The possible role of Helicobacter pylori in GERD

A variety of abnormalities contribute to the development of gastroesophageal reflux disease (GERD) including transient lower esophageal sphincter relaxation, low esophageal sphincter pressure, presence of a hiatal hernia, diminished esophageal clearance of refluxed gastric contents, and alterations in esophageal mucosal resistance. Helicobacter pylori infection clearly plays a role in the pathogenesis of peptic ulcer disease and mucosa associated lymphoma of the stomach and is a definite risk factor for distal gastric cancer. The role of H. pylori infection in GERD remains controversial and incompletely understood. Although H. pylori infection does not cause reflux disease, circumstantial evidence suggests that it may protect against the development of GERD and its complications in some patients. The most likely mechanism whereby H. pylori infection protects against GERD is by decreasing the potency of the gastric refluxate in patients with corpus predominant gastritis. A variety of implications of H. pylori infection on GERD treatment have also arisen in recent years. These focus on the risk of gastric atrophy while on proton pump inhibitor therapy and the efficacy of proton pump inhibitors before and after eradication of H. pylori. This article puts into perspective our current understanding of the complex, incompletely understood relationship between H. pylori infection and GERD.     

幽门螺杆菌与胃食管反流病

幽门螺杆菌（Helicobacter pylori，H．pylori）与胃食管反流病（gastroesophageal reflux disease，GERD）的关系各研究结果不尽一致，流行病学研究表明，在GERD中不仅Mpylori感染率较低，而且cagA的检出率也低，二者都与食管疾病严重程度呈负相关。亦有文献报告H．pylori感染与GERD发生无明显关系。H．pylori对食管保护作用机制可能与其能提高LES压力、降低胃内酸度和影响食管对酸的敏感性有关。有研究表明，H．pylori可以提高质子泵抑制剂的抑酸效果，亦有人认为H．pylori并不影响GERD疗效。因此H．pylori与GERD的关系仍需进一步的临床和基础研究来评价。     

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.     

GERD and H. pylori: is there a link?

The incidence of gastroesophageal reflux disease (GERD) and esophageal adenocarcinoma have increased in recent years as the incidence of peptic ulcer disease and distal gastric cancer have declined. Given the simultaneous decline in Helicobacter pylori infection, it is tempting to propose a relationship between H. pylori infection and these opposing time trends. Although H. pylori infection clearly does not cause GERD, it may protect certain susceptible individuals from developing GERD and its complications. The most likely mechanism in which H. pylori infection protects against GERD is by decreasing the potency of the gastric refluxate in patients with corpus predominant gastritis. A variety of implications of H. pylori infection on GERD treatment have also arisen in recent years. These focus on the risk of gastric atrophy while on proton pump inhibitor therapy and the efficacy of proton pump inhibitors before and after eradication of H. pylori. This article puts into perspective our current understanding of the complex, incompletely understood relationship between H. pylori infection and GERD.     

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.     

Patients with <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection have less severe gastroesophageal reflux disease: a study using endoscopy, 24-hour gastric and esophageal pH metry

Background and aim  

The relationship between gastroesophageal reflux disease (GERD) and Helicobacter pylori is controversial. We evaluated endoscopic, 24-h gastric and esophageal acid profile among patients with GERD in relation to H. pylori, as the latter might alter gastric acid secretion.     

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.     

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.     

Current understandings of Helicobacter pylori, peptic ulcer and gastroesophageal reflux disease

H. pylori infection is a major pathogen inducing gastric mucosal inflammation and causing dysregulation of normal acid inhibitory regulatory mechanisms. The overall effect on gastric acid secretion is dependent on the location and severity of inflammation. Eradication results in healing of gastric mucosal inflammation, healing of peptic ulcers, prevention of new peptic ulcers, prevention or reduction in gastric cancer risk and in transmission of the infection. Neither H. pylori infection nor H. pylori eradication causes gastroesophageal reflux disease (GERD). H. pylori eradication also does not impede anti-secretory drug therapy of GERD. Misunderstandings of the negative association between H. pylori infection and GERD and/or Barrett's esophagus and misuse of the epidemiologic concept of 'protection' led to considerable confusion and likely resulted in some patients receiving poor care. Current evidence is consistent with the notion that H. pylori should be eliminated whenever the organism is found. However, H. pylori infection has become increasing difficult to cure in part due to the emergence of antimicrobial resistance. In Western countries, triple therapy consisting of a proton pump inhibitor, amoxicillin and clarithromycin no longer achieves adequate eradication rates and will soon need to be abandoned. When used, legacy triple therapy should be given for 14 days. Fluorquinolones may temporarily be useful: 10-14 day duration is superior to 7 days. However, worldwide resistance is rapidly increasing. Other potential replacement therapies and strategies are discussed including sequential therapies, high-dose proton pump inhibitor plus amoxicillin, and new quadruple therapies.     

Motion--Helicobacter pylori worsens GERD: arguments for the motion.

