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Background: Helicobacter pylori ( H. pylori ) eradication rates have declined with the rise of antibiotic-resistant strains in recent years. Although highly effective with a low prevalence of resistance, standard dose tetracycline is associated with frequent adverse events. The efficacy and safety of low-dose tetracycline as part of tetracycline and amoxicillin-containing bismuth quadruple therapy are not well described., Aim: To compare the efficacy and safety of low-dose compared to standard dose tetracycline with combined amoxicillin-containing bismuth quadruple therapy in patients with H. pylori infection., Methods: Consecutive patients with H. pylori infection receiving tetracycline, amoxicillin, proton pump inhibitor, and bismuth for 14 days at Sir Run Run Shaw Hospital (1/2022-6/2023) were evaluated. The low-dose tetracycline group received tetracycline 500 mg twice daily (bid) while the standard dose group received 750 mg bid or 500 mg three times daily (tid). Primary endpoints were H. pylori eradication rate and treatment-related adverse events., Results: The mean age of the 218 patients was 48.7 ± 14.0 years, 120 (55%) were male, and 118 (54.1%) received treatment as primary therapy. Furthermore, 73 (33%) patients received low-dose tetracycline (500 mg bid) and 145 (67%) received standard dose tetracycline including 500 mg tid in 74 (33%) and 750 mg bid in 71 (33%). On intention-to-treat analysis, H. pylori eradication rates were 89% [95% confidence interval (CI): 82%-96%] in the 500 mg bid group, 82% (95%CI: 74%-91%) in the 500 mg tid group, and 79% (95%CI: 69%-89%) in the 750 mg bid group without a statistically significant difference ( P = 0.25). The incidence of adverse events was lower in the low-dose compared to the standard dose group (12.3% vs 31.1% or 23.9%; P = 0.02)., Conclusion: Low-dose tetracycline combined with amoxicillin quadruple therapy for 14 days achieved a high eradication rate and fewer adverse events compared to the standard dose tetracycline regimen in patients with H. pylori infection., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Helicobacter pylori ( H. pylori ) is a widespread microorganism related to gastric adenocarcinoma (AC). In contrast, it has been reported that an inverse association exists between H. pylori infection and esophageal carcinoma. The mechanisms underlying this supposedly protective effect remain controversial., Aim: To determine the prevalence of H. pylori infection in esophageal carcinoma patients, we performed a retrospective observational study of esophageal tumors diagnosed in our hospital., Methods: We retrospectively reviewed the prevalence of H. pylori infection in a cohort of patients diagnosed with esophageal carcinoma. Concomitant or previous proton pump inhibitor (PPI) usage was also recorded., Results: A total of 89 patients with esophageal carcinoma (69 males, 77.5%), with a mean age of 66 years (range, 26-93 years) were included. AC was the most frequent pathological variant ( n = 47, 52.8%), followed by squamous cell carcinoma ( n = 37, 41.6%). Fourteen ACs (29.8%) originated in the gastroesophageal junction and 33 (70.2%) in the esophageal body. Overall, 54 patients (60.7%) presented at stages III and IV. Previous H. pylori infection occurred only in 4 patients (4.5%), 3 with AC (6.3% of all ACs) and 1 with squamous cell carcinoma (2.7% of all squamous cell tumors). All patients with previous H. pylori infection had stage III-IV. Only one patient had received prior H. pylori eradication therapy, whereas 86 (96.6%) had received previous or concomitant PPI treatment., Conclusion: In our cohort of patients, and after histologic evaluation of paraffin-embedded primary tumors, we found a very low prevalence of previous H. pylori infection. We also reviewed the medical history of the patients, concluding that the majority had received or were on PPI treatment. The minimal prevalence of H. pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Difficulty in obtaining tetracycline, increased adverse reactions, and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy. Therefore, the search for new alternative drugs has become one of the research hotspots. In recent years, minocycline, as a semisynthetic tetracycline, has demonstrated good potential for eradicating Helicobacter pylori ( H. pylori ) infection, but the systematic evaluation of its role remains lacking., Aim: To explore the efficacy, safety, and compliance of minocycline in eradicating H. pylori infection., Methods: We comprehensively retrieved the electronic databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang database as of October 30, 2023, and finally included 22 research reports on H. pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria. The eradication rates of H. pylori were calculated using a fixed or a random effect model, and the heterogeneity and publication bias of the studies were measured., Results: The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H. pylori eradication rates, reaching 82.3% [95% confidence interval (CI): 79.7%-85.1%] in the intention-to-treat analysis and 90.0% (95%CI: 87.7%-92.4%) in the per-protocol analysis. The overall safety and compliance of the minocycline-containing regimens were good, demonstrating an overall incidence of adverse reactions of 36.5% (95%CI: 31.5%-42.2%). Further by traditional meta-analysis, the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects. Most of the adverse reactions were mild to moderate and well-tolerated, and dizziness was relatively prominent in the minocycline-containing regimens (16%)., Conclusion: The minocycline-containing regimens demonstrated good efficacy, safety, and compliance in H. pylori eradication. Minocycline has good potential to replace tetracycline for eradicating H. pylori infection., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Although highly effective as a component of Helicobacter pylori ( H. pylori ) treatment regimen, tetracycline is associated with a high incidence of medication-related adverse events. Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates., Aim: To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H. pylori infection., Methods: Consecutive patients (10/2020-12/2021) who received tetracycline and furazolidone quadruple therapy for H. pylori infection at Sir Run Run Shaw Hospital were identified. All patients received tetracycline, furazolidone, proton pump inhibitor, and bismuth for 14 d as primary or rescue therapy. Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily., Results: Three hundred and ninety-four patients [mean age = 46.3 ± 13.9, male = 137 (34.8%), and 309 (78.4%) primary therapy] completed tetracycline and furazolidone quadruple therapy for H. pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118 (750 mg twice daily) and 119 (500 mg three times daily). Eradication rates in the modified tetracycline dose group were 92.40% and in the standard groups, eradication rates were 93.20% for 750 mg twice daily group and 92.43% for 500 mg three times daily group, respectively, without statistical difference ( P = 0.959). The incidence of adverse events was lower in the modified tetracycline dose (15.3% vs 32.3% and 29.4%; P = 0.002) compared to the standard dose group., Conclusion: In a real-world experience, modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy, comparable to standard tetracycline dose regimens, with a favorable safety profile., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Due to increasing resistance rates of Helicobacter pylori ( H. pylori ) to different antibiotics, failures in eradication therapies are becoming more frequent. Even though eradication criteria and treatment algorithms for first-line and second-line therapy against H. pylori infection are well-established, there is no clear recommendation for third-line and rescue therapy in refractory H. pylori infection., Aim: To perform a systematic review evaluating the efficacy and safety of rescue therapies against refractory H. pylori infection., Methods: A systematic search of available rescue treatments for refractory H. pylori infection was conducted on the National Library of Medicine's PubMed search platform based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or non-randomized clinical trials and observational studies evaluating the effectiveness of H. pylori infection rescue therapies were included., Results: Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy, and 21 of these were selected for analysis of mean eradication rate as third-line treatment. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple-therapy as third-line treatment, mean eradication rates of 81.6% and 84.4%, 79.4% and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in intention-to-treat (ITT) and per-protocol (PP) analysis, respectively. For third-line quadruple therapy, mean eradication rates of 69.2% and 72.1% were found for bismuth quadruple therapy (BQT), 88.9% and 90.9% for bismuth quadruple therapy, three-in-one, Pylera ® (BQT-Pylera), and 61.3% and 64.2% for non-BQT) in ITT and PP analysis, respectively. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple therapy as rescue therapy, mean eradication rates of 75.4% and 78.8%, 79.4 and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in ITT and PP analysis, respectively. For quadruple therapy as rescue treatment, mean eradication rates of 76.7% and 79.2% for BQT, 84.9% and 87.8% for BQT-Pylera, and 61.3% and 64.2% for non-BQT were found in ITT and PP analysis, respectively. For susceptibility-guided therapy, mean eradication rates as third-line and rescue treatment were 75.0% in ITT and 79.2% in PP analysis., Conclusion: We recommend sitafloxacin-based triple therapy containing vonoprazan in regions with low macrolide resistance profile. In regions with known resistance to macrolides or unavailability of bismuth, rifabutin-based triple therapy is recommended., Competing Interests: Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

