Our study showed that the frequency of H. pylori infection in the erosive GERD and non-GERD groups was not significantly different. In addition, there was no significant difference in the frequency of H. pylori between mild and severe GERD (Table 3). According to Robust Poisson regression models analysis, some variables including smoking, increased BMI, older age, presence of hiatus hernia, and peptic ulcer diseases (but not H. pylori infection) were significantly associated with GERD compared with the non-GERD group (Table 6). These results, in agreement with some studies (12–14), support the hypothesis that there is no association between the frequency of H. pylori infection and GERD.
GERD is a common GI disorder with different risk factors including obesity, smoking, alcohol use, pregnancy, scleroderma, and some foods or medications (1–3). Lifestyle modification is recommended as the first step in the treatment of GERD. Proton pump inhibitors are the mainstay of medical treatment for GERD if medication is needed, although a possible link between long-term use of these drugs and an increased risk of some side effects has been shown (1, 2, 15). H. pylori, as a common infection, plays an important role in the pathogenesis of various benign and malignant gastroduodenal diseases including gastric ulcer, gastric mucosal lymphoma and gastric cancer (4), however, there is still no agreement on its role in GERD. According to some reports, an inverse relationship between H. pylori and GERD has been observed (5, 16–19), but some other studies have not shown this relationship (12–14).
A study in healthy young Japanese volunteers, conducted by Tanaka et al., aimed to determine the prevalence and risk factors of H. pylori and GERD and their interrelationship. In this study, similar to our results, H. pylori infection had no effect on the prevalence of GERD, but obesity was a risk factor for GERD. They also showed that gender was a risk factor for GERD, but the frequency of smoking or abdominal hernia was not significantly different between groups that was different from our results. (12). Mahdi et al. investigated the association between CagA+ H. pylori and GERD and compared them with the healthy group. They concluded that the presence of H. pylori in patients with GERD was significantly increased compared to controls group (20).
In a research from Iran, 470 patients with dyspepsia and GERD were studied. The rate of H. pylori infection was 78.1%, which was almost similar to our results (Table 3) but the mean age of our patients was lower than their participants. They found no relationship between hiatus hernia and H. pylori, which was inconsistent with our results. (21). In another study from Iran, they did not find any association between H. pylori in patients with GERD compared to controls (22), which was consistent with our results.
Grand et al. conducted a study to examine 184 patients with reflux symptoms who underwent endoscopy with biopsy, esophageal pH-metry, and manometry. They showed that the role of H. pylori infection in the development of GERD as well as in the pathogenesis of esophageal reflux esophagus was not significant but hiatus hernia was significantly associated with the presence of reflux esophagus (23). In a study by Gisbert et al., they used pH-metry and endoscopy to diagnose GERD. In their research, H. pylori infection was not associated with GERD based on both procedures (24). Another study based on esophageal manometry, 24-hour pH monitoring, and EGD showed that GERD features, such as abnormal esophageal acid, erosive esophagus, or Barrett's esophagus, were not related to H. pylori (25), which is consistent with our results.
A prospective study of 146 patients with GERD, to determine the prevalence of H. pylori infection, found that there was no significant evidence for an important role in H. pylori infection in causing GERD and erosive esophagitis. In addition, although there was a significant relationship between hiatus hernia and reflux esophagitis, there was no significant correlation between HP and hiatus hernia, which was completely consistent with our results (26). Two other prospective evaluations by O'Connor et al. and Pieramico et al. also did not support the significant association between H. pylori infection and GERD (27, 28).
A study of 2508 GERD populations by Mari et al. showed that H. pylori infection was observed in 299 (11.9%) patients. Patients with GERD and H. pylori in this study were significantly younger, smoked more, and had less severe esophagitis, which was not similar to our study results (19). In Another study by Wang et al., in a non-erosive esophageal esophagus, showed that H. pylori infection was inversely associated with GERD, whereas male hiatus hernia were important factors associated with GERD (16). Other than the effect of hiatus hernia, other results of this study were inconsistent with our study.
