Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report.

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

Mycophenolate mofetil therapy for refractory inflammatory bowel disease.

BACKGROUND: Mycophenolate mofetil (MMF) is an immunomodulatory drug, and its use in inflammatory bowel disease has previously been reported. The aim of this study was to review the Leeds Colitis Clinic experience of the safety and efficacy of MMF in treating patients with refractory Crohn's disease (CD) and ulcerative colitis (UC). This is an extension of a previously published study from our center with a longer follow-up period and approximately twice the number of patients. METHODS: A retrospective analysis was performed of the records of all patients treated with MMF for inflammatory bowel disease over a 5-year period. RESULTS: Of 70 patients identified, 67 had previously been treated with azathioprine unsuccessfully. Seventeen of the 70 patients had been successfully maintained in remission with MMF for an average duration of 33 months. Treatment with MMF was discontinued for 53 patients, 17 because of side effects and 36 because they had not responded to the treatment. CONCLUSIONS: In our series, 17 patients (24.3%) had a sustained steroid-free remission with MMF therapy. Nineteen patients (27%) experienced side effects, of which 17 (24.3% of the total group) had to discontinue therapy. An additional 36 (51.4%) required an escalation in medical therapy or surgery because of failure of the MMF therapy. MMF may have a role in the treatment of refractory inflammatory bowel disease, especially in patients who have previously failed standard therapies such as azathioprine.

Clinical trial: knowledge of negative Helicobacter pylori status reduces subsequent dyspepsia-related resource use.

BACKGROUND: Screening for Helicobacter pylori reduces dyspepsia and dyspepsia-related costs in positive individuals. AIMS: To assess effect of knowledge of H. pylori status on healthcare-seeking in negative individuals. METHODS: H. pylori-negative subjects in a community screening programme were randomized to placebo triple therapy or informed of their negative H. pylori status. Dyspepsia-related resource data were extracted from primary care records at 2 years, and National Health Service reference costs were applied to calculate the total cost per subject. Proportions of individuals incurring any cost were compared using a relative risk (RR) and 95% confidence interval (CI). Differences in costs were compared using an independent sample t-test. RESULTS: A total of 1353 H. pylori-negative individuals were randomized to placebo whilst 1355 were informed of their infection status. In the placebo arm, 212 (16%) subsequently incurred any dyspepsia-related cost compared to 172 (13%) informed of their infection status (RR of incurring cost = 0.81; 95% CI: 0.67-0.97). Those informed of their infection status incurred lower costs (mean saving per individual = pound 11.02; 95% CI: - pound 3.52 to 25.56). CONCLUSIONS: H. pylori-negative individuals informed of infection status sought health care for dyspepsia less often than those who were unaware. Population screening may reduce dyspepsia-related costs in uninfected, as well as infected individuals.

Low-grade dysplasia in Barrett's esophagus has a high risk of progression.

BACKGROUND AND STUDY AIMS: Surveillance in Barrett's esophagus relies on the detection of dysplasia by histopathology. However, the natural history of this condition, particularly that of low-grade dysplasia (LGD) is poorly understood. This paper describes our experience of LGD over a period of 21 years. PATIENTS AND METHODS: Between 1984 and January 1995, 357 patients with Barrett's esophagus without dysplasia were recruited for annual surveillance: 34 of these patients developed LGD during this period. This was a retrospective cohort study of this group in terms of survival and cancer outcomes >/= 8 years after the original diagnosis of LGD, comparing them with the patients who did not develop LGD over the same period, with a histopathological review of the original diagnoses of LGD. The outcomes of 356/357 (99.7 %) of the patients were established in December 2004. RESULTS: After 8 years, high-grade dysplasia (HGD) or cancer had developed in 9/34 patients with LGD (27 %) and in 16/322 controls (5 %). Cox's proportional hazards model revealed that the time from the first diagnosis of Barrett's esophagus to the first "event" of either HGD, esophageal cancer, or death did not show a statistically significant difference between the two groups. A further analysis treating death as "loss to follow-up" showed a significantly increased risk for the LGD group to progress to HGD or cancer (hazard ratio 5.9 [95 % confidence interval 2.6 - 13.4], P< 0.001). The histopathology review demonstrated a fair level of agreement between pathologists, with a kappa value of 0.48. CONCLUSIONS: Patients diagnosed with LGD during surveillance of Barrett's esophagus are at a considerably increased risk of progressing to develop esophageal cancer over an 8-year period but most deaths are not cancer-related.

