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Effect of Helicobacter pylori Eradication on Reflux Esophagitis Therapy: A Multi-center Randomized Control Study.

Byline: Yan. Xue, Li-Ya. Zhou, San-Ren. Lin, Xiao-Hua. Hou, Zhao-Shen. Li, Min-Hu. Chen, Xiu-E. Yan, Ling-Mei. Meng, Jing. Zhang, Jing-Jing. Lu

Background: Helicobacter pylori (H. pylori) frequently colonizes the stomach. Gastroesophageal reflux disease (GERD) is a common and costly disease. But the relationship of H. pylori and GERD is still unclear. This study aimed to explore the effect of H. pylori and its eradication on reflux esophagitis therapy. Methods: Patients diagnosed with reflux esophagitis by endoscopy were enrolled; based on rapid urease test and Warth-Starry stain, they were divided into H. pylori positive and negative groups. H. pylori positive patients were randomly given H. pylori eradication treatment for 10 days, then esomeprazole 20 mg bid for 46 days. The other patients received esomeprazole 20 mg bid therapy for 8 weeks. After treatment, three patient groups were obtained: H. pylori positive eradicated, H. pylori positive uneradicated, and H. pylori negative. Before and after therapy, reflux symptoms were scored and compared. Healing rates were compared among groups. The ?[sup]2 test and t-test were used, respectively, for enumeration and measurement data. Results: There were 176 H. pylori positive (with 92 eradication cases) and 180 negative cases. Healing rates in the H. pylori positive eradicated and H. pylori positive uneradicated groups reached 80.4% and 79.8% (P = 0.911), with reflux symptom scores of 0.22 and 0.14 (P = 0.588). Healing rates of esophagitis in the H. pylori positive uneradicated and H. pylori negative groups were, respectively, 79.8% and 82.2% (P = 0.848); reflux symptom scores were 0.14 and 0.21 (P = 0.546). Conclusions: Based on esomeprazole therapy, H. pylori infection and eradication have no significant effect on reflux esophagitis therapy.

Introduction

Helicobacter pylori ( H. pylori ) is a type of bacterium that frequently colonizes the lining of the stomach. H. pylori infection is recognized to be the most important acquired factor in the etiology of ulcers of the stomach and duodenum. H. pylori infection was also shown to be associated with active gastritis, gastric carcinoma and gastric mucosal associated lymphatic tissue (MALT) lymphoma. It is believed that eradication therapy is a powerful way to cure H. pylori -related diseases. [sup][1] But the relationship between H. pylori and gastroesophageal reflux disease (GERD) is still unclear, and the effect of H. pylori eradication on GERD treatment is unknown. In this study, we selected patients with reflux esophagitis to explore the effect of H. pylori and its eradication on reflux esophagitis treatment.

Methods

Patients

Patients from Digestive Disease Center of Peking University Third Hospital, Wu Han Union Hospital, Shanghai Changhai Hospital, and The First Affiliated Hospital, Sun Yat-Sen University were enrolled between January 2007 and October 2010.

Included criteria were: Almost 18-70 years of age, typical reflux symptoms (heartburn, acid regurgitation and chest pain), and diagnosis of reflux esophagitis (Los Angeles [LA] A-D degree). The LA classification was used for the patients with reflux esophagitis, and those with reflux esophagitis LA-A to LA-D were all enrolled.

Patients were excluded with: Peptic ulcer, carcinoma of upper gastrointestinal tract, esophageal varices, Zollinger-Ellison syndrome, esophageal stricture, Barrett's esophagus, other severe gastrointestinal disease (for example ulcerative colitis), and accompanying severe diseases of other systems. Pregnant or lactating females, and patients who had undergone proton pump inhibitor (PPI) or bismuth therapy during the preceding 2 weeks were also excluded. All patients signed the informed consent forms. The Ethics Committee of Health Center of Peking University approved this study.

Criteria for Helicobacter pylori presence

Biopsy specimens for rapid urease test (RUT) were obtained from biopsy forceps with a sterile needle and assessed immediately; the results were examined by an experienced observer blinded to the clinical details. The biopsy specimens for pathology were examined by an experienced pathologist after Warthin-Starry (WS) staining. A sample was considered H. pylori positive with both RUT and WS staining results positive. H. pylori negative samples showed negative results in both tests. When discordant results were obtained for RUT and WS, the patients were excluded from the study. After eradication treatment, the patients underwent gastroscopy again. Biopsy specimens were examined by WS staining, and samples were considered H. pylori positive with positive WS staining.

