Risk of Reflux-Related Symptoms and Reflux Esophagitis after Helicobacter pylori Eradication Treatment in the Japanese Population
by
,
Mitsushige Sugimoto
1,2,*
,
Masaki Murata
3,
Eri Iwata
1,
Naoyoshi Nagata
1,
Takao Itoi
4 and
Takashi Kawai
1 
1
Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Shinjuku, Tokyo 160-0023, Japan
2
Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu 520-2192, Japan
3
Department of Gastroenterology, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
4
Department of Gastroenterology and Hepatology, Tokyo Medical University Hospital, Shinjuku, Tokyo 160-0023, Japan
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2021, 10(7), 1434; https://doi.org/10.3390/jcm10071434
Submission received: 5 March 2021
/
Revised: 29 March 2021
/
Accepted: 31 March 2021
/
Published: 1 April 2021
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
Abstract
:Backgrounds: A meta-analysis of reports primarily from Western countries showed no association between Helicobacter pylori eradication and reflux esophagitis development. The risk of reflux esophagitis may differ among different populations based on H. pylori virulence factors and acid secretion ability. We evaluated the prevalence rates of reflux esophagitis in H.-pylori-positive Japanese subjects and assessed risk factors for reflux esophagitis after eradication. Methods: Among 148 H.-pylori-positive subjects who underwent H. pylori eradication from August 2015 to December 2019, we evaluated the prevalence of reflux esophagitis on endoscopy at 12 months after eradication success and the severity of reflux-related symptoms by the F-scale questionnaire at 2 months after treatment and 12 months after eradication success. Results: The prevalence of reflux esophagitis in H.-pylori-positive patients at entry was 2.0% (3/148). At 12 months after eradication success, the prevalence was 10.8% (16/148) (p < 0.01). In the F scale, the median total score before treatment was 4 (range: 0–49), which significantly decreased to 2 (range: 0–22) (p < 0.01) at 2 months after treatment and 3 (range: 0–23) (p < 0.01) at 12 months after eradication success. Following multivariate analysis, the pretreatment total F-scale score was a risk factor for the development of reflux esophagitis (odds ratio: 1.069, 95% confidence interval: 1.003–1.139, p < 0.01). Conclusions: In this H.-pylori-positive Japanese population, eradication therapy was associated with reflux esophagitis in around 10% of patients, particularly in those with severe reflux-related symptoms at baseline. Reflux-related symptoms may improve throughout the 12 months after successful eradication therapy, irrespective of the development of reflux esophagitis.
1. Introduction
Gastroesophageal reflux disease (GERD) is one of the most common upper gastrointestinal diseases worldwide [1]. In Japan, acid-reflux-related symptoms are mild and less frequent than in Western populations [2]. In general, although the pathogenesis of GERD is multifactorial (i.e., frequent and prolonged reflux of gastric acid, status and size of hiatal hernia, severity of esophageal sphincter dysfunction, decrease in esophageal motility dysfunction, increase in hypersensitivity, and status of Helicobacter pylori infection) [3], recent attention has focused on the association of H. pylori with the development of reflux esophagitis [4,5]. In particular, long-term H. pylori infection decreases the stomach’s ability to secrete gastric acid via the progression of gastric mucosal atrophy and exacerbation of gastric mucosal inflammation [6], and H. pylori infection is therefore inversely associated with the development of reflux esophagitis [7,8,9]. Because the incidence of reflux esophagitis differs among different populations, however, it is unknown whether the association of reflux esophagitis with H. pylori is similar among different populations.
Although eradication therapy for H. pylori infection reduces the risk of gastric cancer development and esophageal cancer, consistent with the H. pylori protective theory [10,11], it is unclear whether H. pylori eradication increases the risk of reflux esophagitis. Eradication therapy for H. pylori infection is considered to increase the severity of esophageal damage and reflux-related symptoms in patients with reflux esophagitis, and after eradication, around 10% of patients experience reflux-related symptoms, irrespective of their experience with reflux-related symptoms before eradication therapy [12]. However, a recent meta-analysis using reports primarily from Western countries showed no association between H pylori eradication and reflux esophagitis [4,5,13,14,15]. Because only a few reports from Japan have investigated reflux esophagitis after eradication [16], and given that the genetic, social, and bacterial background related to acid secretion differs between Western and East Asian populations [17,18], a study focused on a Japanese population may be valuable in clarifying associations with H. pylori infection, acid secretion, reflux esophagitis, and reflux-related symptoms.
Accordingly, the aims of this study were: (1) to determine the prevalence of reflux esophagitis and reflux-related symptoms in H.-pylori-positive Japanese patients; (2) to evaluate the association between H. pylori eradication and reflux esophagitis in the Japanese population; and (3) to investigate the risk of reflux esophagitis after eradication in the Japanese population.
2. Materials and Methods
2.1. Patients and Study Protocol
The protocol of this study was reviewed and approved by the Institutional Review Board of Shiga University of Medical Science. This study enrolled 148 H.-pylori-positive patients from August 2015 to December 2019 (Table 1). Inclusion criteria were age ≥20 years with H. pylori infection, no medication by vonoprazan, proton pump inhibitor (PPI) and histamine 2 receptor antagonist (H2RA), performance of endoscopy to evaluate reflux esophagitis before eradication therapy and at 12 months after eradication success, use of a questionnaire to evaluate reflux-related symptoms before eradication therapy and at 2 months after treatment and 12 months after eradication success in our University Hospital, and conclusive evaluation of eradication outcome by the 13C-urea breath test (UBIT 100 mg tablets, Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan, using a cut-off of 2.5‰). Because this study was conducted under a retrospective observational design and written informed consent was not obtained from each enrolled patient, a document that reported an opt-out policy by which potential patients and/or relatives could refuse inclusion was uploaded on the web page of Shiga University of Medical Science Hospital. The study protocol conformed to the ethical guidelines of the Declaration of Helsinki [19].
H. pylori infection was diagnosed in all patients using the rapid urease test (Helicocheck®; Institute of Immunology, Co., Ltd., Tochigi, Japan) and a culture test (BML, Inc., Tokyo, Japan). Patients were diagnosed H. pylori infection positive if at least one of the two tests was positive.
For bacterial culture and antimicrobial sensitivity testing, agar plates were inoculated with biopsy specimens and incubated at 37 °C under microaerophilic conditions (5% O2, 10% CO2, and 85% N2) for approximately 7 days at 37 °C. H. pylori was identified using oxidase production. H. pylori colonies were subcultured using the agar dilution method to determine the minimum inhibitory concentration (MIC) for amoxicillin, metronidazole, clarithromycin, and sitafloxacin, according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI) [20] and the manufacturer’s instructions. Cut-off MICs used to define resistance were >1.0 µg/mL for clarithromycin and sitafloxacin and >8 µg/mL for metronidazole [21,22,23]. For amoxicillin, the cut-off MICs used to define resistance and the absence of sensitivity were >0.5 and >0.06 µg/mL, respectively.