Review article: gastro-oesophageal reflux disease--the extent of the problem.

There have been little review data on the period prevalence of heartburn symptoms in the community. We analysed reflux symptom data from a test-and-treat trial that evaluated community Helicobacter pylori levels and added these to data identified from a literature search. We found 31 papers reporting on 77,671 subjects who provided information on the frequency of heartburn symptoms in the community. Pooled data from these papers suggested that, in Western populations, 25% had symptoms at least once per month, 12% had symptoms at least weekly and 5% had heartburn daily. Reflux symptoms were less common in East Asian populations with only 7% having heartburn at least once per month. Heartburn is a significant problem in Western societies.

Gastro-oesophageal reflux is more prevalent in Western dyspeptics: a prospective comparison of British and South-East Asian patients with dyspepsia.

BACKGROUND: There is a paucity of data directly comparing dyspepsia in Western and Eastern populations. AIM: To compare clinical symptoms, epidemiological factors and endoscopic diagnoses in two sample populations with dyspepsia from the United Kingdom and South-East Asia in a cross-sectional study. METHODS: Patients with uncomplicated dyspepsia attending endoscopy units in Leeds, UK, and Kuala Lumpur, Malaysia, were prospectively interviewed and underwent subsequent endoscopy. RESULTS: A total of 1003 Malaysian patients (January 2002 to August 2003) and 597 Caucasian British patients (January 2000 to October 2002) were studied. The mean age was 48.7 +/- 15.8 and 47.5 +/- 13.8 years for the Malaysian and British patients respectively (P = NS). There was a higher proportion of cigarette smoking (35.7% vs. 12.4%, P < 0.0001) and alcohol consumption (34.4% vs. 2.0%, P < 0.0001) amongst British patients, but no difference in non-steroidal anti-inflammatory drug use nor having Helicobacter pylori infection. Gastro-oesophageal reflux disease (GERD) symptoms were more common in British compared with South-East Asian patients [heartburn (72% vs. 41%), regurgitation (66% vs. 29.8%) and dysphagia (21.1% vs. 7.3%), P < 0.0001]. This correlated with an increased endoscopic finding of oesophagitis (26.8% vs. 5.8%) and columnar-lined oesophagus (4.4% vs. 0.9%) amongst British patients (P < 0.001). A logistic regression model revealed that British Caucasian race (OR 9.7; 95% CI = 5.0-18.8), male gender (OR 2.0; 95% CI = 1.4-2.9) and not having H. pylori infection (OR 0.5; 95% CI = 0.3-0.7) were independent predictors for oesophagitis. CONCLUSION: GERD is more common in British compared with South-East Asian dyspeptic patients suggesting that race and/or western lifestyle are important risk factors.

Helicobacter pylori infection is related to atheroma in patients undergoing coronary angiography.

OBJECTIVES: Helicobacter pylori infection has been related to an increased risk of ischaemic heart disease (IHD) possibly by raising plasma fibrinogen. The evidence for this association is conflicting. Furthermore, no attempt has been made to distinguish between an effect on atheroma and thrombosis. We have determined the association of H. pylori status with IHD assessed by coronary angiography. We have also evaluated the influence of H. pylori infection on haemostatic factors. METHODS: Caucasian patients undergoing coronary angiography for suspected IHD were recruited. H. pylori status was determined by serology (Helico G). Plasma fibrinogen was measured by the Clauss assay. Coronary angiograms were assessed and significant atheroma defined as > or = 50% stenosis. A history of myocardial infarction was ascertained by WHO criteria. RESULTS: 292 patients were recruited (median age 59, 95 female); 204 (70%) patients had IHD and 185 (64%) of all patients were H. pylori-positive; 68% patients with IHD were H. pylori-positive compared with 50% without IHD (P = 0.003). When adjusted for other risk factors by logistic regression, H. pylori remained significantly associated with IHD (odds ratio = 2.4, 95% CI = 1.2-5.1, P = 0.02). H. pylori status was not related to a history of myocardial infarction. Circulating levels of PAI-1, vWF, Factor VII and fibrinogen were not related to H. pylori status. CONCLUSION: This study suggests that infection with H. pylori is associated with coronary atheroma, but that this relationship is unlikely to be mediated through raised plasma fibrinogen.

