Helicobacter pylori (H. pylori) infect more than 50% of humans globally. It is the principal cause of chronic gastritis, gastric ulcer, duodenal ulcer, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma (MALToma). The Real-world Practice \& Expectation of Asia-Pacific Physicians and Patients in H. pylori Eradication (REAP-HP) Survey demonstrated that standard triple therapy was still the most commonly used anti-H. pylori regimen in the Asia Pacific region. However, the eradication rates of standard triple therapy have declined to less than 80% in most countries worldwide. The main reasons for eradication failure of standard triple therapy include antibiotic resistance, poor compliance and CYP2C19 genotype of host. Clarithromycin resistance of H. pylori has been identified as the main reason for the failure of standard triple therapy. Pooled data from 20 studies involving 1,975 patients treated with standard triple therapy showed an eradication rate of 88% in clarithromycin-sensitive strains versus 18% in clarithromycin-resistant strains. Therefore, the background rate of clarithromycin resistance is critically important for the efficacy of standard triple therapy. Recently, several strategies including bismuth-containing quadruple therapy, non-bismuth quadruple therapy (i.e., sequential therapy, concomitant therapy and hybrid therapy) and high-dose dual therapy have been proposed to increase the eradication rate.

Hybrid therapy developed by our study group in 2011 consists of a dual therapy with a proton pump inhibitor (PPI) and amoxicillin for 7 days followed by a quadruple regimen with a PPI, amoxicillin, clarithromycin and metronidazole for 7 days \[10\]. It achieved an eradication rate of 97.4% by intention-to-treat (ITT) analysis and 99.1% by per-protocol (PP) analysis in a Taiwan population with clarithromycin resistance rate of 7%. Subsequent randomized controlled trials demonstrated that 14-day hybrid therapies were comparable or more effective than 10-day sequential therapies. A recent large multicentre randomized controlled trial documented that 14-day hybrid and 14-day concomitant therapies had comparable efficacy in the treatment of H. pylori infection, and both could cure more than 90% of patients with H. pylori infections in areas of high clarithromycin and metronidazole resistance \[24\]. Therefore, hybrid therapy has a great potential to replace bismuth quadruple therapy in the first-line treatment of H. pylori infection. Currently, hybrid therapy is a recommended first-line treatment for H. pylori infection in the ACG guideline

, Bangkok Consensus Report and Taiwan Consensus Report. High-dose dual therapy developed by Yang et al. is another emerging treatment for H pylori infection. The new therapy consists of high-dose PPI and amoxicillin, which keep the intragastric pH at a value higher than 6.5 regardless of CYP2C19 genotype and maintain steady plasma concentration of amoxicillin above the minimal inhibitory concentration (MIC) for H pylori \[28\]. The efficacy of the new therapy was significantly higher than that of standard triple therapy in Taiwan. However, it was less effective as the first-line therapy for eradicating H pylori in Korea and in the United States.

This study aims to better understand the potential of both hybrid and igh-dose dual therapies in the treatment of H. pylori infection.