Standard triple therapy fails to eradicate Helicobacter pylori (H. pylori) in at least 20% of the cases, largely due to antibiotic resistance. Non-bismuth concomitant quadruple therapy has emerged as a widely used alternative therapy.
Aim
To conduct a meta-analysis evaluating the efficacy and safety of concomitant therapy—comprising a proton pump inhibitor, clarithromycin, amoxicillin, and a nitroimidazole—for H. pylori eradication.
Methods
A systematic search of PubMed, EMBASE, and relevant conference abstracts was conducted through November 2025. Meta-analyses included studies assessing concomitant therapy and comparisons with standard triple, sequential, hybrid, and bismuth-based quadruple therapies.
Results
A total of 144 studies (92 randomized clinical trials), involving 26,467 patients were included. Pooled eradication rates for concomitant therapy were 86% (intention-to-treat) and 91% (per-protocol). Analysis of randomized clinical trials showed that concomitant therapy demonstrated significantly higher efficacy than triple therapy (risk difference [RD] = 0.11; 95% CI = 0.08–0.13) and sequential therapy (RD = 0.03; 0.01–0.05), but similar efficacy to hybrid and bismuth quadruple regimens (containing nitroimidazole–tetracycline and clarithromycin–amoxicillin). Concomitant therapy achieved 87% and 95% eradication rates in clarithromycin- and metronidazole-resistant strains, respectively, but only 67% in dual-resistant strains. Adverse events were frequent (38%), although generally mild.
Conclusions
Concomitant therapy is a highly effective first-line option for H. pylori eradication, particularly in single clarithromycin- or nitroimidazole-resistant strains. However, its efficacy is reduced in dual-resistant cases, in which alternative regimens may be preferred. Overall, its efficacy is comparable to that of hybrid and bismuth quadruple therapy. Its tolerability is generally acceptable.
{"title":"Non-Bismuth Quadruple Concomitant Treatment for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis","authors":"Pablo Parra, Olga P. Nyssen, Javier P. Gisbert","doi":"10.1111/hel.70099","DOIUrl":"https://doi.org/10.1111/hel.70099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Standard triple therapy fails to eradicate <i>Helicobacter pylori</i> (<i>H. pylori</i>) in at least 20% of the cases, largely due to antibiotic resistance. Non-bismuth concomitant quadruple therapy has emerged as a widely used alternative therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To conduct a meta-analysis evaluating the efficacy and safety of concomitant therapy—comprising a proton pump inhibitor, clarithromycin, amoxicillin, and a nitroimidazole—for <i>H. pylori</i> eradication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search of PubMed, EMBASE, and relevant conference abstracts was conducted through November 2025. Meta-analyses included studies assessing concomitant therapy and comparisons with standard triple, sequential, hybrid, and bismuth-based quadruple therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 144 studies (92 randomized clinical trials), involving 26,467 patients were included. Pooled eradication rates for concomitant therapy were 86% (intention-to-treat) and 91% (per-protocol). Analysis of randomized clinical trials showed that concomitant therapy demonstrated significantly higher efficacy than triple therapy (<i>risk difference</i> [RD] = 0.11; 95% CI = 0.08–0.13) and sequential therapy (RD = 0.03; 0.01–0.05), but similar efficacy to hybrid and bismuth quadruple regimens (containing nitroimidazole–tetracycline and clarithromycin–amoxicillin). Concomitant therapy achieved 87% and 95% eradication rates in clarithromycin- and metronidazole-resistant strains, respectively, but only 67% in dual-resistant strains. Adverse events were frequent (38%), although generally mild.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Concomitant therapy is a highly effective first-line option for <i>H. pylori</i> eradication, particularly in single clarithromycin- or nitroimidazole-resistant strains. However, its efficacy is reduced in dual-resistant cases, in which alternative regimens may be preferred. Overall, its efficacy is comparable to that of hybrid and bismuth quadruple therapy. Its tolerability is generally acceptable.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gasser El-Azab, Sherief Abdel Salam, Ehab Moustafa, Ahmed Abuoelhassan, Ayman Shamseya, Ahmed Ellakany, Usama Abdelaal, Medhat Assem, Fatma Khalil, Amal Mahmoud, Maha Elsabaawy, Boshra Hussein, Mohammed Ezz-Eldin, Sahar Hassany, Nariman Zaghloul, Mai Magdy
Background
Eradication of Helicobacter pylori remains challenging in countries with high antimicrobial resistance and limited access to bismuth-based therapies. Quinolone-containing regimens represent a practical alternative, yet comparative data between levofloxacin- and moxifloxacin-based nitazoxanide quadruple therapies are scarce, particularly in Egypt. This multicenter trial evaluated the efficacy, safety, and tolerability of two nitazoxanide-based second-line regimens after failure of first-line eradication therapy.
Methods
In this prospective, randomized, single-blind, parallel-group study conducted at six Egyptian centers, adults aged 18–70 years with documented failure of first-line H. pylori therapy were enrolled. Patients were randomized 1:1 to receive either LNDL (levofloxacin 750 mg once daily, nitazoxanide 500 mg twice daily, doxycycline 100 mg twice daily, lansoprazole 30 mg twice daily) or MNDL (moxifloxacin 400 mg once daily with the same adjunct medications) for 14 days. Eradication was assessed using a stool antigen test ≥ 4 weeks after treatment. Safety, tolerability, and symptom improvement were recorded. Analyses were performed using both intention-to-treat (ITT) and per-protocol (PP) populations.
Results
A total of 430 patients were randomized. ITT eradication rates were 65.6% (95% CI: 59.2% – 72%) for LNDL and 74.9% (95% CI: 69% – 80.7%) for MNDL (p = 0.035). PP eradication rates were 70.9% (95% CI: 64.5% – 77.2%) and 78.5% (95% CI: 72.9% – 84.2%), respectively (p = 0.076). Among patients previously treated with levofloxacin, MNDL achieved significantly higher eradication rates than LNDL (65.8%, 95% CI: 50–81.6 vs. 42.6%, 95% CI: 29–56.2, p = 0.028). Both regimens produced significant symptom improvement and were well tolerated; no serious adverse events occurred.