When several Helicobacter pylori eradication treatments fail, guidelines recommend a cultured guided approach; however, culture is not widely available. Therefore, a rifabutin based regimen could be the best solution. Rifabutin indeed shows a low rate of antibiotic resistance. Rifabutin is generally used in combination with amoxicillin in a triple therapy, with eradication rates about 80% in third-line regimens. The ideal duration of this therapy should range between 10 and 12 d. Combinations with antibiotics other than amoxicillin have demonstrated even better results, such as vonoprazan, which is a type of novel acid suppressor drug. Finally, a new formulation of triple therapy in a single capsule is under investigation, which is a field that deserves further investigation. Some notes of caution about rifabutin should be mentioned. This drug is used to treat tuberculosis or atypical mycobacteria; therefore, before starting a rifabutin-based eradication regimen, Mycobacterium tuberculosis infection should be thoroughly tested, since its use could promote the development of antibiotic resistance, thus affecting its effectiveness against Koch's bacillus. Additionally, some serious side effects must be evaluated before starting any rifabutin-based therapy. Adverse effects include fever, nausea, vomiting and bone marrow suppression. For this reason, full blood count surveillance is required., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Helicobacter pylori ( H. pylori ) is generally regarded as a human pathogen and a class 1 carcinogen, etiologically related to gastric and duodenal ulcers, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. However, H. pylori can also be regarded as a commensal symbiont. Unlike other pathogenic/ opportunistic bacteria, H. pylori colonization in infancy is facilitated by T helper type 2 immunity and leads to the development of immune tolerance. Fucosylated gastric mucin glycans, which are an important part of the innate and adaptive immune system, mediate the adhesion of H. pylori to the surface of the gastric epithelium, contributing to successful colonization. H. pylori may have beneficial effects on the host by regulating gastrointestinal (GI) microbiota and protecting against some allergic and autoimmune disorders and inflammatory bowel disease. The potential protective role against inflammatory bowel disease may be related to both modulation of the gut microbiota and the immunomodulatory properties of H. pylori . The inverse association between H. pylori and some potentially proinflammatory and/or procarcinogenic bacteria may suggest it regulates the GI microbiota. Eradication of H. pylori can cause various adverse effects and alter the GI microbiota, leading to short-term or long-term dysbiosis. Overall, studies have shown that gastric Actinobacteria decrease after H. pylori eradication, Proteobacteria increase during short-term follow-up and then return to baseline levels, and Enterobacteriaceae and Enterococcus increase in the short-term and interim follow-up. Various gastric mucosal bacteria ( Actinomyces , Granulicatella , Parvimonas , Peptostreptococcus , Prevotella , Rothia , Streptococcus, Rhodococcus , and Lactobacillus ) may contribute to precancerous gastric lesions and cancer itself after H. pylori eradication. H. pylori eradication can also lead to dysbiosis of the gut microbiota, with increased Proteobacteria and decreased Bacteroidetes and Actinobacteria. The increase in gut Proteobacteria may contribute to adverse effects during and after eradication. The decrease in Actinobacteria, which are pivotal in the maintenance of gut homeostasis, can persist for > 6 mo after H. pylori eradication. Furthermore, H. pylori eradication can alter the metabolism of gastric and intestinal bacteria. Given the available data, eradication cannot be an unconditional recommendation in every case of H. pylori infection, and the decision to eradicate H. pylori should be based on an assessment of the benefit-risk ratio for the individual patient. Thus, the current guidelines based on the unconditional "test-and-treat" strategy should be revised. The most cautious and careful approach should be taken in elderly patients with multiple eradication failures since repeated eradication can cause antibiotic-associated diarrhea, including severe Clostridioides difficile -associated diarrhea and colitis and antibiotic-associated hemorrhagic colitis due to Klebsiella oxytoca . Furthermore, since eradication therapy with antibiotics and proton pump inhibitors can lead to serious adverse effects and/or dysbiosis of the GI microbiota, supplementation of probiotics, prebiotics, and microbial metabolites ( e.g., butyrate + inulin) should be considered to decrease the negative effects of eradication., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

