gerbils was significantly delayed by indomethacin. H. pylori infection resulted in a relapse of healed ulcers from 1 to 6 months after infection, with a gradual increase in size. Omeprazole markedly prevented the ulcer relapse caused by H. pylori infection. 2) Four or 8 months after H. pylori inoculation, eradication was performed by concurrent treatment with omeprazole + clarithromycin. Immediately after treatment ended in both the 5 and 9 month groups, it was verified that H. pylori were completely eradicated. Autopsy performed 18 months after H. pylori inoculation revealed gastric hyperplastic polyps with erosive lesions and ulcers that were grossly visible; and atrophic gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were histologically observed in the non-treated control group. In animals eradicated after 4 months and autopsied after 18 months, however, such mucosal changes were not observed. In contrast, intestinal metaplasia and mucosal atrophy was observed in animals eradicated after 8 months and autopsied after 18 months. It was concluded that 1) H. pylori infection delayed the healing of preexisting gastric ulcers and resulted in the relapse of healed ulcers, yet indomethacin had little or no effect on ulcer healing or relapse; and 2) early eradication of H. pylori infection with drug therapy can prevent severe gastric mucosal changes, to include adenocarcinomas, in M gerbils.     

Does eradication of Helicobacter pylori alone heal duodenal ulcers?

BACKGROUND: Eradication of Helicobacter pylori infection prevents duodenal ulcer (DU) relapse, but it remains uncertain whether eradication of H. pylori alone heals duodenal ulceration. AIM: To test the hypothesis that eradication of H. pylori infection is accompanied by healing of duodenal ulcer. METHODS: A total of 115 consecutive patients with endoscopically confirmed H. pylori-infected duodenal ulcer were randomly assigned to one of two groups. Group BTC patients received a 1-week course of colloidal bismuth subcitrate 220 mg b.d., tinidazole 500 mg b.d., clarithromycin 250 mg b.d. Group OBTC patients received omeprazole 20 mg daily for 4 weeks with the BTC regimen during the first week. Endoscopy with antral biopsies and 13C-urea breath test (UBT) were performed before and 4 weeks after completion of the 7-day triple or quadruple therapy. RESULTS: Eight patients dropped out (four in BTC and four in OBTC). Duodenal ulcer healing rates on an intention-to-treat basis in BTC and OBTC were 86% (95% CI: 77-95%) and 90% (95% CI: 82-98%), respectively. The eradication rates of H. pylori on an intention-to-treat basis in BTC and OBTC were 88% (95% CI: 79-96%) and 91% (95% CI: 84-99%), respectively. There were no statistically significant differences in ulcer healing rates and eradication rates between these two groups (P > 0.05). Epigastric pain resolved more rapidly in patients assigned to OBTC compared with those assigned to BTC. Both of the two regimens were well tolerated with only minor side-effects (3% of the 115 patients) and the compliance was good. CONCLUSIONS: BTC is a very effective H. pylori eradication regimen. Almost all duodenal ulcers heal spontaneously after cure of H. pylori infection using a 1-week low-dose bismuth-based triple therapy. Treating duodenal ulcer with simultaneous administration of omeprazole achieves ulcer pain relief more rapidly.     

Omeprazole versus ranitidine: short-term triple-therapy in patients with Helicobacter pylori-positive duodenal ulcers

Aim : To compare the results of two short triple-therapy regimens, different only in the antisecretory drugs used, in patients with active duodenal ulcer and Helicobacter pylori infection.
Methods : All patients received a combination of clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for 1 week, in addition to an antisecretory drug: omeprazole 20 mg (50 patients) or ranitidine 300 mg (50 patients) twice daily for 1 week, followed by a single daily dose for a further 3 weeks. Upper gastrointestinal endoscopy, with rapid urease test and histological examination of antral and corpus biopsies, was performed prior to the treatment and at least 2 months after the discontinuation of the antisecretory therapy.
Results : Duodenal ulcer healing was documented in all patients at the endoscopic examination after therapy. H. pylori eradication was achieved in 46 of 50 patients (92%, 95% CI=85–99%) in the omeprazole group and in 43 of 50 patients (86%, 95% CI=76–96%) in the ranitidine group; the difference is not significant.
Conclusion : Omeprazole or ranitidine, in combination with clarithromycin and tinidazole, are equally effective in the eradication of H. pylori infection and healing of duodenal ulcers.     