Definition of reflux esophagitis

Before and after treatment, patients underwent gastroscopy and were examined by experienced doctors. Reflux esophagitis was defined as mucosal breaks extending proximally from the Z-line. Patients from LA-A to LA-D were all enrolled. The severity of reflux symptoms was scored by the frequency and severity of the symptoms [Table 1].{Table 1}

Treatment

H. pylori positive patients were first randomly divided into eradicated and uneradicated groups by random envelope. In the eradication group, patients underwent H. pylori eradication for 10 days, then received esomeprazole 20 mg bid for the following 46 days. Two eradiation regimens were randomly selected in this study: The EAC regimen consisted of esomeprazole 20 mg bid, amoxicillin 1.0 bid and clarimothin 0.5 bid; in the sequential regimen, esomeprazole 20 mg bid and amoxicillin 1.0 bid were administered for the first 5 days, while esomeprazole 20 mg bid, clarimothin 0.5 bid and tinidazole 0.5 bid were given for the following 5 days. In H. pylori positive uneradicated and H. pylori negative groups, patients were treated with esomeprazole 20 mg bid for 8 weeks. Afterward, all patients underwent gastroscopy again, and the WS staining test was repeated. Therefore, three groups were obtained: H. pylori positive eradicated, H. pylori positive uneradicated (patients without H. pylori eradicated or unsuccessful eradication) and H. pylori negative groups.

Endpoint and indicator evaluation

For all patients, the course of treatment was 8 weeks. Then, the healing rate of reflux esophagitis and remission of reflux symptoms were evaluated.

*"Healed" was considered if there was no esophageal mucosal break after treatment; "unhealed" indicated the presence of mucosal breaks. The healing rates among groups were compared *Remission of reflux symptoms. The main reflux symptoms, including acid regurgitation, heartburn, and chest pain were scored before and after treatment. The remission of reflux symptoms was compared among groups.

Statistical analysis

The ? [sup]2 test and t -test were used, respectively, for enumeration and measurement data. All statistical analyses were carried out with SPSS 15.0 (SPSS Inc., USA). All statistical tests were two-sided, and a P < 0.05 was considered statistically significant.

Results

General status

A total of 356 patients were enrolled, including 259 males and 97 females. There were 176 patients infected with H. pylori and 180 patients without H. pylori . For H. pylori positive patients, 122 were given H. pylori eradication treatment. Ninety-two patients showed successful eradication, while the remaining 30 still had the bacteria, indicating an eradication rate of 75.4%. Therefore, there were 92 and 84 patients in the H. pylori positive eradicated and H. pylori positive uneradicated groups, respectively. No significant difference in age, gender, height, and weight was obtained among groups [Table 2].{Table 2}

Comparison between Helicobacter pylori positive groups

Before treatment, reflux symptom scores in the H. pylori positive eradicated and H. pylori positive uneradicated groups were 8.04 and 7.13, respectively ( P = 0.062). There was no statistically significant difference in the LA degree between the two groups ( P = 0.307) [Table 3].{Table 3}

After treatment, reflux symptom scores of 0.22 and 0.14 were obtained for the H. pylori positive eradicated and H. pylori positive uneradicated groups, respectively ( P = 0.588).The healing rate of reflux esophagitis were 80.4% and 79.8%, respectively, in the H. pylori positive eradicated and H. pylori positive uneradicated groups ( P = 0.911) [Table 4]. There was no significant difference between the two groups.{Table 4}

Comparison between Helicobacter pylori positive uneradicated group and Helicobacter pylori negative group

Before treatment, reflux symptom scores in the H. pylori positive uneradicated and H. pylori negative groups were 7.13 and 7.18, respectively ( P = 0.910), and no statistically significant difference in LA degree between the two groups was obtained ( P = 0.848) [Table 5].{Table 5}

After treatment, reflux symptom scores in the H. pylori positive uneradicated and H. pylori negative groups were 0.14 and 0.21, respectively ( P = 0.546). The healing rates of reflux esophagitis were 79.8% and 82.2%, respectively, in H. pylori positive uneradicated and H. pylori negative groups, respectively ( P = 0.632) [Table 6]. There was no significant difference between the two groups.{Table 6}

Discussion

H. pylori is one of the most common bacteria around the world. H. pylori infection leads to chronic active gastritis with the potential for the subsequent development of peptic ulcer, MALT lymphoma, and distal gastric cancer in some patients. H. pylori should be eradicated in these patients. [sup][1] GERD is a common and costly disease in the community, with a negative impact on patients' quality of life. Unfortunately, GERD incidence is increasing worldwide. [sup][2] The major mechanisms associated with GERD include decreased pressure and increased frequency of spontaneous relaxation of the lower esophageal sphincter, with normal or increased secretion of gastric acid. The relationship between H. pylori infection and GERD remains unclear, and the treatment of H. pylori in patients with GERD is highly controversial.

