Published online Dec 28, 2015. doi: 10.3748/wjg.v21.i48.13548
Peer-review started: June 3, 2015
First decision: August 26, 2015
Revised: September 3, 2015
Accepted: October 17, 2015
Article in press: October 20, 2015
Published online: December 28, 2015
AIM: To evaluate the effect of first line esomeprazole (EPZ)-based triple therapy on Helicobacter pylori (H. pylori) eradication.
METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or 13C-urea breath tests were included in this study. The average age of the patients was 57.2 years (male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen (PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry (UMIN000009642).
RESULTS: The H. pylori eradication rates by EPZ-based triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors (PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM (P < 0.05). The serum PG I level and PG I/II ratio were significantly increased after eradication of H. pylori (P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZ-based triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other first-generation PPIs in the Japanese population.
CONCLUSION: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other first-generation PPIs.
Core tip: Esomeprazole (EPZ) is considered to be more effective for inhibition of gastric acid secretion than other first-generation proton pump inhibitors (PPIs) because its metabolism is not influenced by CYP2C19 genotype. In the present study, however, first-line eradication by EPZ-based triple therapy for patients with Helicobacter pylori (H. pylori)-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with triple therapies with other first-generation PPIs in the Japanese population. Unlike previous studies, our results suggest that there is no advantage for EPZ-based triple therapy on H. pylori eradication in comparison with other first-generation PPIs.
- Citation: Saito Y, Serizawa H, Kato Y, Nakano M, Nakamura M, Saito H, Suzuki H, Kanai T. First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype. World J Gastroenterol 2015; 21(48): 13548-13554
- URL: https://www.wjgnet.com/1007-9327/full/v21/i48/13548.htm
- DOI: https://dx.doi.org/10.3748/wjg.v21.i48.13548
Helicobacter pylori (H. pylori) is one of the most prevalent bacterial pathogens and is associated with upper gastrointestinal disorders, such as gastritis, peptic ulcers, functional dyspepsia, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer[1-3]. Eradication of H. pylori infection is reported to be an effective approach to curing or preventing these H. pylori-associated diseases[4,5]. One-week of triple therapy with a proton pump inhibitor (PPI), amoxicillin (AMPC), and clarithromycin (CAM) is recommended as first-line H. pylori eradication therapy and covered under the national health insurance system in Japan. However, the eradication rates for H. pylori have declined to approximately 70%[6].
The use of PPIs combined with antibiotics in H. pylori eradication therapy has been demonstrated to not only protect the stomach, but also increase the eradication rate. As antibiotics are more stable in higher pH gastric environments, strong gastric acid inhibition increases the efficacy of H. pylori eradication. The metabolism of first-generation PPIs such as omeprazole (OPZ) is influenced by genetic polymorphism of CYP2C19[7]. Based on the wild-type allele (*1) and the two mutated alleles (*2 and *3) of the CYP2C19 gene, patients can be categorized into three groups: extensive metabolizer (EM; *1/*1), intermediate metabolizer (IM; *1/*2 or *1/*3), and poor metabolizer (PM; *2/*2, *2/*3, or *3/*3). As EM metabolizes OPZ rapidly, the success rate of H. pylori eradication by OPZ-based therapy in EM is lower than that of PM[7-9].
Esomeprazole (EPZ), the S-isomer of OPZ, is the most recent member of the PPI family and is a more potent acid inhibitor than other first-generation PPIs[10,11]. The metabolism of EPZ is considered to be unaffected by CYP2C19 genotype. Indeed, recent studies have reported that there were no significant differences in H. pylori eradication by EPZ-based therapy among EM, IM, and PM of the CYP2C19 genotype, and that EPZ showed better overall H. pylori eradication rates than first-generation PPIs[9,12-14]. However, Nishida et al[15] demonstrated that the H. pylori eradication rate of EPZ-based triple therapy was lower than lansoprazole (LPZ) in the Japanese population. Thus, the effect of H. pylori eradication by EPZ-based therapy is controversial. To evaluate the effect of first line EPZ-based triple therapy on H. pylori eradication, we investigated eradication rate, CYP2C19 genotype, and serum pepsinogen (PG) level in Japanese patients with H. pylori-positive gastritis.
