Efficacy and Safety of Vonoprazan-Based versus Proton Pump Inhibitor-Based Triple Therapy for<i> Helicobacter pylori</i> Eradication: A Meta-Analysis of Randomized Clinical Trials

Lyu, Qiu-Ju; Pu, Qiang-Hong; Zhong, Xian-Fei; Zhang, Jin

doi:https://doi.org/10.1155/2019/9781212

BioMed Research International

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Research Article | Open Access

Volume 2019 | Article ID 9781212 | https://doi.org/10.1155/2019/9781212

Efficacy and Safety of Vonoprazan-Based versus Proton Pump Inhibitor-Based Triple Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Clinical Trials

Qiu-Ju Lyu,¹Qiang-Hong Pu,²Xian-Fei Zhong,³and Jin Zhang¹

Academic Editor: David Bernardo

Received07 Jan 2019

Revised28 Mar 2019

Accepted17 Apr 2019

Published09 May 2019

Abstract

Aims. To compare the efficacy and safety of vonoprazan-based versus proton pump inhibitor (PPI)-based triple therapy in the eradication of Helicobacter pylori. Methods. We performed a systematic search in PubMed, Embase, and the Cochrane Library databases for relevant randomized controlled trials up to March 2019. Studies were included if they compared the efficacy and safety of H. pylori eradication of vonoprazan-based and PPI-based triple therapy. Results. Three studies with 897 patients were evaluated in this meta-analysis. The H. pylori eradication rate of vonoprazan-based triple therapy was higher than that of PPI-based triple therapy as first-line regimens (intention-to-treat analysis: pooled eradication rates, 91.4% vs 74.8%; odds ratio [OR], 3.68; 95% confidence interval (CI): [1.87–7.26]; P<0.05). The incidence of adverse events in vonoprazan-based triple therapy was lower than that in PPI-based triple therapy (pooled incidence, 32.7% vs 40.5%; OR, 0.71; 95%CI: [0.53–0.95]; P<0.05). Conclusions. Efficacy of vonoprazan-based triple therapy is superior to that of PPI-based triple therapy for first-line H. pylori eradication. Additionally, vonoprazan-based triple therapy is better tolerated than PPI-based triple therapy.

1. Introduction

In 2015, over four billion people were estimated to be infected with Helicobacter pylori (H. pylori) worldwide [1]. H. pylori infection causes many gastrointestinal diseases, such as peptic ulcer, chronic gastritis, gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma [2–4].

For H. pylori infection, the recommended first-line eradication regimen was proton pump inhibitor (PPI)-based triple therapy, which consisted of a PPI plus amoxicillin and clarithromycin or metronidazole [5, 6]. However, the eradication rate of PPI-based triple therapy has been declining in recent years, owing to increased H. pylori resistance to clarithromycin and metronidazole [7, 8]. In China, H. pylori resistance rates for clarithromycin and metronidazole were 63.4% and 52.6%, respectively [9]. Currently, bismuth-containing quadruple therapy and concomitant therapy (PPI and three antibiotics) are recommended as first-line options in China and Taiwan, where the prevalence of primary clarithromycin resistance is >15% [10–12].

Vonoprazan is a new oral acid suppressant, which, like PPIs, belongs to a group of H⁺-K⁺ ATPase inhibitors. However, unlike PPIs, vonoprazan is a reversible H⁺-K⁺ ATPase inhibitor [13]. Vonoprazan has been approved to treat H. pylori infection, gastroduodenal ulcer, and reflux esophagitis in Japan since February 2015, but it has still not been approved by Chinese, American, and European agencies. Vonoprazan has a potency of H⁺-K⁺ ATPase inhibition approximately 350 times higher than that of PPIs and has a faster, stronger, and longer-lasting acid-inhibitory effect than PPIs have in clinical trials [14–16]. Therefore, vonoprazan was expected to improve the H. pylori eradication rate compared with PPIs. Recently, several meta-analyses showed that vonoprazan-containing triple therapy was superior to PPI-containing triple therapy [17–19]. However, these meta-analyses included mostly nonrandomized controlled trials (NRCTs) and were likely to have reported less accurate or robust results when compared to analyses that included only RCTs. Therefore, we performed a meta-analysis including only RCTs to assess the efficacy and safety of vonoprazan-based and PPI-based triple therapy for H. pylori eradication.