Conclusion
Both nitazoxanide-based quinolone quadruple regimens demonstrated modest but clinically relevant efficacy as second-line therapy. Moxifloxacin showed superior performance in patients with prior levofloxacin exposure. These findings support the use of moxifloxacin-based rescue therapy in settings with high resistance and limited access to bismuth-containing regimens.
{"title":"Efficacy and Safety of Levofloxacin- Versus Moxifloxacin-Based Nitazoxanide Quadruple Therapy as Second-Line Treatment for Helicobacter pylori in Egypt: A Randomized Multicenter Trial","authors":"Gasser El-Azab, Sherief Abdel Salam, Ehab Moustafa, Ahmed Abuoelhassan, Ayman Shamseya, Ahmed Ellakany, Usama Abdelaal, Medhat Assem, Fatma Khalil, Amal Mahmoud, Maha Elsabaawy, Boshra Hussein, Mohammed Ezz-Eldin, Sahar Hassany, Nariman Zaghloul, Mai Magdy","doi":"10.1111/hel.70104","DOIUrl":"10.1111/hel.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Eradication of <i>Helicobacter pylori</i> remains challenging in countries with high antimicrobial resistance and limited access to bismuth-based therapies. Quinolone-containing regimens represent a practical alternative, yet comparative data between levofloxacin- and moxifloxacin-based nitazoxanide quadruple therapies are scarce, particularly in Egypt. This multicenter trial evaluated the efficacy, safety, and tolerability of two nitazoxanide-based second-line regimens after failure of first-line eradication therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective, randomized, single-blind, parallel-group study conducted at six Egyptian centers, adults aged 18–70 years with documented failure of first-line <i>H. pylori</i> therapy were enrolled. Patients were randomized 1:1 to receive either LNDL (levofloxacin 750 mg once daily, nitazoxanide 500 mg twice daily, doxycycline 100 mg twice daily, lansoprazole 30 mg twice daily) or MNDL (moxifloxacin 400 mg once daily with the same adjunct medications) for 14 days. Eradication was assessed using a stool antigen test ≥ 4 weeks after treatment. Safety, tolerability, and symptom improvement were recorded. Analyses were performed using both intention-to-treat (ITT) and per-protocol (PP) populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 430 patients were randomized. ITT eradication rates were 65.6% (95% CI: 59.2% – 72%) for LNDL and 74.9% (95% CI: 69% – 80.7%) for MNDL (<i>p</i> = 0.035). PP eradication rates were 70.9% (95% CI: 64.5% – 77.2%) and 78.5% (95% CI: 72.9% – 84.2%), respectively (<i>p</i> = 0.076). Among patients previously treated with levofloxacin, MNDL achieved significantly higher eradication rates than LNDL (65.8%, 95% CI: 50–81.6 vs. 42.6%, 95% CI: 29–56.2, <i>p</i> = 0.028). Both regimens produced significant symptom improvement and were well tolerated; no serious adverse events occurred.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Both nitazoxanide-based quinolone quadruple regimens demonstrated modest but clinically relevant efficacy as second-line therapy. Moxifloxacin showed superior performance in patients with prior levofloxacin exposure. These findings support the use of moxifloxacin-based rescue therapy in settings with high resistance and limited access to bismuth-containing regimens.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The global rise of antimicrobial resistance necessitates innovative strategies to combat persistent infections, including those caused by Helicobacter pylori. This study investigates potential inhibitors of the H. pylori urease enzyme, a key virulence factor that enables survival in the highly acidic gastric environment. A virtual screening of 1773 FDA-approved drugs was performed, followed by molecular dynamics simulations. Among the top candidates, Natamycin, Zavegepant, Midostaurin, Avacopan, and Metolazone displayed significant binding affinities towards urease. Further simulations confirmed the stability and favorable interaction profiles of these drug–enzyme complexes, with the Avacopan–urease complex exhibiting the highest stability based on RMSD and binding free energy analyses. Natamycin and Avacopan were subsequently selected for in vitro validation, where both significantly inhibited urease activity and demonstrated antibacterial effects against clinical isolates and the reference strain H. pylori B128. Avacopan exhibited inhibition ranging from 30.0% in strain CL2 to 99.7% in B128, whereas Natamycin showed consistently stronger inhibition across all clinical strains, ranging from 89.2% in CL4 to 99.9% in CL1, and exceeding 90% in CL1, CL2, CL3, and B128. Both inhibitors were effective against cag-positive and cag-negative clinical isolates, indicating broad-spectrum urease inhibition. However, the bactericidal activities of these compounds were more strain-specific with increased efficacies observed in cag− isolates. Therefore, further studies are warranted to fully explore the specific mechanisms and selectivity of their individual inhibitory activities. These findings highlight Avacopan and Natamycin as promising urease-targeted drug repurposing candidates for future therapeutic development against H. pylori.
