High incidence of reflux oesophagitis after eradication therapy for Helicobacter pylori: impacts of hiatal hernia and corpus gastritis

BACKGROUND: Although several recent studies have shown that the eradication of Helicobacter pylori provokes reflux oesophagitis, the results are conflicting. AIM: To investigate the prevalence of reflux oesophagitis in patients after eradication of H. pylori and consider its association with hiatal hernia and corpus gastritis. METHODS: A total of 286 patients who underwent H. pylori eradication therapy and 286 age- and disease-matched H. pylori-positive controls who did not undergo eradication therapy were followed prospectively. All patients and controls underwent endoscopy at 1-year intervals or when upper gastrointestinal symptoms recurred. The presence of hiatal hernia and histology of the gastric corpus were evaluated at the time of initial endoscopy. RESULTS: The estimated prevalence of reflux oesophagitis within 3 years was 18% after eradication therapy and 0.3% without therapy. Patients who developed reflux oesophagitis after therapy had a greater prevalence of hiatal hernia (P=0.0008) and more severe corpus gastritis (P=0.0005) before therapy. Cumulative prevalence of reflux oesophagitis was 26% in patients with hiatal hernia, 7.7% in those without hiatal hernia, 33% in those with corpus atrophic gastritis and 13% in those without corpus atrophic gastritis. When patients had both hiatal hernia and corpus gastritis, the prevalence of reflux oesophagitis was 37%. The newly developed reflux oesophagitis was classified as mild in 35 out of 36 (97%) patients who developed reflux oesophagitis after eradication therapy. CONCLUSIONS: Eradication of H. pylori increased the prevalence of reflux oesophagitis in our patient group. The presence of hiatal hernia and corpus gastritis are closely related to the development of reflux oesophagitis after H. pylori eradication therapy.     

H. pylori eradication in NSAID-associated ulcers

Helicobacter pylori infection and NSAID therapy are each closely associated with gastric and duodenal ulceration. The presence of both could have a major influence on the natural history of such disease or the efficacy of its treatment. Here we discuss the impact of eradicating H. pylori on the development and treatment of ulcers associated with NSAID therapy.     

Sucralfate diminishes basal acid output without affecting gastrin, H. pylori or gastritis in duodenal ulcer patients

Twelve patients with active duodenal ulcer disease and Helicobacter pylori infection were treated with 1 g sucralfate q.d.s. for 1 month. Ulcers healed in 8 of the 12 patients without an alteration in the H. pylori-associated antral gastritis. Sucralfate produced a significant fall in basal acid output in all the patients, from a median of 4.8 (range 2.1-12.1) to 1.6 (0.4-8) mmol/h, P less than 0.01, whereas peak acid output was unchanged from 41 (21-59) before to 38 (24-55) mmol/h after treatment. Basal plasma gastrin concentrations and the meal-stimulated integrated gastrin response were not altered significantly by sucralfate: 8 (2-17) pmol/L and 732 (188-1045) pmol. min/L pre-treatment and 6 (2-17) pmol/L and 600 (140-1302) pmol. min/L post-treatment, respectively. The fall in basal acid output observed may contribute to prolonged duodenal ulcer remission after treatment with sucralfate.     

The long-term effect of Helicobacter pylori eradication therapy on symptoms in dyspeptic patients with fundic atrophic gastritis

AIM: To investigate whether curing Helicobacter pylori infection improves symptoms over the long-term in Japanese patients with nonulcer dyspepsia and fundic atrophic gastritis. METHODS: Ninety H. pylori-positive dyspeptic patients with fundic atrophic gastritis were enrolled in this study. We performed a randomized double-blind placebo-controlled trial comparing triple therapy (n=45) with that of placebo alone (n=45). Inflammation and mucosal atrophy were scored according to the Updated Sydney System. Symptoms were scored on a scale of 0 to 3 for six items. Fasting samples of gastric juice were taken before endoscopy, and gastric pH was determined. Serum gastrin and pepsinogen levels were measured, and body mass index was determined. These patients were followed up for 3 years, and all measures were evaluated both before and after therapy. RESULTS: Significant improvement in dyspeptic symptoms and gastritis scores, significant decrease in gastric pH, and significant increase in body mass index were found after 3 years eradication in nonulcer dyspepsia patients treated successfully for H. pylori infection. There were no significant changes in the placebo group. CONCLUSION: Our study shows that eradicating of H. pylori results in significant long-term reduction in symptoms of nonulcer dyspepsia with fundic atrophic gastritis.     

