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      Treatment of Helicobacter pylori Infection in Korea: A Systematic Review and Meta-analysis

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          Abstract

          The efficacy of seven-day clarithromycin-based standard triple therapy (STT) for Helicobacter pylori has decreased in Korea over the past decade. The aim of this meta-analysis was to clarify the efficacy of first-line and second-line therapies in Korea. This systematic review will provide an overview of H. pylori eradication and present new therapeutic strategies used in Korea. An extensive search of the literature concerning STT, sequential therapy (SET), concomitant therapy (CT), bismuth-containing quadruple therapy (BCQT) and various other therapies used in Korea was performed. All selected studies were randomized controlled trials (RCTs). Eighteen RCTs were eligible for systematic review. The alternative regimens comparing seven-day STT as a first-line therapy include SET, CT, levofloxacin-based therapy (LBT), BCQT, and STT with prolonged duration. The results of the meta-analysis suggest that SET is superior to seven-day STT. The overall eradication rate by intention to treat (ITT) analysis was 69.8% for STT and 79.7% for SET. The overall eradication rate by per-protocol (PP) analysis was 77.0% for STT and 85.0% for SET. The odds ratios for the ITT and PP eradication rate were 0.57 (95% confidence interval [CI], 0.43 to 0.74) and 0.52 (95% CI, 0.35 to 0.76), respectively. In the subgroup analysis, however, there were no significant differences between SET and STT with prolonged durations. Alternative regimens to seven-day BCQT as second-line therapy include LBT, moxifloxacin-based therapy and 14-day BCQT. The eradication rates of these alternative regimens were not superior to that of the conventional treatment. SET is superior to seven-day STT but not to STT with prolonged duration.

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          Global eradication rates for Helicobacter pylori infection: systematic review and meta-analysis of sequential therapy

          Objective To do a systematic review and meta-analysis of studies comparing sequential therapy for eradication of Helicobacter pylori with pre-existing and new therapies, thus providing a glimpse of eradication success worldwide. Design Systematic review and meta-analysis. Data sources Medline, Embase, and Cochrane Central Register of Controlled Trials up to May 2013; abstract books of major European, American, and Asian gastroenterological meetings. Study selection Randomised controlled trials in previously untreated adults, in which sequential therapy was compared with a pre-existing or new therapy. Results 46 randomised controlled trials were reviewed and analysed. 5666 patients were randomised to sequential therapy and 7866 to other (established and new) treatments. The overall eradication rate of sequential therapy was 84.3% (95% confidence interval 82.1% to 86.4%). Sequential therapy was superior to seven day triple therapy (relative risk 1.21, 95% confidence interval 1.17 to 1.25; I2=29.3%; number needed to treat 6 , 95% confidence interval 5% to 7%), marginally superior to 10 day triple therapy (1.11, 1.04 to 1.19; I2= 67.2%; NNT 10, 7 to 15), but not superior to 14 day triple therapy (1.00, 0.94 to 1.06; I2=54.3%), bismuth based therapy (1.01, 0.95 to 1.06; I2=21.1%), and non-bismuth based therapy (0.99, 0.94 to 1.05; I2=52.3%). Data on eradication according to pre-treatment antimicrobial susceptibility testing were available in eight studies, and sequential therapy was able to eradicate 72.8% (61.6% to 82.8%) of the strains resistant to clarithromycin. Conclusions Eradication rates with pre-existing and new therapies for H pylori are suboptimal. Regional monitoring of resistance rates should help to guide treatment, and new agents for treatment need to be developed.
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            Bismuth-containing quadruple therapy as second-line treatment for Helicobacter pylori infection: effect of treatment duration and antibiotic resistance on the eradication rate in Korea.

