BACKGROUND:Japan has a high incidence of gastric cancer and is currently the only nation in which guidelines recommend Helicobacter pylori screening for adolescents. However, the implementation and implications of these initiatives have not been comprehensively characterized. The aim of this study was to provide a comprehensive overview of H. pylori screening programs for adolescents in Japan. MATERIALS AND METHODS:A narrative review was conducted to summarize the studies on H. pylori screening among adolescents in Japan. Literature searches were performed in PubMed, Ichushi-Web, CiNii Research, and J-STAGE for articles published up to February 12, 2026. Studies that described H. pylori screening programs targeting adolescents in Japan were included. Data were extracted on study background and objectives, target age, screening methods, participation rates, infection prevalence, eradication regimens, eradication success rates, and adverse events. RESULTS:Seventeen studies met the inclusion criteria. Screening programs were typically local-government-led and school-based and primarily targeted junior high school students. A two-step diagnostic strategy employing noninvasive tests was commonly used. The median prevalence of H. pylori infection was 3.1%. Eradication regimens varied across programs; metronidazole- or vonoprazan-containing regimens generally showed higher eradication success rates than proton pump inhibitor-based clarithromycin-containing regimens, although cross-study comparisons should be interpreted cautiously because of heterogeneity. Adverse events were generally mild and predominantly gastrointestinal, and no serious complications were reported. CONCLUSIONS:Local-government-led and school-based H. pylori screening among adolescents in Japan represents a feasible approach to the prevention of gastric cancer within a well-established school health system. The applicability of this strategy to other countries depends on several contextual factors, including the incidence of gastric cancer, health care infrastructure, and the presence of organized school health systems. In settings that lack these conditions, alternative community-based strategies may be required.
BACKGROUND:Helicobacter pylori infection is a primary cause of gastric cancer. Although eradication therapy in adulthood suppresses carcinogenesis, its efficacy is limited due to the progression of advanced gastric mucosal atrophy before eradication. Implementing a "screen-and-treat" strategy during adolescence represents a promising approach to prevent advanced atrophy and subsequent gastric cancer. METHODS:This prospective cohort study included first-year high school students in Kyoto Prefecture, Japan, from 2015 to 2023. Screening was performed using a primary urine H. pylori antibody test, followed by a secondary stool antigen test for confirmation. Confirmed positive individuals were referred to designated medical institutions for 7-day eradication therapy. The primary therapeutic regimen was shifted from rabeprazole, amoxicillin, and clarithromycin (PAC) in 2015 to rabeprazole, amoxicillin, and metronidazole (PAM) from 2016 onward. Clostridium butyricum MIYAIRI 588 strain (CBM588) was co-administered starting in 2017. Eradication success was verified via a stool antigen test at least 8 weeks post-treatment. RESULTS:A total of 50,031 students were targeted over the 9-year period, with an overall consent rate ranging from 59.9% to 83.9%. The confirmed H. pylori infection rate declined from 4.7% in 2015 to 1.5% in 2023. The medical consultation rate among positive screenees exhibited a declining trend, peaking at 84.6% (2015) and dropping to 15.8% (2023), despite a temporary increase in 2019 (65.9%). The eradication success rate significantly improved from 76.5% with the PAC regimen (2015) to over 93.8% with the PAM regimen (2016 onward), exceeding 96.0% after the addition of CBM588. No serious adverse events were reported throughout the study period. CONCLUSIONS:The prospective adolescent screen-and-treat program demonstrated a significant decrease in H. pylori infection rates among first-year high school students over the decade. While the safety and efficacy of the PAM-based eradication regimen were verified, declining medical consultation rates present a continuous challenge for public health implementation.