{"title":"Drug Repurposing Identifies Natamycin and Avacopan as Urease-Targeted Therapeutic Candidates Against Helicobacter pylori","authors":"Shwetlaxmi Patil, Sohinee Sarkar, Renitta Jobby, Songmin Yu, Abhishek Chowdhury, Atanuka Paul, Vipin Kumar Mishra, Vinothkannan Ravichandran","doi":"10.1111/hel.70094","DOIUrl":"10.1111/hel.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>The global rise of antimicrobial resistance necessitates innovative strategies to combat persistent infections, including those caused by <i>Helicobacter pylori</i>. This study investigates potential inhibitors of the <i>H. pylori</i> urease enzyme, a key virulence factor that enables survival in the highly acidic gastric environment. A virtual screening of 1773 FDA-approved drugs was performed, followed by molecular dynamics simulations. Among the top candidates, Natamycin, Zavegepant, Midostaurin, Avacopan, and Metolazone displayed significant binding affinities towards urease. Further simulations confirmed the stability and favorable interaction profiles of these drug–enzyme complexes, with the Avacopan–urease complex exhibiting the highest stability based on RMSD and binding free energy analyses. Natamycin and Avacopan were subsequently selected for in vitro validation, where both significantly inhibited urease activity and demonstrated antibacterial effects against clinical isolates and the reference strain <i>H. pylori</i> B128. Avacopan exhibited inhibition ranging from 30.0% in strain CL2 to 99.7% in B128, whereas Natamycin showed consistently stronger inhibition across all clinical strains, ranging from 89.2% in CL4 to 99.9% in CL1, and exceeding 90% in CL1, CL2, CL3, and B128. Both inhibitors were effective against <i>cag</i>-positive and <i>cag</i>-negative clinical isolates, indicating broad-spectrum urease inhibition. However, the bactericidal activities of these compounds were more strain-specific with increased efficacies observed in <i>cag</i><sup>−</sup> isolates. Therefore, further studies are warranted to fully explore the specific mechanisms and selectivity of their individual inhibitory activities. These findings highlight Avacopan and Natamycin as promising urease-targeted drug repurposing candidates for future therapeutic development against <i>H. pylori</i>.</p>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bojan Tepeš, Tatjana Kofol Bric, Mitja Oblak, Jernej Završnik, Helena Blažun Vošner, Danute Ražuka-Ebela, Mārcis Leja, Viktoria Knaze, Jin Young Park, Tamara Matysiak-Budnik
Background
Most gastric cancer cases are attributable to chronic Helicobacter pylori (H. pylori) infection and can theoretically be prevented. The objectives of the EUROHELICAN project were to assess the feasibility, acceptability, effectiveness, and adverse events of the H. pylori screen-and-treat program in younger adults aged 30 to 34 years, for the first time in Europe; to evaluate long-term effects of H. pylori eradication in middle-aged adults (starting from 45 years of age) previously enrolled for at least 5 years in the GISTAR study in Latvia, and to prepare the IARC expert Working Group Report on population-based H. pylori screen-and-treat strategies for gastric cancer prevention.
Methods
The study of H. pylori screen-and-treat in younger adults was conducted in the Community Healthcare Center Dr. Adolf Drolc Maribor following methodology prepared by the National Institute of Public Health of Slovenia. Assessment of possible effects of H. pylori screen-and-treat in the long term was conducted by following up on the long-running GISTAR study conducted by the Institute of Clinical and Preventive Medicine at the University of Latvia. A team of experts led by the Nantes University Hospital evaluated the study protocols and their progress at different stages. The IARC convened a Working Group of international experts to develop globally applicable guidance on best practices for implementing population-based H. pylori screen-and-treat strategies in adult populations to prevent gastric cancer.
Conclusions
Both studies received a positive evaluation at different stages of completion and were deemed appropriate for testing the feasibility of H. pylori screen-and-treat in a community health care setting and investigating possible adverse effects of the strategy in the long-term. The IARC expert group guidance report on the implementation of population-based H. pylori screen-and-treat strategies to prevent gastric cancer in adults will guide future primary gastric cancer prevention programs in Europe and beyond.
背景：大多数胃癌病例可归因于慢性幽门螺杆菌感染，理论上是可以预防的。EUROHELICAN项目的目的是在欧洲首次评估30至34岁年轻人幽门螺杆菌筛查和治疗项目的可行性、可接受性、有效性和不良事件；评估先前在拉脱维亚参加了至少5年GISTAR研究的中年人（45岁起）根除幽门螺杆菌的长期效果，并编写IARC专家工作组关于以人群为基础的幽门螺杆菌筛查和治疗策略用于胃癌预防的报告。方法：在社区卫生保健中心Dr. Adolf Drolc Maribor按照斯洛文尼亚国家公共卫生研究所制定的方法对年轻人进行幽门螺杆菌筛查和治疗研究。通过跟踪拉脱维亚大学临床和预防医学研究所进行的长期GISTAR研究，对幽门螺杆菌筛查和治疗的长期可能影响进行了评估。由南特大学医院领导的一个专家小组评估了研究方案及其在不同阶段的进展。国际癌症研究机构召集了一个国际专家工作组，就在成人人群中实施基于人群的幽门螺杆菌筛查和治疗策略以预防胃癌制定全球适用的最佳实践指南。结论：两项研究在完成的不同阶段都获得了积极的评价，被认为适合于在社区卫生保健环境中测试幽门螺杆菌筛查和治疗的可行性，并调查该策略在长期内可能产生的不良影响。IARC专家组关于实施以人群为基础的幽门螺杆菌筛查和治疗策略以预防成人胃癌的指导报告将指导欧洲及其他地区未来的原发性胃癌预防项目。
{"title":"EUROHELICAN—Accelerating Gastric Cancer Reduction Through Helicobacter pylori Eradication","authors":"Bojan Tepeš, Tatjana Kofol Bric, Mitja Oblak, Jernej Završnik, Helena Blažun Vošner, Danute Ražuka-Ebela, Mārcis Leja, Viktoria Knaze, Jin Young Park, Tamara Matysiak-Budnik","doi":"10.1111/hel.70097","DOIUrl":"10.1111/hel.70097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Most gastric cancer cases are attributable to chronic <i>Helicobacter pylori (H. pylori)</i> infection and can theoretically be prevented. The objectives of the EUROHELICAN project were to assess the feasibility, acceptability, effectiveness, and adverse events of the <i>H. pylori</i> screen-and-treat program in younger adults aged 30 to 34 years, for the first time in Europe; to evaluate long-term effects of <i>H. pylori</i> eradication in middle-aged adults (starting from 45 years of age) previously enrolled for at least 5 years in the GISTAR study in Latvia, and to prepare the IARC expert Working Group Report on population-based <i>H. pylori</i> screen-and-treat strategies for gastric cancer prevention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study of <i>H. pylori</i> screen-and-treat in younger adults was conducted in the Community Healthcare Center Dr. Adolf Drolc Maribor following methodology prepared by the National Institute of Public Health of Slovenia. Assessment of possible effects of <i>H. pylori</i> screen-and-treat in the long term was conducted by following up on the long-running GISTAR study conducted by the Institute of Clinical and Preventive Medicine at the University of Latvia. A team of experts led by the Nantes University Hospital evaluated the study protocols and their progress at different stages. The IARC convened a Working Group of international experts to develop globally applicable guidance on best practices for implementing population-based <i>H. pylori</i> screen-and-treat strategies in adult populations to prevent gastric cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Both studies received a positive evaluation at different stages of completion and were deemed appropriate for testing the feasibility of <i>H. pylori</i> screen-and-treat in a community health care setting and investigating possible adverse effects of the strategy in the long-term. The IARC expert group guidance report on the implementation of population-based <i>H. pylori</i> screen-and-treat strategies to prevent gastric cancer in adults will guide future primary gastric cancer prevention programs in Europe and beyond.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anja Šterbenc, Bor Vratanar, Eva Miler Mojškerc, Matjaž Homan
Background
To achieve eradication rates > 90%, the ESPGHAN/NASPGHAN guidelines for pediatric Helicobacter pylori infection recommend tailored antimicrobial therapy using sufficiently high doses over 10–14 days. However, prolonged treatment often leads to suboptimal compliance in children, which is a major contributor to reduced eradication rates. To address this, we evaluated the efficacy and safety of a shorter, 7 day triple therapy with bismuth compared with the 14 day standard triple therapy without bismuth in H. pylori infected children.
