Helicobacter pylori eradication and gastroesophageal reflux disease: a Meta-analysis

<正>Objective To systematically evaluate whether eradication of Helicobacter pylori(H.pylori)is associated with the development of endoscopic gastroesophageal reflux disease(GERD)and reflux symptoms.Methods Pub Med,CENTRAL,Embase,CNKI and Wanfang Database from April 1978 to April 2015 were retrieved to collect the randomized controled trials(RCTs)comparing the incidence of reflux symptoms or reflux esophagitis in     

Helicobacter pylori eradication does not exacerbate reflux symptoms in gastroesophageal reflux disease.

BACKGROUND & AIMS: Observational studies have suggested that Helicobacter pylori may protect against gastrointestinal reflux disease (GERD), but these results could be due to bias or confounding factors. We addressed this in a prospective, double blind, randomized, controlled trial. METHODS: H. pylori-positive patients with at least a 1-year history of heartburn with a normal endoscopy or grade A esophagitis were recruited. Patients were randomized to 20 mg omeprazole, 250 mg clarithromycin, and 500 mg tinidazole twice a day for 1 week or 20 mg omeprazole twice a day and identical placebos. A second concurrently recruited control group of H. pylori-negative patients were given open label 20 mg omeprazole twice a day for 1 week. All patients received 20 mg omeprazole twice a day for the following 3 weeks and 20 mg omeprazole once daily for a further 4 weeks. Omeprazole was discontinued at 8 weeks and patients were followed up for a further 10 months. A relapse was defined as moderate or severe reflux symptoms. H. pylori eradication was determined by 13C-urea breath test. RESULTS: The H. pylori-positive cases were randomized to antibiotics (n = 93) or placebo (n = 97). Relapse of GERD occurred in 83% of each of the antibiotic, placebo, and H. pylori-negative groups during the 12-month study period. Life tables revealed no statistical difference between the 2 H. pylori-positive groups (log rank test, P = 0.84) or between the 3 groups (log rank test, P = 0.94) in the time to first relapse. Two patients in each group developed grade B esophagitis at 12 months. CONCLUSIONS: H. pylori eradication therapy does not seem to influence relapse rates in GERD patients.     

The effect of Helicobacter pylori eradication on gastroesophageal reflux disease

BACKGROUND: The effect of Helicobacter pylori (H. pylori) eradication on gastroesophageal reflux disease is controversial. We aimed to investigate the effect of H. pylori eradication in this group of patients. MATERIALS AND METHODS: Thirty-four consecutive patients with H. pylori infection and reflux esophagitis (grade 1 or 2) were enrolled into the study. Twenty-four hour intra-esophageal pH recording and esophageal manometry were performed before and 3 months after eradication of H. pylori, which was achieved using lansoprazole 30 mg b.i.d., amoxycillin 1 g b.i.d., and clarithromycin 500 mg b.i.d. for 14 days. H. pylori was evaluated in biopsy specimens taken from the antrum and corpus by rapid urease test and by histopathologic examination before and 3 months after eradication. RESULTS: Eighteen patients (11 men and 7 women, median age 42 years) completed the study. Three months after the treatment, there was no significant change in any of the 24-hour esophageal pH recording parameters and mean lower esophageal sphincter resting pressure (P > 0.05). The percentage of total time esophageal pH <4 increased in 10 patients, and decreased in 8 patients. There was a significant decrease in the scores of heartburn and regurgitation (P < 0.01). Esophagitis persisted in 16 patients and disappeared in 2 patients. Esophagitis score decreased in 6 patients, and did not change in 12 patients (P < 0.05). CONCLUSION: H. pylori eradication does not have any effect on gastroesophageal acid reflux in patients with reflux esophagitis 3 months after eradication, but significant improvement is achieved in some reflux associated symptoms.     

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.     

Helicobacter pylori infection, pattern of gastritis, and symptoms in erosive and nonerosive gastroesophageal reflux disease.