Helicobacter pylori eradication therapy improves atrophic gastritis and intestinal metaplasia: a 5-year prospective study of patients with atrophic gastritis

AIM: : To investigate the effect of the eradication of Helicobacter pylori on histological gastritis. METHODS: : Twenty-six patients with moderate to severe atrophy received successful eradication therapy of H.pylori. Four patients dropped out and 22 were followed up prospectively for 5 years. The grades of gastritis were estimated from gastric biopsy specimens. The grade of intestinal metaplasia was also evaluated by dye-endoscopy using methylene blue (methylthioninium chloride). The serum levels of pepsinogen, gastrin and anti-parietal cell antibody were also determined. RESULTS: : The grades of atrophy decreased in patients with successful eradication therapy in the gastric corpus (before vs. 5 years after eradication, 2.09 +/- 0.15 vs. 0.91 +/- 0.17; P < 0.01) and in the antrum (2.14 +/- 0.17 vs. 1.36 +/- 0.17; P < 0.01). The levels of intestinal metaplasia were also decreased in the corpus (0.91 +/- 0.24 vs. 0.50 +/- 0.16; P < 0.05) and in the antrum (1.41 +/- 0.20 vs. 1.00 +/- 0.16; P < 0.05), which was also demonstrated by the methylene blue (methylthioninium chloride) staining method (33.4 +/- 8.2% vs. 23.0 +/- 6.5%; P < 0.05). The improvement of corpus atrophy correlated well with the high serum level of pepsinogen I (P = 0.005), but showed no correlation with the levels of anti-parietal cell antibody. CONCLUSIONS: : These results suggest that gastric atrophy and intestinal metaplasia are reversible events in some patients.     

Helicobacter pylori eradication in patients with non-ulcer dyspepsia

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

Role of Helicobacter pylori serology in atrophic body gastritis after eradication treatment

BACKGROUND: It has been reported that 50% of patients with atrophic body gastritis have positive Helicobacter pylori antibody titres only. In atrophic body gastritis, a decrease in H. pylori antibodies after eradication treatment has been reported, suggesting that serology may indicate an active H. pylori infection. AIM: To investigate the time course of H. pylori antibodies and gastric inflammation after eradication treatment in patients with atrophic body gastritis, and to determine whether serology alone can be considered as a valid tool to assess the efficacy of eradication treatment in patients with atrophic body gastritis. METHODS: Twenty-seven patients with atrophic body gastritis (12 serologically H. pylori-positive only, ABG-S+; 15 H. pylori-positive at histology and serology, ABG-H+) were included in the treatment group, and 17 patients (all ABG-S+) in the no treatment group. All patients had gastroscopy plus biopsies evaluated according to the updated Sydney system and H. pylori immunoglobulin G determination: in the treatment group, at baseline and 6 and 24 months after eradication (bismuth-based triple regimens); in the no treatment group, at baseline and after 3 years. RESULTS: In the treatment group, in ABG-S+ patients, H. pylori antibodies decreased significantly 6 months after treatment [37.5 U/mL (16-100 U/mL) vs. 15 U/mL (0--100 U/mL), P < 0.01], but 2 years after treatment no further decrease occurred. In addition, in ABG-H+ patients, a significant decrease in H. pylori antibodies occurred 6 months after treatment [45 U/mL (12.5-100 U/mL) vs. 31 U/mL (0-65 U/mL), P < 0.01], but a further decrease was also observed 2 years after treatment [20 U/mL (0-56 U/mL), P < 0.01]. In ABG-S+ patients, no correlation was observed between the H. pylori antibodies and gastric inflammation score, whereas, in the ABG-H+ group, this correlation was extremely significant (r=0.5991, P < 0.0001). In the no treatment group, at follow-up, a significant decrease in H. pylori antibodies was observed [26 U/mL (15-100 U/mL) vs. 22 U/mL (0-53 U/mL), P < 0.05], but the gastric body inflammation remained unchanged. CONCLUSIONS: This study shows that, in ABG-S+ patients after eradication treatment, serology does not keep in step with gastric inflammation. This suggests that, in patients with atrophic body gastritis, serology alone may not be valid for the assessment of the efficacy of eradication treatment.     