All H.-pylori-positive patients underwent gastroduodenal endoscopy for evaluation of the presence of reflux esophagitis, Barrett’s esophagus, and hiatal hernia, as well as the endoscopic severity of gastritis. Patients infected with H. pylori received eradication treatment, as below. At 6 to 8 weeks after eradication treatment, success was evaluated by the 13C-urea breath test with a cut-off value of 2.5 ‰. At 12 months after eradication success, the development of reflux esophagitis was evaluated by endoscopy. It is usually recommended to undergo a second endoscopy after 12 months for patients by the guidelines for the management of Helicobacter pylori infection in Japan [24]. Patients were also evaluated at 2 months after treatment and 12 months after eradication success for the severity of abdominal symptoms using the F scale [25,26]. Significant differences in reflux-related symptoms before eradication therapy and at 2 months after treatment and 12 months after eradication success were evaluated. Patients were not evaluated at 12 months after eradication success for the presence of H. pylori by the urea breath test or other tests.
2.2. H. pylori Eradication Therapy
In Japan, as the standard of care, H. pylori eradication therapies are currently limited to regimens comprising acid-inhibitory drugs such as a PPI or vonoprazan, amoxicillin, and clarithromycin for 7 days as a first-line eradication regimen, as well as PPI or vonoprazan, amoxicillin, and metronidazole for 7 days as a second-line eradication regimen [24]. Given that a recent meta-analysis showed greater efficacy for vonoprazan-containing regimens compared with a PPI-containing regimen [27], all patients in the present study underwent eradication with vonoprazan 20 mg twice-daily dosing (bid) and a combination of two antibiotics, namely clarithromycin (200 mg bid) and amoxicillin (750 mg bid) as first-line eradication treatment (n = 107), metronidazole (250 mg bid) and amoxicillin (750 mg bid) as second-line treatment (n = 26), and sitafloxacin (100 mg bid) and amoxicillin (500 mg bid) as third-line treatment (n = 15), all for 7 days. When initial eradication therapy failed, patients received advanced eradication therapy, namely a second-line eradication regimen for patients who failed a first-line regimen, a third-line regimen for patients who failed a second-line regimen, and a fourth-line regimen (sitafloxacin (100 mg bid) and metronidazole (250 mg bid)) for those who failed a third-line regimen.
2.3. Endoscopy and Severity of Gastritis
Reflux esophagitis was assessed according to the Los Angeles classification (grades A to D) [28]. In addition, redness was endoscopically defined as mucosal findings of redness, edema, or white granules in the EG junction, irrespective of the presence of reflux-related symptoms. GERD was defined as reflux esophagitis or redness.
Severity of gastritis was evaluated using the Kyoto classification [29,30]. Barrett’s esophagus was diagnosed endoscopically if columnar-appearing mucosa was observed between the squamocolumnar and EG junction. Hiatal hernia was diagnosed when greater than 2 cm dislocation of EG junction toward the esophageal site was found endoscopically [31].
2.4. Data Analysis
Values for age, height, and body weight are given as the mean ± standard deviation (S.D.). Scores for the Endoscopic Kyoto classification and the questionnaire are given as the median and range. The eradication rate of H. pylori was evaluated by intention-to-treat (ITT) analysis and calculated with 95% confidence intervals (CIs). Statistically significant differences in endoscopic scores and symptom scores among the three groups (non-GERD, redness, and reflux esophagitis) were determined by the Mann–Whitney U test when significant differences were observed by the Kruskal–Wallis test. To determine whether endoscopic and symptom scores differed among the observational time points (0, 2, and 12 months), the Wilcoxon signed-rank test was used. Statistically significant differences in mean values of age, height, and body weight among the three groups (non-GERD, redness, and reflux esophagitis) were determined by one-way ANOVA followed by the Scheffé multiple comparisons test. Statistically significant differences in category data among the three groups were determined by the χ2 test. Univariate and multivariate logistic regression analyses were used to test the associations of 16 candidate variables with the development of reflux esophagitis. Multicollinearity among the variables was tested using the variance inflation factor (VIF). The multivariate analysis examined the risk of reflux esophagitis using factors that showed p < 0.2 in the univariate analysis with adjustment for age and sex. A value of p < 0.05 was considered statistically significant and all p-values were two-sided. Calculations were conducted using SPSS version 20 (IBM Inc.; Armonk, NY, USA).
The sample size and power were calculated by the t-test and set such that the effects size was 0.3, the correlation coefficient was 0.6, the desired power was 80%, with a significance level of 0.05 in a two-sided test, and the required sample number was 134. In addition, we expected that 10% of patients enrolled in the study would delete by loss of data; we therefore aimed to enter 148 patients for a valid analysis.
3. Results
3.1. Patient Characteristics
Of the 148 H.-pylori-positive Japanese patients, the prevalence of reflux esophagitis findings on endoscopy at baseline was 2.0% (3/148), and a total of 21.6% (32/148) had redness (Table 1). Most characteristics and endoscopic findings were similar among the redness, reflux esophagitis, and non-GERD groups (Table 1). In addition, in the F-scale questionnaire, all scores in H.-pylori-positive patients for redness, reflux esophagitis, and the non-GERD groups at baseline were similar (Table 1).
Eradication rates in the ITT analysis were 85.0% (95% CI: 76.9–91.2%, 91/107) for first-line therapy, 88.5% (95% CI: 69.8–97.6%, 23/26) for second-line therapy, and 93.3% (95% CI: 68.1–99.8%, 14/15) for third-line therapy. Twenty patients who failed initial eradication therapy received advanced eradication therapy, which was successful in all patients.
3.2. Endoscopic Reflux Esophagitis after H. pylori Eradication Therapy
At 12 months after eradication success, esophagitis was evaluated using endoscopy. The prevalence of GERD was 10.8% for reflux esophagitis (16/148), including 6.8% GERD grade A (10/148), 4.1% grade B (6/148), and 17.6% redness (26/148) (Table 2). The prevalence of reflux esophagitis differed between baseline and after treatment (2.0% (3/148) vs. 10.8% (16/148), p < 0.01). Reflux esophagitis developed de novo in 7.1% (8/113) in the non-GERD group at pretreatment and in 18.8% (6/32) in the redness group (Table 3).
There was no significant difference in rates of hiatus hernia and SSBE, or in the severity of endoscopic atrophy and intestinal metaplasia, among the redness, reflux esophagitis, and non-GERD groups at 12 months after eradication success (Table 2). For the F scale, the acid reflux, dysmotility-related, and total scores in the reflux esophagitis group were higher than those in the non-GERD group (Table 2).
