The internalization of Helicobacter pylori plays a role in the failure of H. pylori eradication.

BACKGROUND: Helicobacter pylori (H. pylori) internalization involves invasion of cells by the bacterium. Several studies have shown that H. pylori can invade human gastric epithelial cells, immune cells, and Candida yeast in vivo and in vitro. Whether bacterial invasion plays a role in eradication failure is unclear. AIM: To investigate the relationship between H. pylori invasion of GES-1 cells and H. pylori eradication failure. MATERIALS AND METHODS: Forty-two clinical strains isolated from H. pylori-positive patients with different outcomes after treatment with furazolidone-based therapy were examined (17 failures and 25 successes). The H. pylori strains were shown to be susceptible to amoxicillin and furazolidone, and the patients also exhibited good compliance. Genotyping was performed for cagA and vacA (s and m). The antibiotic susceptibility of the strains to amoxicillin, furazolidone, clarithromycin, metronidazole, and levofloxacin was determined by E-tests. The levels of H. pylori invasion of GES-1 cells were detected by gentamicin colony-forming unit assays. RESULTS: The internalization level in the eradication success group was 5.40±5.78 × 10-3  cfu/cell, and the median was 6.194 × 10-3  cfu/cell; the internalization level in the eradication failure group was 8.98±5.40 × 10-3  cfu/cell, and the median was 10.28 × 10-3  cfu/cell. The eradication failure group showed a greater invasion level than the eradication success group (P<.05). No significant difference was observed between the susceptible strains and the resistant strains when the internalization levels were compared (P>.05). CONCLUSIONS: The results showed that H. pylori invasion of the gastric epithelia might play a role in eradication failure.

Meta-analysis: is combination of tetracycline and amoxicillin suitable for Helicobacter pylori infection?

AIM: To access the efficacy of combination with amoxicillin and tetracycline for eradication of Helicobacter pylori (H. pylori), thus providing clinical practice guidelines. METHODS: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index, China National Knowledge Infrastructure, Wanfang, and Chinese Biomedical Literature databases and abstract books of major European, American, and Asian gastroenterological meetings were searched. All clinical trials that examined the efficacy of H. pylori eradication therapies and included both tetracycline and amoxicillin in one study arm were selected for this systematic review and meta-analysis. Statistical analysis was performed with Comprehensive Meta-Analysis Software (Version 2). Subgroup, meta-regression, and sensitivity analyses were also carried out. RESULTS: Thirty-three studies met the inclusion criteria. The pooled odds ratio (OR) was 0.90 (95%CI: 0.42-1.78) for quadruple therapy with amoxicillin and tetracycline vs other quadruple regimens, and total eradication rates were 78.1% by intention-to-treat (ITT) and 84.5% by per-protocol (PP) analyses in the experimental groups. The pooled eradication rates of 14-d quadruple regimens with a combination of amoxicillin and tetracycline were 82.3% by ITT and 89.0% by PP, and those of 10-d regimens were 84.6% by ITT and 93.7% by PP. The OR by ITT were 1.21 (95%CI: 0.64-2.28) for triple regimens with amoxicillin and tetracycline vs other regimens and 1.81 (95%CI: 1.37-2.41) for sequential treatment with amoxicillin and tetracycline vs other regimens, respectively. CONCLUSION: The effectiveness of regimens employing amoxicillin and tetracycline for H. pylori eradication may be not inferior to other regimens, but further study should be necessary.

Review: efficacy and safety of hybrid therapy for Helicobacter pylori infection: a systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy and safety of hybrid therapy compared to other pre-existing therapies and to new therapies. METHODS: Through a search of PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and Conference Proceedings Citation Index, two independent reviewers systemically identified randomized, controlled trials that compared hybrid therapy to other pre-existing and new therapies. Dichotomous data were pooled to obtain the relative risk (RR) of the eradication rate, with 95% confidence intervals (CIs). RESULTS: We identified 6 studies, 5 of which compared hybrid therapy and sequential therapy, and 3 of which compared hybrid therapy and concomitant therapy. Pooled estimates of the 5 randomized controlled trials (RCTs) revealed no significant differences between hybrid therapy and sequential therapy and no evidence of heterogeneity (I(2)  = 0%; p = .803), the pooled RRs were 1.02 (95% CI: 0.93-1.12) (intention-to-treat (ITT)), and 1.03 (95% CI: 0.94-1.13) (per protocol (PP)). Pooled estimates of the 3 RCTs showed no significant differences between hybrid therapy and concomitant therapy with no evidence of heterogeneity (I(2)  = 0%; p = .967), the pooled RRs were 0.99 (95% CI: 0.89-1.10) (ITT) and 0.99 (95% CI: 0.89-1.10) (PP). No significant differences in adverse events were noted among hybrid therapy, sequential therapy, and concomitant therapy ((RR: 1.13; 95% CI: 0.87-1.48; I(2)  = 13.2%; p = .327), (RR: 0.89; 95% CI: 0.73-1.08; I(2)  = 0%; p = .978) (ITT), respectively). After consideration of all treatment arms, the ITT eradication rates with hybrid therapy, concomitant therapy, and sequential therapy were 88.6, 86.3, and 84.7%, respectively. And the PP eradication rates were 92.1, 92.5, and 87.5%. No significant differences were observed between the groups in terms of compliance. CONCLUSIONS: All three of these therapies yielded good eradication rates. Hybrid therapy could be an alternative to sequential therapy and concomitant therapy, but additional RCTs are needed to confirm this finding.

