Helicobacter pylori and the efficacy of omeprazole therapy for gastroesophageal reflux disease

OBJECTIVE: Helicobacter pylori infection may affect gastric acid output and intragastric pH. In patients with an insufficient lower esophageal sphincter, this effect may theoretically influence the severity of reflux disease, as well as the efficacy of acid suppressive therapy. To evaluate whether the H. pylori status of patients with gastroesophageal reflux disease (GERD) affects the severity of disease and the efficacy of omeprazole therapy to maintain disease remission, we conducted this study. METHODS: Patients with GERD were prospectively studied by upper gastrointestinal endoscopy with biopsy sampling for histology and H. pylori culture before start of treatment and at annual follow-up. At endoscopy, esophagitis was graded according to the criteria of Savary-Miller, and the presence of Barrett's esophagus, hiatal herniation, or other abnormalities was recorded. Omeprazole was started at an initial dose of 20 mg daily; the dose was adjusted based on symptoms and the endoscopical findings. RESULTS: One hundred thirty-seven GERD patients were included and followed up for a mean 56.6 months; 49 (36%) of them were infected with H. pylori. H. pylori-infected and -uninfected patients did not differ with respect to age (60 +/- 13 vs 61 +/- 14 yr, p = 0.65) or duration of follow-up (54 +/- 30 vs 58 +/- 31 months, p = 0.12). H. pylori-negative patients tended to present with more severe esophagitis at baseline (median Savary-Miller score 3 vs 2, p = 0.06) and had a higher prevalence of Barrett's esophagus (39/88 vs 10/49, p = 0.006). However, no difference was found with respect to the dose of omeprazole needed for maintained relief of symptoms and endoscopical signs of esophagitis (median 40 mg in both groups, p = 0.35). CONCLUSIONS: H. pylori-negative GERD patients have a higher prevalence of Barrett's esophagus, but do not need a higher dose of omeprazole to maintain symptomatic and endoscopical disease remission.     

Efficacy of omeprazole for the treatment of symptomatic acid reflux disease without esophagitis

BACKGROUND: Up to three quarters of patients with gastroesophageal reflux disease (GERD) have symptoms, such as heartburn, but no macroscopic evidence of erosive esophagitis, making symptomatic GERD a common clinical problem in the primary care setting. OBJECTIVE: To compare the efficacy and safety of omeprazole, 20 mg once daily; omeprazole, 10 mg once daily; and placebo in the treatment of symptomatic GERD without erosive esophagitis. METHODS: Patients with a history of heartburn (> or =12 months) and episodes of moderate to severe heartburn on 4 or more of the 7 days before endoscopy were eligible to participate in this 4-week, randomized, double-blind, placebo-controlled trial. The absence of erosive esophagitis was established through endoscopy. Eligible patients were randomized to 1 of 3 treatment groups: omeprazole, 20 mg once daily; omeprazole, 10 mg once daily; or placebo. Patients were assessed at weeks 2 and 4. The efficacy of omeprazole for the treatment of heartburn was determined mainly through the following diary card data: daily resolution of heartburn and complete resolution of heartburn every day during 1 week of treatment. The efficacy of omeprazole for the treatment of acid regurgitation, dysphagia, epigastric pain, and nausea was also assessed. RESULTS: Of 359 randomized patients, 355 were included in the statistical analysis (intention-to-treat population). Daily proportions of patients with no heartburn were consistently greater in the 20-mg omeprazole group (62%, day 7; 74%, day 27) than in the 10-mg omeprazole group (41%, day 7; 49%, day 27) or the placebo group (14%, day 7; 23%; day 27). Complete resolution of heartburn every day during the last treatment week was significantly (P< or =.002) higher in the 20-mg omeprazole group (48%) than in the 10-mg omeprazole (27%) or placebo (5%) group. Omeprazole was significantly (P< or =.003) more effective than placebo for the treatment of acid regurgitation, dysphagia, epigastric pain, and nausea. CONCLUSIONS: Patients with symptomatic GERD require profound acid suppression to achieve symptomatic relief. Omeprazole, 20 mg once daily, was superior to omeprazole, 10 mg once daily, and to placebo in providing early and sustained resolution of heartburn, as well as treatment of other troublesome GERD symptoms.     