Ranitidine bismuth citrate and clarithromycin twice daily in the eradication of Helicobacter pylori

Background : Ranitidine bismuth citrate (RBC) 400 mg when given twice daily (b.d.) for 4 weeks with clarithromycin 250 mg four times daily (q.d.s.) for the first 2 weeks effectively heals duodenal ulcers and eradicates Helicobacter pylori .
Aims : To compare two dosage regimens of clarithromycin, 250 mg q.d.s. and 500 mg b.d., used with ranitidine bismuth citrate (Pylorid) 400 mg b.d., for the eradication of H. pylori and for symptom relief in patients with active duodenal ulcers.
Subjects : 236 patients with active duodenal ulcer and confirmed H. pylori infection.
Methods : In a randomized, double-blind, parallel group, multi-centre study, RBC was given with clarithromycin for 2 weeks followed by 2 weeks treatment with RBC alone to allow for ulcer healing. Ulcer status was assessed by endoscopy at entry. H. pylori status was assessed by CLO Test and ¹³C-urea breath test (UBT) at entry and UBT alone 4 weeks after the end of treatment. At entry, during the study and at follow-up, ulcer symptoms were recorded on a scale of none, mild, moderate or severe.
Results : 176 patients had an evaluable UBT at least 4 weeks post-treatment. H. pylori eradication rates were 96.2% for the RBC plus clarithromycin b.d. regimen and 91.8% for the RBC plus clarithromycin q.d.s. regimen (observed data). Four weeks post-treatment, 92% of patients receiving RBC b.d. plus clarithromycin q.d.s. and 89% receiving RBC b.d. plus clarithromycin b.d. were considered symptom successes (none or mild symptoms).
Conclusions : RBC 400 mg b.d. plus clarithromycin 500 mg b.d. was as effective as RBC 400 mg b.d. plus clarithromycin 250 mg q.d.s. in eradicating H. pylori and both regimens were well tolerated. The simpler dual therapy in a b.d. regimen might well encourage greater patient compliance.     

High effectiveness and safety of one-week antibiotic regimen in Helicobacter pylori eradication

Background: Helicobacter pylori is strongly associated with peptic ulcer: H. pylori eradication markedly decreases the recurrence rate of duodenal and gastric ulcer, but the optimum length of antibiotic therapy in the eradication of H. pylori is still unclear.
Aim: To verify the effectiveness and side-effect profile of an eradicating regimen consisting of omeprazole 20 mg daily for 4 weeks and, during the first week, combination antimicrobial treatment with tinidazole 500 mg b.d. plus clarithromycin 250 mg b.d. in patients with active duodenal and gastric ulcer.
Methods: One hundred and ninety-six duodenal ulcer patients and 27 gastric ulcer patients with H. pylori infection were admitted into an open prospective study. Compliance was assessed by an accurate interview.
Results: Overall, H. pylori was successfully eradicated in 201 of 223 patients (intention-to-treat 90.1%; 95% CI=85–94%): 176 of 196 duodenal ulcer patients became H. pylori- negative (89.8%; CI=85–94%) as well as 25 of 27 gastric ulcer patients (92.6%; CI=76–99%). Compliance was excellent in 221 of 223 (99.1%) patients evaluated as having taken all the medication as prescribed. Sixteen patients (7.2%) developed mild side effects during treatment.
Conclusion: This combination treatment had excellent results with almost absolute compliance and a very low rate of minor side effects.     

Role of proton pump inhibitors in non-H. pylori-related ulcers

The proportion of ulcers that are not associated with Helicobacter pylori infection is increasing, especially in the United States and Australia. The alarming increase in this type of ulcer warrants an analysis of the diagnostic and treatment approaches to H. pylori -negative ulcers, which was the aim of this study. The medical literature was reviewed to gather information about the prevalence, aetiology, and treatment of H. pylori -negative ulcers. The reports indicated that up to 52% of duodenal ulcers and 47% of gastric ulcers are not caused by H. pylori infection. The cause of H. pylori -negative ulceration appears to be multifactorial. Contributing factors include covert non-steroidal anti-inflammatory drug use, false-negative H. pylori tests, genetic predisposition, and in rare cases, Crohn's disease or Zollinger–Ellison syndrome. H. pylori -negative ulcers tend to be associated with hypersecretion and can have serious clinical sequelae. H. pylori -negative ulcers are often refractory to treatment, possibly because they lack the beneficial effect of H. pylori infection on antisecretory therapy. Proton pump inhibitors (PPIs) appear to effectively treat both H. pylori -positive and H. pylori -negative ulcers. We conclude that H. pylori -negative ulcers are becoming more prevalent in the United States and Australia. These ulcers may have an aggressive clinical course and can be refractory to treatment. PPI therapy is indicated for treating and preventing H. pylori -negative peptic ulcers.     