Levels of malondialdehyde-deoxyguanosine in the gastric mucosa: relationship with lipid peroxidation, ascorbic acid, and Helicobacter pylori.

Helicobacter pylori infection is associated with elevated gastric mucosal concentrations of the lipid peroxidation product malondialdehyde and reduced gastric juice vitamin C concentrations. Malondialdehyde can react with DNA bases to form the mutagenic adduct malondialdehyde-deoxyguanosine (M(1)-dG). We aimed to determine gastric mucosal levels of M(1)-dG in relation to H. pylori infection and malondialdehyde and vitamin C concentrations. Patients (n = 124) attending for endoscopy were studied. Levels of antral mucosal M(1)-dG were determined using a sensitive immunoslot-blot technique; antral mucosal malondialdehyde was determined by thiobarbituric acid extraction, and gastric juice and antral mucosal ascorbic acid and total vitamin C were determined by high-performance liquid chromatography. Sixty-four H. pylori-positive patients received eradication therapy, and endoscopy was repeated at 6 and 12 months. Levels of M(1)-dG did not differ between subjects with H. pylori gastritis (n = 85) and those with normal mucosa without H. pylori infection (n = 39; 56.6 versus 60.1 adducts/10(8) bases) and were unaffected by age or smoking habits. Malondialdehyde levels were higher (123.7 versus 82.5 pmol/g; P < 0.001), gastric juice ascorbic acid was lower (5.7 versus 15.0 micromol/ml; P < 0.001), and antral mucosal ascorbic acid was unchanged (48.0 versus 42.7 micromol/g) in H. pylori gastritis compared with normal mucosa. Multiple regression analysis revealed that M(1)-dG increased significantly with increasing levels of malondialdehyde, antral ascorbic acid, and total antral vitamin C. M(1)-dG levels were unchanged 6 months (63.3 versus 87.0 adducts/10(8) bases; P = 0.24; n = 38) and 12 months (66.7 versus 77.5 adducts/10(8) bases; P = 0.8; n = 13) after successful eradication of H. pylori. M(1)-dG thus is detectable in gastric mucosa, but is not affected directly by H. pylori.

Colonic cancer surveillance in ulcerative colitis is not essential for every patient.

It is generally recognised that there is an increased risk of colonic cancer in patients with long-standing extensive colitis, and regular annual or biennial colonoscopic surveillance protocols have been recommended in order to detect early cancer. There is, however, little evidence to suggest that these protocols are of value. There have been no properly conducted controlled trials in this area, and the studies that have been reported are flawed by selection bias, the inclusion of patients with "pseudo disease" and protocol violators. Many studies have not distinguished between "screening colonoscopy" and "colonoscopic surveillance". Some have not drawn attention to the failures in the surveillance, i.e. patients with Dukes' grade C or worse, and overall the conclusions drawn have been unrealistically optimistic. The diagnosis of low grade dysplasia which has been accorded importance is insensitive, non-specific and is subject to gross interobserver error. It is of little clinical value. Colonoscopic surveillance using currently available techniques is of only marginal benefit to patients included within the protocol. It is not cost-effective and cannot be made to be so.

Personal view: to treat or not to treat? Helicobacter pylori and gastro-oesophageal reflux disease - an alternative hypothesis.