Gastric Helicobacter pylori infection accelerates healing of reflux esophagitis during treatment with the proton pump inhibitor pantoprazole.

BACKGROUND & AIMS: In previous studies an exaggerated effect of proton pump inhibitors (PPIs) on intragastric pH in Helicobacter pylori-infected patients was observed. Because healing and improvement of symptoms in patients with gastroesophageal reflux disease (GERD) is directly associated with an increase of intragastric pH during treatment, we hypothesized that the response to treatment with a PPI in patients with reflux esophagitis would be better in H. pylori-infected patients than in patients without H. pylori infection. METHODS: We recruited 971 patients with endoscopically verified reflux esophagitis grades II and III (Savary/Miller). At study entry, H. pylori status was assessed by a 13C-urea breath test and baseline characteristics were recorded. Physicians and patients were not notified about the results of the breath test until completion of the study. All patients underwent treatment with pantoprazole, 40 mg orally once daily for 4 weeks. Healing was verified by endoscopy after 4 or 8 weeks of treatment. If the esophagitis had not completely healed at this time, treatment was continued for a further 4-week period. Healing rates and symptom relief were compared for patients with and without H. pylori infection. RESULTS: The prevalence of H. pylori was 39.9% (95% confidence interval [CI], 36.9-42.9), and neither gender, smoking, nor alcohol consumption were associated with the H. pylori infection (P > 0.4). The trial was completed by 846 patients without protocol violation. Overall healing rates of reflux esophagitis were 80.4% (95% CI, 77.7-83.1) and 93.6% (95% CI, 91.8-95.2) after 4 and 8 weeks, respectively. In H. pylori-positive patients, healing rates were significantly higher after 4 (86.6% vs. 76.3%; P = 0.0005) and 8 weeks (96.4% vs. 91.8%; P < 0.004). Relief of symptoms after 4 weeks was also significantly (P < 0.05) better in H. pylori-infected patients than in uninfected patients. CONCLUSIONS: Patients with reflux esophagitis and H. pylori infection respond significantly better than H. pylori-negative patients to the PPI pantoprazole.     

Effect of acid-suppressive therapy on Helicobacter pylori production of interleukin-8 in the gastric mucosa.

BACKGROUND: Recent studies have shown that acid-suppressive therapy increases the severity of Helicobacter pylori- associated gastritis in the corpus. PURPOSE: To evaluate interleukin (IL)-8 production in the gastric corpus mucosa before and during acid-suppressive therapy in H pylori-infected patients. PATIENTS AND METHODS: Ten patients with reflux esophagitis (five H pylori-positive and five H pylori-negative) were treated with omeprazole 20 mg. Serum gastrin concentrations, H pylori colonization density and mucosal IL-8 levels in the corpus were investigated at entry and two weeks after starting therapy. IL-8 levels were measured by ELISA. The organism density was determined, and scored according to area occupied by the bacterial colonies. The presence of H pylori was assessed by rapid urease testing and histological finding of gastric biopsy specimens. RESULTS: In H pylori-positive patients, concentrations of IL-8 during therapy significantly exceeded those before therapy (36.2+/-6. 8 versus 18.3+/-3.8 pg/mg protein; P<0.05) without altering H pylori density. In H pylori-negative patients, IL-8 levels were similar before and during therapy (6.1+/-2.7 versus 6.3+/-3.0 pg/mg protein). Concentrations of gastrin during therapy were significantly higher than those before therapy in all patients. CONCLUSIONS: The results suggest that acid suppression increases mucosal IL-8 levels in H pylori-infected patients with reflux esophagitis.     