2. Methods

2.1. Criteria for Considering Studies for This Meta-Analysis

2.1.1. Types of Studies

Only RCTs that compared vonoprazan-based versus PPI-based triple therapy as first-line regimens for H. pylori eradication were included. The language of the studies was restricted to English. The following were excluded: (1) animal studies; (2) other study designs (letters, case reports, editorials, commentaries and reviews, etc.); (3) studies with incomplete data such as abstract-only publications; and (4) studies with duplicate data.

2.2. Types of Participants

2.2.1. Inclusion Criteria

RCTs were eligible for inclusion if enrolled participants were diagnosed as positive for H. pylori (with one or more confirmatory tests) on the basis of the urea breath test (UBT), rapid urease test, culture, and stool H. pylori antigen [20]. Participants had to be naïve to H. pylori eradication treatment.

2.2.2. Exclusion Criteria

RCTs were excluded if enrolled participants were diagnosed as H. pylori-positive solely on the basis of serology or polymerase chain reaction (PCR) or if the participants had previously been treated with any eradication therapy[20].

2.3. Types of Interventions

Vonoprazan-based triple therapy consisted of vonoprazan and two antibiotics, and PPI-based triple therapy consisted of a PPI and two antibiotics. Antibiotic types and doses and duration of treatment were similar between the vonoprazan-based and PPI-based regimens.

2.4. Types of Outcome Measures

Relevant trials were included that assessed the following outcomes: (1) Eradication rate: intention-to-treat (ITT) and per-protocol (PP) analyses. Trials were eligible if H. pylori eradication was confirmed by UBT or stool H. pylori antigen, at least 4 weeks after completion of treatment. (2) Incidence of adverse events (ITT analysis). Adverse events included diarrhea, dysgeusia, and any type of adverse events.

2.5. Search Strategy

2.5.1. Electronic Searches

We performed a systematic search of PubMed, Embase, and the Cochrane Library databases for relevant RCTs up to March 18, 2019. The following terms were used: (“vonoprazan” or “takecab” or “TAK438” or “TAK-438” or “potassium-competitive acid blocker”) and (“proton pump inhibitors” or “omeprazole” or “lansoprazole” or “pantoprazole” or “rabeprazole” or “esomeprazole” or “ilaprazole” or “dexlansoprazole” or “dexrabeprazole” or “tenatoprazole”) and (“Helicobacter pylori” or “Campylobacter pylori”) and (“randomized controlled trial”). The detailed search strategies are shown in Appendix S1. The language of the studies was restricted to English.

2.5.2. Searching Other Resources

Two investigators (Qiang-Hong Pu and Qiu-Ju Lyu) carefully screened the reference lists of the retrieved articles to identify additional studies.

2.6. Data Collection and Analysis

2.6.1. Selection of Studies

First, we excluded the duplicate studies using Endnote software Version X8 and manual screening (author, title, journal, publication year, journal volume, and issue). Second, we excluded the irrelevant studies through examining the title and abstract of articles. Lastly, we examined the full text of the remaining studies according to the inclusion and exclusion criteria. Two investigators (Qiang-Hong Pu and Qiu-Ju Lyu) independently assessed the studies identified by the literature search. Any disagreement was resolved in a consensus meeting with all the authors.

2.6.2. Data Extraction

Two investigators (Qiang-Hong Pu and Qiu-Ju Lyu) independently extracted data using a predesigned data extraction form, according to the method developed by Li and Jung [18, 19]: first author, publication year, country, eradication regimens (dosage and frequency of vonoprazan, PPIs and antibiotics), duration of treatment, confirmative test for eradication, eradication rate (ITT and PP analyses), and adverse events.

2.7. Assessment of Risk of Bias in Included Studies

Two investigators (Qiang-Hong Pu and Qiu-Ju Lyu) independently assessed the risk of bias of included RCTs using the Cochrane Risk of Bias assessment tool [21]: (1) how the random sequence was generated; (2) how patient allocation was concealed; (3) blinding of the patients and researchers; (4) blinding of outcome assessment; (5) whether there were incomplete outcome data; (6) whether there was selective outcome reporting; and (7) other potential biases.

2.8. Assessment of Heterogeneity

Heterogeneity was evaluated by Cochrane’s Q test, which was considered statistically significant for heterogeneity if P was <0.1, and I² statistics, for which 30%–60% and 60%–90% suggested moderate and substantial heterogeneity, respectively.