BACKGROUND:Non-invasive Helicobacter pylori (H. pylori) tests are widely used in clinical practice in Japan; however, their diagnostic accuracy may vary with the composition of the target population, and no systematic review has synthesized their performance specifically in Japanese populations. Therefore, we conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of serum antibody, urine antibody, and stool antigen tests for H. pylori infection in Japanese populations. MATERIALS AND METHODS:MEDLINE, Embase, and Ichushi-Web were searched for studies published between 2005 and 2024 evaluating serum antibody, urine antibody, or stool antigen tests in Japanese participants. The primary objective involved evaluation of diagnostic accuracy for current H. pylori infection, and the secondary objective involved assessment of accuracy for ever-infected individuals. Summary estimates were calculated using bivariate random-effects models. A subgroup analysis was performed under clinically relevant conditions, restricted to studies without previously infected individuals, with composite reference standards, and without application of post hoc cutoff values. RESULTS:Among 806 publications, 43 studies were selected (serum antibody, 29; urine antibody, six; stool antigen, eight). For diagnosing current H. pylori infection, the summary sensitivity/specificity measured 0.922/0.956 for serum antibody, 0.885/0.970 for urine antibody, and 0.928/0.972 for stool antigen tests. For diagnosing ever-infected individuals, the summary sensitivity/specificity measured 0.908/0.960 for serum antibody and 0.888/0.969 for stool antigen. Under clinically relevant conditions, serum antibody and stool antigen yielded sensitivities/specificities of 0.908/0.968 and 0.935/0.985, respectively. In serum antibody studies, studies with previously infected individuals showed lower accuracy (sensitivity/specificity, 0.876/0.861) than studies without previously infected individuals (0.929/0.967). CONCLUSIONS:Serum antibody and stool antigen tests demonstrated high diagnostic accuracy for current H. pylori infection in Japanese populations, although accuracy declined in studies with previously infected individuals.
OBJECTIVES:To evaluate the diagnostic accuracy in Helicobacter pylori detection using blood test with FliD and CagA antibodies (Pylori DuoTect), comparing with rapid urease test (RUT) and urease breath test (UBT) in Vietnamese patients with upper GI symptoms. METHODS:A cross-sectional study was conducted at the Institute of Gastroenterology and Hepatology in Hanoi, Vietnam on adults with upper GI symptoms, no prior treatment of peptic ulcers, and no history of H. pylori infection. Participants underwent upper GI endoscopy and three H. pylori tests, including rapid urease test (RUT), urea breath test (UBT), and Pylori DuoTect. Pylori DuoTect was considered positive if either FliD or CagA antibodies were detected. The H. pylori infection was defined as both RUT and UBT positive. Endoscopic findings were classified using the Kyoto classification score for gastritis. Diagnostic accuracy was evaluated using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS:From December 1, 2023, to August 9, 2024, 333 patients were recruited (mean age 45.9 years, 39.9% male). The most common symptom was epigastric pain (49.5%). The prevalences of gastritis, gastric ulcers, and duodenal ulcers were 92.7%, 12.1%, and 8.1%, respectively. Pylori DuoTect was positive in 51.9% of patients (FliD: 34.8% and CagA: 66.6%). Using the gold standard, 33.6% were diagnosed with H. pylori infection. The sensitivity, specificity, PPV, and NPV of Pylori DuoTect were 83.0%, 64.0%, 54.0%, and 88.0%, respectively. Combining Pylori DuoTect and endoscopy findings (peptic ulcer or Kyoto score ≥ 2) improved the sensitivity from 0.83 to 0.88 and increased NPV. CONCLUSION:Pylori DuoTect had moderate sensitivity and low specificity in the diagnosis of H. pylori infection in Vietnamese adult patients.
BACKGROUND:The escalating antibiotic resistance of Helicobacter pylori (H. pylori) poses a significant threat to global public health. Continuous local surveillance is crucial due to substantial geographical and temporal variations in resistance patterns. OBJECTIVE:This study aimed to characterize the antimicrobial resistance profile of H. pylori in Shenzhen, China, between 2021 and 2024, and to assess temporal trends and demographic associations. METHODS:We conducted a retrospective analysis of patients who underwent gastroscopy at Shenzhen Hospital of Southern Medical University from March 2021 to October 2024. Gastric mucosal biopsies were collected for H. pylori culture, and antimicrobial susceptibility testing was performed using the agar dilution method. RESULTS:Among culture-positive isolates, 225 were from treatment-naïve patients and 975 from previously treated patients. Resistance rates in the treatment-naïve vs. previously treated groups were: clarithromycin 17.8% vs. 68.0%, metronidazole 87.1% vs. 97.4%, levofloxacin 11.1% vs. 50.9%, amoxicillin 0.4% vs. 3.1%, and furazolidone 0% vs. 0.1%. No tetracycline-resistant isolates were identified. Significant temporal increases were observed in secondary resistance to clarithromycin, amoxicillin, and metronidazole, as well as in the prevalence of multidrug resistance (all p < 0.05). No sex-based differences were detected in either primary or secondary resistance rates (all p > 0.05). Secondary resistance to clarithromycin, metronidazole, and levofloxacin varied significantly across age groups (p < 0.05), whereas primary resistance rates did not. CONCLUSIONS:Between 2021 and 2024, H. pylori isolates in Shenzhen exhibited high resistance rates to metronidazole, clarithromycin, and levofloxacin, while susceptibility to amoxicillin, furazolidone, and tetracycline remained preserved. Secondary resistance rates increased progressively over time, accompanied by a growing burden of multidrug resistance. Bismuth-containing quadruple therapy and high-dose dual therapy are recommended as first-line empirical regimens for treatment-naïve patients, whereas susceptibility-guided therapy is warranted for those with prior treatment failure.