3.3. Symptomatic Reflux Esophagitis after H. pylori Eradication Therapy
At 2 months after treatment and 12 months after eradication success, acid-reflux-related symptoms were evaluated. The acid reflux, dysmotility-related, and total scores in the F scale were significantly decreased from scores at baseline (median total score of the F-scale questionnaire: 4 (range: 0–49) at baseline, 2 (range: 0–22) at 2 months after treatment (p < 0.01), and 3 (range: 0–23) at 12 months after eradication success (p < 0.01)) (Figure 1).
3.4. Reflux Esophagitis after H. pylori Eradication and Outcome of Eradication Therapy
The total score for the F-scale questionnaire at 2 months after treatment showed significant differences between patients with successful (n = 128) and failed treatment (n = 20) (p = 0.04) (Figure 2). Acid reflux scores, dysmotility-related scores, and total scores in patients with failed treatment did not differ between pretreatment and after treatment, while scores in patients with successful treatment decreased (Figure 2).
3.5. Time Course of F-Scale Questionnaire Scores between Patients with Non-Erosive and Reflux Esophagitis
When we compared the scores for the F-scale questionnaire in patients with reflux esophagitis and patients with redness, baseline scores were similar between the two groups. The acid reflux, dysmotility-related, and total scores significantly differed between the two groups at 2 months after treatment (p < 0.01, 0.02 and <0.01, respectively) and 12 months after eradication success (p < 0.01, <0.01, and <0.01) (Figure 3). The acid reflux, dysmotility-related, and total scores in patients with no erosive esophagitis significantly decreased from pretreatment to 2 months after treatment and 12 months after eradication success. In contrast, scores in patients with reflux esophagitis showed no remarkable changes between pretreatment and 2 months after treatment and 12 months after eradication success (Figure 3).
We evaluated associations with scores of the F-scale questionnaire and different categories using sex, SSBE, and hiatal hernia (Table 4). The acid-related and total F-scale scores at entry (before eradication therapy) significantly differed among groups based on sex, SSBE, and hiatus hernia (p < 0.01 and p = 0.03, respectively). The F-scale scores in patients with both SSBE and hiatus hernia were higher than SSBE-negative, hiatal-hernia-negative, or both-negative patients, irrespective of sex, both before eradication therapy and at 12 months after eradication success.
3.6. Risk Factors for Reflux Esophagitis after H. pylori Eradication Therapy
On univariate analysis, risk factors for reflux esophagitis development were the total baseline F-scale score (OR: 1.069, 95% CI: 1.009–1.132, p = 0.02) and the dysmotility-related score of the F scale at pretreatment (1.200, 1.055–1.364, p < 0.01) (Table 5). Following multivariate analysis using factors showing p < 0.2 in the univariate analysis (hiatal hernia and total score of F scale) and age and sex as adjustment factors, the total baseline F-scale score was again shown to be a significant risk factor (OR: 1.069, 95% CI: 1.003–1.139, p = 0.04) (Table 5).
4. Discussion
We investigated the association between H. pylori eradication therapy and reflux esophagitis development in Japanese subjects, who are generally at lower risk of reflux esophagitis than Western populations. This H.-pylori-positive cohort had a GERD rate of 23.6%, including 2.0% with reflux esophagitis and 21.6% with redness. In addition, although H. pylori eradication may affect the severity of reflux esophagitis and reflux-related symptoms, and de novo reflux esophagitis was revealed in 4.8–20.5% of Japanese H.-pylori-positive patients after eradication [12], the prevalence of reflux esophagitis at 12 months after eradication success was 10.8%. On the other hand, questionnaires revealed that reflux-related symptoms were improved at 2 months after treatment and 12 months after eradication success, especially in patients with successful treatment and patients without GERD or reflux esophagitis.
In a meta-analysis of cohort studies, the prevalence of H. pylori in GERD patients was 38.2%, which was lower than that in patients without GERD (49.5%, OR: 0.58) [32]. In general, while GERD results from abnormal transient lower esophageal sphincter relaxation (TLESR) and an imbalance between esophageal mucosa exposure to acid and clearance mechanisms [33,34], the acidity of gastric juice, volume of gastric juice, and frequency of acid reflux into the esophagus also plays a role in the development of reflux esophagitis and symptoms. H. pylori is similarly known to potently inhibit gastric acid secretion through progressive atrophic changes in acid-producing gastric mucosal cells and the infiltration of activated inflammatory cells that secrete proinflammatory cytokines (e.g., IL-1β and TNF-α) [6]. In addition, as host genetic factors, the TNF-A, IL-1B, and IL-1RN genetic polymorphisms, which influence serum and gastric mucosal TNF-α and IL-1β levels, are inversely associated with the risk of reflux esophagitis development in H.-pylori-positive patients because their specific genotypes (e.g., IL-1B-511 T/T, IL-1RN *2/*2, TNF-A-857 T/T, -863 A/A, and -1031 C/C types) are linked to severe gastric mucosal atrophy, development of peptic ulcers and gastric cancer, and hypochlorhydria [6]. Infection with H. pylori strains with high virulence factors induces a more severe degree of gastric mucosal inflammation with hypochlorhydria. Epidemiological studies show that infection with the H. pylori cagA-positive strain is strongly negatively related to the development of reflux esophagitis [35]. However, because the infection rate of H. pylori is decreasing year by year, the prevalence of reflux esophagitis is expected to increase.
Many studies have evaluated the effects of H. pylori eradication on the development of reflux esophagitis and/or GERD, but results have been inconsistent and inconclusive [5]. The Maastricht V Consensus Report recommended that H. pylori eradication therapy should not exacerbate pre-existing reflux esophagitis or affect treatment efficacy [36]. A recent meta-analysis evaluated whether eradication therapy affects the prevalence of GERD or reflux esophagitis and the severity of GERD or reflux esophagitis and found no significant difference in the prevalence of reflux esophagitis and/or GERD after eradication between patients with successful and unsuccessful eradication, irrespective of follow-up period after treatment or the presence or absence of baseline disease [5]. The frequency of GERD or reflux esophagitis was similar between patients with successful and unsuccessful eradication at 6 months (OR: 1.85, 95% CI: 0.68–5.04; p = 0.23) and 12 months (OR: 0.99, 95% CI: 0.64–1.52; p = 0.97) [5]. However, most of the studies included in this meta-analysis were from Europe and North America. Schwizer et al. [37] reported that eradication therapy did not result in the recovery of gastric acid secretion after eradication therapy in Western populations. In our meta-analysis, which focused on reflux esophagitis with endoscopic mucosal injury, we showed that incidences of de novo reflux esophagitis in Western and East Asian populations in the eradication group were 9.1% (132/1444; control noneradication group, 4.5%, 53/1176) and 21.2% (324/1530; control noneradication group, 10.7%, 48/447), respectively [38]. An East Asian report [39] showed that the total percentage of time at pH < 2 (2.1 ± 0.5 vs. 0.8 ± 0.2) increased in the eradication group compared with the noneradication group. Recently, a large study of 10,102 H.-pylori-positive Korean patients revealed that eradication therapy increased the prevalence of reflux esophagitis to 4.9% (490/10,102) [40]. In the present study, endoscopy showed a 10.8% rate of reflux esophagitis (16/148) at 12 months after eradication success. These differing results for the development of GERD or reflux esophagitis after eradication between Western and East Asian populations may be ascribable to differences in lifestyle, genetic factors, and/or virulence factors of H. pylori strains.