BACKGROUND: The aim of this study was to evaluate the prevalence of Helicobacter pylori infection and the characteristics of gastritis and symptoms of patients with erosive and nonerosive gastroesophageal reflux disease (GERD). METHODS: We studied 202 consecutive patients with a diagnosis of GERD (symptoms score and endoscopy): group A (n = 110), erosive GERD; group B (n = 92), nonerosive GERD; 200 patients with upper abdominal complaints without abnormalities at endoscopy (functional dyspepsia, group C); and 200 asymptomatic controls tested for H. pylori serum antibody (group D). Antral and body biopsy specimens were taken for histology and the rapid urease test in groups A, B, and C. RESULTS: The prevalence of H. pylori infection was higher in groups B and C (62% and 55%, respectively) than in A and D (36% and 40%) (P < 0.05). In positive patients H. pylori colonization and gastritis grade scores in the gastric body were higher in nonerosive than in erosive GERD and functional dyspepsia (P < 0.05). No differences in H. pylori colonization or gastritis grades were found in the antrum. Fifty-nine patients with nonerosive GERD (64%) and 42 with erosive GERD (38%) showed other dyspeptic symptoms associated with reflux symptoms (P < 0.05). CONCLUSIONS: H. pylori prevalence is higher in patients with nonerosive GERD than in normal subjects and in patients with erosive GERD and similar to that of patients with dyspepsia. Patients with nonerosive GERD often show dyspeptic symptoms and higher H. pylori colonization and inflammation grades in the proximal stomach. Our data support the hypothesis that in GERD H. pylori gastritis may, on the one hand, protect against the development of esophageal erosions and, on the other, contribute to the esophageal hypersensitivity to acid which is a feature of GERD.     

Influence of Helicobacter pylori eradication on reflux esophagitis in Japanese patients

The relationship between Helicobacter pylori eradication and reflux esophagitis is controversial. We analyzed the development of reflux esophagitis and the change in the grade of pre-existing reflux esophagitis after eradication. Enrolled were 559 Japanese patients who received eradication therapy for H. pylori . The grade of reflux esophagitis by endoscopy before and after therapy was evaluated retrospectively. No esophagitis was present before eradication in 526 patients. H. pylori was and was not eradicated in 429 and 97, respectively. Reflux esophagitis developed in 40 of the eradication group and in three of the treatment failure group, with prevalence higher with successful eradication ( P  = 0.04). Successful eradication and hiatus hernia were significant risk factors for reflux esophagitis development. Twenty-seven of 33 patients with pre-existing reflux esophagitis had successful eradication and six treatment failure. The reflux esophagitis grade worsened in two (Los Angeles classification from A to B) and improved in 14 patients after eradication. With treatment failure, reflux esophagitis worsened in none and improved in three patients. There showed no significant change in the grade of pre-existing reflux esophagitis after H. pylori eradication but the sample size was too small to evaluate the difference. In conclusion, the eradication of H. pylori increases the prevalence of reflux esophagitis, and hiatus hernia was a significant risk factor for the development of reflux esophagitis.     

Effect of Helicobacter pylori eradication on gastroesophageal function

BACKGROUND: To elucidate the cause of possible occurrence of reflux esophagitis after Helicobacter pylori eradication, gastric and esophageal function among H. pylori infected Japanese patients were evaluated both before and after eradication therapy. METHODS: Nine H. pylori-positive patients were studied before and 6 months after successful H. pylori eradication. Studies included gastric emptying, esophageal manometry, gastric and esophageal pH monitoring as well as measuring serum levels of gastrin, pepsinogen I and pepsinogen II. RESULTS: Helicobacter pylori eradication was associated with a significant change in serum gastrin and pepsinogen levels, consistent with the improvement in mucosal inflammation. There was no significant change in gastric emptying, fasting or postprandial lower esophageal sphincter (LES) pressure, esophageal primary peristaltic contractions, frequency of transient LES relaxation, or gastroesophageal reflux, as assessed by 24 h pH monitoring. The percent time of the gastric pH>4 at night decreased significantly. A 41-year-old male developed erosive gastroesophageal reflux disease (GERD) (Los Angeles Classification Grade A) after eradication. Physiological studies showed he had abnormal esophageal motility prior to H. pylori eradication. CONCLUSIONS: With the exception of gastric pH at night, most patients did not experience a significant change in gastric or esophageal function after H. pylori eradication. Development of GERD post H. pylori eradication likely reflects an increase in the acidity of the refluxate superimposed on pre-existing abnormalities in gastroesophageal motility.     