A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by a 13C-urea breath test (UBT) or endoscopic biopsy-based test (i.e., histologic examination and H. pylori culture) were included in this study. Patients were recruited between January and September 2013 at the Kitasato Institute Hospital (Tokyo, Japan). The average age of the patients was 57.2 years (male/female, 42/38).
These patients were treated by first-line eradication therapy with EPZ 40 mg/d, AMPC 1500 mg/d, and CAM 400 mg/d for 7 d. All drugs were given twice per day. Three months after eradication, H. pylori infection was validated by UBT. Correlations between H. pylori eradication, CYP2C19 genotype, and serum PG level were analyzed. The study was approved by the ethics committee of the Kitasato Institute Hospital, and written informed consent was obtained from all patients prior to examinations. This study was registered with the UMIN Clinical Trials Registry, number UMIN000009642.
Blood samples were collected from the patients before eradication therapy. The CYP2C19 genotyping for wild-type allele (*1) and two mutated alleles (*2 and *3) was conducted by SRL (Tokyo, Japan). The patients were categorized into three groups based on the CYP2C19 genotype, EM (*1/*1), IM (*1/*2 or *1/*3), and PM (*2/*2, *2/*3, or *3/*3).
Serum PG I and II levels were measured before and after eradication therapy. Gastric atrophy was evaluated as described previously[16,17]: (-), PG I ≥ 70 ng/mL and PG I/PG II ratio ≥ 3.0; (1+), PGI < 70 ng/mL and PG I/PG II ratio < 3.0; (2+), PG I < 50 ng/mL and PG I/PG II ratio < 3.0; (3+), PG I < 30 ng/mL and PG I/PG II ratio < 2.0.
Data were analyzed using the SPSS statistics version 22 software package (IBM Corp., Armonk, NY, United States). The data were also analyzed using χ2 test and multiple logistic regression analysis. H. pylori eradication rate was evaluated by intention-to-treat (ITT) and per protocol (PP). Differences at P < 0.05 were considered significant.
Among 80 patients who were treated by first-line eradication therapy with EPZ, AMPC, and CAM, one patient did not return for a UBT after the therapy. The H. pylori eradication rates of this first-line therapy evaluated by ITT and PP were 67.5% and 68.4%, respectively, which were similar to first-line therapy with LPZ, AMPC, and CAM (67.5%) in the Kitasato Institute Hospital. The results of CYP2C19 genotype and serum PG level in association with H. pylori eradication are shown in Tables 1, 2, 3. The eradication rates of first-line therapy with EPZ in the three CYP2C19 genotypes, EM, IM, and PM, were 52.2% (12/23), 72.1% (31/43), and 84.6% (11/13), respectively. The H. pylori eradication rate of EM was significantly lower than that of non-EM (P = 0.048).