Materials and Methods
From 2020 to 2024, we carried out a randomized controlled trial involving treatment-naïve children and adolescents (5–18 years old) with confirmed H. pylori infection. Eligible participants were randomly allocated to receive either a 7 day triple therapy with bismuth (bismuth subcitrate, a proton pump inhibitor [PPI], amoxicillin, plus clarithromycin/metronidazole) or a 14 day standard triple therapy (a PPI, amoxicillin, plus clarithromycin/metronidazole) without bismuth. Two months after completing therapy, treatment success was determined using either a two-step monoclonal stool antigen assay or a urea breath test. Any adverse events were documented using a structured questionnaire.
Results
Seventy-three children were enrolled in the study. In the intention-to-treat analysis, eradication was achieved in 91% of children treated with the 7 day triple therapy with bismuth and 87% of those receiving the 14 day standard triple therapy (p = 0.695). Per-protocol eradication rates were 94% and 87%, respectively (p = 0.418). No serious adverse events were reported, and most adverse events were mild to moderate. A metallic taste was significantly more frequent in the 14 day standard triple therapy group, while other adverse events occurred with similar frequency.
Conclusions
Adding bismuth to a 7 day triple regimen achieved high eradication rates and a safety profile similar to 14 day standard triple therapy, supporting its use as an effective and safe treatment option for pediatric H. pylori infection.
{"title":"An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of a 7-Day Triple Therapy With Bismuth Versus 14-Day Standard Triple Therapy for Helicobacter pylori Eradication in Children and Adolescents","authors":"Anja Šterbenc, Bor Vratanar, Eva Miler Mojškerc, Matjaž Homan","doi":"10.1111/hel.70103","DOIUrl":"https://doi.org/10.1111/hel.70103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To achieve eradication rates > 90%, the ESPGHAN/NASPGHAN guidelines for pediatric <i>Helicobacter pylori</i> infection recommend tailored antimicrobial therapy using sufficiently high doses over 10–14 days. However, prolonged treatment often leads to suboptimal compliance in children, which is a major contributor to reduced eradication rates. To address this, we evaluated the efficacy and safety of a shorter, 7 day triple therapy with bismuth compared with the 14 day standard triple therapy without bismuth in <i>H. pylori</i> infected children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>From 2020 to 2024, we carried out a randomized controlled trial involving treatment-naïve children and adolescents (5–18 years old) with confirmed <i>H. pylori</i> infection. Eligible participants were randomly allocated to receive either a 7 day triple therapy with bismuth (bismuth subcitrate, a proton pump inhibitor [PPI], amoxicillin, plus clarithromycin/metronidazole) or a 14 day standard triple therapy (a PPI, amoxicillin, plus clarithromycin/metronidazole) without bismuth. Two months after completing therapy, treatment success was determined using either a two-step monoclonal stool antigen assay or a urea breath test. Any adverse events were documented using a structured questionnaire.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-three children were enrolled in the study. In the intention-to-treat analysis, eradication was achieved in 91% of children treated with the 7 day triple therapy with bismuth and 87% of those receiving the 14 day standard triple therapy (<i>p</i> = 0.695). Per-protocol eradication rates were 94% and 87%, respectively (<i>p</i> = 0.418). No serious adverse events were reported, and most adverse events were mild to moderate. A metallic taste was significantly more frequent in the 14 day standard triple therapy group, while other adverse events occurred with similar frequency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adding bismuth to a 7 day triple regimen achieved high eradication rates and a safety profile similar to 14 day standard triple therapy, supporting its use as an effective and safe treatment option for pediatric <i>H. pylori</i> infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jae Yong Park, Su Jin Hong, Il Ju Choi, Gwang Ho Baik, Sun Moon Kim, Jong-Jae Park, Seong Woo Jeon, Kyung-Oh Kim, Sang Kil Lee, Hwoon-Yong Jung, Jung-Hwan Oh, Chan Hyuk Park, Sang Wook Kim, Ki-Nam Shim, Sam Ryong Jee, Hee Seok Moon, Jeong Seop Moon, Cheol Woong Choi, Wan-Sik Lee, Jae Gyu Kim
Background: Tegoprazan, a potassium-competitive acid blocker, offers potent and sustained acid inhibition and potentially improves eradication efficacy.
Aim: This study aimed to evaluate the efficacy and safety of tegoprazan-based triple therapy with two dosing regimens compared with that of lansoprazole-based therapy for first-line Helicobacter pylori eradication.
Methods: This randomized, double-blind, active-controlled, multicenter trial was conducted at 19 referral hospitals in South Korea (February 2023-April 2024). Treatment-naïve adults with H. pylori infection were randomized 1:1:1 to receive 14-day triple therapy with tegoprazan, 50 mg (TAC1), tegoprazan, 100 mg (TAC2), or lansoprazole, 30 mg (LAC), each combined with amoxicillin 1000 mg and clarithromycin 500 mg, administered twice daily. The primary endpoint was H. pylori eradication rate in the modified intention-to-treat (mITT) population, with a non-inferiority margin of -10%. Secondary endpoints included subgroup analyses based on clarithromycin resistance and safety assessments.