BACKGROUND:The price of vonoprazan in the United States, as with many newly introduced drugs, is currently high. Here, we examined the cost-effectiveness of vonoprazan clarithromycin triple therapy for treatment of Helicobacter pylori in the United States. We compared cure rates and total treatment costs to achieve ≥ 90% cure with either vonoprazan or proton pump inhibitor (PPI) triple therapy. MATERIALS AND METHODS:We simulated a theoretical population and compared 4 scenarios comparing vonoprazan 20 mg twice daily or esomeprazole 40 mg twice daily. These included: (1) empiric vonoprazan versus esomeprazole clarithromycin triple therapy, (2) susceptibility-based vonoprazan versus esomeprazole clarithromycin triple therapy, (3) empiric vonoprazan versus esomeprazole clarithromycin triple therapy with treatment failures receiving bismuth quadruple therapy, and (4) susceptibility-based vonoprazan versus esomeprazole clarithromycin triple therapy with treatment failures receiving bismuth quadruple therapy. The prevalence of clarithromycin resistance was estimated at 30%. Cure rates were based on the H. pylori treatment nomogram and drug costs on U.S. 2025 retail prices (i.e., $50 for PPI and $960 for vonoprazan triple therapy). RESULTS:With 30% resistance, susceptibility-based therapy was the most effective (cure rate 92%). With empiric therapy, the cure rate with vonoprazan was higher than esomeprazole (88% vs. 77%) but overall costs increased 2.4-5.2 times. The cost per 1000 patients receiving vonoprazan was approximately $1000,000 versus $50,000 for esomeprazole. The least expensive, highly effective scenario was empiric esomeprazole triple therapy with treatment failures receiving bismuth quadruple therapy. CONCLUSIONS:Any treatment advantage of vonoprazan over PPI in clarithromycin triple therapy is restricted to those with clarithromycin resistance. Vonoprazan triple therapies cost 2 to 5 times more than a high potency PPI with small gains in cure rates. For susceptible infections, triple therapy using a high potency PPI should be preferred, and the most cost-effective strategy is to reserve vonoprazan for refractory cases.
BACKGROUND:Helicobacter pylori (Hp) infection is the primary risk factor for gastric cancer, yet the consequences of the infection vary by bacterial and host factors. The outer membrane protein HopQ plays a key role in Hp adhesion, but its genetic diversity and clinical implications are unclear. HopQ-CEACAM interaction facilitates the translocation of the cytotoxin-associated gene A (CagA). MATERIALS AND METHODS:We analyzed hopQ sequences from 1038 Hp strains, mainly from the Helicobacter pylori Genome Project, integrating phylogenetic, genotypic, and disease association analyses. Logistic regression models assessed the association between hopQ genotypes and disease, accounting for cagA status and Hp ancestry. RESULTS:hopQ genotypes have a strong population structure. The hpAfrica1 and hpNorthAsia (including hspIndigenousAmerica) populations exhibited distinct hopQ patterns, suggesting ancestry-specific pathogenicity. hopQ genotypes were classified as hopQI and hopQII; hopQI was further divided into high-risk and low-risk variants. Ancestry-adjusted analyses showed that hopQI high-risk was associated (odds ratio = 3.1; p < 0.0001) with advanced disease (intestinal metaplasia and gastric cancer combined vs. non-atrophic gastritis), independently of cagA. In contrast, hopQII and hopQI low-risk variants correlated with a reduced risk. CONCLUSIONS:The hopQ diversity is a key determinant of Hp pathogenicity. hopQI high-risk is a predictor of advanced disease, whereas hopQII and hopQI low-risk may be protective. Understanding hopQ variability could improve risk stratification and the targeted therapies for gastric cancer.