In a previous meta-analysis, no significant differences were observed in the incidence of “heartburn” between H.-pylori eradicated patients and infected patients [38]. In this study, however, reflux-related symptoms evaluated by the F-scale questionnaire (combined scores of seven questions) significantly improved from baseline in all patients (Figure 1). In double-blind RCTs, H. pylori eradication decreased the severity of reflux-related symptoms in patients with duodenal ulcers [41]. Saad et al. [13] reported a significantly lower prevalence of reflux-related symptoms in the eradication group (13.8%) than the noneradication group (24.9%) (OR: 0.55, 95% CI: 0.35–0.87). However, it is unknown why reflux-related symptoms improve after eradication in East Asian populations with risk of reflux esophagitis after eradication. In this study, reflux-related symptoms in patients with GERD showed no remarkable changes throughout the observation period, as shown in Figure 3. This observation suggests that reflux-related symptoms in H.-pylori-positive symptomatic patients without GERD improved after eradication therapy and that most reflux-related symptoms on the F scale may be considered to be H. pylori infection-related abdominal symptoms, namely H.-pylori-associated dyspepsia. A meta-analysis reported that eradication therapy was effective in approximately 10% of functional dyspepsia patients, especially in Asian populations [42]. In addition, the Kyoto Global Consensus Meeting recently defined H.-pylori-associated dyspepsia as a condition in which abdominal symptoms disappeared or improved 6–12 months after eradication treatment [43]. On this basis, the improvement in abdominal symptoms after eradication in H.-pylori-positive patients might be attributable to improved H.-pylori-related and functional dyspepsia-related symptoms rather than to GERD-related symptoms, irrespective of the recovery of acid secretory ability after eradication therapy. We consider that it would be better to investigate the association of outcome of eradication therapy and improvement in reflux-related symptoms using 24 h intragastric and intraesophageal pH monitoring, as a further study.
Antimicrobial Stewardship Team (AST)-orientated treatment in Japan is major for most infectious diseases. In Japan, however, H. pylori eradication therapies are currently limited by the Japanese insurance system to regimens comprising an acid-inhibitory drug bid, amoxicillin 750 mg bid, and clarithromycin 200 mg or 400 mg bid for 7 days as a first-line eradication regimen, as well as PPI or VPZ bid, amoxicillin 750 mg bid, and metronidazole 250 mg bid for 7 days as a second-line eradication regimen, irrespective of the infection of resistant strains to antimicrobial agents [24]. Therefore, AST-orientated treatment is not given for H. pylori infection in Japan. I think that susceptibility-based tailored treatment should be selected for H. pylori eradication therapies in Japan.
This study has a few limitations. First, this is a single-center retrospective study with a small sample number. Second, although reflux esophagitis has multifactorial pathogenesis related to gastric acid and esophageal dysfunction and is influenced by the intake of PPI/vonoprazan and other medications (nonsteroidal anti-inflammatory drugs, aspirin, and calcium channel blockers), we had no data on intake of medications. Third, because this study did not enroll H.-pylori-positive patients who did not receive H. pylori eradication therapy, it is unclear whether the rate of de novo reflux esophagitis after eradication therapy is high or not. Fourth, because we did not limit the medication of acid secretion inhibitors after H. pylori eradication therapy, two patients received additional PPI therapy for reflux-related abdominal symptoms after successful H. pylori eradication therapy. This is considered to be a major methodological problem. Fifth, the sample size of this study is not great, and because this study was performed in Japan, as a single-center retrospective study, this study might have a bias of diagnosis/association for esophagitis
5. Conclusions
We found that the prevalence of erosive gastritis in Japanese H.-pylori-positive patients is <3% and that eradication for H. pylori infection is a risk factor for the de novo development of endoscopic reflux esophagitis, especially in patients with severe abdominal symptoms at baseline. However, eradication improved symptoms over a long period. Because H. pylori eradication effectively reduces the risk of gastric cancer development, irrespective of a past history of previous cancer, we recommend eradication therapy for H. pylori infection, as currently suggested by the treatment guidelines [36]. A comprehensive investigation of the development of reflux esophagitis and reflux-related symptoms after eradication therapy will be aided by prospective randomized trials enrolling both Western and East Asian populations (eradication group vs. placebo group) and considered confounding factors.
Author Contributions
Conceptualization, M.S.; methodology, M.S.; software, M.S.; formal analysis, M.S.; investigation, M.S. and M.M.; writing—original draft preparation, M.S.; writing—review and editing, M.S., M.M., E.I., N.N., T.I. and T.K.; supervision, M.S.; project administration, M.S. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of Shiga University of Medical Science.
Informed Consent Statement
Patient consent was waived. Because this study was conducted under a retrospective observational design and written informed consent was not obtained from each enrolled patient, a document that reported an opt-out policy by which potential patients and/or relatives could refuse inclusion was uploaded on the web page of Shiga University of Medical Science Hospital.
Conflicts of Interest
None of the authors have any conflicts of interest related to this study.