A number of studies have revealed the association between Helicobacter pylori ( H. pylori ) infection and the gut microbiota. More than half of the investigations on the impact of H. pylori on the gut microbiota have been the sub-analyses of the influence of eradication therapy. It was observed that H. pylori eradication altered gut microbiota within a short period after eradication, and majority of the alterations took a long period of time to reverse back to the original. Changes in the gut microbiota within a short period after eradication may be attributed to antibiotics and proton pump inhibitors. Modification of gastric acidity in the stomach caused by a long-term H. pylori infection alters the gut microbiota. Analysis of the gut microbiota should be conducted in a large population, adjusting for considerable biases associated with the composition of the gut microbiota, such as age, sex, body mass index, diet and the virulence of H. pylori ., Competing Interests: Conflict-of-interest statement: The authors declare that there are no conflicts of interest regarding the publication of this paper., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Helicobacter pylori ( H. pylori ) , a bacterium that infects approximately half of the world's population, is associated with various gastrointestinal diseases, including peptic ulcers, non-ulcer dyspepsia, gastric adenocarcinoma, and gastric lymphoma. As the burden of antibiotic resistance increases, the need for new adjunct therapies designed to facilitate H. pylori eradication and reduce negative distal outcomes associated with infection has become more pressing. Characterization of the interactions between H. pylori , the fecal microbiome, and fecal fatty acid metabolism, as well as the mechanisms underlying these interactions, may offer new therapeutic approaches., Aim: To characterize the gut microbiome and metabolome in H . pylori patients in a socioeconomically challenged and underprivileged inner-city community., Methods: Stool samples from 19 H. pylori patients and 16 control subjects were analyzed. 16S rRNA gene sequencing was performed on normalized pooled amplicons using the Illumina MiSeq System using a MiSeq reagent kit v2. Alpha and beta diversity analyses were performed in QIIME 2. Non-targeted fatty acid analysis of the samples was carried out using gas chromatography-mass spectrometry, which measures the total content of 30 fatty acids in stool after conversion into their corresponding fatty acid methyl esters. Multi-dimensional scaling (MDS) was performed on Bray-Curtis distance matrices created from both the metabolomics and microbiome datasets and a Procrustes test was performed on the metabolomics and microbiome MDS coordinates., Results: Fecal microbiome analysis showed that alpha diversity was lowest in H. pylori patients over 40 years of age compared to control subjects of similar age group. Beta diversity analysis of the samples revealed significant differences in microbial community structure between H. pylori patients and control subjects across all ages. Thirty-eight and six taxa had lower and higher relative abundance in H. pylori patients, respectively. Taxa that were enriched in H. pylori patients included Atopobium, Gemellaceae, Micrococcaceae, Gemellales and Rothia ( R. mucilaginosa) . Notably, relative abundance of the phylum Verrucomicrobia was decreased in H. pylori patients compared to control subjects. Procrustes analysis showed a significant relationship between the microbiome and metabolome datasets. Stool samples from H. pylori patients showed increases in several fatty acids including the polyunsaturated fatty acids (PUFAs) 22:4n6, 22:5n3, 20:3n6 and 22:2n6, while decreases were noted in other fatty acids including the PUFA 18:3n6. The pattern of changes in fatty acid concentration correlated to the Bacteroidetes:Firmicutes ratio determined by 16S rRNA gene analysis., Conclusion: This exploratory study demonstrates H. pylori -associated changes to the fecal microbiome and fecal fatty acid metabolism. Such changes may have implications for improving eradication rates and minimizing associated negative distal outcomes., Competing Interests: Conflict-of-interest statement: The authors report no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Antibiotic resistance to Helicobacter pylori (H. pylori ) infection, which ultimately results in eradication failure, has been an emerging issue in the clinical field. Recently, to overcome this problem, an antibiotic sensitivity-based tailored therapy (TT) for H. pylori infection has received attention., Aim: To investigate the efficacy and safety profiles of TT for H. pylori infection treatment compared to a non-bismuth quadruple therapy, concomitant therapy (CT) regimen., Methods: We included patients (> 18 years) with an H. pylori infection and without a history of Helicobacter eradication who visited the Gil Medical Center between March 2016 and October 2020. After being randomly assigned to either the TT or CT treatment group in 1 to 1 manner, patient compliance, eradication success rate (ESR), and patient-reported side effects profiles were assessed and compared between the two groups. H. pylori infection was diagnosed using a rapid urease test, Giemsa stain, or dual priming oligonucleotide polymerase chain reaction (DPO-PCR). Tailored eradication strategy based through the presence of a 23S ribosomal RNA point mutation. For the TT group, a DPO-PCR test, which detected A2142G and/or A2143G point mutations, and a clarithromycin resistance test were performed. Patients in the clarithromycin-resistant group were treated with a bismuth-containing quadruple combination therapy, while those with sensitive results were treated with the standard triple regimen., Results: Of the 217 patients with a treatment naive H. pylori infection, 110 patients [mean age: 58.66 ± 13.03, men, n = 55 (50%)] were treated with TT, and 107 patients [mean age: 56.67 ± 10.88, men, n = 52 (48.60%)] were treated with CT. The compliance (TT vs CT, 100% vs 98.13%, P = 0.30), and follow-up loss rates (8.18% vs 9.35%, P = 0.95) were not significantly different between the groups. The ESR after treatment was also not statistically different between the groups (TT vs CT, 82.73% vs 82.24%, P = 0.95). However, the treatment-related and patient-reported side effects were significantly lower in the TT group than in the CT group (22.77% vs 50.52%, P < 0.001)., Conclusion: The DPO-based TT regimen shows promising results in efficacy and safety profiles as a first-line Helicobacter eradication regimen in Korea, especially when physicians are confronted with increased antibiotic resistance rates., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Helicobacter pylori ( H. pylori ) is an important pathogen that can cause a variety of diseases. Yet, full eradication of H. pylori remains a significant challenge in clinical practice. H. pylori and other microbial communities have complex interactions in the unique gastric microecological environment. However, it is not clear whether the interactions have any effect on the therapeutic effect of H. pylori ., Aim: The aim was to investigate the characteristics of the gastric microbiota with H. pylori infection and the influence on the H. pylori eradication treatment., Methods: Patients with H. pylori infection underwent gastroscopy and received treatment for eradication. The prescription included esomeprazole 20 mg bid, Livzon Dele 220 mg bid, amoxicillin 1000 mg bid, and clarithromycin 500 mg bid for 14 d. Patients who did not respond to treatment and failed eradication were compared with those who achieved eradication by 1:2 propensity matching. High-throughput sequencing of the gastric mucosal microbiota was performed, and the results were evaluated by alpha diversity analysis, beta diversity analysis, species correlation analysis, and metabolic pathway correlation analysis., Results: The eradication rate of all the patients was 95.5% (171/179). Twenty-four patients were enrolled in the study after propensity-matched scoring. There were eight cases in the failure group (patients who did not respond well to therapy) and 16 cases in the success group. The majority phyla in the two groups were the same, and included Proteobacteria, Bacteroides, Firmicutes, Actinomycetes, and Fusobacteria. The microbial diversity in the failure group had a decreasing trend ( P = 0.092) and the species abundance was significantly lower ( P = 0.031) compared with the success group. The high rate of H. pylori eradication was associated with Rhodococcus , Lactobacillus, and Sphingomonas , as they were significantly enriched in the successful group ( P < 0.05). Veronococcus and Cilium were enriched in the mucosa of chronic atrophic gastritis patients compared with chronic superficial gastritis patients ( P = 0.0466 and 0.0122, respectively). In both study groups, H. pylori was negatively correlated with other bacterial genera. More bacterial genera were directly related to H. pylori in the successful group compared with the failure group., Conclusion: The effectiveness of quadruple H. pylori eradication therapy containing bismuth depended on gastric microbiota, and the high rate of H. pylori eradication was associated with the presence of Rhodococcus , Lactobacillus, and Sphingomonas ., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The Helicobacter pylori ( H. pylori ) eradication rate is decreasing in the general population of China., Aim: To evaluate the H. pylori eradication status in real-world clinical practice and to explore factors related to eradication failure., Methods: Patients with H. pylori infection who were treated with standard 14-d quadruple therapy and received a test of cure at a provincial medical institution between June 2018 and May 2019 were enrolled. Demographic and clinical data were recorded. Eradication rates were calculated and compared between regimens and subgroups. Multivariate analysis was performed to identify predictors of eradication failure., Results: Of 2610 patients enrolled, eradication was successful in 1999 (76.6%) patients. Amoxicillin-containing quadruple regimens showed a higher eradication rate than other quadruple therapy regimens (83.0% vs 69.0%, P < 0.001). The quadruple therapy containing amoxicillin plus clarithromycin achieved the highest eradication rate (83.5%). Primary therapy had a higher eradication rate than rescue therapy (78.3% vs 66.5%, P < 0.001). In rescue therapy, the amoxicillin- and furazolidone-containing regimens achieved the highest eradication rate (80.8%). Esomeprazole-containing regimens showed a higher eradication rate than those containing other proton pump inhibitors (81.8% vs 74.9%, P = 0.001). Multivariate regression analysis found that older age, prior therapy, and use of omeprazole or pantoprazole were associated with an increased risk of eradication failure., Conclusion: The total eradication rate is 76.6%. Amoxicillin-containing regimens are superior to other regimens. Age, prior therapy, and use of omeprazole or pantoprazole are independent risk factors for eradication failure., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Few studies have compared the efficacy and safety profile of a tailored eradication (TR) strategy based on the presence of a 23S ribosomal RNA point mutation with those of empirical bismuth-based quadruple therapy (EBQT) for first-line eradication of Helicobacter pylori ( H. pylori ) in Korean patients., Aim: To compare the efficacy and safety of a TR strategy and those of EBQT regimen as first-line eradication therapy for H. pylori ., Methods: This is an open-label, comparative study in which we prospectively enrolled patients over 18 years of age with H. pylori infection and retrospectively reviewed their data. H. pylori- positive patients diagnosed by rapid urease test, Giemsa staining, or dual priming oligonucleotide polymerase chain reaction (DPO-PCR) were enrolled from May 2016 to September 2018 at Gil Medical Center. Patients with H. pylori infection received either a TR regimen or the EBQT regimen. In the tailored therapy group that underwent DPO-PCR testing, patients with A2142G and/or A2143G point mutations were treated with a bismuth-containing quadruple regimen. The eradication rate, patient-reported side effect rate, and H. pylori eradication success rate were evaluated and compared between the groups., Results: A total of 150 patients were assigned to the TR ( n = 50) or EBQT group ( n = 100). The first-line eradication rate of H. pylori did not differ between the groups (96.0% vs 95.7%, P = 0.9). The rate of eradication-related side effects for TR was 12.0%, which differed significantly from that of EBQT (43.0%) for first-line treatment ( P < 0.001)., Conclusion: DPO-PCR-based TR for H. pylori eradication may be equally efficacious, with less treatment-related complications, compared to EBQT in Korea, where clarithromycin resistance is high., Competing Interests: Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