Third-line rescue therapy with levofloxacin is more effective than rifabutin rescue regimen after two Helicobacter pylori treatment failures

BACKGROUND: In patients with a first eradication failure, a second (rescue) therapy still fails in > 20% of cases. AIM: To compare rifabutin and levofloxacin rescue regimens in patients with two consecutive Helicobacter pylori eradication failures. METHODS: Patients, in whom first treatment with omeprazole-clarithromycin-amoxicillin and a second trial with omeprazole-bismuth-tetracycline-metronidazole (or ranitidine bismuth citrate with these antibiotics) had failed, received 10 days of treatment with either rifabutin (150 mg b.d.) or levofloxacin (500 mg b.d.), plus amoxicillin (1 g b.d.) and omeprazole (20 mg b.d.). Cure rates were evaluated by the (13)C-urea breath test. RESULTS: Twenty patients received rifabutin, and 20 levofloxacin. All the patients returned for follow-up. Compliance in the rifabutin group was 100%. Four patients in the levofloxacin group did not take the medication correctly (in two cases due to adverse effects: myalgia and rash). Side effects in the rifabutin and levofloxacin groups were reported in 60% and 50% of the cases, respectively. Five patients (25%) treated with rifabutin presented with leucopenia, and six (30%) treated with levofloxacin presented with myalgias. Per-protocol cure rates were 45% (95% confidence interval, 26-66%) in the rifabutin group, and 81% (57-93%) in the levofloxacin group (P < 0.05). Intention-to-treat cure rates were, 45% (26-66%) and 85% (64-95%), respectively (P < 0.01). CONCLUSIONS: After two previous H. pylori eradication failures, a 10-day triple levofloxacin-based rescue regimen is more effective than the same regimen with rifabutin.     

The effect of Helicobacter pylori eradication on the natural course of atrophic gastritis with dysplasia

BACKGROUND: There are few data on the natural course of Helicobacter pylori-related atrophic gastritis. AIM: To investigate the effect of H. pylori eradication on advanced atrophic gastritis in the corpus. METHODS: Twenty-two elderly men with H. pylori infection and moderate or severe atrophic corpus gastritis formed the study population. These men were under endoscopic surveillance because of the presence of indefinite or definite dysplastic gastric lesions in addition to atrophic corpus gastritis. The men were gastroscopically and bioptically examined four times before they received H. pylori eradication therapy (mean follow-up time, 7.5 years), and once again 2.5 years after eradication therapy. Serum levels of pepsinogen I and H. pylori antibodies were analysed at baseline, immediately before and 2.5 years after eradication therapy. RESULTS: During the 7.5-year period prior to eradication therapy, no significant changes were observed in the mean atrophy and intestinal metaplasia scores or in the mean serum level of pepsinogen I. However, a significant improvement occurred in the mean histological scores of inflammation (from 2.2 to 0.5), atrophy (from 2.2 to 1.2) and intestinal metaplasia (from 1.6 to 1.1) in the corpus mucosa after H. pylori eradication. In addition, the mean serum level of pepsinogen I increased from 16.3 to 25.7 microg/L (P=0.0071, Wilcoxon signed rank test) after eradication therapy. CONCLUSIONS: The results suggest that advanced atrophic corpus gastritis (and intestinal metaplasia) improves and may even heal after the eradication of H. pylori.     

High eradication rates of Helicobacter pylori with a new sequential treatment

BACKGROUND: Eradication rates of Helicobacter pylori with standard triple therapy are disappointing, and studies from several countries confirm this poor performance. AIM: To assess the eradication rate of a new sequential treatment regimen compared with conventional triple therapy for the eradication of H. pylori infection. METHODS: One thousand and forty-nine dyspeptic patients were studied prospectively. H. pylori-infected patients were randomized to receive 10-day sequential therapy [rabeprazole (40 mg daily) plus amoxicillin (1 g twice daily) for the first 5 days, followed by rabeprazole (20 mg), clarithromycin (500 mg) and tinidazole (500 mg) twice daily for the remaining 5 days] or standard 7-day therapy [corrected] [rabeprazole (20 mg), clarithromycin (500 mg) and amoxicillin (1 g) twice daily]. H. pylori status was assessed by histology, rapid urease test and 13C-urea breath test at baseline and 6 weeks or more after completion of treatment. RESULTS: Higher eradication rates were found with the sequential regimen compared to the standard regimen (intention-to-treat: 92% vs. 74%, P < 0.0001; per protocol: 95% vs. 77%, P < 0.0001). Higher eradication rates were also seen in patients with peptic ulcer disease and non-ulcer dyspepsia. In both treatments, compliance was similar (> 90%), as was the rate of side-effects, which were mild. CONCLUSIONS: This 10-day sequential treatment regimen achieves high eradication rates in peptic ulcer disease and non-ulcer dyspepsia.     