| Case | Age | Sex | PG I/II | UBT | Eradication | |||
| Before eradication | After eradication | |||||||
| E1 | 45 | F | 3.6 | - | 5.0 | - | 0.1 | ○ |
| E2 | 39 | M | 3.3 | - | 6.7 | - | 0.4 | ○ |
| E3 | 59 | M | 3.1 | - | 5.2 | - | 0.5 | ○ |
| E4 | 58 | M | 2.9 | - | 7.1 | - | 0.4 | ○ |
| E5 | 50 | F | 2.2 | 1+ | 5.1 | - | 0.3 | ○ |
| E6 | 43 | F | 2.2 | 1+ | 4.9 | - | 0.3 | ○ |
| E7 | 63 | F | 1.6 | 1+ | 4.1 | - | 0.0 | ○ |
| E8 | 56 | F | 2.8 | 2+ | 4.1 | - | 0.3 | ○ |
| E9 | 36 | F | 2.2 | 2+ | 4.6 | - | 0.0 | ○ |
| E10 | 75 | F | 2.5 | 2+ | 4.8 | - | 0.9 | ○ |
| E11 | 67 | M | 3.7 | - | 2.2 | 2+ | 0.0 | ○ |
| E12 | 64 | M | 0.8 | 3+ | 2.2 | 2+ | 1.3 | ○ |
| E13 | 48 | M | 3.4 | - | 3.1 | - | 12.7 | × |
| E14 | 50 | F | 4.3 | - | 6.4 | - | 12.7 | × |
| E15 | 67 | M | 3.5 | - | 3.7 | - | 41.6 | × |
| E16 | 34 | F | 3.0 | - | 3.4 | - | 19.5 | × |
| E17 | 63 | M | 3.1 | - | 3.0 | - | 26.8 | × |
| E18 | 71 | F | 1.2 | 3+ | 3.1 | - | 11.0 | × |
| E19 | 55 | M | 2.4 | 1+ | 2.6 | 1+ | 24.6 | × |
| E20 | 56 | M | 2.0 | 2+ | 2.2 | 1+ | 24.9 | × |
| E21 | 80 | M | 1.7 | 2+ | 1.8 | 2+ | 20.9 | × |
| E22 | 53 | M | 2.2 | 2+ | 2.2 | 2+ | 26.6 | × |
| E23 | 43 | F | 2.2 | 2+ | 2.3 | 2+ | 11.5 | × |
| Case | Age | Sex | CYP2C19 genotype | PG I/II | UBT | Eradication | |||
| Before eradication | After eradication | ||||||||
| I1 | 61 | F | *1/*2 | 2.6 | - | 4.5 | - | 1.1 | ○ |
| I2 | 66 | M | *1/*2 | 3.6 | - | 6.0 | - | 0.0 | ○ |
| I3 | 65 | F | *1/*2 | 2.5 | - | 4.1 | - | 0.2 | ○ |
| I4 | 71 | F | *1/*2 | 3.5 | - | 7.4 | - | 0.9 | ○ |
| I5 | 59 | M | *1/*3 | 2.2 | - | 5.3 | - | 1.1 | ○ |
| I6 | 62 | M | *1/*3 | 3.3 | - | 8.3 | - | 0.0 | ○ |
| I7 | 67 | M | *1/*2 | 4.9 | - | 5.0 | - | 0.3 | ○ |
| I8 | 64 | F | *1/*2 | 2.8 | - | 5.2 | - | 0.5 | ○ |
| I9 | 64 | F | *1/*2 | 3.2 | - | 5.4 | - | 0.1 | ○ |
| I10 | 34 | M | *1/*2 | 3.1 | - | 6.9 | - | 0.3 | ○ |
| I11 | 52 | M | *1/*2 | 3.7 | - | 4.9 | - | 0.8 | ○ |
| I12 | 64 | M | *1/*2 | 3.6 | - | 4.5 | - | 0.2 | ○ |
| I13 | 55 | M | *1/*3 | 2.0 | - | 4.7 | - | 1.1 | ○ |
| I14 | 58 | M | *1/*2 | 3.8 | - | 9.4 | - | 0.6 | ○ |
| I15 | 66 | F | *1/*3 | 1.4 | - | 3.7 | - | 1.0 | ○ |
| I16 | 47 | M | *1/*2 | 4.0 | - | 5.4 | - | 0.0 | ○ |
| I17 | 42 | M | *1/*3 | 2.8 | 1+ | 5.3 | - | 0.4 | ○ |
| I18 | 53 | M | *1/*2 | 2.3 | 1+ | 3.7 | - | 0.8 | ○ |
| I19 | 56 | M | *1/*3 | 2.0 | 1+ | 4.0 | - | 2.4 | ○ |
| I20 | 51 | F | *1/*2 | 1.1 | 1+ | 3.3 | - | 0.0 | ○ |
| I21 | 62 | F | *1/*2 | 2.3 | 1+ | 4.1 | - | 0.3 | ○ |
| I22 | 39 | F | *1/*2 | 2.7 | 2+ | 6.0 | - | 0.4 | ○ |
| I23 | 63 | F | *1/*3 | 2.1 | 2+ | 4.0 | - | 0.1 | ○ |
| I24 | 53 | F | *1/*2 | 2.3 | 2+ | 4.1 | - | 0.3 | ○ |