BACKGROUND:Helicobacter pylori is a globally prevalent gastric pathogen, and chronic infection accounts for most gastric cancer (GC) cases worldwide. Major oncogenic determinants, including CagA, VacA, and the type IV secretion system, show marked geographic heterogeneity, yet the evolutionary forces shaping this uneven distribution remain unclear. Prophages can mediate horizontal gene transfer and modulate bacterial fitness and virulence, but their contribution to H. pylori carcinogenicity has not been systematically evaluated. METHODS:We characterized prophage diversity, population structure, and virulence potential using 2379 H. pylori host genomes and 139 complete prophage genomes. Prophage population structure and intergenomic relatedness were inferred, and the prophage pangenome and protein-sharing network were reconstructed. Homology-based association analyses were performed to test enrichment of prophage orthologous groups (POGs) with major oncogenic virulence factors (CagA and/or VacA) across the 2379 host genomes. RESULTS:Prophages segregated into geographically structured populations. The EastAsia and EastAsia2 prophage groups were tightly coupled to high-risk hspEAsia hosts and exhibited the largest and most diverse accessory repertoires. Virulence-associated genes were strongly population-specific and were detected only in the EastAsia/EastAsia2 prophage populations. Moreover, carriage of POGs homologs from 1961P, HPy1R, and phiHP33 showed significant positive associations with CagA and/or VacA across the 2379 genomes, whereas no enrichment was observed for KHP30 or KHP40. CONCLUSIONS:H. pylori prophages are not passive genomic remnants but population-structured reservoirs whose gene repertoires track high-risk virulence backgrounds and may contribute to the bacterium's carcinogenic potential.
BACKGROUND:Resistance to antibiotics has resulted in the effectiveness of conventional eradication therapies for Helicobacter pylori being reduced, creating a need for regimens that are effective, safe, and simple. In this study, we evaluated the eradication efficacy, adverse events, and medication adherence of four different tegoprazan-based regimens administered as first-line therapy for H. pylori infection. We also explored the clinical value of adding bismuth to a triple therapy regimen. METHODS:In this prospective, randomized controlled trial, 640 treatment-naive patients with confirmed H. pylori infection were randomly assigned to one of the four groups undergoing 14-day treatment regimens of tegoprazan-amoxicillin (TA), tegoprazan-tetracycline (TT), tegoprazan-amoxicillin-tetracycline (TAT), or tegoprazan-amoxicillin-tetracycline-bismuth (TATB), with 160 patients in each group. The outcomes were the eradication rate, incidence of adverse events, and medication adherence. RESULTS:In the intention-to-treat analysis, the H. pylori eradication rates in the TA, TT, TAT, and TATB groups were 80.0% (95% confidence interval [CI]: 73.0-85.9), 61.9% (95% CI: 53.9-69.4), 93.1% (95% CI: 88.0-96.5), and 89.4% (95% CI: 83.5-93.7), respectively. Compared with the TATB regimen, the TAT regimen was non-inferior (95% CI, -3.9% to 11.5%; non-inferiority p < 0.001), whereas demonstrating non-inferiority in the TA and TT regimens failed. Adverse events were less frequent in the TA (10.6%), TT (17.5%), and TAT (20.0%) groups than in the TATB group (36.9%; all p < 0.001). Medication adherence was high across groups, with no significant between-group differences observed. CONCLUSIONS:High eradication efficacy was demonstrated for the TAT regimen; this regimen was non-inferior to the TATB regimen, and it was associated with fewer adverse events. These findings suggest that it may be an effective first-line treatment option for H. pylori infection. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT06977841.
BACKGROUND/AIMS:The eradication efficacy of proton pump inhibitor (PPI)-based standard triple therapy (STT) for Helicobacter pylori infection has declined in Korea, largely because of increasing clarithromycin resistance. High-dose dual therapy (HDDT) using potent acid suppression represents a promising clarithromycin-sparing strategy. This study evaluated the efficacy and safety of fexuprazan-based modified HDDT (m-HDDT) including bismuth, compared with conventional PPI-based STT as first-line eradication therapy. METHODS:This prospective, multicenter, randomized, open-label, non-inferiority trial was conducted at eight tertiary hospitals in Korea. Treatment-naïve adults with confirmed H. pylori infection were randomized to receive either m-HDDT (fexuprazan 40 mg twice daily, amoxicillin 1000 mg three times daily, and bismuth subcitrate potassium 300 mg three times daily) or STT (lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all twice daily) for 14 days. Eradication was assessed by urea breath test 4-8 weeks after therapy. The primary endpoint was the eradication rate in the full analysis set (FAS), with a prespecified non-inferiority margin of -10%. Safety and compliance were evaluated as secondary outcomes. RESULTS:In total, 196 patients were included in the FAS (m-HDDT, n = 96; STT, n = 100). Helicobacter pylori eradication was achieved in 81.3% of patients in the m-HDDT group and 79.0% in the STT group, demonstrating non-inferiority of m-HDDT (one-sided Wald test, p = 0.0158). Per-protocol analysis yielded consistent results (p = 0.0215). Drug compliance was high in both groups, with mean compliance rates of 97.0% in the m-HDDT group and 99.0% in the STT group; more than 95% of patients in each group achieved ≥ 80% compliance. The incidence of treatment-emergent adverse events was comparable between groups (16.7% vs. 14.0%); most events consisted of mild gastrointestinal symptoms. No serious adverse events or treatment discontinuations due to adverse events were observed in either group. CONCLUSIONS:Fexuprazan-based m-HDDT with bismuth was non-inferior to PPI-based STT for H. pylori eradication and demonstrated comparable safety and excellent compliance. This clarithromycin-sparing regimen can be considered an alternative treatment option in regions with high macrolide resistance.