莫西沙星与阿莫西林对幽门螺杆菌根除率的对比研究

目的比较莫西沙星与阿莫西林对幽门螺杆菌根除率的临床疗效。方法采用平行对照实验设计,入选幽门螺杆菌阳性的消化性溃疡患者102例,随机分为2组：莫西沙星组（n=52）和阿莫西林组（n=50）。莫西沙星组给予埃索美拉唑20mgbid、构椿酸铋雷尼替丁0．4gbid、莫西沙星（拜复乐）0．4gqd和替硝唑0．5gbid;阿莫西林组给予埃索美拉唑20nagbid、构橼醒铋雷尼替丁0．4gbid、阿莫西林1．0gbid和替硝唑0．5gbid。2组疗程均为7天。治疗结束4周后采用^13 C呼气实验（^13 C-UBT）检查患者幽门螺杆菌的情况。结果莫西沙星组幽门螺杆菌的根除率高于阿莫西林组（94．2％vs80．096）,具有显著性差异（P〈0．05）。结论莫西沙星对幽门螺杆菌的根除率明显优于阿莫西林。     

Effectiveness of two quadruple, tetracycline- or clarithromycin-containing, second-line, Helicobacter pylori eradication therapies

BACKGROUND: There are no guidelines on second-line therapies for Helicobacter pylori eradication failures of omeprazole-clarithromycin-amoxicillin triple therapy. AIM: To compare the efficacy of two second-line therapies for persistent H. pylori infection. METHODS: Over a 6-year period, patients with persistent H. pylori infection following omeprazole-clarithromycin-amoxicillin eradication therapy were randomized to receive omeprazole, 20 mg twice daily, bismuth, 120 mg four times daily, metronidazole, 500 mg twice daily, and either tetracycline, 500 mg four times daily, or clarithromycin, 500 mg twice daily, given for 7 days. Before therapy, patients underwent endoscopy with biopsies for histology, culture and antibiotic susceptibility tests. H. pylori infection was confirmed by histology. RESULTS: Of the 95 randomized patients, 88 (93%) completed the study. Age, sex, smoking, ulcer/non-ulcer dyspepsia ratio and antibiotic resistance were not significantly different between the treatment groups. On intention-to-treat analysis, eradication was achieved in 41 of the 49 patients (84%; 95% confidence interval, 70.4-92.7%) and 27 of the 46 patients (59%; 95% confidence interval, 43.3-73.0%) of the tetracycline- and clarithromycin-containing groups, respectively (P=0.007). On multivariate regression analysis, the sensitivity of H. pylori to metronidazole had a likelihood ratio of 5.2 (P=0.022), followed by the type of quadruple therapy (likelihood ratio, 4.4; P=0.036). CONCLUSIONS: Tetracycline-containing quadruple rescue therapy is highly effective in treating H. pylori eradication failures of the omeprazole-amoxicillin-clarithromycin regimen.     

Bleeding peptic ulcers: audit of eradication treatment for H pylori.

AIMS: To determine the outcomes after presentation with bleeding peptic ulcer and to assess the implementation of H. pylori testing, treatment and follow-up testing. METHODS: Case notes and endoscopy records of patients presenting to Auckland Hospital between 1993-95 were reviewed. Patients were recalled for interview and urea breath test. RESULTS: Mean follow-up after presentation was three years. Eighty-nine patients were reviewed; 62% were confirmed as H. pylori positive, although 20% had no biopsies. H. pylori eradication treatment was given to 49 patients. Thirty-five patients had a definite treatment success; eight were failures (eradication rate of 81%) and six received treatment without proof of H. pylori by biopsy. Forty patients received acid suppression only. Twelve patients had biopsy evidence of H. pylori, and a further nine were proven H. pylori positive at follow-up by urea breath test (initial tests had been negative or not performed). Nine patients had a rebleed; seven were confirmed H pylori positive either at presentation, or by follow-up breath test or endoscopic biopsies. CONCLUSIONS: The incidence of H. pylori in patients with bleeding peptic ulcer is underestimated and many infected patients do not receive eradication treatment. Rebleeding is largely preventable if more attention is given to diagnosis and treatment of H. pylori and follow-up of treatment with a urea breath test.