2.9. Assessment of Reporting Biases

Since there were <10 included studies, the publication bias (test for funnel plot asymmetry) was not evaluated.

2.10. Data Synthesis and Statistical Analysis

Meta-analyses were conducted using RevMan version 5.3 (Cochrane Collaboration, Copenhagen, Denmark) with random-effect model by default. All statistical tests were two-tailed; P<0.05 was considered statistically significant in all tests (except for the heterogeneity test), and pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated.

3. Results

3.1. Studies Selection and Characteristics of Included Studies

The flow diagram of study identification, screening, inclusion, and exclusion is shown in Figure 1. We identified 67 studies in our search of PubMed, Embase, and Cochrane Library databases using the defined terms. Twenty duplicate studies were removed using Endnote software Version X8 and manual screening. Another 27 irrelevant studies were discarded through examining the title and abstract of the articles. After examination of the full text of the remaining 20 articles, we finally selected three with sufficient data for inclusion in this meta-analysis (Table 1). These studies were published between 2016 and 2018, and their enrollment periods ranged from 2012 to 2016. Because vonoprazan was only approved in Japan, all three studies were conducted in Japan. Four hundred and fifty-six patients who received vonoprazan-based triple therapy and 441 who received PPI-based triple therapy were included in this meta-analysis. In all three studies, vonoprazan-based triple therapy consisted of 20 mg vonoprazan, 750 mg amoxicillin, and 200 or 400 mg clarithromycin, twice daily for 7 days. In PPI-based triple therapy, a standard dose of PPI was used instead of vonoprazan. In all three studies, eradication success was confirmed using the UBT at least 4 weeks after completing treatment.

3.2. Risk of Bias

Two RCTs showed low risk of bias, but one showed high risk of bias according to the Cochrane Risk of Bias tool (Figure 2).

3.3. Efficacy of Vonoprazan-Based versus PPI-Based Triple Therapy

In the ITT analysis (Figure 3), H. pylori eradication rate of vonoprazan-based triple therapy was higher than that of PPI-based triple therapy (pooled eradication rates, 91.4% vs 74.8%; OR, 3.68; 95%CI: [1.87–7.26]; P<0.05). A similar tendency was found in the PP analysis (pooled eradication rates, 92.6% vs 76.4%; OR, 3.55; 95%CI: [1.46–8.66]; P<0.05) (Figure 4). No significant heterogeneity was identified in the ITT analysis (Cochrane’s Q test, df=2, P>0.1, I²=46%), but significant heterogeneity was identified in the PP analysis (Cochrane’s Q test, df=2, P<0.1, I²=61%).

3.4. Safety of Vonoprazan-Based versus PPI-Based Triple Therapy

Two studies [22, 23] provided an overall incidence of adverse events and all three studies provided detailed incidence of common adverse events. The overall incidence of adverse events in vonoprazan-based triple therapy was significantly lower than that in PPI-based triple therapy (pooled incidences, 32.7% vs 40.5%; OR, 0.71; 95%CI: [0.53–0.95]; P<0.05; Cochrane’s Q test, df=1, P>0.1, I²=0%) (Figure 5). To analyze further the safety of the two regimens, we examined the incidence of two common adverse events, namely, diarrhea and dysgeusia. There was no difference in the two regimens (diarrhea: 11.6% vs 18.4%; dysgeusia: 5.7% vs 4.8%; P>0.05) (Table 2).

4. Discussion

Our meta-analysis demonstrated that vonoprazan-based triple therapy had a higher eradication rate than PPI-based triple therapy as first-line regimen (91.4% vs 74.8%, 95%CI: [1.87–7.26] in ITT analysis; 92.6% vs 76.4%, 95%CI: [1.46–8.66] in PP analysis). These results were consistent with another study that reported eradication rates of >90% for vonoprazan-based triple therapy and <80% for PPI-based triple therapy [25]. According to a report card introduced by Graham to grade H. pylori therapy [26], the 91.4% eradication rate in vonoprazan-based triple therapy is good (Grade B), while the 76.4% eradication rate in PPI-based triple therapy is unacceptable (Grade F). Such superiority of vonoprazan-containing triple therapy is because of its faster, stronger, and more stable acid-inhibitory effect [14, 15]. A previous meta-analysis demonstrated that high-dose PPIs seem more effective than standard dose for eradicating H. pylori infection in 7-day triple therapy (82% vs 74%, 95% CI:[1.01–1.17]) [27]. Increased gastric pH may drive H. pylori to reenter the replicative state and thus become susceptible to antibiotics [28, 29].