BACKGROUNDS:Although Helicobacter pylori (Hp) eradication reduces gastric cancer (GC) risk, GC still develops in some patients after successful eradication. Population-based data on post-eradication GC incidence and lifestyle-related risk factors remain limited. This study aimed to assess GC incidence after Hp eradication and to identify associated lifestyle factors in a nationwide cohort. MATERIALS AND METHODS:We conducted a retrospective cohort study using Japanese healthcare insurance claims and medical check-up data from 2014 to 2023. Patients who have successfully eradicated Hp were included. GC development 1 year or more after eradication was the primary outcome. The follow-up period extended from 1 year after the initiation of eradication medication until the final insurance record, GC development, or death. GC incidence and risk factors were evaluated using Kaplan-Meier analysis and Cox proportional hazards models adjusted for age and sex. RESULTS:Among 59,274 patients (mean age 64.9 years; 44.6% male), 649 (1.44%) developed GC during a mean follow-up of 3.66 years, with a cumulative incidence of 1.47% at 5 years. Male and older age at the Hp eradication was significantly associated with increased GC incidence (p < 0.001, 1og-rank test). Among various lifestyle factors, only smoking was independently associated with GC risk (adjusted hazard ratio (aHR) 1.37, 95% Confidence Intervals (CI) 1.05-1.78). Everyday alcohol consumption in the current smokers is associated with GC risk (aHR 1.80, 95% CI 1.22-2.66), compared with non-smokers/drinkers. CONCLUSION:GC remains a clinically important outcome even after Hp eradication. Smoking was associated with a higher risk of post-eradicated GC, and smoking cessation may contribute to risk reduction in this population. These findings suggest that lifestyle factors, together with host characteristics such as age, male sex, and alcohol consumption, may be considered when designing risk-stratified surveillance strategies.
BACKGROUND AND AIMS:Helicobacter pylori is a persistent gastric microbe with systemic consequences beyond the stomach, yet its contribution to host lipid dysregulation remains unclear. METHODS:We analyzed clinical data from 57,295 adults with documented H. pylori status and detailed lipid profiles, including the non-HDL-C to HDL-C ratio (NHHR). Mechanistic validation was performed using in vitro and in vivo H. pylori PMSS1 infection models, combined with single-cell RNA sequencing, molecular analyses, histopathology, and lipidomics. RESULTS:Helicobacter pylori infection was associated with increased LDL cholesterol and triglycerides, reduced HDL cholesterol, and elevated NHHR, which independently predicted hyperlipidemia risk. At the mechanistic level, H. pylori infection consistently suppressed gastric expression of Gpihbp1, a key mediator of lipoprotein lipase-dependent lipid transport. Infected mice developed systemic hyperlipidemia and exhibited lipidomic remodeling characterized by glycerolipid accumulation and reduced phosphatidylcholine species. Importantly, genetic deficiency of Gpihbp1 promoted gastric H. pylori colonization and exacerbated mucosal inflammation, revealing a reciprocal interaction between host lipid metabolism and bacterial persistence. CONCLUSION:These findings define a microbiota-host lipid transport axis linking chronic H. pylori infection to dyslipidemia and suggest that integrated targeting of microbial infection and metabolic dysfunction may offer therapeutic benefit.