The survival and replication cycle of Helicobacter pylori ( H. pylori ) is strictly dependant on intragastric pH, since H. pylori enters replicative phase at an almost neutral pH (6-7), while at acid pH (3-6) it turns into its coccoid form, which is resistant to antibiotics. On these bases, it is crucial to increase intragastric pH by proton pump inhibitors (PPIs) when an antibiotic-based eradicating therapy needs to be administered. Therefore, several tricks need to be used to optimize eradication rate of different regimens. The administration of the highest dose as possible of PPI, by doubling or increasing the number of pills/day, has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies, even if specific trials have not been performed. A pre-treatment with PPI before starting antibiotics does not seem to be effective, therefore it is discouraged. However, the choice of PPI molecule could have a certain weight, since second-generation substances (esomeprazole, rabeprazole) are likely more effective than those of first generation (omeprazole, lansoprazole). A possible explanation is due to their metabolism, which has been proven to be less dependent on cytochrome P450 (CYP) 2C19 genetic variables. Finally, vonoprazan, a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy, due to both its highest acid inhibition power and rapid pharmacologic effect. However current data come only from Eastern Asia, therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates., Competing Interests: Conflict-of-interest statement: None declared.

Aim: To evaluate the outcomes of furazolidone- and amoxicillin-based quadruple therapy for treatment of Helicobacter pylori ( H. pylori ) infection and identify predictors of failed eradication., Methods: Patients with H. pylori infection treated with furazolidone, amoxicillin, bismuth, and proton pump inhibitor therapy (January 2015 to December 2015) who received the 13 C-urea breath test > 4 wk after treatment were evaluated. Demographic and clinical data including prior H. pylori treatment attempts, medication adherence, alcohol and cigarette consumption during therapy, and treatment-related adverse events were recorded by reviewing medical records and telephone surveys. H. pylori eradication rates for overall and subgroups were evaluated. Multivariate analysis was performed to identify independent predictors of failed H. pylori eradication., Results: Of the 992 patients treated and retested for H. pylori infection, the overall eradication rate was 94.5% [95% confidence interval (CI): 94.1%-95.9%]. H. pylori eradication rate of primary therapy was 95.0% (95%CI: 93.5%-96.5%), while that of rescue therapy was 91.3% (95%CI: 86.8%-95.8%). Among the 859 patients who completed the study protocol, 144 (17%) reported treatment-related adverse events including 24 (3%) leading to premature discontinuation. On multivariate analysis, poor medication adherence [adjusted odds ratio (AOR) = 6.7, 95%CI: 2.8-15.8], two or more previous H. pylori treatments (AOR = 7.4, 95%CI: 2.2-24.9), alcohol consumption during therapy (AOR = 4.4, 95%CI: 1.5-12.3), and possibly smoking during therapy (AOR = 1.9, 95%CI: 0.9-4.3) were associated with failed H. pylori eradication., Conclusion: Furazolidone- and amoxicillin-based quadruple therapy for H. pylori infection in an area with a high prevalence of clarithromycin resistance demonstrated high eradication rates as primary and rescue therapies with a favorable safety profile. Patient education targeting abstinence from alcohol during therapy and strict medication adherence may further optimize H. pylori eradication., Competing Interests: Conflict-of-interest statement: The authors received grants from Zhejiang Science and Technology Project during the conduct of the study and declare no other conflict of interest related to this study.

Aim: To assess the efficacy and safety of fourth-generation quinolones for Helicobacter pylori ( H. pylori ) eradication, we conducted this systematic review and meta-analysis of randomized clinical trials., Methods: Major literature databases (PubMed, EMBASE and the Cochrane Central Register of Controlled Trials) were searched for relevant articles published prior to February 2018. We performed a meta-analysis of all randomized clinical trials that examined the efficacy of H. pylori eradication therapies and included fourth-generation quinolones in the experimental arm. Subgroup analyses by regions and different types of fourth-generation quinolones were also performed., Results: Ten studies including a total of 2198 patients were assessed. A meta-analysis of randomized controlled trials showed that the eradication rate of therapies containing non-fourth-generation quinolones was significantly lower than that of therapies containing fourth-generation quinolones by intention-to-treat (ITT) analysis [75.4% vs 81.8%; odds ratio (OR) = 0.661; 95% confidence interval (CI): 0.447-0.977; P = 0.038]. This analysis also showed that the eradication rate of the therapies containing non-fourth-generation quinolones was inferior to that of therapies containing fourth-generation quinolones by per-protocol analysis (79.1% vs 84.7%; OR = 0.663; 95%CI: 0.433-1.016; P = 0.059). Moreover, the occurrence of side effects was significantly different between the control and experimental groups by ITT analysis (30.6% vs 19.5%; OR = 1.874; 95%CI: 1.120-3.137; P = 0.017). The sub-analyses also showed significant differences in moxifloxacin therapies vs other fourth-generation quinolone therapies (84.3% vs 71.9%) and in Asian vs European groups (76.7% vs 89.1%)., Conclusion: Therapies containing fourth-generation quinolones achieved a poor eradication rate in the treatment of H. pylori infection. Such regimens might be useful as a rescue treatment based on antimicrobial susceptibility testing. Different antibiotics should be chosen in different regions., Competing Interests: Conflict-of-interest statement: The authors deny any conflict of interest.

Helicobacter pylori ( H. pylori ) eradication can reduce gastric cancer. However, gastric cancer still develops after eradication, and cases who received eradication therapy are increasing. In this study, we have reviewed the characteristics and predictors of primary gastric cancer developing after H. pylori eradication. In terms of the characteristics, endoscopic, histologic, and molecular characteristics are reported. Endoscopically, gastric cancer after eradication is often depressed-type and shows a gastritis-like appearance, which sometimes makes the diagnosis difficult. Histologically, most gastric cancer after eradication is intestinal type, and non-neoplastic epithelium, also called epithelium with low-grade atypia, is frequently seen over the tumor, which is presumably the cause of the endoscopic gastritis-like appearance. As for molecular characteristics, some markers, such as Ki67, MUC2, and Wnt5a expression, are lower in cancer from patients in whom H. pylori has been eradicated. In terms of predictors, several Japanese studies have reported that severe endoscopic atrophy at eradication is a risk factor for gastric cancer development. Histologic intestinal metaplasia, especially in the corpus, and long-term use of proton pump inhibitors, are also reported as risk factors for gastric cancer after H. pylori eradication. These studies on the characteristics and predictors of gastric cancer development will become the cornerstone for establishing a novel surveillance program based on the gastric cancer risk stratification specific to H. pylori- eradicated patients., Competing Interests: Conflict-of-interest statement: The authors declare that no competing interests exist.