References
- Heading, R.C. Prevalence of upper gastrointestinal symptoms in the general population: A systematic review. Scand. J. Gastroenterol. Suppl. 1999, 231, 3–8. [Google Scholar] [PubMed]
- Fujiwara, Y.; Arakawa, T. Epidemiology and clinical characteristics of GERD in the Japanese population. J. Gastroenterol. 2009, 44, 518–534. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Miwa, H.; Minoo, T.; Hojo, M.; Yaginuma, R.; Nagahara, A.; Kawabe, M.; Ohkawa, A.; Asaoka, D.; Kurosawa, A.; Ohkusa, T.; et al. Oesophageal hypersensitivity in Japanese patients with non-erosive gastro-oesophageal reflux diseases. Aliment. Pharmacol. Ther. 2004, 20 (Suppl. 1), 112–117. [Google Scholar] [CrossRef] [PubMed]
- Tan, J.; Wang, Y.; Sun, X.; Cui, W.; Ge, J.; Lin, L. The effect of Helicobacter pylori eradication therapy on the development of gastroesophageal reflux disease. Am. J. Med. Sci. 2015, 349, 364–371. [Google Scholar] [CrossRef]
- Qian, B.; Ma, S.; Shang, L.; Qian, J.; Zhang, G. Effects of Helicobacter pylori eradication on gastroesophageal reflux disease. Helicobacter 2011, 16, 255–265. [Google Scholar] [CrossRef]
- Furuta, T.; El-Omar, E.M.; Xiao, F.; Shirai, N.; Takashima, M.; Sugimura, H.; Sugimurra, H. Interleukin 1beta polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan. Gastroenterology 2002, 123, 92–105. [Google Scholar] [CrossRef] [PubMed]
- McColl, K.E.; Dickson, A.; El-Nujumi, A.; El-Omar, E.; Kelman, A. Symptomatic benefit 1-3 years after H. pylori eradication in ulcer patients: Impact of gastroesophageal reflux disease. Am. J. Gastroenterol. 2000, 95, 101–105. [Google Scholar] [CrossRef]
- Labenz, J.; Blum, A.L.; Bayerdorffer, E.; Meining, A.; Stolte, M.; Borsch, G. Curing Helicobacter pylori infection in patients with duodenal ulcer may provoke reflux esophagitis. Gastroenterology 1997, 112, 1442–1447. [Google Scholar] [CrossRef]
- Hamada, H.; Haruma, K.; Mihara, M.; Kamada, T.; Yoshihara, M.; Sumii, K.; Kajiyama, G.; Kawanishi, M. High incidence of reflux oesophagitis after eradication therapy for Helicobacter pylori: Impacts of hiatal hernia and corpus gastritis. Aliment. Pharmacol. Ther. 2000, 14, 729–735. [Google Scholar] [CrossRef]
- Kumar, S.; Metz, D.C.; Ginsberg, G.G.; Kaplan, D.E.; Goldberg, D.S. Oesophageal and proximal gastric adenocarcinomas are rare after detection of Helicobacter pylori infection. Aliment. Pharmacol. Ther. 2020, 51, 781–788. [Google Scholar] [CrossRef]
- Sugimoto, M.; Murata, M.; Yamaoka, Y. Chemoprevention of gastric cancer development after Helicobacter pylori eradication therapy in an East Asian population: Meta-analysis. World J. Gastroenterol. 2020, 26, 1820–1840. [Google Scholar] [CrossRef]
- Yamamori, K.; Fujiwara, Y.; Shiba, M.; Watanabe, T.; Tominaga, K.; Oshitani, N.; Matsumoto, T.; Higuchi, K.; Arakawa, T. Prevalence of symptomatic gastro-oesophageal reflux disease in Japanese patients with peptic ulcer disease after eradication of Helicobacter pylori infection. Aliment. Pharmacol. Ther. 2004, 20 (Suppl. 1), 107–111. [Google Scholar] [CrossRef] [PubMed]
- Saad, A.M.; Choudhary, A.; Bechtold, M.L. Effect of Helicobacter pylori treatment on gastroesophageal reflux disease (GERD): Meta-analysis of randomized controlled trials. Scand. J. Gastroenterol. 2012, 47, 129–135. [Google Scholar] [CrossRef] [PubMed]
- Yaghoobi, M.; Farrokhyar, F.; Yuan, Y.; Hunt, R.H. Is there an increased risk of GERD after Helicobacter pylori eradication?: A meta-analysis. Am. J. Gastroenterol. 2010, 105, 1007–1013. [Google Scholar] [CrossRef]
- Raghunath, A.S.; Hungin, A.P.; Wooff, D.; Childs, S. Systematic review: The effect of Helicobacter pylori and its eradication on gastro-oesophageal reflux disease in patients with duodenal ulcers or reflux oesophagitis. Aliment. Pharmacol. Ther. 2004, 20, 733–744. [Google Scholar] [CrossRef] [PubMed]
- Fujiwara, Y.; Higuchi, K.; Watanabe, Y.; Shiba, M.; Watanabe, T.; Tominaga, K.; Oshitani, N.; Matsumoto, T.; Nishikawa, H.; Arakawa, T. Prevalence of gastroesophageal reflux disease and gastroesophageal reflux disease symptoms in Japan. J. Gastroenterol. Hepatol. 2005, 20, 26–29. [Google Scholar] [CrossRef]
- Yamaoka, Y.; Orito, E.; Mizokami, M.; Gutierrez, O.; Saitou, N.; Kodama, T.; Osato, M.S.; Kim, J.G.; Ramirez, F.C.; Mahachai, V.; et al. Helicobacter pylori in North and South America before Columbus. FEBS Lett. 2002, 517, 180–184. [Google Scholar] [CrossRef] [Green Version]
- Sahara, S.; Sugimoto, M.; Vilaichone, R.K.; Mahachai, V.; Miyajima, H.; Furuta, T.; Yamaoka, Y. Role of Helicobacter pylori cagA EPIYA motif and vacA genotypes for the development of gastrointestinal diseases in Southeast Asian countries: A meta-analysis. BMC Infect. Dis. 2012, 12, 223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- World Medical, A. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 2013, 310, 2191–2194. [Google Scholar] [CrossRef] [Green Version]
- CLSI. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria. In Approved Standard, 3rd ed.; CLSI Document M45-A2; Clinical and Laboratory Standards Institute: Wayne, PA, USA, 2015. [Google Scholar]
- Kobayashi, I.; Murakami, K.; Kato, M.; Kato, S.; Azuma, T.; Takahashi, S.; Uemura, N.; Katsuyama, T.; Fukuda, Y.; Haruma, K.; et al. Changing antimicrobial susceptibility epidemiology of Helicobacter pylori strains in Japan between 2002 and 2005. J. Clin. Microbiol. 2007, 45, 4006–4010. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sugimoto, M.; Sahara, S.; Ichikawa, H.; Kagami, T.; Uotani, T.; Furuta, T. High Helicobacter pylori cure rate with sitafloxacin-based triple therapy. Aliment. Pharmacol. Ther. 2015, 42, 477–483. [Google Scholar] [CrossRef] [PubMed]