| I25 | 45 | M | *1/*2 | 2.4 | 2+ | 4.9 | - | 0.6 | ○ |
| I26 | 55 | M | *1/*2 | 2.6 | 2+ | 4.2 | - | 0.5 | ○ |
| I27 | 50 | M | *1/*2 | 1.8 | 2+ | 3.9 | - | 0.6 | ○ |
| I28 | 55 | M | *1/*2 | 1.3 | 3+ | 3.6 | - | 0.0 | ○ |
| I29 | 53 | F | *1/*2 | 1.7 | 2+ | 2.9 | 2+ | 0.4 | ○ |
| I30 | 64 | M | *1/*2 | 1.2 | 3+ | 2.5 | 2+ | 1.5 | ○ |
| I31 | 66 | F | *1/*2 | 0.8 | 3+ | 0.8 | 3+ | 1.4 | ○ |
| I32 | 53 | M | *1/*3 | 4.1 | - | 4.5 | - | 49.8 | × |
| I33 | 61 | M | *1/*2 | 4.2 | - | 3.2 | - | 24.8 | × |
| I34 | 44 | F | *1/*2 | 3.2 | - | 3.2 | - | 44.5 | × |
| I35 | 51 | F | *1/*2 | 2.4 | 2+ | 3.1 | - | 21.7 | × |
| I36 | 28 | F | *1/*3 | 2.2 | - | 2.2 | 1+ | 43.6 | × |
| I37 | 70 | M | *1/*3 | 2.7 | 1+ | 2.7 | 1+ | 9.3 | × |
| I38 | 70 | F | *1/*2 | 2.5 | 1+ | 2.0 | 1+ | 39.2 | × |
| I39 | 65 | M | *1/*3 | 3.1 | - | 3.0 | 2+ | 28.0 | × |
| I40 | 45 | F | *1/*3 | 2.8 | - | 2.5 | 2+ | 13.0 | × |
| I41 | 78 | F | *1/*2 | 0.8 | 3+ | 1.4 | 3+ | 4.1 | × |
| I42 | 45 | F | *1/*2 | 1.5 | 3+ | 1.6 | 3+ | 17.0 | × |
| I43 | 70 | M | *1/*3 | 1.1 | 3+ | 1.1 | 3+ | 37.4 | × |
| Case | Age | Sex | CYP2C19 genotype | PG I/II | UBT | Eradication | |||
| Before eradication | After eradication | ||||||||
| P1 | 64 | F | *2/*2 | 3.6 | - | 5.8 | - | 0.2 | ○ |
| P2 | 46 | M | *2/*2 | 4.0 | - | 5.5 | - | 1.2 | ○ |
| P3 | 64 | F | *2/*2 | 2.2 | 1+ | 3.8 | - | 1.1 | ○ |
| P4 | 63 | F | *2/*2 | 2.1 | 2+ | 3.9 | - | 0.0 | ○ |
| P5 | 62 | F | *2/*3 | 2.3 | 2+ | 4.2 | - | 0.2 | ○ |
| P6 | 64 | M | *2/*3 | 2.2 | 2+ | 5.0 | - | 0.0 | ○ |
| P7 | 63 | M | *2/*2 | 2.7 | 2+ | 4.9 | - | 1.2 | ○ |
| P8 | 77 | F | *3/*3 | 1.7 | 3+ | 2.9 | 2+ | 0.1 | ○ |
| P9 | 68 | M | *2/*2 | 1.3 | 2+ | 1.9 | 3+ | 1.2 | ○ |
| P10 | 60 | M | *2/*2 | 0.6 | 3+ | 1.4 | 3+ | 0.8 | ○ |
| P11 | 57 | M | *2/*2 | 4.1 | - | ND | ND | 0.2 | ○ |
| P12 | 65 | F | *2/*2 | 2.0 | 1+ | 2.0 | 1+ | 30.2 | × |
| P13 | 38 | F | *2/*2 | 2.3 | 2+ | 2.5 | 1+ | 63.8 | × |
In addition to H. pylori infection, serum PG level is associated with gastric mucosal atrophy and gastric cancer risk, which is used for gastric cancer screening[17-19]. Serum PG I level and PG I/II ratio in association with H. pylori eradication are shown in Tables 1, 2, and 3. Table 4 is a summary of PG I/II ratio and H. pylori eradication. Serum PG I level and PG I/II ratio were significantly increased after eradication of H. pylori (P = 0.007), suggesting that gastric atrophy was improved by H. pylori eradication therapy. We performed a multiple logistic regression analysis to identify independent predictors associated with H. pylori eradication. As shown in Table 5, only CYP2C19 genotype was statistically significant as an independent predictor associated with H. pylori eradication.