Two studies from Korea showed that H. pylori seropositivity is preventive (17) and absence of H. pylori and male gender were associated with reflux esophagitis (18), which is not consistent with our study. But in one of the mentioned studies, reflux esophagitis was significantly associated with hiatal hernia and BMI that was similar to our results (18). A study by Yalaki et al., aimed at comparing and evaluating the relationship between GERD and H. pylori in adult patients with gastric localization of H. pylori infection and its historical features, the incidence of H. pylori has been shown to be significantly lower in patients with GERD than in the control group. This result is not consistent with the results of our study (5).
In a research from Indonesia, 104 patients with dyspepsia was analyzed to determine the prevalence of GERD and its risk factors. 53.8% of their patients had GERD that, similar to our results, smoking was significantly associated with GERD and most participants were classified as LA grade A. They also showed that higher economies increase the risk of GERD (29). In our study, although the frequency of H. pylori in the rural was significantly higher than the urban participants, there was no significant difference between the two groups in terms of GERD (Table 2,6).
As shown in this Table 4, among our patients with GERD, the frequency of H. pylori infection was significantly higher in those with gastric ulcer than normal gastric findings but in non- GERD group, this difference was not significant. Peptic ulcer disease is commonly associated disease with GERD (2) and EGD plays an important role in the diagnosis and differentiation of benign and malignant GI diseases and its complications include peptic ulcer disease and GERD (8–11). In a retrospective research by Jie et al., 953 peptic ulcer patients, 180 peptic ulcers and GERD patients, and 298 GERD patients were analyzed. They concluded that in patients with GERD, the prevalence of H. pylori infection in gastric ulcer patients was higher than without gastric ulcer (30), which was consistent with our results (Table 4). Moreover, gastric and duodenal ulcers, but not H. pylori infection, were significantly associated with GERD compared with the non-GERD group, according to Robust Poisson regression models analysis (Table 6).
Different treatment regimens have been suggested for H. pylori and some reports have been published on the effect of H. pylori eradication on GERD, however, their results have been inconsistent. (31–37). Although some reports have shown an inverse association between H. pylori eradication with GERD development (33, 35, 36), others have shown no beneficial effect of H. pylori eradication on GERD (31, 32, 34). Finally, there is no consensus on the hypothesis that eradicating H. pylori may cause or worsen GERD (4, 38).
The relationship between H. pylori and GERD is a complex and confusing issue due to the influence of various pathophysiological factors between them (5, 6). One reason for the heterogeneity of the results of previous researches to find the true relationship between H. pylori and GERD may be that the design of many studies was only to find a simple relationship between them, whereas in the final analysis of many of these reports, the effect of confounding factors for this association have not been measured. For instance, The H. pylori infection may make people susceptible to GERD by increasing gastric acid secretion, either directly infecting the gastric-type columnar epithelium, or by the action of noxious substances secreted by the infection into refluxed gastric juice (39). H. pylori seems to lead to much more complex changes in the gastric mucosa, including the modification of afferent neural signals and the secretion of specific gastric hormones. Ghrelin is a hormone that is mainly produced and released by the stomach with numerous functions. Ghrelin, in addition to enhancing gastric secretion, has a potent prokinetic function in the LES; this phenomenon, together with impaired vaginal control, may play a role in the association of H. pylori infection with the development of GERD. Therefore, ghrelin and vagal activity may be missing links that partly explain the relationship between GERD and H. pylori infection (40).
The strength of our study was to analyze the association between GERD and H. pylori infection, taking into account many confounding factors. Other strengths of our study were the size of the considerable sample size, the presence of the comparison group, and the appropriate diagnostic evaluation for all participants. Our research also had limitations. One important limitation was that we included only erosive GERD patients, so the results of this study may not be generalizable to patients with non-erosive reflux disease. Another limitation was that the effects of some pathophysiological factors for both GERD and H pylori were not measured in this study. Endoscopic biopsies to detect H pylori in our study were sent to the laboratory as a mixture of gastric body and antrum in one sample container. It is recommended that in future studies, biopsies of different areas of the stomach be sent to the laboratory in separate sample containers for more accurate evaluation. Finally, this research was conducted in only one center, so a multicenter study is suggested.