- Murakami, K.; Okimoto, T.; Kodama, M.; Tanahashi, J.; Fujioka, T.; Ikeda, F.; Muraoka, H.; Takigawa, M.; Saika, T.; Hasegawa, M.; et al. Sitafloxacin activity against Helicobacter pylori isolates, including those with gyrA mutations. Antimicrob. Agents Chemother. 2009, 53, 3097–3099. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kato, M.; Ota, H.; Okuda, M.; Kikuchi, S.; Satoh, K.; Shimoyama, T.; Suzuki, H.; Handa, O.; Furuta, T.; Mabe, K.; et al. Guidelines for the management of Helicobacter pylori infection in Japan: 2016 Revised Edition. Helicobacter 2019, 24, e12597. [Google Scholar] [CrossRef] [PubMed]
- Kusano, M.; Shirai, N.; Yamaguchi, K.; Hongo, M.; Chiba, T.; Kinoshita, Y. It is possible to classify non-erosive reflux disease (NERD) patients into endoscopically normal groups and minimal change groups by subjective symptoms and responsiveness to rabeprazole—A report from a study with Japanese patients. Dig. Dis. Sci. 2008, 53, 3082–3094. [Google Scholar] [CrossRef] [PubMed]
- Sugimoto, M.; Hasegawa, T.; Nishino, M.; Sahara, S.; Uotani, T.; Ichikawa, H.; Kagami, T.; Sugimoto, K.; Yamato, Y.; Togawa, D.; et al. Improvement of gastroesophageal reflux disease in Japanese patients with spinal kyphotic deformity who underwent surgical spinal correction. Dig. Endosc. 2016, 28, 50–58. [Google Scholar] [CrossRef]
- Sugimoto, M.; Yamaoka, Y. Role of Vonoprazan in Helicobacter pylori Eradication Therapy in Japan. Front. Pharmacol. 2018, 9, 1560. [Google Scholar] [CrossRef] [PubMed]
- Armstrong, D.; Bennett, J.R.; Blum, A.L.; Dent, J.; De Dombal, F.T.; Galmiche, J.P.; Lundell, L.; Margulies, M.; Richter, J.E.; Spechler, S.J.; et al. The endoscopic assessment of esophagitis: A progress report on observer agreement. Gastroenterology 1996, 111, 85–92. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sugimoto, M.; Ban, H.; Ichikawa, H.; Sahara, S.; Otsuka, T.; Inatomi, O.; Bamba, S.; Furuta, T.; Andoh, A. Efficacy of the Kyoto Classification of Gastritis in Identifying Patients at High Risk for Gastric Cancer. Intern. Med. 2017, 56, 579–586. [Google Scholar] [CrossRef] [Green Version]
- Tanaka, F.; Tominaga, K.; Fujikawa, Y.; Morisaki, T.; Otani, K.; Hosomi, S.; Nagami, Y.; Kamata, N.; Taira, K.; Nakano, A.; et al. Association between Functional Dyspepsia and Gastric Depressive Erosions in Japanese Subjects. Intern. Med. 2019, 58, 321–328. [Google Scholar] [CrossRef] [Green Version]
- Amano, K.; Adachi, K.; Katsube, T.; Watanabe, M.; Kinoshita, Y. Role of hiatus hernia and gastric mucosal atrophy in the development of reflux esophagitis in the elderly. J. Gastroenterol. Hepatol. 2001, 16, 132–136. [Google Scholar] [CrossRef]
- Raghunath, A.; Hungin, A.P.; Wooff, D.; Childs, S. Prevalence of Helicobacter pylori in patients with gastro-oesophageal reflux disease: Systematic review. BMJ 2003, 326, 737. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Iwakiri, K.; Kawami, N.; Sano, H.; Tanaka, Y.; Umezawa, M.; Kotoyori, M.; Hoshihara, Y.; Sakamoto, C. Mechanisms of excessive esophageal acid exposure in patients with reflux esophagitis. Dig. Dis. Sci. 2009, 54, 1686–1692. [Google Scholar] [CrossRef] [PubMed]
- Iwakiri, K.; Kawami, N.; Sano, H.; Tanaka, Y.; Umezawa, M.; Futagami, S.; Hoshihara, Y.; Sakamoto, C. The effects of nizatidine on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux in healthy subjects. J. Smooth Muscle Res. 2011, 47, 157–166. [Google Scholar] [CrossRef] [Green Version]
- Corley, D.A.; Kubo, A.; Levin, T.R.; Block, G.; Habel, L.; Rumore, G.; Quesenberry, C.; Buffler, P.; Parsonnet, J. Helicobacter pylori and gastroesophageal reflux disease: A case-control study. Helicobacter 2008, 13, 352–360. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Malfertheiner, P.; Megraud, F.; O’Morain, C.A.; Gisbert, J.P.; Kuipers, E.J.; Axon, A.T.; Bazzoli, F.; Gasbarrini, A.; Atherton, J.; Graham, D.Y.; et al. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut 2017, 66, 6–30. [Google Scholar] [CrossRef] [Green Version]
- Schwizer, W.; Thumshirn, M.; Dent, J.; Guldenschuh, I.; Menne, D.; Cathomas, G.; Fried, M. Helicobacter pylori and symptomatic relapse of gastro-oesophageal reflux disease: A randomised controlled trial. Lancet 2001, 357, 1738–1742. [Google Scholar] [CrossRef]
- Sugimoto, M.; Murata, M.; Mizuno, H.; Iwata, E.; Nagata, N.; Itoi, T.; Kawai, T. Endoscopic Reflux Esophagitis and Reflux-Related Symptoms after Helicobacter pylori Eradication Therapy: Meta-Analysis. J. Clin. Med. 2020, 9, 3007. [Google Scholar] [CrossRef]
- Wu, J.C.; Chan, F.K.; Wong, S.K.; Lee, Y.T.; Leung, W.K.; Sung, J.J. Effect of Helicobacter pylori eradication on oesophageal acid exposure in patients with reflux oesophagitis. Aliment. Pharmacol. Ther. 2002, 16, 545–552. [Google Scholar] [CrossRef]
- Nam, S.Y.; Choi, I.J.; Ryu, K.H.; Kim, B.C.; Kim, C.G.; Nam, B.H. Effect of Helicobacter pylori infection and its eradication on reflux esophagitis and reflux symptoms. Am. J. Gastroenterol. 2010, 105, 2153–2162. [Google Scholar] [CrossRef]
- Malfertheiner, P.; Dent, J.; Zeijlon, L.; Sipponen, P.; Veldhuyzen Van Zanten, S.J.; Burman, C.F.; Lind, T.; Wrangstadh, M.; BayerdOrffer, E.; Lonovics, J. Impact of Helicobacter pylori eradication on heartburn in patients with gastric or duodenal ulcer disease—Results from a randomized trial programme. Aliment. Pharmacol. Ther. 2002, 16, 1431–1442. [Google Scholar] [CrossRef]
- Moayyedi, P.; Deeks, J.; Talley, N.J.; Delaney, B.; Forman, D. An update of the Cochrane systematic review of Helicobacter pylori eradication therapy in nonulcer dyspepsia: Resolving the discrepancy between systematic reviews. Am. J. Gastroenterol. 2003, 98, 2621–2626. [Google Scholar] [CrossRef] [PubMed]
- Sugano, K.; Tack, J.; Kuipers, E.J.; Graham, D.Y.; El-Omar, E.M.; Miura, S.; Haruma, K.; Asaka, M.; Uemura, N.; Malfertheiner, P.; et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut 2015, 64, 1353–1367. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Figure 1.