| Eradication | PG I/II ratio | Total | ||
| Increase | No change | Decrease | ||
| Success | 26 | 26 | 1 | 53 |
| Failure | 4 | 18 | 3 | 25 |
| Total | 30 | 44 | 4 | 78 |
| Variable | P value |
| CYP2C19 genotype (EM vs non-EM) | 0.048 |
| Age | 0.603 |
| Sex | 0.637 |
| Pepsinogen I/II before eradication | 0.809 |
EPZ is a second-generation PPI that is broadly used for the treatment of acid-peptic diseases. It is believed that EPZ is more effective for inhibition of gastric acid secretion than other first-generation PPIs, because it is the S-isomer of OPZ and its metabolism is not affected by CYP2C19 genotype. Recent studies have also shown that H. pylori eradication by EPZ-based therapy is not influenced by CYP2C19 genotype, and that overall H. pylori eradication rates of EPZ-based therapy was better than first-generation PPIs[9,12-14]. On the other hand, Hunfeld et al[11] revealed that the acid-inhibitory effect of EPZ was influenced by CYP2C19 genotype. Nishida et al[15] demonstrated that the H. pylori eradication rate of EPZ-based triple therapy was lower than LPZ in the Japanese population. Thus, the effect of EPZ-based therapy on H. pylori eradication is controversial.
In this study we evaluated the influence of CYP2C19 genotype in patients with H. pylori-positive gastritis treated by EPZ-based triple therapy. Our results demonstrated that the H. pylori eradication rate was significantly lower in EM phenotype patients having the wild-type CYP2C19 genotype, compared to the non-EM patients with at least one mutant allele (*2 and *3). The result of multiple logistic regression analysis also showed that CYP2C19 genotype is an independent predictor associated with H. pylori eradication. These findings suggest that EM metabolizes EPZ more rapidly, and therefore plasma concentrations of EPZ become lower, resulting in a lower H. pylori eradication rate than that of non-EM. Nishida et al[15] conducted a multicenter, randomized, open-label, non-inferiority trial comparing EPZ and LPZ in triple therapy for H. pylori eradication in Japan. They reported that the H. pylori eradication rates of EPZ-based triple therapy (69.4%/76.9%, ITT/PP) were lower than LPZ-based triple therapy (73.9%/79.8%, ITT/PP). In this study, the overall H. pylori eradication rates of EPZ-based triple therapy were 67.5%/68.4% (ITT/PP), which were similar to the previous report. A recent study with a Japanese population has also shown that the H. pylori eradication rates by the regimen with rabeprazole, AMPC, and CAM were 73.3%/77.2% (ITT/PP)[6]. Thus, these findings indicate that the H. pylori eradication rate by EPZ-based triple therapy is at the same level with triple therapies with other first-generation PPIs.
Serum PG level is associated with gastric mucosal atrophy and gastric cancer risk[17-19]. In the present study, the serum PG I level and PG I/II ratio were significantly increased after eradication of H. pylori, suggesting that gastric atrophy was improved by H. pylori eradication. Serum PG level and PG I/II ratio can be noninvasive biomarkers for screening of gastric atrophy and gastric cancer. H. pylori eradication has clinical benefit for improvement of gastric mucosal atrophy and prevention against gastric cancer.
In conclusion, first-line H. pylori eradication by EPZ-based triple therapy was influenced by CYP2C19 genotype, and the overall eradication rate was on the same level with triple therapies with other first-generation PPIs in Japanese patients with H. pylori-positive gastritis. Unlike previous reports, the results in this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication in comparison to other first-generation PPIs. Further studies are needed in a large population of patients in different countries before an accurate correlation between the EPZ-based therapy and CYP2C19 genotype is completed. Evaluation of CYP2C19 genotype and serum PG level is important to develop more effective personalized H. pylori eradication therapy with EPZ.
Esomeprazole (EPZ) is a second-generation proton pump inhibitor (PPI) that is broadly used for the treatment of acid-peptic diseases. Recent studies have shown that EPZ is more effective for inhibition of gastric acid secretion than other first-generation PPIs because its metabolism is not influenced by CYP2C19 genotype. However, the effect of Helicobacter pylori (H. pylori) eradication by EPZ-based therapy is controversial.