            The eradication rate of first-line Helicobacter pylori treatment is only 70-85% and has been decreasing due to the increase in antibiotic resistance. The aim of this study was to evaluate the efficacy of bismuth-containing quadruple therapy as second-line treatment for H. pylori infection based on treatment duration. We prospectively enrolled 227 patients that were found to have persistent H. pylori infection after first-line proton-pump inhibitor-clarithromycin-amoxicillin triple therapy. Patients were randomized to 1-week (112 patients) and 2-week (115 patients) quadruple therapy with tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. and esomeprazole 20 mg b.i.d. The eradication rate, drug compliance, and adverse events were compared based on treatment duration. The eradication rates were 72/112 (64.3%, 95% CI: 0.504-0.830) and 71/92 (77.2%, 0.440-0.749) with 1-week group, and 95/115 (82.6%, 1.165-2.449) an 88/94 (93.6%, 1.213-5.113) with 2-week group by intention-to-treat therapy (p = .002) and per-protocol analysis (p = .001), respectively. The adverse events increased as the treatment durations increased from 7 to 14 days (20.0 and 42.5%, respectively, p < .001). However, there was no significant difference in the patient compliance or the rate of major adverse events between the 1- and 2-week groups (6.3 and 12.5%, respectively, p = .133). Two-week bismuth-containing quadruple therapy was more effective than the 1-week treatment, and should be considered for second-line treatment in Korea.
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              Update on non-bismuth quadruple (concomitant) therapy for eradication of Helicobacter pylori

              Background Traditional standard triple therapy for Helicobacter pylori (H. pylori) infection (proton pump inhibitor-clarithromycin-amoxicillin) can easily be converted to non-bismuth quadruple (concomitant) therapy by the addition of a nitroimidazole twice daily. Aim To critically review evidence on the role of non-bismuth quadruple therapy (proton pump inhibitor-clarithromycin-amoxicillin-nitroimidazole) in the treatment of H. pylori infection. Methods Bibliographical searches were performed in MEDLINE and relevant congresses up to December 2011. We performed a meta-analysis of the studies evaluating the concomitant therapy, and of the randomized controlled trials comparing the concomitant and the standard triple therapy. Results A meta-analysis of 19 studies (2070 patients) revealed a mean H. pylori cure rate (intention-to-treat) of 88% (95% confidence interval from 85% to 91%) for non-bismuth quadruple therapy. We performed a meta-analysis of the randomized controlled studies comparing the concomitant (481 patients) and the standard triple therapy (503 patients). The former was more effective than the latter: 90% versus 78% (intention-to-treat analysis). Results were homogeneous (I 2 = 0%). The odds ratio for this comparison was 2.36 (95% confidence interval from 1.67 to 3.34). A tendency toward better results with longer treatments (7–10 days versus 3–5 days) has been observed, so it seems reasonable to recommend the length of treatment achieving the highest cure rates (10 days). Clarithromycin resistance may reduce the efficacy of non-bismuth quadruple therapy, although the decrease in eradication rates seems to be far lower than in standard triple therapy. Experience with the non-bismuth quadruple therapy in patients with metronidazole-resistant strains is still very limited. Conclusion Non-bismuth quadruple (concomitant) therapy appears to be an effective, safe, and well-tolerated alternative to triple therapy and is less complex than sequential therapy. Therefore, this regimen appears well suited for use in settings where the efficacy of triple therapy is unacceptably low.
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                Author and article information

                Journal
                J Korean Med Sci
                J. Korean Med. Sci
                JKMS
                Journal of Korean Medical Science
                The Korean Academy of Medical Sciences
                1011-8934
                1598-6357
                August 2015
                15 July 2015
                : 30
                : 8
                : 1001-1009
                Affiliations
                [1 ]Division of Gastroenterology, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
                [2 ]Institute for Evidence-based Medicine, Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea.
                Author notes
                Address for Correspondence: Jae Gyu Kim, MD. Division of Gastroenterology, Department of Internal Medicine, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 156-755, Korea. Tel: +82.2-6299-3147, Fax: +82.2-6299-1137, jgkimd@ 123456cau.ac.kr

                *Sang Wook Lee and Hyun Jung Kim contributed equally to this work.

                Article
                10.3346/jkms.2015.30.8.1001
                4520928
                26240475
                fbe88844-e886-45b9-8b60-dc0e24df9a01
                © 2015 The Korean Academy of Medical Sciences.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 November 2014
                : 27 April 2015
                Categories
                Review
                Gastroenterology & Hepatology

                Medicine
                helicobacter pylori,treatment,disease eradication,review,systematic
                Medicine
                helicobacter pylori, treatment, disease eradication, review, systematic

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