Indeed, some epidemiological studies suggested H. pylori as a protective factor in GERD. The prevalence of H. pylori infection has been steadily decreasing while GERD incidence is increasing in developed countries, suggesting a possible protective role of H. pylori infection in the development of GERD. Other evidences include the following: The infection rate of H. pylori in GERD patients is much lower than in the general population; H. pylori is associated with the severity of GERD; the infection rate of H. pylori in severe GERD patients is much lower than those with mild GERD. [sup][3] In addition, GERD incidence is increased after H. pylori eradication. [sup][4] There were also studies suggesting no relationship between H. pylori and GERD. Indeed, the prevalence of H. pylori was shown to be similar between GERD and other patients, and H. pylori was not related to the severity of GERD. [sup][5],[6] Recently, Japanese studies suggested that after H. pylori eradication, GERD symptoms are relieved, and life quality improved. [sup][7],[8] The Management of Helicobacter pylori Infection the Maastricht IV/Florence Consensus Report declares that H. pylori status has no effect on symptom severity, symptom recurrence and treatment efficacy in GERD. H pylori eradication does not exacerbate preexisting GERD or affect treatment efficacy. [sup][9] In the Chinese guideline for H. pylori treatment, it was indicated that GERD incidence may be increased in some eastern countries after H. pylori eradication. Therefore, the question remains as whether for GERD patients with H. pylori infection, H. pylori eradication is necessary or useful.

For the treatment of GERD, an agreement has been reached that PPI is the most important medicine. In the definition of Montreal, the symptoms of GERD could be relieved significantly by PPI. [sup][10] However, in case of H. pylori infection combined with gastroesophageal reflux, H. pylori eradication therapy is needed, which is confusing to the clinicians; this problem needs to be clarified as soon as possible.

For most patients, H. pylori infection does not affect acid secretion significantly. But for different infection sites and types of gastritis, acid secretion may be decreased or increased after H. pylori infection. [sup][11] Based on this theory, some scientists have suggested that if acid secretion is increased by H. pylori infection, then the bacteria should be eradicated. On the other hand, if acid secretion is decreased by H. pylori , its eradication is not necessary. So before H. pylori eradication, its effect on acid secretion should be first evaluated. [sup][12],[13] But it is difficult in clinical practice for doctors.

In a study by Calleja et al ., [sup][14] 846 patients with reflux esophagitis underwent treatment with pantoprazole 40 mg qd. After 4 weeks treatment, the healing rate of reflux esophagitis was 86.6% in H. pylori positive patients. In H. pylori negative patients, the healing rate was 76.1%. After 8 weeks treatment, the healing rates in positive and negative groups were 96.4% and 91.8%, respectively. The healing rates in the positive group were, therefore, higher than in the negative group, with significant differences. Also, the rate of GERD symptom relief was higher in H. pylori positive patients compared with negative patients. These findings suggested that based on the same treatment, a better outcome was obtained in H. pylori positive patients. In a prospective study by Tefera et al ., [sup][15] GERD patients with H. pylori infection were included. After 15 months of H. pylori eradication, there was no significant difference between acid secretion and GERD symptoms. In a study by De Boer et al ., [sup][16] 1548 GERD patients underwent treatment with Rabeprazole; there was no significant difference between H. pylori positive and negative patients in rates of GERD symptom relief. From the above studies, a clear misunderstanding can be seen in this field. A large-scale study to compare the treatment outcome between H. pylori positive and negative comprehensively is needed.

This was a multi-center, randomized, control, prospective study, with 356 patients enrolled. Based on the treatment of PPI, we explored the effect of H. pylori eradication on the treatment of reflux esophagitis. We analyzed the effect of H. pylori infection first, and patients in H. pylori negative and H. pylori positive control groups were compared. After PPI treatment, no significant differences in healing rates of reflux esophagitis and the severity of reflux symptoms were obtained, indicating that H. pylori infection has no significant effect on the treatment of reflux esophagitis. Then, we analyzed the effect of H. pylori eradication. Patients with H. pylori infection were enrolled, and H. pylori eradicated and H. pylori positive uneradicated groups were compared. After the treatment with PPI, no significant difference was found in healing rates of reflux esophagitis and the severity of reflux symptoms. It was concluded that H. pylori eradication has no significant effect on the treatment of reflux esophagitis.