Results: Of the 564 screened patients, 382 were randomized. In the mITT analysis (mean age, 54.9 years; 54.3% male), eradication rates were 86.0%, 85.5%, and 78.7% for TAC1, TAC2, and LAC, respectively. Both tegoprazan-based regimens met the non-inferiority criteria. Among clarithromycin-resistant infections, the eradication rates were higher for TAC1 (47.8%) and TAC2 (50.0%) than for LAC (35.5%), although the difference was not statistically significant. Safety profiles were comparable across the groups, with no serious drug-related adverse events.
Conclusion: Tegoprazan-based triple therapies, at 50- and 100-mg doses, were non-inferior to lansoprazole-based therapy and were well tolerated. Our findings indicated that tegoprazan-based triple therapy is a viable first-line option for H. pylori eradication.
{"title":"Tegoprazan-Based Triple Therapy for Helicobacter pylori Eradication: A Phase III Multicenter Randomized Clinical Trial.","authors":"Jae Yong Park, Su Jin Hong, Il Ju Choi, Gwang Ho Baik, Sun Moon Kim, Jong-Jae Park, Seong Woo Jeon, Kyung-Oh Kim, Sang Kil Lee, Hwoon-Yong Jung, Jung-Hwan Oh, Chan Hyuk Park, Sang Wook Kim, Ki-Nam Shim, Sam Ryong Jee, Hee Seok Moon, Jeong Seop Moon, Cheol Woong Choi, Wan-Sik Lee, Jae Gyu Kim","doi":"10.1111/hel.70106","DOIUrl":"10.1111/hel.70106","url":null,"abstract":"<p><strong>Background: </strong>Tegoprazan, a potassium-competitive acid blocker, offers potent and sustained acid inhibition and potentially improves eradication efficacy.</p><p><strong>Aim: </strong>This study aimed to evaluate the efficacy and safety of tegoprazan-based triple therapy with two dosing regimens compared with that of lansoprazole-based therapy for first-line Helicobacter pylori eradication.</p><p><strong>Methods: </strong>This randomized, double-blind, active-controlled, multicenter trial was conducted at 19 referral hospitals in South Korea (February 2023-April 2024). Treatment-naïve adults with H. pylori infection were randomized 1:1:1 to receive 14-day triple therapy with tegoprazan, 50 mg (TAC1), tegoprazan, 100 mg (TAC2), or lansoprazole, 30 mg (LAC), each combined with amoxicillin 1000 mg and clarithromycin 500 mg, administered twice daily. The primary endpoint was H. pylori eradication rate in the modified intention-to-treat (mITT) population, with a non-inferiority margin of -10%. Secondary endpoints included subgroup analyses based on clarithromycin resistance and safety assessments.</p><p><strong>Results: </strong>Of the 564 screened patients, 382 were randomized. In the mITT analysis (mean age, 54.9 years; 54.3% male), eradication rates were 86.0%, 85.5%, and 78.7% for TAC1, TAC2, and LAC, respectively. Both tegoprazan-based regimens met the non-inferiority criteria. Among clarithromycin-resistant infections, the eradication rates were higher for TAC1 (47.8%) and TAC2 (50.0%) than for LAC (35.5%), although the difference was not statistically significant. Safety profiles were comparable across the groups, with no serious drug-related adverse events.</p><p><strong>Conclusion: </strong>Tegoprazan-based triple therapies, at 50- and 100-mg doses, were non-inferior to lansoprazole-based therapy and were well tolerated. Our findings indicated that tegoprazan-based triple therapy is a viable first-line option for H. pylori eradication.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT05933031.</p>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":"e70106"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12800724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kavinda Tissera, Ashansa Ramanayake, Myeong-A Kim, Eui-Jeong Noh, Sacheera Angulmaduwa, Dowon Seo, Yong-Joon Cho, Jeong-Heon Cha
<div> <section> <h3> Introduction</h3> <p>The virulence factor CagA is critical in mediating inflammation, and <i>Helicobacter pylori</i> PMSS1 dynamically modulates <i>cagA</i> copy number in response to host immune pressure. Co-infection with <i>Salmonella enterica serotype Typhimurium</i> has been shown to heighten systemic inflammation and reduce <i>H. pylori</i> colonization while maintaining type IV secretion system functionality. This suggests that the inflammatory environments induced by co-infection may influence <i>H. pylori</i> virulence mechanisms. This study investigates whether <i>H. pylori</i> PMSS1 regulates its <i>cagA</i> copy number during systemic co-infection in a mouse model.</p> </section> <section> <h3> Methods</h3> <p>Across three independent mouse experiments, <i>H. pylori</i> isolated from control and co-infected mice was analyzed for <i>cagA</i> gene copy number using quantitative real-time polymerase chain reaction. Three isolates with the highest <i>cagA</i> copy numbers observed to date were further characterized for their virulence phenotypes and subjected to whole-genome sequencing to identify the mutations associated with co-infection.</p> </section> <section> <h3> Results</h3> <p><i>H. pylori</i> isolates recovered from the stomachs of co-infected mice exhibited significantly higher <i>cagA</i> copy numbers than those from control mice, with the mean copy number increasing from 2.64 (±1.03) in the control group to 3.22 (±1.63) in the co-infected group. Three <i>H. pylori</i> isolates with high <i>cagA</i> copy numbers (6.1, 9.1, and 11.0 copies) were assessed for virulence features. Notably, two of these isolates maintained elevated <i>cagA</i> phosphorylation and cell elongation, suggesting their potential relevance as a model for <i>H. pylori</i> infection studies in mice. Whole-genome sequencing further revealed co-infection-associated nonsynonymous mutations, notably in the <i>fur</i> gene and membrane transport-related genes such as an MFS transporter and a corrinoid ABC transporter substrate-binding protein.</p> </section> <section> <h3> Conclusions</h3> <p>These findings suggest that co-infection with <i>S.</i> promotes an increase in the <i>cagA</i> copy number, thereby enhancing the virulence potential of <i>H. pylori</i>. The study highlights the complex interplay between <i>H. pylori</i> and co-infecting pathogens and their combined impact on <i>H. pylori</i>-mediated disease, and the utility of high-<i>cagA</i> copy isolates as valuable models for in vivo studies addressing pathogenesis.</p>