Another interesting finding was that vonoprazan-based triple therapy was safer than PPI-based triple therapy, so vonoprazan-based triple therapy would be safe and well-tolerated. If vonoprazan is available and can be afforded by the patients, vonoprazan-based triple therapy should be preferentially recommended, on account of its high efficacy and safety.

Although vonoprazan-based triple therapy was beneficial, significant heterogeneity was still a concern. The heterogeneity may have resulted from the different participants in the included studies. Clarithromycin-susceptible and clarithromycin-resistant subjects participated in the RCTs of Murakami and Maruyama, but only clarithromycin-susceptible patients participated in the RCT of Sue. Clarithromycin resistance is an important factor affecting the efficacy of triple eradication therapy. Many guidelines emphasize that PPI-clarithromycin-containing triple therapy should be rejected if clarithromycin resistance is >15% [3, 4]. In many countries including China and Japan, clarithromycin resistance is >15%. Nevertheless, PPI-clarithromycin-containing triple therapy is commonly used without clarithromycin susceptibility testing because testing is more time-consuming and costlier than empirical treatment. In the presence of clarithromycin resistance, vonoprazan-clarithromycin-containing triple therapy had significantly higher eradication rates as compared to PPI-clarithromycin-containing triple therapy (82.0% vs 40.0%, 95% CI:[3.63–12.86]), and the eradication rate was >80% and an acceptable grade [19, 26]. Vonoprazan-clarithromycin-containing triple therapy may therefore be recommended as empirical treatment when there is no clarithromycin susceptibility test.

Our meta-analysis had several limitations. First, the number of RCTs included was small, and more RCTs are needed to confirm our results. Second, because vonoprazan was only approved in Japan, all studies included in the analysis were performed in Japan, which may have increased selection bias. Our findings may not be generalized to other populations. Third, treatment duration in all RCTs was 7 days; therefore, we cannot assess if vonoprazan-based triple therapy was superior to PPI-based triple therapy other than for 7-days duration. Seven-day triple therapy is not recommended in most guidelines [3, 4]; thus, 14-day triple therapy should be implemented to compare vonoprazan and PPIs. Fourth, all studies enrolled only adult patients, so our results may not be generalized to children. Fifth, all RCTs used triple therapy; thus other eradication regimens, such as bismuth-containing quadruple therapy, concomitant therapy, sequential therapy, and hybrid therapy, should be performed to evaluate if vonoprazan is still superior to PPIs.

5. Conclusions

Given the results of our meta-analysis, for the Japanese population, vonoprazan-based triple therapy efficacy is superior to that of PPI-based triple therapy when used as a first-line regimen for H. pylori eradication. Additionally, vonoprazan-based triple therapy is better tolerated than PPI-based triple therapy. However, owing to the small number and significant heterogeneity of the included studies and absence of clinical results for other populations, the above conclusions need to be considered with caution.

Data Availability

All data was provided in the article.

Conflicts of Interest

The authors have declared no conflicts of interest.

Authors’ Contributions

Qiang-Hong Pu, Qiu-Ju Lyu, Xian-Fei Zhong, and Jin Zhang jointly conceived of and designed the studies. Qiang-Hong Pu and Qiu-Ju Lyu carried out the studies and prepared the manuscript and the statistical analyses. Xian-Fei Zhong and Jin Zhang revised the paper. All of the authors read and approved the final manuscript. Qiu-Ju Lyu and Qiang-Hong Pu contributed equally to this work.