Although we found that H. pylori eradication itself has no significant effect on erosive esophagitis treatment, the Asia-Pacific consensus on H. pylori infection [sup][1] mentioned that long-term use of PPI therapy causes increased risk of gastric atrophy, which is a precancerous lesion. For patients with GERD, PPI is used for a long time, therefore, H. pylori therapy is recommended. In this study, patients were followed-up for only 8 weeks, and we plan to continue follow-up for years in order to determine the changes by H. pylori eradication therapy; reflux esophagitis and relapse of reflux symptoms will be monitored, as well as gastric pathology.

References

1. Fock KM, Katelaris P, Sugano K, Ang TL, Hunt R, Talley NJ, et al. Second Asia-Pacific consensus guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol 2009;24:1587-600.

2. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013;108:308-28.

3. Polat FR, Polat S. The effect of Helicobacter pylori on gastroesophageal reflux disease. JSLS 2012;16:260-3.

4. Xie T, Cui X, Zheng H, Chen D, He L, Jiang B. Meta-analysis: Eradication of Helicobacter pylori infection is associated with the development of endoscopic gastroesophageal reflux disease. Eur J Gastroenterol Hepatol 2013;25:1195-205.

5. Ramus JR, Gatenby PA, Caygill CP, Watson A. Helicobacter pylori infection and severity of reflux-induced esophageal disease in a cohort of patients with columnar-lined esophagus. Dig Dis Sci 2007;52:2821-5.

6. Fallone CA, Barkun AN, Mayrand S, Wakil G, Friedman G, Szilagyi A, et al. There is no difference in the disease severity of gastro-oesophageal reflux disease between patients infected and not infected with Helicobacter pylori . Aliment Pharmacol Ther 2004;20:761-8.

7. Den Hollander WJ, Sostres C, Kuipers EJ, Lanas A. Helicobacter pylori and nonmalignant diseases. Helicobacter 2013;18 Suppl 1:24-7.

8. Hirata K, Suzuki H, Matsuzaki J, Masaoka T, Saito Y, Nishizawa T, et al . Improvement of reflux symptom related quality of life after Helicobacter pylori eradication therapy. J Clin Biochem Nutr 2013;52:172-8.

9. Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, et al. Management of Helicobacter pylori infection - The Maastricht IV/Florence Consensus Report. Gut 2012;61:646-64.

10. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: A global evidence-based consensus. Am J Gastroenterol 2006;101:1900-20.

11. Souza RC, Lima JH. Helicobacter pylori and gastroesophageal reflux disease: A review of this intriguing relationship. Dis Esophagus 2009;22:256-63.

12. Wu JC, Chan FK, Wong SK, Lee YT, Leung WK, Sung JJ. Effect of Helicobacter pylori eradication on oesophageal acid exposure in patients with reflux oesophagitis. Aliment Pharmacol Ther 2002;16:545-52.

13. Delaney B, McColl K. Review article: Helicobacter pylori and gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2005;22 Suppl 1:32-40.

14. Calleja JL, Suarez M, De Tejada AH, Navarro A, Pantogerd Group. Helicobacter pylori infection in patients with erosive esophagitis is associated with rapid heartburn relief and lack of relapse after treatment with pantoprazole. Dig Dis Sci 2005;50:432-9.

15. Tefera S, Hatlebakk JG, Berstad AE, Berstad A. Eradication of Helicobacter pylori does not increase acid reflux in patients with mild to moderate reflux oesophagitis. Scand J Gastroenterol 2002;37:877-83.

16. De Boer W, de Wit N, Geldof H, Hazelhoff B, Bergmans P, Smout A, et al . Does Helicobacter pylori infection influence response rate or speed of symptom control in patients with gastroesophageal reflux disease treated with rabeprazole? Scand J Gastroenterol 2006;41:1147-54.
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Article Details
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Title Annotation:Original Article
Author:Xue, Yan; Zhou, Li-Ya; Lin, San-Ren; Hou, Xiao-Hua; Li, Zhao-Shen; Chen, Min-Hu; Yan, Xiu-E; Meng, L
Publication:Chinese Medical Journal
Article Type:Report
Geographic Code:9CHIN
Date:Aug 1, 2015
Words:2928
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