There are several reasons for eradicating Helicobacter pylori in patients with chronic gastroesophageal reflux disease (GERD). Perhaps the most compelling is the evidence that chronic acid suppression therapy can lead to the development of atrophic gastritis, a premalignant condition, in patients with H pylori infection. Epidemiological data that suggest that H pylori is less prevalent in GERD patients than in control subjects may be susceptible to publication bias, and confounding social and environmental factors may also be involved. Although it has been thought that eradication of the organism might lead to increased esophageal acid exposure, this has not been demonstrated in practice. Studies that appeared to show that GERD could be provoked by antimicrobial therapy of duodenal ulcers also have methodological weaknesses. Underlying GERD symptoms might be unmasked after withdrawal of acid-suppression therapy, for reasons that are unrelated to H pylori. In fact, eradication of the organism has been shown to decrease heartburn in patients with peptic ulcer disease. When H pylori is successfully eradicated in patients with GERD, relapse rates are not increased, and the disease-free interval seems to be prolonged. Eradication of the organism is a wise policy in patients who face long term acid-suppression therapy for GERD.     

莫沙必利治疗胃食管反流病的随机、双盲、安慰剂交叉对照研究

目前对促胃肠动力药莫沙必利改善中国汉族胃食管反流病（GERD）患者胃食管反流症状和食管运动障碍的作用尚缺乏系统观察。目的：观察莫沙必利对中国汉族人群中GERD患者的治疗作用。方法：采用随机、双盲、安慰剂交叉对照研究设计，选取有典型胃食管反流症状的GERD患者23例行胃食管反流症状评估、食管测压以及24h食管DH和胆红素联合监测，对比研究莫沙必利和安慰剂各1周交叉治疗对胃食管反流症状的改善情况，以及对食管运动功能和胃食管反流事件的影响。结果：与安慰剂治疗相比，莫沙必利治疗可降低胃食管反流总症状积分，加快食管体部蠕动波传导速度，增加湿咽成功率，减少食管下端pH〈4总反流次数和长时间（≥5min）反流次数，降低pH〈4总时间百分比和DeMeester计分，降低食管下端胆汁反流总时间百分比，差异均有统计学意义（P〈0．05）。结论：莫沙必利治疗1周可有效改善本组中国汉族GERD患者的胃食管反流症状，部分改善食管运动障碍以及酸反流和胆汁反流．是治疗GERD安全、有效的药物。     

Effects of environment and lifestyle on gastroesophageal reflux disease

BACKGROUND: Gastroesophageal reflux disease (GERD) is comprised of a spectrum of related disorders, including hiatal hernia, reflux disease with its associated symptoms, erosive esophagitis, peptic stricture, Barrett's esophagus, and esophageal adenocarcinoma. Besides multiple pathophysiological associations among these disorders, they are also characterized by their comorbid occurrence in identical patients and by their similar epidemiologic behavior. The occurrence of GERD is shaped by marked temporal and geographic variations, suggesting the influence of environmental risk factors in the etiology of these diseases. VARIATIONS BY TIME, GEOGRAPHY, AND RACE: Between 1975 and 2005, the incidence of GERD and esophageal adenocarcinoma increased fivefold in most Western countries. The incidence of GERD also appears to be rising in the most developed countries of Asia. All severe forms of GERD, such as erosive esophagitis, peptic stricture, Barrett's metaplasia, and esophageal adenocarcinoma, are more common among whites than other ethnic groups. AFFLUENCE AND OBESITY AS RISK FACTORS: Barrett's esophagus and esophageal adenocarcinoma tend to occur slightly more often in subjects with higher income. Overweight and obesity contribute to the development of hiatal hernia, increase intra-abdominal pressure, and promote gastroesophageal reflux. Weight gain increases reflux symptoms, whereas weight loss decreases such symptoms. Other risk factors, such as smoking, alcohol, dietary fat, or drugs, play only a minor role in shaping the epidemiologic patterns of GERD. PROTECTION THROUGH HELICOBACTER PYLORI: On a population level, a high prevalence of H. pylori infection is likely to reduce levels of acid secretion and protect some carriers of the infection against reflux disease and its associated complications. Several studies have confirmed a lesser prevalence of H. pylori among subjects with than without GERD. Until recently, populations in Africa and Asia may have been protected against the development of GERD and esophageal adenocarcinoma by their higher prevalence of H. pylori infection. CONCLUSION: The study of environmental risk factors may provide an opportunity to better understand GERD and develop a means of its prevention.     