Relapse prevention in reflux oesophagitis with regard to Helicobacter pylori status: a double-blind, randomized, multicentre trial to compare the efficacy of pantoprazole versus ranitidine

OBJECTIVE: To compare prospectively the effectiveness of 1 year's treatment with pantoprazole versus ranitidine in order to prevent relapse after initial cure of reflux oesophagitis. For the first time the influence of the initial Helicobacter pylori status on therapeutic results was also taken into account. METHODS: In order to cure reflux oesophagitis, 396 patients with Savary/Miller stage II or III reflux oesophagitis were treated with pantoprazole 40 mg once daily for 8 weeks. Those who were H. pylori positive (n = 140) were also given 1 week of eradication treatment with clarithromycin 2 x 250 mg daily, metronidazole 2 x 400 mg daily, and a further 40 mg pantoprazole daily. The 303 patients who were endoscopically cured after the 8-week period were randomized and treated with either pantoprazole 20 mg (n = 199) or ranitidine 150 mg (n = 104) daily in double-blind fashion. The primary objective was to assess the time to endoscopically proven recurrence of reflux oesophagitis. RESULTS: In the intention-to-treat (ITT) population, 66.3% (118/178) of the pantoprazole group and 34.0% (32/94) of the ranitidine group showed neither endoscopic nor clinical symptoms of relapse after the 1-year treatment period (P < 0.0001) (per-protocol populations: 70.3% [109/155] in the pantoprazole group and 39.4% [28/71] in the ranitidine group). In the pantoprazole group, the relapse rate in initially H. pylori-positive patients who underwent eradication was 30.9% (17/55) and in H. pylori-negative patients 29% (29/100). CONCLUSIONS: Long-term treatment with 20 mg pantoprazole daily to prevent relapse of reflux oesophagitis in H. pylori-negative patients is significantly more effective than 150 mg ranitidine daily. The initial H. pylori eradication treatment does not influence the outcome of the long-term treatment.     

The effect of omeprazole on asthmatic adolescents with gastroesophageal reflux disease

The prevalence of gastroesophageal reflux disease (GERD) is increasing in patients with asthma and the effect of proton pump inhibitor therapy on asthma outcome has shown variable results. The aim of this study was to determine the efficacy of omeprazole in the treatment of asthma and improvement of pulmonary function in adolescents with GERD. Thirty-six consecutive patients (range, 13-20 years old) with moderate persistent asthma and GERD were recruited on regular follow-up in Mashhad City. The case group included 18 patients who received oral omeprazole (20 mg twice a day for 6 weeks) and the control group included 18 patients who received placebo. A pulmonary function test was examined in two groups immediately before and 6 weeks after medication. The symptoms of GERD were significantly improved with omeprazole in the case group. After 6 weeks of study, the mean values of forced vital capacity, forced expiratory volume in 1 second, and peak expiratory flow rate were higher in patients treated with omeprazole (p<0.0001). Treatment by omeprazole is effective for treatment of asthmatic patients with GERD.     

Nizatidine versus placebo in gastroesophageal reflux disease

In a randomized, multicenter trial, nizatidine 150 mg or 300 mg, or placebo, was administered twice daily for six weeks to 515 patients with gastroesophageal reflux disease (GERD). Gelusil antacid tablets were taken as needed for pain. Significantly superior rates of endoscopically proven complete healing (normal-appearing mucosa) versus placebo occurred after three weeks with nizatidine 150 mg, and after six weeks with nizatidine 300 mg. Six-week healing rates were 38.5% for nizatidine 300 mg, 41.1% for nizatidine 150 mg, and 25.8% for placebo. The nizatidine 150 mg treatment group had significantly greater improvement in daytime and nighttime heartburn severity after one day of therapy versus placebo. Twice-daily administration of nizatidine 150 mg or 300 mg provides prompt relief from the major symptom of GERD, heartburn, and complete healing of esophagitis is seen in many patients.     