Helicobacter pylori: a debated factor in gastroesophageal reflux disease

The prevalence of Helicobacter pylori infection is steadily decreasing in developing countries, and this has been paralleled by an increasing incidence of gastroesophageal reflux disease (GERD) and adenocarcinomas of the esophagus and of the esophagogastric junction. The prevalence of H. pylori infection, which is on the decline in Europe and in the United States, is probably related to improvements in sanitary conditions and socioeconomic status. These epidemiological data do not support a role for H. pylori in the pathogenesis of GERD, but at the same time suggest a negative association with the rising incidence in esophageal diseases. While H. pylori infection clearly does not cause GERD, it may protect certain susceptible individuals from the development of GERD and its complications. There are conflicting reports that GERD can develop after H. pylori eradication and that proton pump inhibitors are less effective in suppressing intragastric acidity in H. pylori negative patients--reasons not to eradicate H. pylori in GERD patients. On the contrary, other data suggest an increase in the development of atrophic gastritis in GERD patients (H. pylori positive) on long-term proton pump inhibitor therapy - a reason to eradicate H. pylori. Preexisting lower esophageal sphincter dysfunction, susceptibility to GERD, unmasking of latent GERD, and patterns and severity of gastritis may be important factors contributing to the development of GERD rather than just the presence or absence of infection with H. pylori.     

Risk factors for the severity of erosive esophagitis in Helicobacter pylori-negative patients with gastroesophageal reflux disease

BACKGROUND: The risk factors for the varying grades of erosive esophagitis (EE) severity could be better understood. For that reason. we evaluated the risk factors associated with EE in patients with gastroesophageal reflux disease. METHOD: We determined the presence and severity of EE (using the Los Angeles Classification) in patients with negative serology Helicobacterpylori who underwent esophagogastroduodenoscopy as part of screening in four prospective, multicenter, randomized, double-blind comparative trials of once-daily esomeprazole and omeprazole for the acute healing of erosive esophagitis. We also examined the baseline characteristics of enrolled patients, and identified risk factors for severe disease using a multivariable logistic regression model. RESULTS: Erosive esophagitis was documented in 6709 patients of a total of 10,294 patients who underwent endoscopy: of these. 34% had grade A. 39% had grade B. 20% had grade C. and 7% had grade D disease. The majority of patients were male (61%) and Caucasian (93%) with a mean age of 46 years. In the regression model, the following were significant independent risk factors for severe (grades C and D) versus mild erosive esophagitis (grades A and B): severe heartburn (adjusted odds ratio 1.79); prolonged heartburn > 5 years in duration (1.16); obesity (1.21); the presence of hiatus hernia (2.13); male gender (1.97); and Caucasian ethnicity (1.53). CONCLUSION: In this large sample of patients with predominantly H. pylori-negative gastroesophageal reflux disease, risk factors for severe erosive esophagitis were the duration and severity of heartburn, and obesity.     

Gastric cardia inflammation: role of Helicobacter pylori infection and symptoms of gastroesophageal reflux disease

OBJECTIVE: Although high prevalences of both chronic inflammation (carditis) and intestinal metaplasia at the gastric cardia have been reported, the pathogenesis is still unclear. This study assesses the role of Helicobacter pylori (H. pylori) infection and symptoms of gastroesophageal reflux disease (GERD) in these histological alterations. METHODS: Consecutive patients who underwent upper endoscopy were enrolled in the study, irrespective of their symptoms. Patients previously treated for H. pylori infection and those using proton pump inhibitors were excluded. Two biopsies were performed in the antrum, two in the gastric body, and two at the gastric cardia. All biopsies were used to look for H. pylori and for histological assessment. RESULTS: A total of 133 patients were enrolled. Carditis and intestinal metaplasia at the cardia were detected in 100 (75.2%) and in 18 (13.5%) patients, respectively. The H. pylori infection rate was significantly higher in patients with carditis than in those without it (87/100 vs 7/33; p < 0.0001), and was higher in those with intestinal metaplasia at the cardia than in those without it (17/94 vs 1/39; p = 0.03). Conversely, the prevalence of GERD symptoms was not significantly different between patients with and without carditis (34/100 vs 16/33; p = NS), and between those with and without intestinal metaplasia (5/50 vs 13/83; p = NS). Interestingly, the prevalence of both H. pylori (64/94 vs 39/94; p = 0.0005) and intestinal metaplasia (18/133 vs 4/133; p = 0.0042) in the gastric cardia was significantly higher than that in gastric body. CONCLUSION: According to our study data, the gastric cardia is frequently infected with H. pylori with consequent development of both carditis and intestinal metaplasia, whereas GERD does not seem to be involved in these histological changes.     