Aim: To define probiotic monotherapy effect on Helicobacter pylori ( H. pylori ) status by performing a systematic review., Methods: Methods of analysis and inclusion criteria were based on PRISMA recommendations. Relevant publications were identified by searching PubMed, MEDLINE, Science Direct, and EMBASE. The end-point was to estimate eradication rate and urea breath test delta value before and after probiotic monotherapy across all studies and, overall, with a pooled data analysis. Adverse events of probiotic therapy were evaluated. The data were expressed as proportions/percentages, and 95%CIs were calculated. For continuous variables, we evaluated the weighted mean difference. Odd ratios (ORs) were calculated according to the Peto method for the comparison of eradication rates between probiotics and placebo., Results: Eleven studies were selected. Probiotics eradicated H. pylori in 50 out of 403 cases. The mean weighted eradication rate was 14% (95%CI: 2%-25%, P = 0.02). Lactobacilli eradicated the bacterium in 30 out of 235 patients, with a mean weighted rate of 16% (95%CI: 1%-31%). Saccharomyces boulardii achieved eradication in 6 out of 63 patients, with a pooled eradication rate of 12% (95%CI: 0%-29%). Multistrain combinations were effective in 14 out of 105 patients, with a pooled eradication rate of 14% (95%CI: 0%-43%). In the comparison of probiotics vs placebo, we found an OR of 7.91 in favor of probiotics (95%CI: 2.97-21.05, P < 0.001). Probiotics induced a mean reduction in delta values higher than placebo (8.61% with a 95%CI: 5.88-11.34, vs 0.19% for placebo, P < 0.001). Finally, no significant difference in adverse events was found between probiotics and placebo (OR = 1, 95%CI: 0.06-18.08)., Conclusion: Probiotics alone show a minimal effect on H. pylori clearance, thus suggesting a likely direct role., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest.

We read with interest the recent meta-analysis by Lin et al who evaluated the effectiveness of concomitant regimen for Helicobacter pylori ( H. pylori ) in Chinese regions. They found that 7-d concomitant regimen is undoubtedly superior to 7-d triple therapy (91.2% vs 77.9%, P < 0.0001). However, it is a common belief that a triple therapy lasting 7 d should be definitively removed from the clinical practice for its ineffectiveness. Only its prolongation to 14 d may give satisfactory success rate. Thus, the assessment of an old and outdated treatment versus a more recent and successful one does not seem to bring novel and useful information. Moreover, a 7-d duration has not been ascertained for concomitant regimen, as main guidelines recommend a 10-d schedule for this scheme. Therefore, only studies comparing 10-d concomitant versus 14-d triple seem to be appropriate according to current Guidelines and would clarify which regimen is the most suitable worldwide. Additionally, in this meta-analysis concomitant and sequential therapy showed similar performances, despite it is common opinion that sequential is more prone than concomitant therapy to fail when metronidazole resistance occurs, and China is characterized by high rate of resistance to this antibiotic. None of the included studies evaluated a priori antibiotic resistances, and the lack of this detail hampers the unveiling of this apparent contradiction. In conclusion, the lack of the evaluation of the quality of included trials as well as their high heterogeneity constitute a burdensome limit to draw solid conclusions in this meta-analysis. On the bases of these considerations and the low number of examined trials, we believe that further studies and the knowledge of antibiotic resistances will support with high quality evidence which is the best regimen and its optimal duration., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.

Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium.

Aim: To assess the efficacy of moxifloxacin-containing triple therapy after non-bismuth quadruple therapy failure for Helicobacter pylori (H. pylori) eradication., Methods: Between January 2010 and December 2012, we screened individuals who were prescribed non-bismuth quadruple therapy for H. pylori eradication. Among them, a total of 98 patients who failed non-bismuth quadruple therapy received 1-wk or 2-wk moxifloxacin-containing triple therapy (400 mg moxifloxacin once daily, and 20 mg of rabeprazole and 1 g of amoxicillin twice daily). H. pylori status was evaluated using the (13)C-urea breath test 4 wk later, after treatment completion. The eradication rates were determined by intention-to-treat and per-protocol analyses., Results: In total, 60 and 38 patients received 1-wk and 2-wk moxifloxacin-containing triple therapy, respectively. The intention-to-treat and per-protocol eradication rates were 56.7% (95%CI: 45.0-70.0) and 59.6% (95%CI: 46.6-71.7) in the 1-wk group and 76.3% (95%CI: 63.2-89.5) and 80.6% (95%CI: 66.7-91.9) in the 2-wk group (P = 0.048 and 0.036, respectively). All groups had good compliance (95% vs 94.9%). Neither group showed serious adverse events, and the proportions of patients experiencing mild side effects were not significantly different (21.1% vs 13.9%). Clinical factors such as age, sex, alcohol and smoking habits, comorbidities, and presence of gastric or duodenal ulcer did not influence the eradication therapy efficacy. The efficacy of second-line eradication therapy did not differ significantly according to the first-line regimen., Conclusion: Two-week moxifloxacin-containing triple therapy showed better efficacy than a 1-wk regimen after non-bismuth quadruple therapy failure.

Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes.

Aim: To investigate the effects of daily telephone-based re-education (TRE) before taking medicine for the eradication of Helicobacter pylori (H. pylori) on the compliance and the eradication rate in a Chinese patient population., Methods: A prospective, physician-blinded, randomized, controlled clinical study was conducted. The patients were randomly assigned to receive TRE every day before taking medicine (TRE group) or no TRE (control group). The patients in the TRE group received regular instructions before taking medicine for the eradication of H. pylori during the entire course of treatment through telephone calls. The patients in the control group received detailed instructions at the time of seeing a doctor for the guidance. The primary outcome was the H. pylori eradication rate after treatment. The secondary outcomes included the clinical remissions after treatment, adverse events, compliance, and patients' satisfaction., Results: A total of 140 patients were randomized, 70 to the TRE group and 70 to the control group. As the primary outcome, the H. pylori eradication rates in the TRE and control groups were 62.7% and 71.2% in per protocol analysis (P = 0.230), and 52.9% and 52.9% in intention-to-treat analysis (P = 0.567), respectively. As the secondary outcomes, there were no significant differences in the patients' satisfaction between the two groups (good, 79.7% vs 76.9%; fair, 13.6% vs 19.2%; poor, 6.7% vs 3.9%, for the TRE group and control group, respectively; P > 0.05 for all); the rates of adverse effects were 15.2% and 63.5% in the TRE and control groups, respectively (P < 0.001); the compliance rates in the TRE and control groups were 85.7% and 74.3%, respectively (P = 0.069)., Conclusion: Daily TRE before taking medicine had no significant impact on the patients' compliance, satisfaction, or H. pylori eradication, but reduced the rate of adverse events.