Mechanisms of reflux perception in gastroesophageal reflux disease: a review

Patients with reflux symptoms often do not have excessive esophageal acid exposure, and patients with severe gastroesophageal reflux often do not have reflux symptoms. Understanding why different types of reflux induce symptoms in different patients is vital for addressing therapeutic gaps in the treatment of gastroesophageal reflux disease (GERD). Here we review studies providing insight into how gastroesophageal reflux is perceived, with a focus on comparing reflux characteristics and esophageal sensitivity among subgroups of patients with GERD. The available studies indicate that patients with nonerosive reflux disease have fewer acid reflux episodes and thus less esophageal acid exposure than patients with reflux esophagitis but perceive less intense stimuli because of greater esophageal sensitivity. Reflux characteristics other than acidity, such as the presence of bile, pepsin, liquid, or gas in reflux, and the proximal extent or volume of reflux, may also contribute to symptom perception. Factors contributing to greater esophageal sensitivity may include impaired mucosal barrier function, peripherally mediated esophageal sensitivity (enhanced esophageal receptor signaling), and centrally mediated esophageal sensitivity (physiological stressors, sensitization of spinal sensory neurons). Further insight into mechanisms of reflux perception may require a shift toward studies aimed at understanding predisposing cellular, molecular, and genetic factors.     

Gastroesophageal reflux disease and Helicobacter pylori infection

The prevalence of Helicobacter pylori infection has been decreasing while the prevalence of gastroesophageal reflux disease and esophageal adenocarcinoma has been increasing in developed countries since the 1930s. This has raised concerns that H. pylori infection may protect against esophageal disease and that the disappearance of H. pylori from the population might lead to a further increase in gastroesophageal reflux disease. Some studies have suggested that eradication of H. pylori in patients with duodenal ulcer disease results in an increase in the incidence of erosive esophagitis, whereas other studies have shown no such increase. Studies on gastric acid secretion have demonstrated that proton pump inhibitors are more effective in controlling gastric pH in individuals who are infected with H. pylori. Studies on the impact of therapy in patients with erosive esophagitis have been conflicting. This article reviews each of the issues in the debate separately and concludes that there is little evidence to suggest a major effect of H. pylori eradication on the outcome of gastroesophageal reflux disease.     

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.     

亚太地区胃食管反流病的特点

亚太地区胃食管反流病（GERD）的患病率呈升高态势。第六届上海国际胃肠病学会议上,来自亚洲、欧洲及澳洲的学者就亚太地区GERD的临床表现、流行病学和诊治现状进行了阐述,交流了中国大陆地区GERD的患病情况,如何处理GERD与幽门螺杆菌（H．pylori）感染、胃癌、消化性溃疡的共患病现象,以及在基于症状的GERD诊治中应当顾及到的问题等。     

Bile and acid reflux in long and short segment Barrett's esophagus, and in reflux disease

Gastroesophageal acid reflux (GER) is the primary risk factor for gastroesophageal reflux disease (GERD). In long segment Barrett's esophagus (LSBE) duodenogastroesophageal reflux (DGER) parallels acid reflux. The role of GER and DGER in short segment Barrett's esophagus (SSBE) remains to be determined. The aim of the present prospective study was to investigate the esophageal bile and acid reflux in patients with LSBE, SSBE and patients with GERD. Three groups of patients were studied: Patients with LSBE (n = 12), SSBE (n = 20) and patients with GERD without intestinal metaplasia (n = 33). Subjects underwent esophageal manometry and simultaneous 24-h pH and bile monitoring (Bilitec 2000). The thresholds for GER and DGER were a deMeester score > 14.7 and an absorbance value > 0.2 for 10.9% of total period, respectively. GER did not differ between the groups (p > 0.05). However, DGER differed between patients with LSBE, SSBE and GERD (14.7 vs 2.1 vs 2.1, respectively; p < 0.05). H. pylori status did not influence GER and DGER significantly. In contrast to patients with LSBE the DGER does not seem to play an important role in patients with SSBE and patients with GERD. This result indicates a different etiopathology of both long and short segment Barrett's esophagus.     

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.     

根除幽门螺杆菌与胃食管反流病的关系研究

目的探讨根除幽门螺杆菌（H．pylori）与胃食管反流病（GERD）的关系。方法本研究采用食管内24hpH监测的方法，定量观察H．pylori阳性GERD患者根除H．pylori和单用兰索拉唑治疗3月后食管酸暴露的变化，以及H．pylori阳性慢性浅表性胃炎（CSG）根除H．pylori和姑息治疗3月后食管酸暴露的变化。RE组：反流性食管炎（RE）表现患者60例，按就诊门诊号随机分为治疗组和对照组。治疗组采用丽珠唯三联＋兰索拉唑方案，对照组单用兰索拉唑。CSG组：慢性浅表性胃炎（CSG）患者60例，按就诊门诊号随机分为治疗组和对照组。治疗组均采用丽珠唯三联方案，对照组不采用药物治疗。以上两组待H．pylori根除后，对比研究H．pylori根除组和对照组3月后食管24hpH监测参数。结果RE组：H．pylori根除和单用兰索拉唑治疗3月后两组24h食管pH监测主要观察5项指标均无显著性差异（P〉0．05）。CSG组：H．pylori根除和姑息治疗3月两组24h食管pH监测主要观察5项指标均无显著性差异（P〉0．05）。结论GERD患者根除幽门螺杆菌后食管酸暴露无明显改变，CSG患者根除幽门螺杆菌后食管酸暴露无明显改变，H．pylori感染可能与GERD的转归和发生无关。