First-line eradication by EPZ-based triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was at the same level found with other first-generation PPIs in the Japanese population.
Unlike previous reports, the results in this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication in comparison to other first-generation PPIs.
Evaluation of CYP2C19 genotype and serum pepsinogen level is important to develop more effective personalized H. pylori eradication therapy with EPZ.
EPZ is the most recent member of the PPI family and is a more potent acid inhibitor than other first-generation PPIs. The metabolism of first-generation PPIs is influenced by genetic polymorphism of CYP2C19. Based on CYP2C19 genotype, patients can be categorized into three groups: extensive metabolizer, intermediate metabolizer, and poor metabolizer.
This study reports that the second-generation PPI inhibitor, EPZ, has no apparent advantage over triple therapies utilizing other first-generation PPIs for overall eradication of H. pylori in patients with gastritis. The EPZ-based therapy was influenced by the CYP2C19 genotype of the studied Japanese patients.
P- Reviewer: Li SD, Slomiany BL S- Editor: Gong ZM L- Editor: Filipodia E- Editor: Zhang DN
| 1. | Suzuki H, Hibi T, Marshall BJ. Helicobacter pylori: present status and future prospects in Japan. J Gastroenterol. 2007;42:1-15. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 114] [Cited by in F6Publishing: 114] [Article Influence: 6.7] [Reference Citation Analysis (0)] |
| 2. | Cover TL, Blaser MJ. Helicobacter pylori in health and disease. Gastroenterology. 2009;136:1863-1873. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 474] [Cited by in F6Publishing: 459] [Article Influence: 30.6] [Reference Citation Analysis (0)] |
| 3. | Suzuki H, Moayyedi P. Helicobacter pylori infection in functional dyspepsia. Nat Rev Gastroenterol Hepatol. 2013;10:168-174. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 121] [Cited by in F6Publishing: 133] [Article Influence: 12.1] [Reference Citation Analysis (0)] |
| 4. | Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, Terao S, Amagai K, Hayashi S, Asaka M. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet. 2008;372:392-397. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 876] [Cited by in F6Publishing: 850] [Article Influence: 53.1] [Reference Citation Analysis (0)] |
| 5. | Suzuki H, Nishizawa T, Hibi T. Helicobacter pylori eradication therapy. Future Microbiol. 2010;5:639-648. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 76] [Cited by in F6Publishing: 82] [Article Influence: 5.9] [Reference Citation Analysis (0)] |
| 6. | Nishizawa T, Maekawa T, Watanabe N, Harada N, Hosoda Y, Yoshinaga M, Yoshio T, Ohta H, Inoue S, Toyokawa T. Clarithromycin Versus Metronidazole as First-line Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Controlled Study in Japan. J Clin Gastroenterol. 2015;49:468-471. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 47] [Cited by in F6Publishing: 49] [Article Influence: 5.4] [Reference Citation Analysis (0)] |
| 7. | Tang HL, Li Y, Hu YF, Xie HG, Zhai SD. Effects of CYP2C19 loss-of-function variants on the eradication of H. pylori infection in patients treated with proton pump inhibitor-based triple therapy regimens: a meta-analysis of randomized clinical trials. PLoS One. 2013;8:e62162. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 63] [Cited by in F6Publishing: 70] [Article Influence: 6.4] [Reference Citation Analysis (0)] |
| 8. | Furuta T, Ohashi K, Kamata T, Takashima M, Kosuge K, Kawasaki T, Hanai H, Kubota T, Ishizaki T, Kaneko E. Effect of genetic differences in omeprazole metabolism on cure rates for Helicobacter pylori infection and peptic ulcer. Ann Intern Med. 1998;129:1027-1030. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 253] [Cited by in F6Publishing: 227] [Article Influence: 8.7] [Reference Citation Analysis (0)] |
| 9. | McNicholl AG, Linares PM, Nyssen OP, Calvet X, Gisbert JP. Meta-analysis: esomeprazole or rabeprazole vs. first-generation pump inhibitors in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther. 2012;36:414-425. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 125] [Cited by in F6Publishing: 121] [Article Influence: 10.1] [Reference Citation Analysis (0)] |