Helicobacter pylori-negative duodenal ulcers: prevalence, clinical characteristics, and prognosis--results from a randomized trial with 2-year follow-up

OBJECTIVE: The proportion of Helicobacter pylori-negative duodenal ulcer disease appears to be increasing. Data on clinical outcome and prognosis in this subgroup are lacking. METHODS: Two hundred seventy-six duodenal ulcer patients randomized, irrespective of H. pylori status, to either eradication therapy or maintenance omeprazole (double-blind, double-dummy design) for 1 yr were studied. Patients were followed up for a total of 2 yr, with visits performed every 2 months the first year and every 6 months the following year. Endoscopies for assessment of ulcer relapse were done at 6 and 12 months or in the event of symptomatic relapse. H. pylori status was assessed by culture, immunohistochemistry, and urea breath test at entry, at 6, 12, and 24 months or at failure. The primary endpoint was discontinuation, irrespective of reason. Patients were considered H. pylori negative if all three tests were negative. Patients were considered H. pylori-positive if any of the three diagnostic tests were positive. Study staff were blinded to H. pylori results. RESULTS: Thirty-two (12%) patients were H. pylori negative at entry. There were no differences according to H. pylori status for a number of clinical and demographic characteristics. However, H. pylori-negative patients had a shorter history of ulcer symptoms and were more likely to be NSAID users (19% vs 1%, p < 0.001). Only 28% of the H. pylori-negative patients completed the study, as compared with 40% of H. pylori-positive patients (p = 0.0005). The main reasons for the poorer prognosis in H. pylori-negative patients were relapse of ulcer/ulcer not healed (35% vs 26%) and relapse of severe dyspepsia symptoms without ulcer relapse (16% vs 7%). H. pylori-negative patients randomized to eradication therapy left the study early compared with H. pylori-negative patients randomized to long-term omeprazole therapy. Outcome in omeprazole-treated patients did not differ according to H. pylori status (p = 0.3). CONCLUSIONS: Clinical characteristics in H. pylori-negative and positive duodenal ulcer patients differ little. Clinical outcome over 2 yr is significantly poorer in H. pylori-negative patients, especially if treated empirically with eradication therapy. These results suggest that H. pylori infection should be assessed in all duodenal ulcer patients before treatment is decided.     

Colonization with cagA-positive Helicobacter pylori strains inversely associated with reflux esophagitis and Barrett's esophagus

AIM: The hypothesis that colonization with cagA(+) Helicobacter pylori strains protects against the development of gastroesophageal reflux disease (GERD) and its complications is tested. METHODS: Patients with reflux esophagitis and Barrett's esophagus were studied. Antral biopsy specimens were obtained for detection of H. pylori. A serum sample was obtained for determination of IgG antibodies to H. pylori and to the CagA protein. RESULTS: 736 patients were studied. 118 patients had reflux esophagitis, 36 had Barrett's esophagus, 108 had hiatal hernia without signs of inflammation (the reflux group), and 20 patients had esophageal or stomach cancer. The remaining 454 patients had no signs of GERD. The 262 patients with reflux disease had a significantly lower prevalence of H. pylori (34.9%) than the 454 controls (54.6%; p<0. 001). Among 310 H. pylori-positive patients from whom serum was available, colonization with cagA(+) strains was detected in 59% in the control group versus 35% in the reflux group (p<0.001). Conclusion: Patients with reflux esophagitis and Barrett's esophagus have a significantly lower prevalence of H. pylori colonization than controls, in particular of the cagA(+) type. These data suggest that colonization with cagA(+) H. pylori strains may be protective against the development of GERD Copyright 2000 S. Karger AG, Basel.     