BACKGROUND:Our previous randomized controlled trial reported that Helicobacter pylori eradication reduced the risk of metachronous gastric cancer over a median follow-up of 5.9 years in patients with early gastric cancer (EGC) and improved corpus gastric atrophy (GA) at the specific 3 year follow-up time. This study aimed to evaluate the long-term effects of H. pylori eradication on GA and intestinal metaplasia (IM) at trial closeout. METHODS:Among 470 patients randomized between 2003 and 2013, 327 who were assessed for GA and IM at both baseline and 3-year follow-up time were included in the study. At trial closeout, H. pylori status, GA, and IM were assessed. Main outcomes were improvement in GA and IM at the corpus lesser curvature (LC) according to the H. pylori status at the closeout time. The secondary outcomes included the Operative Link for Gastritis Assessment (OLGA) and Operative Link for Gastric Intestinal Metaplasia assessment (OLGIM) stage improvements. RESULTS:At a median follow-up of 5.9 years (interquartile range: 4.0-8.2 years), an improvement in GA grades at the corpus LC was observed in 88 of the 150 patients (58.7%) in the H. pylori-eradicated group and 31 of the 158 patients (19.6%) in the H. pylori-persistent group (odds ratio [OR] in the H. pylori-eradicated group, 5.81; 95% confidence interval [CI], 3.49-9.68). IM grades showed greater improvement in the H. pylori-eradicated group (42.4% [67/158 patients]) compared with the H. pylori-persistent group (18.6% [31/167 patients]); OR in the eradicated group (3.23; 95% CI, 1.96-5.33). Similarly, the H. pylori-eradicated group exhibited significantly higher rates of improvement in both OLGA (OR 6.48; 95% CI, 3.85-10.91) and OLGIM stages (OR 2.31; 95% CI, 1.42-3.77). CONCLUSIONS:In patients with EGC who have far advanced histologic changes in the background mucosa, H. pylori eradication was associated with a significant improvement in GA and IM.
BACKGROUND:Management of refractory Helicobacter pylori (H. pylori) infection remains challenging due to increasing antibiotic resistance and limited effective rescue options. Minocycline and furazolidone retain low resistance rates, while potassium-competitive acid blockers (P-CABs) provide potent and sustained acid suppression. This study aimed to evaluate the efficacy and safety of a 14-day P-CAB-based regimen combining minocycline, furazolidone, and bismuth in patients with refractory H. pylori infection. METHODS:From January 2023 to October 2025, clinical data were collected from patients with refractory H. pylori infection who received the above regimen at Tongji Hospital, Wuhan, China. Eradication was assessed by a urea breath test performed at least 4 weeks after treatment. Adverse events during treatment were recorded. RESULTS:A total of 368 patients were included in modified intention-to-treat analysis. Of them, 183 (49.7%) had two previous eradication failures, 165 (44.8%) had three to four failures, and 20 (5.4%) had five or more failures. Among the 143 patients who underwent antibiotic resistance gene testing, the resistance rates to clarithromycin and quinolones were 96.5% and 79.7%, respectively. The H. pylori eradication rate was 92.7% (95% CI 89.5%-94.9%) in modified intention-to-treat analysis and 96.4% (95% CI 93.8%-97.9%) in per-protocol analysis. Adverse events occurred in 25.8% of patients and were predominantly mild to moderate, with dizziness (9.5%), nausea (5.2%), and abdominal distension (5.2%) most common. Poor compliance (OR = 18.14, 95% CI 6.39-51.51) and peptic ulcer (OR = 4.34, 95% CI 1.27-14.82) were independently associated with eradication failure. CONCLUSIONS:The 14-day regimen of P-CAB, minocycline, furazolidone, and bismuth is highly effective and well tolerated in patients with refractory H. pylori infection. This regimen represents a promising empirical rescue therapy, particularly in settings where antimicrobial susceptibility testing is unavailable.
BACKGROUND:Vonoprazan-based dual therapy has been proposed as a simplified strategy for Helicobacter pylori eradication, but head-to-head comparisons of different antibiotic partners are limited. We compared the efficacy, safety, and adherence of vonoprazan-based dual regimens with those of bismuth-containing quadruple therapy (BQT). METHODS:In this randomized controlled trial, H. pylori-infected patients were allocated (1:1:1:1) to receive VA (vonoprazan [20 mg, bid] plus amoxicillin [1000 mg, tid]), VT (vonoprazan [20 mg, bid] plus tetracycline [500 mg, tid]), VM (vonoprazan [20 mg, bid] plus minocycline [100 mg, bid]), or VACB (vonoprazan [20 mg, bid], amoxicillin [1000 mg, bid], clarithromycin [500 mg, bid], and bismuth [220 mg, bid]) for 14 days. The primary endpoint was the H. pylori eradication rate, and the secondary endpoints were the incidence of adverse events and patient adherence. RESULTS:The ITT eradication rates were 83.0% (83/100), 74.0% (74/100), 82.0% (82/100), and 83.0% (83/100) in the VA, VT, VM, and VACB groups, respectively (p = 0.304). The PP eradication rates were 90.2% (83/92), 83.1% (74/89), 88.2% (82/93), and 92.2% (83/90), respectively (p = 0.262). Adverse events occurred in 21.5% of the patients overall and differed across groups (10.0%, 15.0%, 29.0%, and 32.0% in VA, VT, VM, and VACB, respectively; p < 0.001); nausea and dizziness were more frequent with VM, whereas bitter taste and black stool were more frequent with VACB. All adverse events were mild or moderate, and no severe events were recorded. Adherence was high and comparable across groups (VA 100.0%, VT 96.0%, VM 99.0%, VACB 99.0%; p = 0.107). CONCLUSION:Vonoprazan-based regimens showed no statistically significant between-group differences in eradication and were associated with good adherence overall. In our setting, VA and VM may represent practical simplified options, whereas VT appeared less robust as an empiric regimen. These exploratory findings warrant confirmation in larger, adequately powered randomized trials. TRIAL REGISTRATION:ClinicalTrials.gov (NCT07068607).