Helicobacter pylori causes acute on chronic gastritis and is responsible for most peptic ulcers and gastric cancer. However, recent papers have suggested that it may protect against gastro-oesophageal reflux, Barrett's oesophagus and oesophageal cancer. Furthermore, the rapid increase in gastro-oesophageal reflux disease, Barrett's oesophagus and adenocarcinoma of the oesophagus in the developed world has been attributed by some to the falling prevalence of H. pylori. These considerations have led to the suggestion that H. pylori infection should not necessarily be treated, especially in patients with gastro-oesophageal reflux disease. Conversely, data from prospective randomized studies have shown that H. pylori eradication does not cause gastro-oesophageal reflux disease in patients with duodenal ulcer or in the normal population, nor does it worsen the outcome of pre-existing gastro-oesophageal reflux disease. Therefore, although H. pylori is negatively associated with gastro-oesophageal reflux disease, its eradication does not induce the disease. A hypothesis is presented suggesting that the increased prevalence of gastro-oesophageal reflux disease is a result of rising acid secretion in the general population, which, in turn, is a consequence of the increased linear height (a predictor of acid secretion). The greater acid secretion could also explain the decline in the prevalence of H. pylori and perhaps account for the inverse relationship between H. pylori and gastro-oesophageal reflux disease. These considerations are explored in discussing whether H. pylori infection should be treated in infected patients presenting with gastro-oesophageal reflux disease.

Treatment of Helicobacter pylori: an overview.

Helicobacter pylori is recognized to be a serious pathogen, but there is still controversy as to who should be treated. There is consensus for treatment of Helicobacter-positive peptic ulcer and B-cell lymphoma. Lymphocytic gastritis and giant-fold gastritis (Ménétrièr's disease) may also respond to treatment. Patients with func-tional dyspepsia have a 20% placebo response with a 5-10% 'eradication' response, results not dissimilar from empirical treatment with a proton pump inhibitor. A 'test and treat' policy for patients with uninvesti-gated dyspepsia remains controversial. Some have suggested that eradication may increase the risk of GERD, or predispose to adenocarcinoma at the gastro-oesophageal junction. However, PPI treatment without Helicobacter eradication induces greater inflammation in the gastric corpus, the phenotype associated with non-cardia gastric cancer. A minority believe that Helicobacter should be eradicated in all individuals. When choosing treatment it is logical to start with a combination of antibiotics that, in the event of failure, will allow a second combination to be used without overlap.

Review article: is Helicobacter pylori transmitted by the gastro-oral route?

The manner in which Helicobacter pylori is transmitted is of fundamental importance when considering strategies for its control, yet to date no satisfactory explanation has been advanced to account for its spread from person to person. This is surprising for a disease that affects 50% of the world's population. Attempts to culture H. pylori from faecal material and saliva have met with difficulty, casting some doubt on the likelihood of a faeco-oral or oro-oral route of transfer. The infection is easily passed from person to person by gastric intubation. The hypothesis advanced in this paper is that the natural route of transmission is by gastric juice, specifically as a result of epidemic vomiting in childhood. This theory is supported by literature indicating that acute infection with H. is characterized by vomiting of achlorhydric mucus that may serve as a vehicle for transmission. The hypothesis is consistent with most of the epidemiological data that have been published on H. pylori infection, including its association with childhood overcrowding, the lack of a fixed hot water supply and disadvantaged social conditions.

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.

Oral tobramycin in ulcerative colitis: effect on maintenance of remission.

Oral tobramycin for 7 days has been shown to be of benefit as an adjunct to conventional medication in acute ulcerative colitis. Eighty-one patients (40 who had received tobramycin; 41 placebo) who had been enrolled in a double-blind placebo-controlled trial of this drug in acute disease were subsequently followed to determine whether this short-term benefit persisted. Relapse was defined as a liquid stool frequency of three times daily with rectal bleeding. Results were analysed by the log-rank test on Kaplan-Meier survival curves. Treatment failure was defined as a lack of response by the end of the acute trial period, or subsequent relapse. In a second analysis, only those entering remission at the end of the acute trial were considered, and followed to relapse. Although at the start of the follow-up period significantly fewer patients in the tobramycin group had failed (failed: tobramycin 9, placebo 24; not failed tobramycin 31; placebo 17; P = 0.001), the failure-free survival curves subsequently converged and did not differ significantly. After 1 and 2 years, the failure-free survival rates were 40% (S.E. = 7.8%) and 20% (S.E. = 6.3%) for the tobramycin group and 24% (S.E. = 6.7%) and 12% (S.E. = 5.1%) for the placebo group. When only those entering remission were considered, there was no significant difference in the relapse rates in the two groups. Benefit from tobramycin is therefore short-lived and may reflect short-term changes in the faecal flora.

Symposium: Helicobacter pylori and clinical risks--focus on gastro-oesophageal reflux disease.