Association of erosive esophagitis with Helicobacter pylori eradication: a role of salivary bicarbonate and glycoprotein secretion

In some populations, Helicobacter pylori eradication is associated with development of erosive esophagitis. The aim of this study was to evaluate the contribution of salivary bicarbonate and glycoprotein secretion to the pathogenesis of erosive esophagitis developing after H. pylori eradication. Gastroscopy and saliva collection were performed at recruitment and 12 months after completion of eradication therapy. Eighty‐eight patients with duodenal ulcer were recruited to the study. Erosive esophagitis was found in 13 patients (grade A, 8 patients; grade B, 4 patients; grade C, 1 patient). Among the 74 subjects who completed the study, erosive esophagitis was detected in 21 patients (grade A, 15 patients; grade B, 6 patients); they all were successfully eradicated. Bicarbonate and glycoprotein secretion was not found to differ significantly between the subjects with and without erosive esophagitis both before and 1 year after H. pylori eradication. However, it was lower in H. pylori‐infected (baseline) than in H. pylori‐noninfected erosive esophagitis subjects (1 year after successful eradication) (bicarbonate 2.34 [1.29–3.40)]vs. 3.64 [2.70–4.58]µmol/min and glycoprotein 0.23 [0.15–0.31]vs. 0.35 [0.28–0.43] mg/min, P= 0.04 and P= 0.04, respectively). We conclude that changes in salivary bicarbonate and glycoprotein secretion related to H. pylori eradication do not promote the development of erosive esophagitis in duodenal ulcer patients.     

Effect of Helicobacter pylori eradication on development of dyspeptic and reflux disease in healthy asymptomatic subjects

BACKGROUND AND AIM: There are few data on the course of Helicobacter pylori infection in asymptomatic subjects. The aim of this study was to assess the effect of eradication therapy on the development of dyspeptic and gastro-oesophageal reflux disease in a cohort of asymptomatic individuals observed over a prolonged period. METHODS: A total of 169 blood donors infected with H pylori who had volunteered for studies on eradication in 1990 formed the cohort. To be included in this cohort subjects had to have no symptoms, as determined by a validated symptom questionnaire at the baseline visit. Eighty eight subjects were infected with H pylori while 81 had successfully undergone eradication therapy. Subjects were followed up (annually) using the same symptom questionnaire and in 2000 they underwent repeat endoscopy. RESULTS: Thirteen subjects developed symptoms during follow up. The incidence of symptoms in H pylori positive subjects was 1.893/100 person-years of follow up and in H pylori negative individuals 0.163/100 person-years of follow up. H pylori infected subjects were significantly more likely to develop symptoms (log rank test, p=0.003) as well as those infected with CagA positive strains (log rank test, p=0.017). The development of symptomatic gastro-oesophageal reflux disease was no different in individuals with and without eradication (odds ratio 0.57 (95% confidence interval 0.26-1.24); p=0.163). CONCLUSIONS: H pylori eradication prevents the development of dyspeptic symptoms and peptic ulcer disease in healthy asymptomatic blood donors and is not associated with an increase in the incidence of symptomatic gastro-oesophageal reflux disease.     

Effect of Helicobacter pylori eradication on the treatment of gastro-oesophageal reflux disease

The important issue of whether Heliobacter pylori eradication leads to increased reflux has been the subject of many apparently contradictory publications, but when we asked two leading authorities to give us their views, there turned out to be considerable consensus, as you can read below.     

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.     

Helicobacter pylori and gastroesophageal reflux disease: a review of this intriguing relationship

A possible association between gastroesophageal reflux disease (GERD) and Helicobacter pylori ( H. pylori ) infection has been the subject of study and debate in recent years. This review discusses the pathophysiological and immunological mechanisms implicated in this relationship. Although gastric secretion in the majority of H. pylori -infected individuals is unaltered, this review considers how the bacteria may interfere with gastric acid production and what role it may play in GERD. We also identify the epidemiological evidence that confirms that GERD develops after the infection has been eradicated. Lastly, we clarify how the host's immune response and bacterial virulence factors interfere with this relationship, explaining the highly conflicting results in the literature.