| 10. | Kendall MJ. Review article: esomeprazole--the first proton pump inhibitor to be developed as an isomer. Aliment Pharmacol Ther. 2003;17 Suppl 1:1-4. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 26] [Cited by in F6Publishing: 26] [Article Influence: 1.2] [Reference Citation Analysis (0)] |
| 11. | Hunfeld NG, Touw DJ, Mathot RA, van Schaik RH, Kuipers EJ. A comparison of the acid-inhibitory effects of esomeprazole and rabeprazole in relation to pharmacokinetics and CYP2C19 polymorphism. Aliment Pharmacol Ther. 2012;35:810-818. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 23] [Cited by in F6Publishing: 25] [Article Influence: 2.1] [Reference Citation Analysis (0)] |
| 12. | Miehlke S, Schneider-Brachert W, Kirsch C, Morgner A, Madisch A, Kuhlisch E, Haferland C, Bästlein E, Jebens C, Zekorn C. One-week once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for eradication of persistent Helicobacter pylori resistant to both metronidazole and clarithromycin. Helicobacter. 2008;13:69-74. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 56] [Cited by in F6Publishing: 43] [Article Influence: 2.7] [Reference Citation Analysis (0)] |
| 13. | Pan X, Li Y, Qiu Y, Tang Q, Qian B, Yao L, Shi R, Zhang G. Efficacy and tolerability of first-line triple therapy with levofloxacin and amoxicillin plus esomeprazole or rabeprazole for the eradication of Helicobacter pylori infection and the effect of CYP2C19 genotype: a 1-week, randomized, open-label study in Chinese adults. Clin Ther. 2010;32:2003-2011. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 23] [Cited by in F6Publishing: 29] [Article Influence: 2.1] [Reference Citation Analysis (0)] |
| 14. | Lee VW, Chau TS, Chan AK, Lee KK, Waye MM, Ling TK, Chan FK. Pharmacogenetics of esomeprazole or rabeprazole-based triple therapy in Helicobacter pylori eradication in Hong Kong non-ulcer dyspepsia Chinese subjects. J Clin Pharm Ther. 2010;35:343-350. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 21] [Cited by in F6Publishing: 22] [Article Influence: 1.6] [Reference Citation Analysis (0)] |
| 15. | Nishida T, Tsujii M, Tanimura H, Tsutsui S, Tsuji S, Takeda A, Inoue A, Fukui H, Yoshio T, Kishida O. Comparative study of esomeprazole and lansoprazole in triple therapy for eradication of Helicobacter pylori in Japan. World J Gastroenterol. 2014;20:4362-4369. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 23] [Cited by in F6Publishing: 18] [Article Influence: 1.8] [Reference Citation Analysis (0)] |
| 16. | Sugimoto M, Furuta T, Shirai N, Nakamura A, Kajimura M, Sugimura H, Hishida A, Ishizaki T. Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection. Aliment Pharmacol Ther. 2005;22:1033-1040. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 30] [Cited by in F6Publishing: 30] [Article Influence: 1.6] [Reference Citation Analysis (0)] |
| 17. | Mizuno S, Kobayashi M, Tomita S, Miki I, Masuda A, Onoyama M, Habu Y, Inokuchi H, Watanabe Y. Validation of the pepsinogen test method for gastric cancer screening using a follow-up study. Gastric Cancer. 2009;12:158-163. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 31] [Cited by in F6Publishing: 33] [Article Influence: 2.4] [Reference Citation Analysis (0)] |
| 18. | Miki K, Fujishiro M, Kodashima S, Yahagi N. Long-term results of gastric cancer screening using the serum pepsinogen test method among an asymptomatic middle-aged Japanese population. Dig Endosc. 2009;21:78-81. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 58] [Cited by in F6Publishing: 63] [Article Influence: 4.2] [Reference Citation Analysis (0)] |
| 19. | Mizuno S, Miki I, Ishida T, Yoshida M, Onoyama M, Azuma T, Habu Y, Inokuchi H, Ozasa K, Miki K. Prescreening of a high-risk group for gastric cancer by serologically determined Helicobacter pylori infection and atrophic gastritis. Dig Dis Sci. 2010;55:3132-3137. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 73] [Cited by in F6Publishing: 66] [Article Influence: 4.7] [Reference Citation Analysis (0)] |