Standard triple therapy for Helicobacter pylori infection in China: a meta-analysis.

AIM: To assess the efficacy and safety of standard triple therapy compared with other pre-existing and new therapies in China. METHODS: Literature searches were conducted in the following databases: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the VIP database, the China National Knowledge Infrastructure database, and the Chinese Biomedical Database. A meta-analysis of all randomized controlled trials (RCTs) comparing standard triple therapy for the eradication of Helicobacter pylori with pre-existing and new therapies in China was performed using Comprehensive Meta-Analysis 2.0. There were 49 studies that met our criteria and the qualities of these studies were assessed using the Jadad scale. The Mantel-Haenszel method was used for pooling dichotomous data. We also conducted subgroup analyses according to age, duration of treatment and drug type. Sensitivity analyses and a cumulative meta-analysis were also performed with CMA 2.0. Publication bias was evaluated using Egger's test, Begg's test or a funnel plot. RESULTS: A total of 49 RCTs including 8332 patients were assessed. This meta-analysis showed that standard triple therapy with proton pump inhibitors (PPIs), amoxicillin (AMO) and clarithromycin (CLA) was inferior to sequential therapy [relative risk (RR) = 0.863; 95% confidence interval (CI): 0.824-0.904], but was not superior to quadruple therapy (RR = 1.073; 95%CI: 0.849-1.357) or other triple therapies (RR = 1.01; 95%CI: 0.936-1.089). The meta-analysis also suggested that standard triple therapy is slightly more effective than dual therapy (RR = 1.14; 95%CI: 0.99-1.31). However, the differences were not statistically significant. We removed the only trial with a regimen lasting 14 d by sensitivity analysis and found that 7-d standard triple therapy was superior to 7-d dual therapy (RR = 1.222; 95%CI: 1.021-1.461). Moreover, a sub-analysis based on the duration of quadruple therapy indicated that the 7-d and 10-d standard triple therapies were inferior to sequential therapy (RR = 0.790; 95%CI: 0.718-0.868; RR = 0.917; 95%CI: 0.839-1.002, respectively). Additionally, there were no significant differences in cure rate or adverse events among standard triple therapy, quadruple therapy, and other triple therapies (RR = 0.940; 95%CI: 0.825-1.072; RR = 1.081; 95%CI: 0.848-1.378, respectively). Standard triple therapy had a higher occurrence of side effects than sequential therapy (RR = 1.283; 95%CI: 1.066-1.544). CONCLUSION: The eradication rates with a standard triple therapy consisting of PPI, AMO, and CLA are suboptimal in China, and new treatment agents need to be developed.

Efficacy and safety of ecabet sodium as an adjuvant therapy for Helicobacter pylori eradication: a systematic review and meta-analysis.

BACKGROUND: Several studies have reported that the application of ecabet sodium during the eradication of Helicobacter pylori can improve the eradication rate and reduce therapy-associated side effects. However, the efficacy and safety of this therapy are controversial. OBJECTIVES: To determine whether ecabet sodium improves the eradication rate of H. pylori and examine treatment safety by conducting a meta-analysis based on randomized controlled trials (RCTs). METHODS: Literature searches were conducted in the following databases: PubMed, Embase, the Cochrane Library, the Science Citation Index, the China National Knowledge Infrastructure Database, and the Wanfang Database. A meta-analysis of all RCTs comparing ecabet sodium supplementation with nonecabet sodium-containing therapy was performed. RESULTS: Thirteen RCTs that included a total of 1808 patients were assessed. The meta-analysis showed that the eradication rate in the ecabet sodium-containing quadruple therapy group was higher than that in the standard triple therapy group (84.5% vs 74.55%, OR 1.757 (95%CI: 1.307 to 2.362), p < .001). The analysis also showed that the eradication rate in the ecabet sodium-containing triple therapy group was significantly higher than that in the PPI plus amoxicillin or clarithromycin therapy group (74.6% vs 43.9%,OR 3.727 (95%CI: 2.320 to 5.988), p < .001)(ITT), (74.6% vs 43.9%,OR 3.863 (95%CI: 2.369 to 6.298), p < .001) (PP). Furthermore, our meta-analysis suggested that the occurrence of side effects did not significantly differ between patients receiving ecabet sodium-containing therapy and patients receiving nonecabet sodium-containing therapy (14.0% vs 13.3%, OR 1.055 (95%CI: 0.632 to 1.759), p = .839). CONCLUSION: Supplementation with ecabet sodium during H. pylori eradication therapy improves the eradication rate. The use of ecabet sodium does not increase the side effects based on our meta-analysis.