Helicobacter pylori is a gastric pathogen that is a major cause of peptic ulcer disease, has a role in mucosa-associated lymphoid tissue (MALT) lymphoma and is associated with gastric cancer. Yet, in a large proportion of the human population, H. pylori infection has no apparent adverse clinical consequences. Furthermore, recent research suggests that H. pylori may even confer protection against gastroesophageal reflux disease. The conflicting evidence surrounding H. pylori infection was discussed at a sponsored symposium in Helsinki, introduced by Professor P. Malfertheiner, with papers presented by Dr H. J. O'Connor, Professor R. M. Genta, Dr P. Unge and Professor A. T. R. Axon. Emerging epidemiological and retrospective evidence suggests that the presence of H. pylori infection may provide some protection against gastroesophageal reflux disease, but there is other evidence that shows no benefit of H. pylori for the protection of the oesophagus. It was felt that prospective, multicentre studies are needed to explore the H. pylori-gastroesophageal disease relationship further, to avoid confusing potential benefits with known risks. Following the symposium, a discussion on the relative risks and benefits for H. pylori eradication was provided by Professor Axon and Professor Blaser. Eradication of H. pylori has been recommended in a series of management guidelines issued by consensus groups. However, accurate estimates of the relative risks and benefits of H. pylori infection in the general population, as well as in specific patient groups, is essential in order to develop a management strategy.

Adverse reactions to sulphasalazine and 5-amino salicylic acid in the same patient.

We report a patient who developed sulphasalazine-related hepatitis with a subsequent adverse reaction to rectal 5-amino salicylic acid, in the form of pain and fever without associated liver dysfunction, suggesting reactions to both components of sulphasalazine. Included is a review of the literature. Caution should be observed when prescribing 5-amino salicylic acid to sulphasalazine-intolerant patients.

Mycophenolate mofetil in refractory inflammatory bowel disease.

BACKGROUND: Mycophenolate mofetil has been claimed to be effective and well tolerated in refractory inflammatory bowel disease although there is little information regarding its use in clinical practice. AIM: To review our experience in achieving and maintaining remission in refractory inflammatory bowel disease and to document tolerability, major toxicity and efficacy. METHODS: A retrospective audit was performed of the records of all patients with inflammatory bowel disease treated with mycophenolate mofetil (1-2 g/day) over a 3-year period. RESULTS: Thirty-nine patients were identified. Almost all had been intolerant of, or had not responded to azathioprine, and 38 were steroid-dependent. mycophenolate mofetil was discontinued in 22 patients, 11 due to intolerance and 10 because of lack of efficacy. Of the 17 on treatment at the end of the study period 16 were in remission and off all steroid therapy, but one needed infliximab to maintain remission. No major toxicity was noted and there was no major sepsis. CONCLUSIONS: Approximately 40% of patients with severe refractory inflammatory bowel disease achieved remission and complete steroid withdrawal on mycophenolate mofetil therapy, almost 30% could not tolerate the drug, and a further 30% did not respond. Mycophenolate mofetil therapy may have a role for steroid-dependent patients refractory to azathioprine.

The efficacy of tobramycin in the treatment of ulcerative colitis.

This paper reports a double-blind placebo-controlled trial of oral tobramycin in acute ulcerative colitis. Eighty-four patients with an acute relapse of ulcerative colitis were randomized to receive oral tobramycin or placebo for 1 week as an adjunct to steroid therapy. At endpoint, 31 of 42 (74%) in the tobramycin group achieved complete symptomatic remission compared with 18 of 42 (43%) in the placebo group (P = 0.008). The tobramycin group achieved better histological scores (P less than 0.05) at endpoint. These findings show that treatment with oral tobramycin improves the short-term outcome of patients with ulcerative colitis in relapse.

Symptomatic and endoscopic duodenal ulcer relapse rates 12 months following Helicobacter pylori eradication treatment with omeprazole and amoxycillin with or without metronidazole.