Aim: To evaluate the efficacy of moxifloxacin-based sequential therapy (MBST) versus hybrid therapy as a first-line treatment for Helicobacter pylori (H. pylori) infection., Methods: From August 2014 to January 2015, 284 patients with confirmed H. pylori infection were randomized to receive a 14-d course of MBST (MBST group, n = 140) or hybrid (Hybrid group, n = 144) therapy. The MBST group received 20 mg rabeprazole and 1 g amoxicillin twice daily for 7 d, followed by 20 mg rabeprazole and 500 mg metronidazole twice daily, and 400 mg moxifloxacin once daily for 7 d. The Hybrid group received 20 mg rabeprazole and 1 g amoxicillin twice daily for 14 d. In addition, the Hybrid group received 500 mg metronidazole and 500 mg clarithromycin twice daily for the final 7 d. Successful eradication of H. pylori infection was defined as a negative (13)C-urea breath test 4 wk after the end of treatment. Patient compliance was defined as "good" if drug intake was at least 85%. H. pylori eradication rates, patient compliance with treatment, and adverse event rates were evaluated., Results: The eradication rates in the intention-to-treat (ITT) analysis were 91.4% (128/140; 95%CI: 90.2%-92.9%) in the MBST group and 79.2% (114/144; 95%CI: 77.3%-80.7%) in the Hybrid group (P = 0.013). The eradication rates in the per-protocol (PP) analysis were 94.1% (128/136; 95%CI: 92.9%-95.6%) in the MBST group and 82.6% (114/138; 95%CI: 80.6%-84.1%) in the Hybrid group (P = 0.003). The H. pylori eradication rate in the MBST group was significantly higher than that of the Hybrid group for both the ITT (P = 0.013) and the PP analyses (P = 0.003). Both groups exhibited full compliance with treatment (MBST/Hybrid group: 100%/100%). The rate of adverse events was 11.8% (16/136) and 19.6% (27/138) in the MBST and Hybrid group, respectively (P = 0.019). The majority of adverse events were mild-to-moderate in intensity; none were severe enough to cause discontinuation of treatment in either group., Conclusion: MBST was more effective and led to fewer adverse events than hybrid therapy as a first-line treatment for H. pylori infection.

Aim: To investigate whether Helicobacter pylori (H. pylori) infection is associated with glycemic control and whether hyperglycemia is modified by eradication therapy., Methods: The databases of PubMed, Cochrane Library, Chinese BioMedicine Web Base and Chinese Science and Technology Journals were searched from inception to June 2014. Studies examining the association between H. pylori infection and glycemic control and/or the effect of eradication treatment on glycemic control in diabetic humans were eligible for inclusion. Meta-analyses were conducted using the Review Manager software version 5.2. The outcome measures are presented as weighed mean differences (WMDs) with 95% confidence intervals (CIs). Statistical heterogeneity was assessed by the Cochran Q test and the I(2) statistic., Results: A total of 21 relevant publications were identified. A meta-analysis of 11 studies with 513 patients with diabetes mellitus (DM) showed significantly lower glycosylated hemoglobin (HbA1c) levels in the H. pylori-negative than H. pylori-positive DM participants (WMD = 0.43, 95%CI: 0.07-0.79; P = 0.02). In children and adolescents with type 1 DM (T1DM), there was a positive association between H. pylori infection and HbA1c level (WMD = 0.35, 95%CI: 0.05-0.64; P = 0.02), but there was no difference in those with type 2 DM (T2DM, WMD = 0.51, 95%CI: -0.63-1.65; P = 0.38). A meta-analysis of six studies with 325 T2DM participants showed a significant difference in the fasting plasma glucose levels between H. pylori-positive and H. pylori-negative participants (WMD = 1.20, 95%CI: 0.17-2.23; P = 0.02). Eradication of H. pylori did not improve glycemic control in the T2DM participants in a three-month follow-up period (HbA1c decrease: WMD = -0.03, 95%CI = -0.14-0.08; P = 0.57; fasting plasma glucose decrease: WMD = -0.06, 95%CI: -0.36-0.23; P = 0.68). Glycemic control was significantly better in T1DM participants who were not reinfected than in those who were reinfected (HbA1c: WMD = 0.72, 95%CI: 0.32-1.13: P = 0.00)., Conclusion: H. pylori infection is associated with poorer glycemic control in T1DM patients, but eradication may not improve glycemic control in DM in a short-term follow-up period.

Aim: To summarize the evidence from randomized controlled trials (RCTs) regarding the effect of probiotics by using a meta-analytic approach., Methods: In July 2013, we searched PubMed, EMBASE, Ovid, the Cochrane Library, and three Chinese databases (Chinese Biomedical Literature Database, Chinese Medical Current Content, and Chinese Scientific Journals database) to identify relevant RCTs. We included RCTs investigating the effect of a combination of probiotics and standard therapy (probiotics group) with standard therapy alone (control group). Risk ratios (RRs) were used to measure the effect of probiotics plus standard therapy on Helicobacter pylori (H. pylori) eradication rates, adverse events, and patient compliance using a random-effect model., Results: We included data on 6997 participants from 45 RCTs, the overall eradication rates of the probiotic group and the control group were 82.31% and 72.08%, respectively. We noted that the use of probiotics plus standard therapy was associated with an increased eradication rate by per-protocol set analysis (RR = 1.11; 95%CI: 1.08-1.15; P < 0.001) or intention-to-treat analysis (RR = 1.13; 95%CI: 1.10-1.16; P < 0.001). Furthermore, the incidence of adverse events was 21.44% in the probiotics group and 36.27% in the control group, and it was found that the probiotics plus standard therapy significantly reduced the risk of adverse events (RR = 0.59; 95%CI: 0.48-0.71; P < 0.001), which demonstrated a favorable effect of probiotics in reducing adverse events associated with H. pylori eradication therapy. The specific reduction in adverse events ranged from 30% to 59%, and this reduction was statistically significant. Finally, probiotics plus standard therapy had little or no effect on patient compliance (RR = 0.98; 95%CI: 0.68-1.39; P = 0.889)., Conclusion: The use of probiotics plus standard therapy was associated with an increase in the H. pylori eradication rate, and a reduction in adverse events resulting from treatment in the general population. However, this therapy did not improve patient compliance.

Aim: To investigate the eradication rate and histological changes after Helicobacter pylori (H. pylori) eradication treatment following subtotal gastrectomy for gastric cancer., Methods: A total of 610 patients with H. pylori infection who had undergone surgery for either early or advanced gastric adenocarcinoma between May 2004 and December 2010 were retrospectively studied. A total of 584 patients with proven H. pylori infection after surgery for gastric cancer were enrolled in this study. Patients received a seven day standard triple regimen as first-line therapy and a 10 d bismuth-containing quadruple regimen as second-line therapy in cases of eradication failure. The patients underwent an esophagogastroduodenoscopy (EGD) between six and 12 mo after surgery, followed by annual EGDs. A further EGD was conducted 12 mo after confirming the result of the eradication and the histological changes. A gastric biopsy specimen for histological examination and Campylobacter-like organism testing was obtained from the lesser and greater curvature of the corpus of the remnant stomach. Histological changes in the gastric mucosa were assessed using the updated Sydney system before eradication therapy and at follow-up after 12 mo., Results: Eradication rates with the first-line and second-line therapies were 78.4% (458/584) and 90% (36/40), respectively, by intention-to-treat analysis and 85.3% (458/530) and 92.3% (36/39), respectively, by per-protocol analysis. The univariate and multivariate analyses revealed that Billroth II surgery was an independent factor predictive of eradication success in the eradication success group (OR = 1.53, 95%CI: 1.41-1.65, P = 0.021). The atrophy and intestinal metaplasia (IM) scores 12 mo after eradication were significantly lower in the eradication success group than in the eradication failure group (0.25 ± 0.04 vs 0.47 ± 0.12, P = 0.023; 0.27 ± 0.04 vs 0.51 ± 0.12, P = 0.015, respectively). The atrophy and IM scores 12 mo after successful eradication were significantly lower in the Billroth II group than in the Billroth I group (0.13 ± 0.09 vs 0.31 ± 0.12, P = 0.029; 0.32 ± 0.24 vs 0.37 ± 0.13, P = 0.034, respectively)., Conclusion: Patients with H. pylori following subtotal gastrectomy had a similar eradication rate to patients with an intact stomach. H. pylori eradication is recommended after subtotal gastrectomy.