BACKGROUND:Helicobacter pylori infection remains a major public health concern in Iran, where high prevalence, alarming antibiotic resistance, and significant gastric cancer burden necessitate a unified and evidence-based national strategy. Despite the availability of international guidelines, gaps in clinical practice persist due to local epidemiology, resistance patterns, and diagnostic challenges. This study presents the first national Iranian consensus guideline for the diagnosis and management of H. pylori infection. METHODS:A multidisciplinary panel of experts from leading Iranian gastroenterology centers convened between August 2023 and October 2025. Using the GRADE framework, the scientific committee conducted systematic literature reviews and formulated evidence-based statements across diagnostic, therapeutic, and clinical management domains. Consensus was defined as ≥ 80% agreement. Twelve structured meetings, including a final hybrid national consensus conference, were held to refine recommendations. RESULTS:The guideline delivers 35 evidence-graded statements addressing indications for testing and treatment, optimal diagnostic modalities, and treatment pathways. Key recommendations include a strong preference for non-invasive testing in patients under 45 without alarm features, endoscopic evaluation with targeted biopsies in high-risk groups, and confirmation of eradication using urea breath test (UBT) or monoclonal stool antigen test (SAT) at ≥ 4 weeks post-treatment. Given Iran's high clarithromycin resistance (> 20%), a course of 10-14 days bismuth quadruple therapy (BQT) is recommended as first-line treatment, with non-bismuth concomitant therapy as an alternative. Susceptibility-guided therapy is encouraged when feasible, particularly after treatment failure. High-dose proton pump inhibitor (PPI) or potassium competitive acid blocker (P-CAB)-based acid suppression is emphasized to enhance eradication efficacy. Special considerations are provided for renal/hepatic impairment and drug interactions. CONCLUSION:This national guideline provides a standardized, evidence-based framework for improving H. pylori diagnosis and management. By integrating local antimicrobial resistance patterns and practical clinical considerations, the guideline helps optimize eradication rates, reinforce antibiotic stewardship, and contribute to gastric cancer prevention efforts across Iran.
BACKGROUND AND AIMS:Early detection of advanced colorectal neoplasia (ACN) is critical for reducing colorectal cancer (CRC) incidence and mortality. Existing prediction models exhibit limited discriminative power. This study aimed to develop and internally validate a novel risk prediction model for ACN, with particular emphasis on incorporating gastric-related indicators to enable integrated gastrointestinal tumor screening. METHODS:Consecutive patients who underwent concurrent gastroscopy and colonoscopy for screening, symptomatic assessment, or surveillance purposes were recruited from the endoscopy center between January 1, 2021, and December 31, 2023. Comprehensive data including demographic characteristics, family history, Helicobacter pylori (H. pylori) infection status, and gastric histopathological results were collected. Patients with incomplete data were excluded a priori with no imputation. Candidate variables were selected using Elastic Net and LASSO regression to develop the prediction model. The model was trained on 80% of the data (n = 2045) and internally validated on the remaining 20% (n = 495). RESULTS:Among 2540 participants [mean age 59.0 years; 1269 males (50.0%)], the overall prevalence of ACN was 13.1% (333/2540). The final Elastic Net model incorporated eight variables, with H. pylori infection as the strongest predictor. In the internal validation cohort, the model achieved an area under the curve (AUC) of 0.837 (95% CI: 0.781-0.892), with 75.8% sensitivity, 82.2% specificity, and 81.4% accuracy. Calibration metrics showed good agreement between predicted and observed ACN risks (Brier score = 0.103; calibration plots showed non-significant deviation from perfect calibration). It significantly outperformed the Asia-Pacific Colorectal Screening (APCS) score (AUC = 0.622), its revised edition (AUC = 0.589), and the Colorectal Tumor Prediction Score (AUC = 0.570) (all p < 0.001, DeLong's test). Using the model's optimal cutoff, 25.1% (124/495) of the internal validation cohort were stratified as high-risk, with an ACN detection rate of 37.9%. The number of participants needed to screen (PNS) to detect one ACN case was only 3 in the high-risk group, compared with 25 in the low-risk group, thus demonstrating markedly improved screening efficiency. CONCLUSIONS:This study develops and internally validates a risk prediction model for ACN that integrates gastric-related indicators, with H. pylori infection as the key predictor. The model exhibits promising retrospective risk stratification performance in patients undergoing concurrent gastroscopy and colonoscopy for screening, symptomatic assessment, or surveillance. It enables retrospective risk assessment during routine endoscopy, but its clinical utility for guiding prospective colonoscopy referral decisions requires further validation in prospective cohorts.