{"title":"Expansion of cagA Copy Number in Helicobacter pylori During Co-Infection in a Mouse Model","authors":"Kavinda Tissera, Ashansa Ramanayake, Myeong-A Kim, Eui-Jeong Noh, Sacheera Angulmaduwa, Dowon Seo, Yong-Joon Cho, Jeong-Heon Cha","doi":"10.1111/hel.70091","DOIUrl":"10.1111/hel.70091","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The virulence factor CagA is critical in mediating inflammation, and <i>Helicobacter pylori</i> PMSS1 dynamically modulates <i>cagA</i> copy number in response to host immune pressure. Co-infection with <i>Salmonella enterica serotype Typhimurium</i> has been shown to heighten systemic inflammation and reduce <i>H. pylori</i> colonization while maintaining type IV secretion system functionality. This suggests that the inflammatory environments induced by co-infection may influence <i>H. pylori</i> virulence mechanisms. This study investigates whether <i>H. pylori</i> PMSS1 regulates its <i>cagA</i> copy number during systemic co-infection in a mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Across three independent mouse experiments, <i>H. pylori</i> isolated from control and co-infected mice was analyzed for <i>cagA</i> gene copy number using quantitative real-time polymerase chain reaction. Three isolates with the highest <i>cagA</i> copy numbers observed to date were further characterized for their virulence phenotypes and subjected to whole-genome sequencing to identify the mutations associated with co-infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>H. pylori</i> isolates recovered from the stomachs of co-infected mice exhibited significantly higher <i>cagA</i> copy numbers than those from control mice, with the mean copy number increasing from 2.64 (±1.03) in the control group to 3.22 (±1.63) in the co-infected group. Three <i>H. pylori</i> isolates with high <i>cagA</i> copy numbers (6.1, 9.1, and 11.0 copies) were assessed for virulence features. Notably, two of these isolates maintained elevated <i>cagA</i> phosphorylation and cell elongation, suggesting their potential relevance as a model for <i>H. pylori</i> infection studies in mice. Whole-genome sequencing further revealed co-infection-associated nonsynonymous mutations, notably in the <i>fur</i> gene and membrane transport-related genes such as an MFS transporter and a corrinoid ABC transporter substrate-binding protein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that co-infection with <i>S.</i> promotes an increase in the <i>cagA</i> copy number, thereby enhancing the virulence potential of <i>H. pylori</i>. The study highlights the complex interplay between <i>H. pylori</i> and co-infecting pathogens and their combined impact on <i>H. pylori</i>-mediated disease, and the utility of high-<i>cagA</i> copy isolates as valuable models for in vivo studies addressing pathogenesis.</p>\u0000 ","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12748022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145855801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer (GC) and multiple other chronic illnesses. Host genetic factors influence the susceptibility to H. pylori infection, as evidenced by elevated concordance in monozygotic twins and racial disparities independent of socioeconomic status. Leveraging meta-analyses and in silico functional annotation, we investigated host genetic susceptibility to H. pylori infection, and to examine how these variants may influence gastric cancer (GC) risk.
Methods
Meta-analyses were performed on 25 candidate genetic variants that had been investigated for the association with H. pylori infection in at least three studies, under five genetic models (allelic, dominant, recessive, homozygous, and heterozygous). Meta-analyses on genome-wide variants were conducted using the allelic model. The Bayesian False-Discovery Probability method and Venice criteria were used to assess genetic association credibility. The Genotype-Tissue Expression (GTEx) and eQTLGen databases were used for cis-expression quantitative trait locus (eQTL) analysis. Differential gene expression in H. pylori-positive (n = 61) vs. -negative (n = 17) samples, and GC (n = 414) vs. non-GC tissues (n = 210) was analyzed leveraging The Cancer Genome Atlas, GTEx, and in-house RNA-sequencing data.
Results
From a total of 103 studies for systematic review, meta-analyses based on 83 studies identified 47 variants across 18 loci associated with H. pylori susceptibility. These loci encompassed 29 cis-eQTLs affecting expression of 42 genes. Of them, seven genes at three loci—4p14 (TLR10, TLR6, KLHL5, TMEM156), 6p21.33 (HLA-DRB6, C4B), and 14q32.2 (WARS)—were consistently upregulated in H. pylori infection and GC, which may contribute to H. pylori infection-related GC development.
Conclusion
Host genetic predisposition alters the odds of H. pylori infection, demonstrating the importance of host-pathogen crosstalk in infection dynamics and subsequent gastric carcinogenesis.