Impact of Helicobacter pylori eradication on the anti-secretory efficacy of lansoprazole in gastroesophageal reflux disease patients

BACKGROUND: Helicobacter pylori eradication was recommended for the prevention of atrophic gastritis in gastroesophageal reflux disease (GERD) patients on long-term omeprazole treatment. It has been also shown that the treatment with proton pump inhibitors produces lower intragastric pH after H. pylori eradication in subjects with peptic ulcer and healthy individuals. The aim of the present study was to test the hypothesis of whether the efficacy of lansoprazole is reduced after the eradication of H. pylori in GERD patients with peptic esophagitis. METHODS: Eight-hour intragastric pH recordings were performed before and after an 8-day course of lansoprazole (30 mg once daily) in 10 H. pylori-positive male patients with reflux esophagitis and were repeated after the H. pylori eradication. Intragastric acidity was measured by using an antimony electrode placed 10 cm below the cardia. RESULTS: Baseline median preprandial, post-prandial, total intragastric pH and the percentage of time with pH < 3 were not different before and after H. pylori eradication without lansoprazole treatment. During lansoprazole treatment, median post-prandial intragastric pH was lower (4 vs 2.7; P < 0.05) and the percentage of time with pH < 3 was longer (3.4%vs 41.8%; P < 0.05) after H. pylori eradication. Median total intragastric pH tended to be lower after eradication but no difference was found in preprandial median pH. CONCLUSIONS: In patients with reflux esophagitis treated with lansoprazole, intragastric pH increased significantly when H. pylori was present, especially in the post-prandial period, whereas baseline pH remained unchanged after H. pylori eradication.     

序贯疗法与三联疗法根除幽门螺杆菌的疗效及对反流性食管炎愈合率的影响

目的比较10天序贯疗法与10天标准三联疗法根除幽门螺杆菌（HP）的疗效,并观察根除HP对反流性食管炎愈合率的影响。方法将76例反流性食管炎合并HP感染的患者随机分为3组：序贯疗法治疗组32例,埃索美拉唑＋阿莫西林,每日2次,共用5天,随后5天用埃索美拉唑＋克拉霉素＋替硝唑,每日2次;三联疗法治疗组24例,埃索美拉唑＋克拉霉素＋阿莫西林,每日2次,疗程10天,两组抗HP疗程结束后继续给予埃索美拉唑,每日2次,总疗程8周;对照组20例：单用埃索美拉唑,每Et2次,疗程8周。疗程结束后复查胃镜,并行HP检测。结果序贯疗法与三联疗法对幽门螺杆菌的根除率分别为87．50％和58．33％,两组比较差异有统计学意义（P〈0．05）。HP根除患者和未根除患者食管炎治愈率分别为83．33％和91．18％,两者比较差异无统计学意义;3组食管炎的治愈率分别为87．50％、83．33％和90％,三者之间比较差异无统计学意义。结论在食管炎患者中,序贯疗法HP根除率明显优于三联疗法;根除幽门螺杆菌对反流性食管炎8周愈合率无明显影响。     

Tolerance to H2 receptor antagonist correlates well with the decline in efficacy against gastroesophageal reflux in patients with gastroesophageal reflux disease

BACKGROUND AND AIM: The attenuated antisecretory activity of H2 receptor antagonists (H2RA) during continuous administration is known as the tolerance phenomenon. The authors recently clarified that presence or absence of Helicobacter pylori infection influences the occurrence of the tolerance phenomenon. The aim of this study was to clarify whether tolerance to H2RA is correlated with attenuation of the inhibitory effect against gastroesophageal acid reflux in patients with gastroesophageal reflux disease (GERD). METHODS: Ten male patients with GERD symptoms and abnormal gastroesophageal reflux were investigated by pH monitoring on days 1 and 15 of continuous oral famotidine administration at 20 mg twice daily, and H. pylori infection was examined using the urea breath test. RESULTS: Intragastric and intraesophageal acidity were significantly decreased on the first day of famotidine administration, but then increased during the 15-day administration period in seven patients who were negative for H. pylori. In contrast, the efficacy of famotidine against gastric acid secretion and gastroesophageal acid reflux was not attenuated in three H. pylori-positive patients. The changes in GERD symptoms were correlated with the change in the degree of gastroesophageal reflux. CONCLUSION: The presence or absence of tolerance to H2RA during 15-day administration is correlated with the efficacy for inhibition of gastroesophageal acid reflux.     