Aim: To determine the efficacy of two quintuple regimens for eradication of Helicobacter pylori (H. pylori) in patients who failed previous therapies., Methods: This prospective, open-label, randomized controlled trial was a phase II study conducted from April 2011 to March 2012 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 208 patients with dyspepsia who failed previous H. pylori eradication with a ten-day quadruple therapy were enrolled. A random block method was used to assign patients to one of two treatment groups. Patients in the first group were treated with 240 mg bismuth subcitrate, 20 mg omeprazole, 1000 mg amoxicillin, 500 mg clarithromycin and 500 mg tinidazole (BOACT group). Patients in the second group received a regimen containing 240 mg bismuth subcitrate, 20 mg omeprazole, 500 mg tetracycline, 500 mg metronidazole and 200 mg ofloxacin (BOTMO group). Both regimens were given twice daily for a duration of seven days. The eradication was confirmed by a (14)C urea breath test 12 wk after completion of therapy. Patient compliance and drug side effects were evaluated at the end of the treatment period. The success rates were calculated by intention-to-treat and per-protocol analyses., Results: A total of 205 patients completed the course of treatment, with three patients excluded due to drug intolerance. The mean age of patients did not differ between the BOACT and BOTMO groups (41.6 ± 12.2 years vs 39.6 ± 11.8 years), and no significant differences were found between the two groups in terms of age, sex, smoking habits or the initial eradication regimen. The intention-to-treat and per-protocol eradication rates were significantly higher in the BOTMO group (86.5%, 95%CI: 0.85-0.87 and 86.7%, 95%CI: 0.80-0.89, respectively) compared with the BOACT group (75.5%, 95%CI: 0.73-0.76 and 76%, 95%CI: 0.69-0.80, respectively) (P < 0.05). Univariate analyses for both groups did not show any association of sex, smoking and initial therapeutic regimen with eradiation rate (P > 0.05 for all). Significantly more patients experienced side effects in the BOACT group compared to the BOTMO group (77.4% vs 36.6%, P < 0.01). This difference was exemplified by increases in headache and taste disturbance (P < 0.05)., Conclusion: Quintuple therapy with a BOTMO regimen is an alternative second-line rescue therapy for Iranian patients with failed first-line eradication treatment of H. pylori.

Aim: To compare the Helicobacter pylori (H. pylori) eradication rate of clarithromycin-based triple therapy, metronidazole-based triple therapy, sequential therapy and concomitant therapy., Methods: A total of 680 patients infected with H. pylori were divided into 4 groups and each group was treated with a different eradication therapy. Clarithromycin-based triple therapy was applied to the first group [rabeprazole, amoxicillin and clarithromycin (PAC) group: proton pump inhibitor (PPI), amoxicillin, clarithromycin], whereas the second group was treated with metronidazole-based triple therapy [rabeprazole, amoxicillin and metronidazole (PAM) group: PPI, amoxicillin, metronidazole]. The third group was treated with rabeprazole and amoxicillin, followed by rabeprazole, clarithromycin and metronidazole (sequential group). The final group was simultaneously treated with rabeprazole, amoxicillin clarithromycin and metronidazole (concomitant therapy group). In the case of a failure to eradicate H. pylori, second-line quadruple and third-line eradication therapies were administered., Results: The per protocol (PP) analysis was performed on 143, 139, 141 and 143 patients in the PAC, PAM, sequential and concomitant groups, respectively. We excluded patients who did not receive a C(13)-urea breath test (22, 20, 23 and 22 patients, respectively) and patients with less than an 80% compliance level (5, 11, 6 and 5 patients, respectively). The eradication rates were 76.2% (109/143) in the PAC group, 84.2% (117/139) in the PAM group, 84.4% (119/141) in the sequential group and 94.4% (135/143) in the concomitant group (P = 0.0002). All 14 patients who failed second-line therapy were treated with third-line eradication therapy. Among these 14 patients, 6 infections were successfully eradicated with the third-line therapy. Both PP and intention-to-treat analysis showed an eradication rate of 42.9% (6/14). In the PAC group, 3 of 4 patients were successfully cured (3/4, 75%); 2 of 2 patients in the PAM group (2/2, 100%) and 1 of 5 patients in the sequential group (1/5, 20%) were also cured. In the concomitant group, all 3 patients failed (0/3, 0%)., Conclusion: The eradication rate for the concomitant therapy was much higher than those of the standard triple therapy or sequential therapy (ClinicalTrials.gov number NCT01922765).

Aim: To evaluate the role of probiotics in the standard triple Helicobacter pylori therapy., Methods: In this meta-analysis, we investigated the efficacy of probiotics in a standard triple H. pylori therapy in adults. Searches were mainly conducted in MEDLINE/PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Fourteen studies met our criteria, and the quality of these studies was assessed using the Jadad scale. We used STATA version 12.0 to extract data and to calculate the odds ratios (ORs), which are presented with the corresponding 95% confidence intervals (CIs). The data are presented as forest plots., Results: The pooled ORs for the eradication rates calculated by intention-to-treat analysis and per-protocol analysis in the probiotic group vs the control group were 1.67 (95%CI: 1.38-2.02) and 1.68 (95%CI: 1.35-2.08), respectively, using the fixed-effects model. The sensitivity of the Asian studies was greater than that of the Caucasian studies (Asian: OR = 1.78, 95%CI: 1.40-2.26; Caucasian: OR = 1.48, 95%CI: 1.06-2.05). The pooled OR for the incidence of total adverse effects was significantly lower in the probiotic group (OR = 0.49, 95%CI: 0.26-0.94), using the random effects model, with significant heterogeneity (I (2) = 85.7%). The incidence of diarrhea was significantly reduced in the probiotic group (OR = 0.21, 95%CI: 0.06-0.74), whereas the incidence of taste disorders, metallic taste, vomiting, nausea, and epigastric pain did not differ significantly between the probiotic group and the control group., Conclusion: Supplementary probiotic preparations during standard triple H. pylori therapy may improve the eradication rate, particularly in Asian patients, and the incidence of total adverse effects.

The known factors that have contributed to the decline of Helicobacter pylori (H. pylori) eradication rate include antibiotic resistance, poor compliance, high gastric acidity, high bacterial load, and cytochrome P450 2C19 (CYP2C19) polymorphism. Proton pump inhibitor (PPI) is important in the eradication regimen. The principal enzyme implicated in the metabolism of PPIs is CYP2C19. The effects of PPI depend on metabolic enzyme, cytochrome P450 enzymes, and CYP2C19 with genetic differences in the activity of this enzyme (the homozygous EM, heterozygous EM (HetEM), and poor metabolizer). The frequency of the CYP2C19 polymorphism is highly varied among different ethnic populations. The CYP2C19 genotype is a cardinal factor of H. pylori eradication in patients taking omeprazole- based or lansoprazole-based triple therapies. In contrast, the CYP2C19 polymorphism has no significant effect on the rabeprazole-based or esomeprazole-based triple therapies. The efficacy of levofloxacin-based rescue triple therapy might be also affected by the CYP2C19 polymorphism, but CYP2C19 genotypes did not show obvious impact on other levofloxacin-based rescue therapies. Choice of different PPIs and/or increasing doses of PPIs should be individualized based on the pharmacogenetics background of each patient and pharmacological profile of each drug. Other possible factors influencing gastric acid secretion (e.g., IL-1β- 511 polymorphism) would be also under consideration.

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.