{"title":"Host Genetic Variants Associated With Helicobacter pylori Infection: A Meta-Analysis Combined With Functional Annotation","authors":"Wen-Jing Zhao, Heng-Min Xu, Chao Zhang, Xiao-Wen Jiang, Kai-Feng Pan, Wen-Qing Li","doi":"10.1111/hel.70098","DOIUrl":"10.1111/hel.70098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p><i>Helicobacter pylori</i> (<i>H. pylori</i>) is a major risk factor for gastric cancer (GC) and multiple other chronic illnesses. Host genetic factors influence the susceptibility to <i>H. pylori</i> infection, as evidenced by elevated concordance in monozygotic twins and racial disparities independent of socioeconomic status. Leveraging meta-analyses and <i>in silico</i> functional annotation, we investigated host genetic susceptibility to <i>H. pylori</i> infection, and to examine how these variants may influence gastric cancer (GC) risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Meta-analyses were performed on 25 candidate genetic variants that had been investigated for the association with <i>H. pylori</i> infection in at least three studies, under five genetic models (allelic, dominant, recessive, homozygous, and heterozygous). Meta-analyses on genome-wide variants were conducted using the allelic model. The Bayesian False-Discovery Probability method and Venice criteria were used to assess genetic association credibility. The Genotype-Tissue Expression (GTEx) and eQTLGen databases were used for cis-expression quantitative trait locus (eQTL) analysis. Differential gene expression in <i>H. pylori</i>-positive (<i>n</i> = 61) vs. -negative (<i>n</i> = 17) samples, and GC (<i>n</i> = 414) vs. non-GC tissues (<i>n</i> = 210) was analyzed leveraging The Cancer Genome Atlas, GTEx, and in-house RNA-sequencing data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From a total of 103 studies for systematic review, meta-analyses based on 83 studies identified 47 variants across 18 loci associated with <i>H. pylori</i> susceptibility. These loci encompassed 29 cis-eQTLs affecting expression of 42 genes. Of them, seven genes at three loci—4p14 (<i>TLR10</i>, <i>TLR6</i>, <i>KLHL5</i>, <i>TMEM156</i>), 6p21.33 (<i>HLA-DRB6</i>, <i>C4B</i>), and 14q32.2 (<i>WARS</i>)—were consistently upregulated in <i>H. pylori</i> infection and GC, which may contribute to <i>H. pylori</i> infection-related GC development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Host genetic predisposition alters the odds of <i>H. pylori</i> infection, demonstrating the importance of host-pathogen crosstalk in infection dynamics and subsequent gastric carcinogenesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miao Duan, Teng Teng, Qingzhou Kong, Yueyue Li, Xiuli Zuo
Background and Aims
The rising antibiotic resistance of Helicobacter pylori has led to variability in efficacy of bismuth-containing quadruple therapy (BcQT). This network meta-analysis (NMA) aimed to compare the efficacy of antibiotic combinations in first-line BcQT.
Methods
Following PRISMA guidelines with PROSPERO registration (CRD420251005598), we systematically searched PubMed, Embase, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) published between January 1, 2005 and March 21, 2025. Eligible studies were selected by predefined criteria. Dichotomous outcomes included H. pylori eradication rates, adverse events, and compliance, analyzed as odds ratios (ORs) with 95% credible intervals (95% CrI) or 95% confidence intervals (95% CI). Treatments were ranked via surface under the cumulative ranking curve (SUCRA).
Results
This NMA included 25 RCTs (n = 7624) evaluating 19 regimens. Amoxicillin-metronidazole ranked highest globally (SUCRA = 0.866) in intention-to-treat analyses and in Asia (SUCRA = 0.851), particularly during 2016–2025 (SUCRA = 0.859; OR = 3.43, 95% CrI 1.17–10.05). Metronidazole-tetracycline was optimal in Europe (SUCRA = 0.969; OR = 2.13, 95% CrI 1.15–3.95), amoxicillin-minocycline in China (SUCRA = 0.733). Notably, regimens including levofloxacin or clarithromycin significantly decreased eradication rates in China (OR = 1.32; 95% CI 1.04–1.66; p = 0.02). Amoxicillin-furazolidone had the poorest adverse events (SUCRA = 0.792). Compliance was highest with amoxicillin-moxifloxacin (SUCRA = 0.878).
Conclusion
Superior eradication was achieved with BcQT by utilizing dual low-resistance antibiotics per local surveillance data. Amoxicillin-metronidazole may represent optimal regimens for primary H. pylori eradication efficacy in BcQT. Substantial efficacy variation in antibiotic combinations necessitates tailored treatment guided by antibiotic resistance surveillance.
背景与目的：幽门螺杆菌耐药性的上升导致含铋四联疗法（BcQT）疗效的变化。本网络荟萃分析（NMA）旨在比较抗生素联合治疗一线BcQT的疗效。方法：遵循PRISMA指南并注册（CRD420251005598），系统检索PubMed、Embase、Web of Science和Cochrane Library，检索2005年1月1日至2025年3月21日发表的随机对照试验（RCTs）。根据预先确定的标准选择符合条件的研究。二分类结果包括幽门螺杆菌根除率、不良事件和依从性，以95%可信区间（95% CrI）或95%可信区间（95% CI）的优势比（ORs）进行分析。在累积排序曲线（SUCRA）下，通过表面对处理进行排序。结果：该NMA纳入25项随机对照试验（n = 7624），评估19种方案。阿莫西林-甲硝唑在意向治疗分析中全球排名最高（SUCRA = 0.866），在亚洲排名最高（SUCRA = 0.851），特别是在2016-2025年期间（SUCRA = 0.859; OR = 3.43, 95% CrI 1.17-10.05）。欧洲以甲硝唑四环素（SUCRA = 0.969; OR = 2.13, 95% CrI 1.15-3.95）、中国以阿莫西林-米诺环素（SUCRA = 0.733）为最佳。值得注意的是，包括左氧氟沙星或克拉霉素在内的方案显著降低了中国的根除率（or = 1.32; 95% CI 1.04-1.66; p = 0.02）。阿莫西林-呋喃唑酮不良事件发生率最低（SUCRA = 0.792）。阿莫西林-莫西沙星的依从性最高（SUCRA = 0.878）。结论：根据当地监测数据，采用双低耐药抗生素治疗BcQT取得了较好的根除效果。阿莫西林-甲硝唑可能是BcQT原发性幽门螺杆菌根除疗效的最佳方案。抗生素组合的巨大疗效差异需要在抗生素耐药性监测的指导下进行量身定制的治疗。