Impact of Helicobacter pylori eradication on heartburn in patients with gastric or duodenal ulcer disease -- results from a randomized trial programme

BACKGROUND: Helicobacter pylori infection has been proposed as a protective factor against the development of gastro-oesophageal reflux disease. AIM: To study heartburn and endoscopic findings before and after H. pylori eradication therapy in patients with peptic ulcer disease. METHODS: In a multicentre trial programme, patients (n = 1497) were randomized to the omeprazole triple therapy group or to the control group, and were followed for 1-6 months after treatment. Patients in whom the infection was eradicated were compared with those in whom infection persisted. The severity of heartburn was measured at baseline and at each return visit. Endoscopy was performed 6 months after therapy in two of the five studies. RESULTS: In patients with duodenal ulcer, there was a significantly lower prevalence of heartburn after successful eradication of H. pylori relative to that after failed eradication (estimated odds ratio, 0.48). The reduction in the prevalence of heartburn in patients with gastric ulcer was independent of the post-treatment H. pylori status. In studies in which ulcer relapse was included in the model, this factor emerged as a significant factor for heartburn. The observed incidence of oesophagitis at the last visit was not influenced by H. pylori status. CONCLUSIONS: Eradication of H. pylori in patients with peptic ulcer disease was associated with a reduced prevalence of heartburn. Prevention of ulcer relapse could be the true cause of this reduction.     

A meta-analysis comparing eradication, healing and relapse rates in patients with Helicobacter pylori-associated gastric or duodenal ulcer

AIM: To compare the effectiveness of Helicobacter pylori eradication in curing peptic ulcer disease in trials involving both gastric ulcer and duodenal ulcer. METHODS: Twenty-four relevant randomized controlled trials and randomized comparative trials met the predefined selection criteria. Only proton pump inhibitor-based eradication trials were considered for the evaluation of eradication efficacy and ulcer healing. For the determination of relapse rates, all trials independent of the eradication therapy regimen were considered. RESULTS: Data from 2102 patients were analysed comparing gastric ulcer with duodenal ulcer. No statistical differences between gastric ulcer and duodenal ulcer patients were found with regard to eradication rates (summarized odds ratio, 1.23; 95% confidence interval, 0.98-1.55) or ulcer relapse rates, whether in successfully H. pylori eradicated patients (summarized odds ratio, 0.69; 95% confidence interval, 0.26-1.84) or unsuccessfully H. pylori eradicated patients (summarized odds ratio, 1.48; 95% confidence interval, 0.85-2.56). Owing to heterogeneity, healing rates were not comparable. CONCLUSIONS: The eradication of H. pylori infection cures both gastric and duodenal ulcer, and the cure rates are similar. This suggests that H. pylori is the key factor in peptic ulcer disease independent of the ulcer site.     

Short report: treatment of Helicobacter pylori-associated duodenal ulcer with omeprazole plus antibiotics

Omeprazole heals most duodenal ulcers after 4 weeks of treatment but relapse is common. Eradication of Helicobacter pylori is associated with reduced rate of ulcer relapse. This study investigates the effect of omeprazole with antibiotics in H. pylori-associated duodenal ulceration. Forty-three patients with endoscopically proven duodenal ulcer and H. pylori entered this study. Treatment consisted of 20 mg omeprazole daily (four weeks) and seven days (first week) treatment with 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. Four weeks after completing the treatment, 81 % (35143) had a healed duodenal ulcer, and 58% (25/43) had H. pylori eradication. In those who healed, at one year 21 remained H. pylori-negative, 12 had persistent H. pylori infection and 2 had re-infection. The ulcer relapse rate at one year was 26%: of the 9 who relapsed, 6 had persistent infection, 2 were re-infected, and only 1 was H. pylori-negative. This combination therapy of antibiotics with omeprazole successfully eradicates Helicobacter pylori and has a lower ulcer replase than omeprazole alone.     