Association with the F scale (A–C) and time course at baseline, 2 months after treatment, and 12 months eradication success in 148 patients with successful H. pylori eradication evaluated in our hospital at 12 months after eradication success. Acid reflux, dysmotility-related, and total scores in the F-scale questionnaire were significantly decreased from scores at baseline. *: p < 0.05 vs. score at pretreatment.
Figure 1.
Association with the F scale (A–C) and time course at baseline, 2 months after treatment, and 12 months eradication success in 148 patients with successful H. pylori eradication evaluated in our hospital at 12 months after eradication success. Acid reflux, dysmotility-related, and total scores in the F-scale questionnaire were significantly decreased from scores at baseline. *: p < 0.05 vs. score at pretreatment.
Figure 2.
Correlation of the F-scale questionnaire score and time course from baseline to 2 months after treatment between patients with successful treatment and failed treatment in all 148 patients with successful H. pylori eradication. Scores in the F-scale questionnaire are acid-related (A), dysmotility-related (B), and total scores (C). *: p < 0.05 vs. score of patients with successful treatment.
Figure 2.
Correlation of the F-scale questionnaire score and time course from baseline to 2 months after treatment between patients with successful treatment and failed treatment in all 148 patients with successful H. pylori eradication. Scores in the F-scale questionnaire are acid-related (A), dysmotility-related (B), and total scores (C). *: p < 0.05 vs. score of patients with successful treatment.
Figure 3.
Correlation between F-scale questionnaire score and time course from baseline to 2 months after treatment and 12 months after eradication success between patients with reflux esophagitis and nonerosive esophagitis. Scores in the F-scale questionnaire are shown as acid-related (A), dysmotility-related (B), and total scores (C). *: p < 0.05 vs. score at pretreatment and #: p < 0.05 vs. score of patients with nonerosive esophagitis.
Figure 3.
Correlation between F-scale questionnaire score and time course from baseline to 2 months after treatment and 12 months after eradication success between patients with reflux esophagitis and nonerosive esophagitis. Scores in the F-scale questionnaire are shown as acid-related (A), dysmotility-related (B), and total scores (C). *: p < 0.05 vs. score at pretreatment and #: p < 0.05 vs. score of patients with nonerosive esophagitis.
Table 1.
Characteristics of patients positive for Helicobacter pylori at baseline.
| All Patients (n = 148) | Non-GERD (n = 113) | Redness (n = 32) | Reflux Esophagitis (n = 3) | p Value | |
|---|---|---|---|---|---|
| Age (years) | 65.5 ± 10.3 | 65.9 ± 10.5 | 64.1 ± 9.8 | 68.7 ± 5.0 | 0.50 |
| Sex (male/female, n/n) | 78/70 | 58/55 | 17/15 | 3/0 | 0.25 |
| Height (cm) | 161.8 ± 7.9 | 161.7 ± 8.1 | 162.0 ± 7.3 | 163.3 ± 6.1 | 0.92 |
| Body weight (kg) | 58.9 ± 10.9 | 59.3 ± 10.8 | 57.5 ± 11.6 | 57.7 ± 6.7 | 0.84 |
| Smoking (no/previous/current, n/n/n) | 85/50/13 | 71/34/8 | 14/14/4 | 0/2/1 | 0.07 |
| Alcohol (no/previous/current) | 71/13/64 | 57/13/43 | 14/0/18 | 0/0/3 | 0.05 |
| Hiatal hernia (−/+) | 128/20 | 98/15 | 27/5 | 3/0 | 0.74 |
| SSBE (−/+) | 106/42 | 85/28 | 19/13 | 2/1 | 0.21 |
| GERD (-/redness/grade A/grade B) | 113/32/2/1 | 113/0/0/0 | 0/32/0/0 | 0/0/2/1 | <0.01 |
| Endoscopic Kyoto classification | |||||
| Atrophy | 2 (0–2) | 2 (0–2) | 2 (1–2) | 2 (2–2) | 0.93 |
| Intestinal metaplasia | 1 (0–2) | 1 (0–2) | 1 (0–2) | 1 (0–2) | 0.79 |
| Diffuse redness | 2 (0–2) | 2 (0–2) | 2 (1–2) | 1 (1–2) | 0.16 |
| Total score | 5 (2–7) | 5 (2–7) | 5 (2–7) | 4 (4–7) | 0.26 |
| Eradication history (1st/2nd/3rd) | 107/26/15 | 84/19/10 | 22/7/3 | 1/0/2 | 0.02 |
| F scale | |||||
| Acid-related score | 2 (0–35) | 2 (0–35) | 2 (0–11) | 7 (0–8) | 0.37 |
| Dysmotility-related score | 2 (0–15) | 2 (0–15) | 2 (0–10) | 4 (0–6) | 0.61 |
| Total score | 4 (0–49) | 4 (0–49) | 4 (0–19) | 11 (1–14) | 0.51 |
BMI, body mass index; GERD, gastroesophageal reflux diseases; SSBE, short-segment Barrett’s esophagus. Values for age, height, and body weight are shown as the mean ± standard deviation. Scores for the Endoscopic Kyoto classification and questionnaire are shown as median (range).
Table 2.
Characteristics of patients at 12 months after eradication success.
| All Patients (n = 148) | Non-GERD (n = 106) | Redness (n = 26) | Reflux Esophagitis (n = 16) | p Value | |
|---|---|---|---|---|---|
| GERD (-/redness/grade A/grade B) | 106/26/10/6 | 106/0/0/0 | 0/26/0/0 | 0/0/10/6 | |
| Hiatal hernia (−/+) | 106/42 | 77/29 | 22/4 | 12/4 | 0.31 |
| SSBE (−/+) | 128/20 | 94/12 | 19/7 | 10/6 | 0.69 |
| Endoscopic Kyoto classification | |||||
| Atrophy | 2 (0–2) | 2 (1–2) | 2 (0–2) | 2 (1–2) | 0.80 |
| Intestinal metaplasia | 1 (0–2) | 1 (0–2) | 1 (0–2) | 1 (0–2) | 0.59 |
| Diffuse redness | 2 (0–2) | 2 (0–2) | 2 (1–2) | 2 (1–2) | 0.93 |
| Total score | 5 (2–7) | 5 (2–7) | 4.5 (2–7) | 5 (2–7) | 0.68 |
| Questionnaire | |||||
| F scale | |||||
| Acid-related score | 3.5 (0–14) | 3 (0–8) | 3.5 (0–9) | 5 (0–14) | 0.14 |
| Dysmotility-related score | 1 (0–14) | 1 (0–10) | 2 (0–7) | 1 (0–14) | 0.16 |
| Total score | 3 (0–23) | 3 (0–14) | 7.5 (0–15) | 6 (1–23) | 0.05 |
GERD, gastroesophageal reflux diseases; SSBE, short-segment Barrett’s esophagus. Scores for the Endoscopic Kyoto classification and questionnaire are shown as median (range).