{"title":"Antibiotic Combinations in Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Systematic Review and Network Meta-Analysis","authors":"Miao Duan, Teng Teng, Qingzhou Kong, Yueyue Li, Xiuli Zuo","doi":"10.1111/hel.70101","DOIUrl":"10.1111/hel.70101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The rising antibiotic resistance of <i>Helicobacter pylori</i> has led to variability in efficacy of bismuth-containing quadruple therapy (BcQT). This network meta-analysis (NMA) aimed to compare the efficacy of antibiotic combinations in first-line BcQT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Following PRISMA guidelines with PROSPERO registration (CRD420251005598), we systematically searched PubMed, Embase, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) published between January 1, 2005 and March 21, 2025. Eligible studies were selected by predefined criteria. Dichotomous outcomes included <i>H. pylori</i> eradication rates, adverse events, and compliance, analyzed as odds ratios (ORs) with 95% credible intervals (95% CrI) or 95% confidence intervals (95% CI). Treatments were ranked via surface under the cumulative ranking curve (SUCRA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This NMA included 25 RCTs (<i>n</i> = 7624) evaluating 19 regimens. Amoxicillin-metronidazole ranked highest globally (SUCRA = 0.866) in intention-to-treat analyses and in Asia (SUCRA = 0.851), particularly during 2016–2025 (SUCRA = 0.859; OR = 3.43, 95% CrI 1.17–10.05). Metronidazole-tetracycline was optimal in Europe (SUCRA = 0.969; OR = 2.13, 95% CrI 1.15–3.95), amoxicillin-minocycline in China (SUCRA = 0.733). Notably, regimens including levofloxacin or clarithromycin significantly decreased eradication rates in China (OR = 1.32; 95% CI 1.04–1.66; <i>p</i> = 0.02). Amoxicillin-furazolidone had the poorest adverse events (SUCRA = 0.792). Compliance was highest with amoxicillin-moxifloxacin (SUCRA = 0.878).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Superior eradication was achieved with BcQT by utilizing dual low-resistance antibiotics per local surveillance data. Amoxicillin-metronidazole may represent optimal regimens for primary <i>H. pylori</i> eradication efficacy in BcQT. Substantial efficacy variation in antibiotic combinations necessitates tailored treatment guided by antibiotic resistance surveillance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Baixiang He, Xiaochi Ma, Mingyue Liu, Xiangyun Zou, Jean Carlo Xin Peng Ye, Ran Zhang, Zhihong Li
Introduction
A central controversy in autoimmune gastritis (AIG) concerns the true incidence of gastric cancer (GC) and gastric neuroendocrine tumors (gNETs). Reported risks vary widely, potentially influenced by Helicobacter pylori (HP) status, AIG subtypes, and age–factors not addressed in prior meta-analyses. This study aimed to determine the pooled incidence of GC and gNETs in AIG and to conduct a comprehensive stratified evaluation.
Methods
We searched PubMed, Embase, and Cochrane Library through May 2025 for observational studies reporting incident GC or gNETs in AIG. Subgroup analyses, sensitivity analyses, and meta-regression were conducted.
Results
Twenty-three studies were included: 19 hospital-based cohorts (n = 4309) and 4 registries (n = 36,015). The pooled incidence of GC was 0.12/100 person-years (PY; 95% CI, 0.06–0.17; I2 = 45.7%) and of gNETs 1.09/100 PY (95% CI, 0.61–1.58; I2 = 81.3%). By subtype, GC incidence was 0.29/100 PY in pernicious anemia (PA), 0.12 in histopathology-defined AIG, and 0.09 in parietal cell antibody (PCA)-positive patients; gNETs were highest in the hypergastrinemia subgroup (1.74/100 PY). By HP status, GC incidence was 0.12/100 PY in HP-naïve and 0.07 in HP-exposed patients. Age-stratified analyses showed a consistent upward trend in patients ≥ 60 years for both GC (0.27 vs. 0.10/100 PY) and gNETs (1.48 vs. 0.87/100 PY).
Conclusion
This study underscores the neoplastic risk associated with AIG. GC incidence is highest in PA and lower in PCA-positive patients, likely reflecting different AIG stages. HP-naïve status does not confer protection, and long-term GC risk persists. Age is a key modifier, providing a useful reference for risk stratification and individualized surveillance.
{"title":"Incidence of Gastric Cancer and Neuroendocrine Tumors in Autoimmune Gastritis: A Systematic Review and Meta-Analysis of Follow-Up Studies","authors":"Baixiang He, Xiaochi Ma, Mingyue Liu, Xiangyun Zou, Jean Carlo Xin Peng Ye, Ran Zhang, Zhihong Li","doi":"10.1111/hel.70096","DOIUrl":"10.1111/hel.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>A central controversy in autoimmune gastritis (AIG) concerns the true incidence of gastric cancer (GC) and gastric neuroendocrine tumors (gNETs). Reported risks vary widely, potentially influenced by <i>Helicobacter pylori</i> (HP) status, AIG subtypes, and age–factors not addressed in prior meta-analyses. This study aimed to determine the pooled incidence of GC and gNETs in AIG and to conduct a comprehensive stratified evaluation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched PubMed, Embase, and Cochrane Library through May 2025 for observational studies reporting incident GC or gNETs in AIG. Subgroup analyses, sensitivity analyses, and meta-regression were conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-three studies were included: 19 hospital-based cohorts (<i>n</i> = 4309) and 4 registries (<i>n</i> = 36,015). The pooled incidence of GC was 0.12/100 person-years (PY; 95% CI, 0.06–0.17; <i>I</i><sup>2</sup> = 45.7%) and of gNETs 1.09/100 PY (95% CI, 0.61–1.58; <i>I</i><sup>2</sup> = 81.3%). By subtype, GC incidence was 0.29/100 PY in pernicious anemia (PA), 0.12 in histopathology-defined AIG, and 0.09 in parietal cell antibody (PCA)-positive patients; gNETs were highest in the hypergastrinemia subgroup (1.74/100 PY). By HP status, GC incidence was 0.12/100 PY in HP-naïve and 0.07 in HP-exposed patients. Age-stratified analyses showed a consistent upward trend in patients ≥ 60 years for both GC (0.27 vs. 0.10/100 PY) and gNETs (1.48 vs. 0.87/100 PY).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study underscores the neoplastic risk associated with AIG. GC incidence is highest in PA and lower in PCA-positive patients, likely reflecting different AIG stages. HP-naïve status does not confer protection, and long-term GC risk persists. Age is a key modifier, providing a useful reference for risk stratification and individualized surveillance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>PROSPERO database (CRD420251047873)</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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