Efficacy And Safety Of First Line Regimens For Eradication Of Helicobacter Pylori:Systematic Review And Network Meta-analysis

Section 1Efficacy and Safety of First line Regimens for Eradication of Helicobacter Pylori In China:Systematic Review and Network Meta-analysisIn an era of antibiotic resistance Helicobacter pylori(H.pylori)represents still a major global health challenge,especially in emerging countries such as China,the prevalence nearly 50%-70%in adults.H.pylori is one of the commonest infections worldwide and there has been well-documented evidence that this baterium is linked to active chronic gastritis,peptic ulcer disease,gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma,as well as ex-alimentary tract diseases.Evidence from Asia,Europe and America has not drawn a consistent conclusion about common regimens for Helicobacter pylori eradication,including standard sequential therapy,bismuth containing quadruple therapy,levofloxacin containing triple therapy and standard triple therapy.Objectives:To compare and rank the efficacy and the adverse events of the five first line interventions.Methods:We searched major electronic databases through December 2014 for randomized controlled trials comparing different interventions for Helicobacter pylori infection.Using a network meta-analysis and a single rate meta-analysis,relative and absolute rates of eradication and side effects were pooled and later acceptability assessed by a benefit-risk analysis.The Jadad score was adopted to evaluate the methodological quality.Funnel plot was constructed to evaluate publication bias.Begg's rank correlation test or Egger's regression intercept test was done for the asymmetry of funnel plot.Results:Forty-five randomized controlled trials for the treatment of 6148 naive patients with Helicobacter pylori were inclued.For eradication rate,sequential therapy,levofloxacin containing triple therapy and bismuth based quadruple therapy were significantly superior over 10-day standard triple therapy with OR 2.90(95%CI 1.99,4.29),2.37(95%CI 1.27,4.48),2.85(95%CI 1.75,4.80),respectively.Sequential therapy had the highest probability(42%)of improving clinical efficacy and levofloxacin containing triple therapy could be related to the lowest adverse effects with a 80%chance,to higher effectiveness,and to the greatest acceptability with a 60%chance.Bismuth based quadruple therapy resulted in the highest probability(55%)of causing adverse effects although effective.Conclusions:Sequential therapy and levofloxacin containing triple therapy could show some trends toward superiority among the interventions for Helicobacter pylori eradication in China.Section 2Tailored and Novel Empirical Quadruple Regimens for Helicobacter Pylori Infection:Systematic Review and Network Meta-analysisIn an era of antibiotic resistance Helicobacter pylori(H.pylori)represents still a major global health challenge,especially in emerging countries such as China,the prevalence nearly 50%-70%in adults.H.pylori is one of the commonest infections worldwide and there has been well-documented evidence that this baterium is linked to active chronic gastritis,peptic ulcer disease,gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma,as well as ex-alimentary tract diseases.Evidence from Asia,Europe and America has not drawn a consistent conclusion about new empirical firstline quadruple regimens for Helicobacter pylori eradication,including concomitant,hybrid,sequential,and bismuth quadruple therapy.Also,the optimal protocol remains inconclusive.Objectives:To compare and rank the major clinical outcome and the adverse events of tailored and empirical interventions for Helicobacter pylori eradication.Methods:We searched major electronic databases through Jun 2015.Studies were considered eligible if designs were randomized controlled trials comparing different pharmacological formulations for Helicobacter pylori infection;using a network meta-analysis and a single rate meta-analysis,relative and absolute rates of eradication and side effects were pooled and later acceptability assessed by a benefit-risk analysis.The Jadad score was adopted to evaluate the methodological quality.Funnel plot was constructed to evaluate the risk of publication bias.Begg's rank correlation test or Egger's regression intercept test was done for the asymmetry of funnel plot.Results:Twenty randomized controlled trials for the treatment of 6753 naive patients with Helicobacter pylori were included.For eradication rate,concomitant therapy and bismuth quadruple therapy were significantly inferior to antimicrobial susceptibility guided therapy with OR 0.47(95%CI 0.24,0,84)and OR 0.43(95%CI 0.23,0.73),respectively;antimicrobial susceptibility guided therapy was significantly superior over hybrid therapy with OR 2.31(95%CI 1.11,4.40)and over sequential therapy with OR 4.06(95%CI 1.95,9.40).The culture-based and antimicrobial susceptibility guided therapy had the highest probability(97%)of improving clinical efficacy,with the lowest adverse effects and the greatest acceptability.Concomitant therapy resulted in the highest probability(79%)of causing adverse effects although effective.Hybrid therapy and bismuth quadruple therapy were associated with lower adverse effects,higher effectiveness,and greater acceptability.Conclusions:The tailored therapy shows a trend toward superiority among the interventions for Helicobacter pylori eradication.Hybrid therapy and bismuth quadruple therapy may be applied in the settings where the culture-based strategy is not available.