Table 3.
Association of severity of GERD with pretreatment and after treatment findings.
| Post-Treatment | Non-GERD (n = 106) | Redness (n = 26) | GERD Grade A (n = 10) | GERD Grade B (n = 6) |
|---|---|---|---|---|
| Pretreatment | ||||
| Non-GERD (n = 113) | 91 | 14 | 5 | 3 |
| Redness (n = 32) | 14 | 12 | 5 | 1 |
| GERD grade A (n = 1) | 0 | 0 | 0 | 1 |
| GERD grade B (n = 2) | 1 | 0 | 0 | 1 |
GERD, gastroesophageal reflux diseases.
Table 4.
Association of category with reflux esophagitis and reflux-related symptoms before and after eradication therapy.
Table 4.
Association of category with reflux esophagitis and reflux-related symptoms before and after eradication therapy.
| Category | Before Eradication Therapy | After eradication Therapy, 12 Months | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sex | SSBE | Hiatal Hernia | Number | Non-GERD/ GERD (n/n) | F Scale Acid-Related Score | F Scale Dysmotility-Related Score | F Scale Total Score | Number | Non-GERD/GERD (n/n) | F Scale Acid-Related Score | F Scale Dysmotility-Related Score | F Scale Total Score |
| Male | − | − | 47 | 36/11 | 2 (0–10) | 1 (0–7) | 4 (0–17) | 47 | 32/15 | 0 (0–9) | 1 (0–14) | 2 (0–15) |
| Male | − | + | 5 | 5/0 | 0 (0–3) | 1 (0–3) | 1 (0–5) | 5 | 5/0 | 0 (0–0) | 1 (1–1) | 1 (1–1) |
| Male | + | − | 23 | 16/7 | 1 (0–18) | 2 (0–15) | 3 (0–33) | 23 | 16/7 | 1 (0–5) | 1 (0–4) | 2 (0–9) |
| Male | + | + | 3 | 1/2 | 8 (3–12) | 6 (2–13) | 14 (5–25) | 3 | 2/1 | |||
| Female | − | − | 46 | 39/7 | 1 (0–15) | 2 (0–15) | 4 (0–30) | 46 | 37/9 | 1.5 (0–7) | 2 (0–10) | 3 (0–14) |
| Female | − | + | 8 | 5/3 | 4 (1–35) | 3 (0–14) | 6.5 (1–49) | 8 | 3/5 | 4 (3–6) | 3 (0–5) | 9 (3–9) |
| Female | + | − | 12 | 7/5 | 2 (0–9) | 3.5 (0–10) | 5.5 (0–19) | 12 | 9/3 | 3 (0–5) | 2 (0–7) | 5 (0–12) |
| Female | + | + | 4 | 4/0 | 6.5 (4–7) | 6 (2–7) | 13 (6–13) | 4 | 2/2 | 9.5 (5–14) | 7 (5–9) | 16.5 (10–23) |
| p Value | <0.01 | 0.12 | 0.03 | - | - | - | ||||||
GERD, gastroesophageal reflux diseases; SSBE, short-segment Barrett’s esophagus. Scores for the questionnaire are shown as median (range).
Table 5.
Univariate and multivariate analysis for the development of reflux esophagitis.
| Univariate Analysis | Multivariate Analysis | |||||
|---|---|---|---|---|---|---|
| Parameters | Odds Ratio | 95% CI | p Value | Odds Ratio | 95% CI | p Value |
| Age (years) | 0.985 | 0.939–1.034 | 0.540 | 0.975 | 0.925–1.028 | 0.356 |
| Sex (male, vs. female) | 2.134 | 0.703–6.482 | 0.181 | 3.499 | 0.987–12.399 | 0.052 |
| Hiatal hernia | 2.417 | 0.695–8.406 | 0.165 | 2.312 | 0.533–10.067 | 0.261 |
| short segment Barrett’s esophagus | 1.600 | 0.542–4.722 | 0.395 | |||
| Smoking | 2.394 | 0.429–13.373 | 0.320 | |||
| Alcohol | 1.496 | 0.523–4.282 | 0.453 | |||
| Kimura–Takemoto (moderate) | 0.398 | 0.064–2.464 | 0.322 | |||
| Kimura–Takemoto (severe) | 0.389 | 0.070–2.163 | 0.389 | |||
| Endoscopic Kyoto classification | ||||||
| Atrophy | 1.094 | 0.248–4.833 | 0.905 | |||
| Intestinal metaplasia | 1.443 | 0.711–2.929 | 0.310 | |||
| Diffuse redness | 1.075 | 0.388–2.977 | 0.890 | |||
| Total score | 1.083 | 0.702–1.672 | 0.718 | |||
| F scale, pretreatment | ||||||
| Acid-related score | 1.085 | 0.989–1.189 | 0.084 | |||
| Dysmotility-related score | 1.200 | 1.055–1.364 | 0.005 | |||
| Total score | 1.069 | 1.009–1.132 | 0.023 | 1.069 | 1.003–1.139 | 0.039 |
| F scale, 2 months after treatment | 1.130 | 1.037–1.233 | 0.006 | |||
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Sugimoto, M.; Murata, M.; Iwata, E.; Nagata, N.; Itoi, T.; Kawai, T. Risk of Reflux-Related Symptoms and Reflux Esophagitis after Helicobacter pylori Eradication Treatment in the Japanese Population. J. Clin. Med. 2021, 10, 1434. https://doi.org/10.3390/jcm10071434
AMA Style
Sugimoto M, Murata M, Iwata E, Nagata N, Itoi T, Kawai T. Risk of Reflux-Related Symptoms and Reflux Esophagitis after Helicobacter pylori Eradication Treatment in the Japanese Population. Journal of Clinical Medicine. 2021; 10(7):1434. https://doi.org/10.3390/jcm10071434
Chicago/Turabian StyleSugimoto, Mitsushige, Masaki Murata, Eri Iwata, Naoyoshi Nagata, Takao Itoi, and Takashi Kawai. 2021. "Risk of Reflux-Related Symptoms and Reflux Esophagitis after Helicobacter pylori Eradication Treatment in the Japanese Population" Journal of Clinical Medicine 10, no. 7: 1434. https://doi.org/10.3390/jcm10071434
APA StyleSugimoto, M., Murata, M., Iwata, E., Nagata, N., Itoi, T., & Kawai, T. (2021). Risk of Reflux-Related Symptoms and Reflux Esophagitis after Helicobacter pylori Eradication Treatment in the Japanese Population. Journal of Clinical Medicine, 10(7), 1434. https://doi.org/10.3390/jcm10071434
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