Efficacy of trimebutine therapy in patients with gastroesophageal reflux disease and irritable bowel syndrome

BACKGROUND/AIMS: GERD (gastroesophageal reflux disease) occurs in 25-51% of IBS (irritable bowel syndrome) patients. Trimebutine has been effective in some IBS patients by modulating colonic motility. Furthermore, it increases gastric emptying rates, and controls esophageal motility. The aim of this study was to investigate the efficacy of trimebutine therapy in GERD patients with IBS. METHODOLOGY: Sixty-nine patients with GERD and IBS underwent upper gastrointestinal endoscopic, histologic and clinical evaluation prior to and 3 months post-treatment. H. pylori presence was determined by histology and CLOtest. Forty patients (Group A) were treated with omeprazole plus trimebutine for 3 months: in 32 H. pylori-positive patients (subgroup A1), a standard triple eradication regimen was introduced. Twenty-nine patients (Group B) were treated with omeprazole for 3 months: in 24 H. pylori-positive patients (subgroup B1), the same eradication therapy was employed. RESULTS: Specialized intestinal metaplasia of the gastroesophageal junction was observed in 20% and in 17.2% of the patients in Groups A and B, respectively. Eradication rates were similar in subgroups A1 (84%) and B1 (83%). In Group A there was a significant improvement in GERD (P = 0.003) and IBS symptoms (P < 0.0001) as well as esophagitis (P = 0.029), when compared with Group B. CONCLUSIONS: Trimebutine appears to be effective in patients with GERD and IBS.     

Helicobacter pylori and gastroesophageal reflux disease.

OBJECTIVES: 1. To determine the prevalence of Helicobacter pylori (H. pylori) infection in patients with gastroesophageal reflux disease (GERD), and to compare it with that in a control group. 2. To study the percentage of H. pylori-positive GERD patients according to different grades of esophagitis. MATERIAL AND METHODS: H. pylori prevalence by serological tests was compared among 692 patients with GERD and 200 healthy volunteer controls. Subsequently, the percentage of H. pylori was analyzed in the different grades of esophagitis, according to the Savary-Miller classification. RESULTS: no differences between the GERD group and control group were detected regarding age (50.5+/-14.7 vs 50.7+/-16.4 years, ns) and sex (63 vs 66% of men, ns); on the other hand the prevalence of H. pylori was 40% in the GERD group facing 66% in the control group, p <0.01. There were no differences in H. pylori prevalence according to the different grades of esophagitis, but logistical regression analysis showed that the absence of H. pylori infection was associated with the presence of grade IV esophagitis. CONCLUSIONS: the prevalence of H. pylori infection in GERD patients is lower than that of the general population, and its absence is associated with more severe grades of the disease. These results indicate that H. pylori plays a protective role against GERD.     

Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa

BACKGROUND & AIMS: The efficacy and safety of long-term acid suppression remains a subject for debate. We report data from patients with refractory reflux esophagitis who were undergoing maintenance therapy with >/=20 mg omeprazole daily for a mean period of 6.5 years (range, 1.4-11.2 years). METHODS: Patients with severe reflux esophagitis resistant to long-term therapy with H(2)-receptor antagonists and who were not eligible for surgery were evaluated at least annually for endoscopic relapse and histological changes in the gastric corpus. RESULTS: In 230 patients (mean age, 63 years at entry; 36% were >/=70 years), there were 158 relapses of esophagitis during 1490 treatment years (1 per 9.4 years), with no significant difference in relapse rates between Helicobacter pylori-positive and -negative patients. All patients rehealed during continued therapy with omeprazole at the same or higher dose. The annual incidence of gastric corpus mucosal atrophy was 4.7% and 0.7% in H. pylori-positive and -negative patients, respectively, which was mainly observed in elderly patients who had moderate/severe gastritis at entry. In patients with baseline moderate/severe gastritis, the incidences were similar: 7.9% and 8.4%, respectively. Corpus intestinal metaplasia was rare, and no dysplasia or neoplasms were observed. The adverse event profile was as might be expected from this elderly group of patients. CONCLUSIONS: Long-term omeprazole therapy (up to 11 years) is highly effective and safe for control of reflux esophagitis.     