Aim: To evaluate the efficacy of furazolidone-based triple and quadruple therapy in eradicating Helicobacter pylori (H. pylori) in a multi-center randomized controlled trial., Methods: A total of 720 H. pylori positive patients with duodenal ulcer disease were enrolled at 10 different hospitals in Jiangxi province in China. The patients were randomly assigned to four treatment groups as follows: patients in Groups 1 and 3 received rabeprazole (10 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively; patients in Groups 2 and 4 received rabeprazole (10 mg), bismuth (220 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively. The primary outcome measure was H. pylori eradication rate 4 wk after treatment by intention-to-treat and per protocol analysis, while the secondary outcome measures were symptom and sign changes at the end of treatment and 4 wk after the end of treatment, as well as the proportion of patients who developed adverse events., Results: The demographic data of the four groups were not significantly different. Overall, 666 patients completed the scheme and were re-assessed with the (13)C-urea breath test. The intention-to-treat analysis of the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 74.44%, 82.78%, 78.89% and 86.11%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. According to the per protocol analysis, the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 81.21%, 89.22%, 85.54% and 92.26%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. The number of adverse events was 15 (8.3%), 16 (8.9%), 15 (8.3%) and 17 (9.4%) in Groups 1, 2, 3 and 4, respectively, including dizziness, vomiting, diarrhea, nausea, skin rash, itchy skin, and malaise. The symptoms were relieved without special treatment in all of the patients., Conclusion: Both 7- and 10-d quadruple furazolidone-based therapies achieve satisfactory H. pylori eradication rates.

The efficacy of triple therapy for Helicobacter pylori infection has dramatically declined over the last decade, largely related to increasing clarithromycin resistance rates. From a microbiological standpoint, bismuth quadruple therapy is the ideal replacement since it combines drugs for which resistance does not impair its efficacy. Nonetheless, several obstacles such as availability, complexity or tolerance prevent a general implementation of bismuth quadruple therapy, so non-bismuth quadruple regimens remain the best first-line treatment in clinical practice in many geographical areas. We review the rationale and efficacy of several optimization tools (increasing the length of duration, high-dose acid suppression, probiotics), which have been largely evaluated over the last 5 years to increase the effectiveness of standard triple therapy. Then, we update available evidence on the effectiveness of several non-bismuth quadruple therapies (sequential, concomitant, hybrid, miscellaneous therapy), which have gained interest lately. We also revise evidence on the efficacy of the aforementioned optimization tools for non-bismuth quadruples schemes and, finally we provide a novel regionalized therapeutic algorithm, based on novel formulas recently developed for predicting the outcome of non-bismuth quadruple regimens, upon local antibiotic resistance rates.

The efficacy of first- and second-line Helicobacter pylori (H. pylori) eradication regimens varies considerably in West Asian countries, mainly due to the variable prevalence of resistant organisms. However, no review article has yet evaluated and compared the efficacy of different regimens among different countries of this region. Therefore, we conducted a review to select the best options and provide recommendations for H. pylori treatment in this geographic region. A search through PubMed was carried out to obtain relevant randomized clinical trials published in English language up to June 2013. According to the results, among different therapeutic regimens used as the first-line protocols, 10-d Bismuth-Furazolidone/Metronidazole quadruple therapy, 14-d Clarithromycin-containing hybrid therapy and 14-d quadruple therapy including a proton pump inhibitor + Bismuth + Tetracycline (500 mg QID) + Metronidazole (500 mg TDS) seemed to be appropriate options. Among second-line therapeutic regimens, Bismuth-based quadruple therapies containing Tetracycline and Furazolidone/Metronidazole, triple therapy containing Amoxicillin and Gatifloxacin and Quadruple therapy including Bismuth + Azithromycin and Ofloxacin seemed to be effective options. Third-line therapies were not evaluated in West Asia; most guidelines, however, recommend choosing optimal eradication regimen according to the pattern of antibiotic susceptibility of H. pylori. Although we limited our investigation to H. pylori eradication regimens in West Asia, the clinical significance of the results goes beyond the countries situated in this geographic region. In fact, the results are transferrable to any region as long as the patterns of resistance are the same.

Helicobacter pylori (H. pylori) is a widespread pathogen infecting about 40% of people living in urban areas and over 90% of people living in the developing regions of the world. H. pylori is well-documented as the main factor in the pathogenesis of peptic ulcer disease, chronic gastritis, and gastric malignancies such as cancer and mucosa-associated lymphoid tissue-lymphoma; hence, its eradication is strongly recommended. The Maastricht IV consensus, which focused on the management of H. pylori infection, set important new strategies in terms of treatment approaches, particularly with regards to first- and second-line treatment protocols and led to improved knowledge and understanding of H. pylori resistance to antibiotics. In recent years, various fluoroquinolone-based protocols, mainly including levofloxacin, have been proposed and effectively tested at all therapeutic lines for H. pylori eradication. The aim of the present paper is to review the scientific literature focused on the use of fluoroquinolones in eradicating H. pylori.

Helicobacter pylori (H. pylori) infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis (AG), or gastric intestinal metaplasia (GIM), and cancer. Various molecular alterations are identified not only in gastric cancer (GC) but also in precancerous lesions. H. pylori treatment seems to improve AG and GIM, but still remains controversial. In contrast, many studies, including meta-analysis, show that H. pylori eradication reduces GC. Molecular markers detected by genetic and epigenetic alterations related to carcinogenesis reverse following H. pylori eradication. This indicates that these changes may be an important factor in the identification of high risk patients for cancer development. Patients who underwent endoscopic treatment of GC are at high risk for development of metachronous GC. A randomized controlled trial from Japan concluded that prophylactic eradication of H. pylori after endoscopic resection should be used to prevent the development of metachronous GC, but recent retrospective studies did not show the tendency. Patients with precancerous lesions (molecular alterations) that do not reverse after H. pylori treatment, represent the "point of no return" and may be at high risk for the development of GC. Therefore, earlier H. pylori eradication should be considered for preventing GC development prior to the appearance of precancerous lesions.

Aim: To evaluate the efficacy and safety of esomeprazole-based triple therapy compared with lansoprazole therapy as first-line eradication therapy for patients with Helicobacter pylori (H. pylori) in usual post-marketing use in Japan, where the clarithromycin (CAM) resistance rate is 30%., Methods: For this multicenter, randomized, open-label, non-inferiority trial, we recruited patients (≥ 20 years of age) with H. pylori infection from 20 hospitals in Japan. We randomly allocated patients to esomeprazole therapy (esomeprazole 20 mg, CAM 400 mg, amoxicillin (AC) 750 mg for the first 7 d, with all drugs given twice daily) or lansoprazole therapy (lansoprazole 30 mg, CAM 400 mg, AC 750 mg for the first 7 d, with all drugs given twice daily) using a minimization method with age, sex, and institution as adjustment factors. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. H. pylori eradication was confirmed by a urea breath test from 4 to 8 wk after cessation of therapy., Results: ITT analysis revealed the eradication rates of 69.4% (95%CI: 61.2%-76.6%) for esomeprazole therapy and 73.9% (95%CI: 65.9%-80.6%) for lansoprazole therapy (P = 0.4982). PP analysis showed eradication rate of 76.9% (95%CI: 68.6%-83.5%) for esomeprazole therapy and 79.8% (95%CI: 71.9%-86.0%) for lansoprazole therapy (P = 0.6423). There were no differences in adverse effects between the two therapies., Conclusion: Esomeprazole showed non-inferiority and safety in a 7 day-triple therapy for eradication of H. pylori compared with lansoprazole.