AIM: To determine the effect of Helicobacter pylori eradication with omeprazole and amoxycillin, with or without metronidazole, on the 12-month course of duodenal ulcer disease. METHODS: In a randomized; double-blind study, conducted in 19 hospitals, 105 H. pylori positive duodenal ulcer patients were healed and symptom-free following either omeprazole dual therapy (omeprazole 40 mg o.m.+amoxycillin 500 mg t.d.s., OA, eradication rate 46%, n = 52) or omeprazole triple therapy (omeprazole 40 mg o.m.+amoxycillin 500 mg t.d.s.+metronidazole 400 mg t.d.s., OAM, eradication rate 92%, n = 53) for 2 weeks, followed by 2 weeks of omeprazole 20 mg o.m. and a 12-month untreated follow-up period, after which time all patients were endoscoped. Endoscopic and symptomatic relapse rates, and effect on H. pylori status measured using 13C-urea breath test, were determined. RESULTS: During the 12-month untreated follow-up period, the life-table endoscopic relapse rates were 12% (95% CI: 2-22%) and 2% (95% CI: 0-6%) for OA and OAM patients, respectively. By 12 months, life-table symptomatic relapse rates were 22% (95% CI: 13-37%) and 19% (95% CI: 8-30%) for OA and OAM, respectively. In the 12 months untreated follow-up period, 2/69 (3%, 95% CI: 0-7%) patients rendered H. pylori negative had an endoscopic relapse at the end of the 12-month follow-up period, compared with 5/31 (16%, 95% CI: 3-29%) patients remaining H. pylori positive (P = 0.03 between H. pylori positive and negative groups). Twelve of 69 (17%, 95% CI: 8-26%) patients rendered H. pylori negative relapsed symptomatically, compared with 9/31 (29%, 95% CI: 13-45%) patients remaining H. pylori positive (P = N.S. between groups). There was a significant improvement in epigastric pain (P = 0.0001), nausea and vomiting (P < 0.05) between entry to the study and 1, 6 and 12 months post-treatment for both treatment groups. CONCLUSIONS: OAM eradicates H. pylori in significantly more patients than OA, but successful H. pylori eradication with either OAM or OA predisposes to low endoscopic and symptomatic relapse rates for duodenal ulcer patients when followed up for 12 months.

Omeprazole is more effective than cimetidine for the relief of all grades of gastro-oesophageal reflux disease-associated heartburn, irrespective of the presence or absence of endoscopic oesophagitis.

BACKGROUND: Previous studies have demonstrated greater efficacy for omeprazole compared with cimetidine in patients with endoscopically verified oesophagitis, but excluded the substantial group of gastro-oesophageal reflux disease (GERD) patients with reflux symptoms but without endoscopic abnormality. This prospective, randomized, double-blind study compared omeprazole and cimetidine in the treatment of GERD-associated heartburn both in patients with symptomatic non-ulcerative oesophagitis and in those with heartburn but without oesophagitis. METHODS: A total of 221 patients with heartburn and oesophageal mucosa grade 0 (normal, n = 51), 1 (no macroscopic erosions, n = 52), 2 (isolated erosions, n = 97) or 3 (confluent erosions, n = 21) were randomized to receive double-blind either omeprazole 20 mg daily or cimetidine 400 mg q.d.s. for a period of 4 weeks. Those still symptomatic after 4 weeks of treatment received omeprazole 20 mg daily for a further 4 weeks. RESULTS: There was no correlation between severity of heartburn and endoscopic grade at entry (correlation coefficient = 0.196). After 4 weeks of treatment, the proportion of patients in whom heartburn was controlled (no more than mild symptoms on no more than 1 day in the previous 7) on omeprazole (66%; 74/112) was more than double that on cimetidine (31%; 34/109) (P < 0.0001). There was no significant difference between the relief of heartburn in the 47% of patients without unequivocal oesophagitis (endoscopic grade 0 or 1) and in the 53% of patients with erosive oesophagitis (grade 2 or 3) (P = 0.31). Only treatment with omeprazole (P < 0.0001) and lower severity of heartburn at entry (P < 0.01) were significant in predicting heartburn relief. Amongst those patients requiring an additional 4 weeks of treatment with omeprazole, 67% (54/81) reported that their heartburn was controlled after 8 weeks of treatment. CONCLUSION: We conclude that omeprazole is superior to cimetidine for the relief of all grades of heartburn in GERD, whether or not the patient has unequivocal endoscopic oesophagitis.