Effectiveness of acid suppression in preventing gastroesophageal reflux disease (GERD) after successful treatment of Helicobacter pylori infection

There is evidence that Helicobacter pylori eradication might predispose to gastroesophageal reflux disease (GERD). The aim of this prospective study was to examine the effectiveness of antisecretory treatment, after successful H. pylori eradication, in preventing GERD, since no data exist so far. Eighty initially H. pylori(+) patients, without GERD at the time of H. pylori eradication [50 peptic ulcer (PU) and 30 nonulcer (NU), 55 men, 25 women, median age 38 years, range 19–57], after successful H. pylori eradication were randomized to recieve either omeprazole 20 mg daily (group A) or no treatment (group B) for one year. All patients underwent upper gastrointestinal endoscopy at 0, 6, and 12 months or when GERD symptoms occurred. There were 40 patients in each group, and there were no statistically significant differences between the two groups in terms of sex, age, body weight, ulcer/no ulcer ratio, and other demographic data. Seven patients from group A and five patients from group B were lost to follow-up, and therefore there were 33 and 35 patients in groups A and B, respectively, who completed the study. One of 33 patients in group A (3%) and 10/35 (28.5%) in group B developed GERD symptoms during follow-up (P = 0.0022). The respective values for esophagitis were 0/33(0%) and 6/35(17.1%) (P = 0.0083). In conclusion, antisecretory treatment in H. pylori(+) patients, after successful eradication, is effective in preventing GERD.     

Omeprazole versus high-dose ranitidine in mild gastroesophageal reflux disease: short- and long-term treatment. The Dutch Reflux Study Group

OBJECTIVE: Patients with reflux esophagitis suffer from a chronic condition that may cause considerable discomfort because of recurrent symptoms and diminished quality of life. This study was designed to evaluate acute and long-term treatment comparing standard doses of omeprazole and high-dose ranitidine. METHODS: Patients with endoscopically verified symptomatic esophagitis grade I or II were initially treated with omeprazole 20 mg daily or ranitidine 300 mg twice daily for 4-8 wk. Patients who were symptom free were randomized to maintenance treatment with omeprazole 10 mg daily or ranitidine 150 mg twice daily. Patients were seen every 3 months or at symptomatic relapse. RESULTS: The percentage of asymptomatic patients after 4 and 8 wk treatment were 61% and 74%, respectively, for omeprazole and 31% and 50%, respectively, for ranitidine. Of 446 patients treated initially, 277 were asymptomatic, of whom 263 entered the maintenance study. The estimated proportion of patients in remission after 12 months of maintenance treatment with omeprazole 10 mg daily (n = 134) and ranitidine 150 mg twice daily (n = 129) were 68% and 39%, respectively (p < 0.0001). CONCLUSIONS: Omeprazole 20 mg daily is superior to high-dose ranitidine in the symptomatic treatment of reflux esophagitis grade I and II. Furthermore, omeprazole at half the standard dose is more effective than ranitidine in a standard dose in keeping patients in remission for a period of 12 months.     

Gastric Acid Normosecretion Is Not Essential in the Pathogenesis of Mild Erosive Gastroesophageal Reflux Disease in Relation to Helicobacter pylori Status

In the pathogenesis of gastroesophageal reflux disease (GERD), gastric acid is considered to be one of the most important factors, but little is known about the degree of gastric acid secretion in GERD patients. In this study, we evaluated it in GERD patients and control subjects by 24-h intragastric pH, and serological and histological investigations, in relation to Helicobacter pylori (H. pylori) status. In H. pylori-negative GERD patients gastric acid secretion was similar to that in H. pylori-negative control subjects. In H. pylori-positive GERD patients, in particular, mild GERD patients, it decreased significantly compared to that in H. pylori-negative control subjects, but the degree of decrease was smaller than in H. pylori-positive control subjects. Results of serological and histological evaluation were supportive. In conclusion, in some GERD patients, gastric acid secretion was significantly decreased. Increased or maintained gastric acid secretion was not essential in the pathogenesis of mild GERD.     