Acknowledgments

The authors would like to thank digestive physician Li-Zhi Yi for his assistance and review of the manuscript. We also thank Cathel Kerr, BSc, PhD, from Liwen Bianji, Edanz Editing China (https://www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

Supplementary Materials

Appendix S1: detailed search strategy. (Supplementary Materials)

References

J. K. Y. Hooi, W. Y. Lai, W. K. Ng et al., “Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis,” Gastroenterology, vol. 153, no. 2, pp. 420–429, 2017.
View at: Publisher Site | Google Scholar
R. H. Hunt, S. D. Xiao, F. Megraud et al., “Helicobacter pylori in developing countries. World gastroenterology organisation global guideline,” Journal of Gastrointestinal and Liver Diseases, vol. 20, no. 3, pp. 299–304, 2011.
View at: Google Scholar
W. Z. Liu, Y. Xie, H. Lu et al., “Fifth chinese national consensus report on the management of Helicobacter pylori infection,” Helicobacter, vol. 23, no. 2, Article ID e12475, 2018.
View at: Publisher Site | Google Scholar
P. Malfertheiner, F. Megraud, C. A. O'Morain et al., “Management of Helicobacter pylori infection-the Maastricht V/florence consensus report,” Gut, vol. 66, no. 1, pp. 6–30, 2017.
View at: Google Scholar
P. Malfertheiner, F. Megraud, C. A. O'Morain et al., “Management of Helicobacter pylori infection—the maastricht IV/ florence consensus report,” Gut, vol. 61, no. 5, pp. 646–664, 2012.
View at: Publisher Site | Google Scholar
W. D. Chey and B. C. Y. Wong, “American College of Gastroenterology guideline on the management of Helicobacter pylori infection,” American Journal of Gastroenterology, vol. 102, no. 8, pp. 1808–1825, 2007.
View at: Publisher Site | Google Scholar
J. M. Liou, M. S. Wu, and J. T. Lin, “Treatment of Helicobacter pylori infection: Where are we now?” Journal of Gastroenterology and Hepatology, vol. 31, no. 12, pp. 1918–1926, 1918.
View at: Google Scholar
I. Thung, H. Aramin, V. Vavinskaya et al., “Review article: the global emergence of Helicobacter pylori antibiotic resistance,” Alimentary Pharmacology & Therapeutics, vol. 43, no. 4, pp. 514–533, 2016.
View at: Publisher Site | Google Scholar
Y.-X. Zhang, L.-Y. Zhou, Z.-Q. Song, J.-Z. Zhang, L.-H. He, and Y. Ding, “Primary antibiotic resistance of Helicobacter pylori strains isolated from patients with dyspeptic symptoms in Beijing: a prospective serial study,” World Journal of Gastroenterology, vol. 21, no. 9, pp. 2786–2792, 2015.
View at: Publisher Site | Google Scholar
B.-S. Sheu, M.-S. Wu, C.-T. Chiu et al., “Consensus on the clinical management, screening-to-treat, and surveillance of Helicobacter pylori infection to improve gastric cancer control on a nationwide scale,” Helicobacter, vol. 22, no. 3, Article ID e12368, 2017.
View at: Publisher Site | Google Scholar
W. Z. Liu, Y. Xie, H. Cheng et al., “Fourth chinese national consensus report on the management of Helicobacter pylori infection,” Journal of Digestive Diseases, vol. 14, no. 5, pp. 211–221, 2013.
View at: Publisher Site | Google Scholar
C. Gower-Rousseau, H. Sarter, and G. Savoye, “Validation of the inflammatory bowel disease Disability Index in a population-based cohort,” Gut, vol. 66, no. 4, pp. 588–596, 2017.
View at: Publisher Site | Google Scholar
Y. Hori, A. Imanishi, J. Matsukawa et al., “1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl] -N-methylmethanamine monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases,” The Journal of Pharmacology and Experimental Therapeutics, vol. 335, no. 1, pp. 231–238, 2010.
View at: Publisher Site | Google Scholar
Y. Sakurai, Y. Mori, H. Okamoto et al., “Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or rabeprazole 10 mg in healthy adult male subjects—a randomised open-label cross-over study,” Alimentary Pharmacology & Therapeutics, vol. 42, no. 6, pp. 719–730, 2015.
View at: Publisher Site | Google Scholar
Y. Sakurai, A. Nishimura, G. Kennedy et al., “Safety, tolerability, pharmacokinetics, and pharmacodynamics of single rising TAK-438 (vonoprazan) doses in healthy male japanese/non-japanese subjects,” Clinical and Translational Gastroenterology, vol. 6, no. 6, p. e94, 2015.