Helicobacter pylori eradication as a surrogate marker for the reduction of duodenal ulcer recurrence

Objectives:

An abundance of data exists documenting the association of H. pylori eradication with the reduction in duodenal ulcer recurrence.

Aim:

To evaluate the validity of using H. pylori eradication as a surrogate marker for the reduction in duodenal ulcer recurrence using rigorously controlled studies.

Methods:

Three controlled clinical trials were conducted in patients with uncomplicated, active duodenal ulcers. Patients were treated with various combinations of omeprazole and amoxycillin. Ulcer healing and H. pylori eradication were assessed. For patients whose duodenal ulcer healed, duodenal ulcer recurrence was determined over a 6-month period in patients with H. pylori eradication and those remaining positive for H. pylori at least 4 weeks after treatment. To support the data obtained from these clinical trials, a search of the medical literature was conducted to identify additional human clinical trials in which duodenal ulcer recurrence rates were measured and categorized by H. pylori status at least 1 month post-treatment.

Results:

In 11 controlled trials, the overall 6–18-month duodenal ulcer recurrence rate was 54% among patients remaining positive for H. pylori at least 4 weeks after treatment compared to 6% among patients with H. pylori eradication following treatment. This finding was corroborated by the uncontrolled trials, in which the duodenal ulcer recurrence rate was 64% among patients found to be H. pylori-positive and 6% for patients found to be H. pylori-negative at least 4 weeks after treatment. A time course of duodenal ulcer recurrence rates using pooled data from both controlled and uncontrolled studies demonstrated that duodenal ulcer recurrence rates for H. pylori-negative patients persisted for up to 4 years following treatment. Duodenal ulcer recurrence rates for H. pylori-positive patients increased for the first year, then levelled off. A comparison of the duodenal ulcer recurrence rates for different treatment regimens revealed that eradication regimens based on omeprazole plus antibiotics and bismuth plus antibiotics exhibited similar duodenal ulcer recurrence rates for H. pylori-positive and -negative patients.

Conclusion:

Regardless of treatment regimens, H. pylori eradication produced a consistent and significant reduction in duodenal ulcer recurrence. Therefore H. pylori eradication, 4 weeks post-therapy, can be used as a surrogate marker for reduced duodenal ulcer recurrence in investigational clinical trials.

     

Occurrence and relapse of bleeding from duodenal ulcer: respective roles of acid secretion and Helicobacter pylori infection

BACKGROUND: Helicobacter pylori infection, gastric acid hypersecretion and NSAID consumption may cause peptic ulcer. AIM: To investigate the respective roles of H. pylori and acid secretion in bleeding duodenal ulcer. PATIENTS AND METHODS: A total of 99 duodenal ulcer patients were referred for evaluation of acid secretion: seven with Zollinger-Ellison Syndrome; 14 with hypersecretory duodenal ulcer, defined by the coexistence of elevated basal acid output and pentagastrin acid output; and 78 duodenal ulcer patients with normal acid output. All non-Zollinger-Ellison Syndrome patients were H. pylori-positive and cured of infection. All patients were followed-up for a 36-month period, to assess the occurrence of bleeding episodes. RESULTS: Twenty-nine patients had at least one bleeding episode in the 4 years before the study. Bleeding was more frequent in males and in patients on NSAIDs. The mean basal acid output was not higher among bleeders. In the 21 patients (14 hypersecretory duodenal ulcer, seven Zollinger-Ellison Syndrome) with basal acid output > 10 meg/h and pentagastrin acid output > 44.5 meg/h, the risk of bleeding was higher (OR 6.5; 95% CI: 2-21). In the follow-up period, three out of 83 (3.3%) non-Zollinger-Ellison Syndrome patients had a H. pylori-negative duodenal ulcer with bleeding. The risk of bleeding after H. pylori cure was not higher in hypersecretory duodenal ulcer patients (P > 0.3), nor among patients with previous bleeding episodes (P > 0.2). CONCLUSIONS: In H. pylori-positive duodenal ulcer patients, the coexistence of elevated basal acid output and pentagastrin acid output leads to a sixfold increase in the risk of bleeding. After H. pylori cure, gastric acid hypersecretion is not a risk factor for bleeding. However, duodenal ulcer recurrence with bleeding may occasionally occur in patients cured of H. pylori, even if acid output is normal.