Effect of Helicobacter pylori eradication on treatment of gastro-oesophageal reflux disease: a double blind, placebo controlled, randomised trial

BACKGROUND: The role of Helicobacter pylori eradication in the management of gastro-oesophageal reflux disease (GORD) is controversial. We hypothesised that H pylori eradication leads to worsened control of reflux disease. METHODS: Consecutive patients with weekly reflux symptoms were prospectively recruited for endoscopy and symptom evaluation. Patients were enrolled if they had H pylori infection and required long term acid suppressants. Eligible patients were randomly assigned to omeprazole triple therapy (HpE group) or omeprazole with placebo antibiotics (Hp+ group) for one week. Omeprazole 20 mg daily was given for eight weeks for healing of oesophagitis and symptom relief. This was followed by a maintenance dose of 10 mg daily for up to 12 months. The primary study end point was the probability of treatment failure within 12 months, which was defined as either incomplete resolution of symptoms or oesophagitis at the initial treatment phase, or relapse of symptoms and oesophagitis during the maintenance phase. Predictors of treatment failure were determined by Cox's proportional hazards model. RESULTS: A total of 236 GORD patients were screened and 113 (47.9%) were positive for H pylori; 104 (92%) patients were included in the intention to treat analysis (53 in the HpE group and 51 in the Hp+ group). Thirty one patients (30%) had erosive oesophagitis at baseline. H pylori was eradicated in 98% of the HpE group and in 3.9% of the Hp+ group. Overall, 15 patients (28.3%) in the HpE group and eight patients (15.7%) in the Hp+ group had treatment failure. The 12 month probability of treatment failure was 43.2% (95% confidence interval (CI) 29.9-56.5%) in the HpE group and 21.1% (95% CI 9.9-32.3%) in the Hp+ group (log rank test, p = 0.043). In the Cox proportional hazards model, after adjustment for the covariates age, sex, erosive oesophagitis, hiatus hernia, degree of gastritis, and severity of symptoms at baseline, H pylori eradication was the only predictor of treatment failure (adjusted hazard ratio 2.47 (95% CI 1.05-5.85)). CONCLUSION: H pylori eradication leads to more resilient GORD.     

Acid-suppressive effects of rabeprazole: Comparing 10 mg and 20 mg twice daily in Japanese Helicobacter pylori-negative and -positive CYP2C19 extensive metabolisers

BACKGROUND: Rabeprazole 10mg b.i.d. is often administered as therapy for eradication of Helicobacter pylori (H. pylori) and is also proposed as therapy for refractory gastro-oesophageal reflux disease. However, there has not been a comprehensive assessment of its acid-suppressive effects. AIMS: To compare the acid-suppressive effects of rabeprazole 10mg b.i.d. with 20mg b.i.d. considering H. pylori status. SUBJECTS: Thirteen H. pylori-negative and eleven H. pylori-positive Japanese CYP2C19 extensive metabolisers (<35 years). METHODS: Intragastric pH was measured for 24h three times in a randomised manner; on day 7 of the repeated administration of rabeprazole 10mg b.i.d. or 20mg b.i.d., or a placebo. RESULTS: In median intragastric pH value and percent time of pH>3.0, >4.0, >5.0, >6.0, and >7.0 for 24h, no significant differences were observed between the two doses in either H. pylori-negative or H. pylori-positive subjects. At either dose, these parameters were significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. Nocturnal acid breakthrough occurred in seven and two of the thirteen H. pylori-negative subjects and one and two of the eleven H. pylori-positive subjects at each dose, respectively. CONCLUSIONS: The effects of rabeprazole 10mg b.i.d. were equal to those of 20mg b.i.d. in H. pylori-positive subjects; whereas in H. pylori-negative subjects, 20mg b.i.d. was superior for prevention of nocturnal acid breakthrough.