View at: Publisher Site | Google Scholar
H. Echizen, “The first-in-class potassium-competitive acid blocker, vonoprazan fumarate: pharmacokinetic and pharmacodynamic considerations,” Clinical Pharmacokinetics, vol. 55, no. 4, pp. 409–418, 2016.
View at: Publisher Site | Google Scholar
S. Q. Dong, T. P. Singh, X. Wei, H. Yao, and H. L. Wang, “Review: A Japanese population-based meta-analysis of vonoprazan versus PPI for Helicobacter pylori eradication therapy: Is superiority an illusion?” Helicobacter, vol. 22, no. 6, Article ID e12495, 2017.
View at: Google Scholar
Y. S. Jung, E. H. Kim, and C. H. Park, “Systematic review with meta-analysis: the efficacy of vonoprazan-based triple therapy on Helicobacter pylori eradication,” Alimentary Pharmacology & Therapeutics, vol. 46, no. 2, pp. 106–114, 2017.
View at: Publisher Site | Google Scholar
M. Li, T. Oshima, T. Horikawa et al., “Systematic review with meta-analysis: vonoprazan, a potent acid blocker, is superior to proton-pump inhibitors for eradication of clarithromycin-resistant strains of Helicobacter pylori,” Helicobacter, vol. 23, no. 4, Article ID e12495, 2018.
View at: Google Scholar
O. P. Nyssen, A. G. McNicholl, F. Megraud et al., “Sequential versus standard triple first-line therapy for Helicobacter pylori eradication,” The Cochrane Database of Systematic Reviews, vol. 6, Article ID Cd009034, 2016.
View at: Google Scholar
J. P. T. Higgins, D. G. Altman, and A. C. Jonathan, Eds., Chapter 8: Assessing risk of bias in included studies, Sterne on behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group, Version 5.1.0. (updated March 2011), The Cochrane Collaboration, 2011, http://handbook-5-1.cochrane.org/.
K. Murakami, Y. Sakurai, M. Shiino, N. Funao, A. Nishimura, and M. Asaka, “Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study,” Gut, vol. 65, no. 9, pp. 1439–1446, 2016.
View at: Publisher Site | Google Scholar
M. Maruyama, N. Tanaka, D. Kubota et al., “Vonoprazan-based regimen is more useful than ppi-based one as a first-line Helicobacter pylori eradication: a randomized controlled trial,” Canadian Journal of Gastroenterology and Hepatology, vol. 2017, Article ID 4385161, 7 pages, 2017.
View at: Publisher Site | Google Scholar
S. Sue, M. Ogushi, I. Arima et al., “Vonoprazan- vs proton-pump inhibitor-based first-line 7-day triple therapy for clarithromycin-susceptible Helicobacter pylori: A multicenter, prospective, randomized trial,” Helicobacter, vol. 23, no. 2, Article ID e12456, 2018.
View at: Google Scholar
H. Ozaki, S. Harada, T. Takeuchi et al., “Vonoprazan, a novel potassium-competitive acid blocker, should be used for the helicobacter pylori eradication therapy as first choice: a large sample study of vonoprazan in real world compared with our randomized control trial using second-generation proton pump inhibitors for helicobacter pylori eradication therapy,” Digestion, vol. 97, no. 3, pp. 212–218, 2018.
View at: Publisher Site | Google Scholar
D. Y. Graham, H. Lu, and Y. Yamaoka, “A report card to grade Helicobacter pylori therapy,” Helicobacter, vol. 12, no. 4, pp. 275–278, 2007.
View at: Publisher Site | Google Scholar
A. Villoria, X. Calvet, P. Garcia, J. P. Gisbert, and V. Puig Diví, “Meta-analysis: high-dose proton pump inhibitors vs. standard dose in triple therapy for Helicobacter pylori eradication,” Alimentary Pharmacology & Therapeutics, vol. 28, no. 7, pp. 868–877, 2008.
View at: Publisher Site | Google Scholar
D. Y. Graham and L. Fischbach, “Helicobacter pylori treatment in the era of increasing antibiotic resistance,” Gut, vol. 59, no. 8, pp. 1143–1153, 2010.
View at: Publisher Site | Google Scholar
D. Y. Graham and A. Shiotani, “New concepts of resistance in the treatment of Helicobacter pylori infections,” Nature Clinical Practice Gastroenterology & Hepatology, vol. 5, no. 6, pp. 321–331, 2008.
View at: Publisher Site | Google Scholar

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Copyright © 2019 Qiu-Ju Lyu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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