OBJECTIVE:The European Committee on Antimicrobial Susceptibility Testing (EUCAST) defines the amoxicillin resistance breakpoint at a minimum inhibitory concentration (MIC) of 0.125 μg/mL. This breakpoint is widely applied, and its clinical relevance has been validated in regions where amoxicillin-based triple therapy is the standard. However, in the context of China's predominant use of quadruple therapy, the applicability of this breakpoint remains unclear. This study aimed to collect Southeastern China resistance data, assess the impact of different amoxicillin MIC thresholds on the efficacy of amoxicillin-containing quadruple therapy, and to explore candidate amoxicillin MIC thresholds potentially associated with treatment outcomes. METHODS:Gastric mucosal specimens were obtained from patients undergoing gastroscopy between March 2024 and March 2025. A total of 4203 Helicobacter pylori isolates were successfully cultured and included for in vitro susceptibility testing. In vitro susceptibility testing of H. pylori isolates was performed using the agar dilution method, with MIC thresholds for amoxicillin set at 0.125 μg/mL, 0.25 μg/mL, 0.5 μg/mL, 1 μg/mL, and 2 μg/mL and other antibiotics (clarithromycin, metronidazole, levofloxacin) was performed on H. pylori isolates via agar dilution method. Patients treated with an amoxicillin-containing quadruple regimen (rabeprazole 10 mg twice daily + bismuth potassium citrate 220 mg twice daily + amoxicillin 1.0 g twice daily + furazolidone 100 mg twice daily or tetracycline 100 mg twice daily) were followed up. Eradication status was assessed by 13C-urea breath test 6-8 weeks post-treatment. Eradication rates were calculated using both intention-to-treat (ITT) and per-protocol (PP) analyses. χ2 test with Yates' continuity correlation and Fisher's exact tests were applied for group comparisons. Kappa statistics were used to evaluate the level of agreement between resistance classification under different MIC thresholds and clinical eradication outcomes. Prespecified stratified analyses were performed, and interaction terms were included in regression models to examine whether the association between amoxicillin MIC and eradication outcomes was consistent across treatment regimens and clinical subgroups. RESULTS:A total of 342 patients were included in the ITT analysis, and 330 patients were included in the PP analysis after excluding 14 patients due to adverse events or loss to follow-up. When the MIC breakpoint was set at 0.125 μg/mL or 0.25 μg/mL, no statistically significant difference was observed between resistant and susceptible groups in eradication rates (0.125 μg/mL: resistant ITT 88.57%, PP 90.29% vs. susceptible ITT 91.56%, PP 95.59%; 0.25 μg/mL: resistant ITT 86.89%, PP 88.33% vs. susceptible ITT 91.46%, PP 95.19%; all p > 0.05). At 0.5 μg/mL, eradication rates in resistant patients were significantly lower (ITT 77.42%, PP 80.00%) than those in susceptible patients (ITT 91.96%, PP 95.33%) (p < 0.05). At 1 μg/mL, eradication in resistant patients was 66.67% (ITT) and 72.73% (PP), significantly lower than susceptible patients (ITT 91.52%, PP 94.67%) (p < 0.05). The highest kappa coefficient (0.180) was observed at the 0.5 μg/mL threshold, indicating the strongest-albeit slight-agreement between resistance classification and treatment outcome. CONCLUSION:In patients receiving bismuth-containing quadruple therapy, an amoxicillin MIC threshold of 0.5 μg/mL appears to better reflect clinically relevant resistance than the EUCAST-defined breakpoint of 0.125 μg/mL. This threshold may serve as a more suitable candidate breakpoint for guiding empirical BQT in this region, although validation in larger, multicenter prospective studies is required.
Gastric cancer (GC) is a public health concern due to estimates indicating it ranks among the most prevalent cancers and leading causes of cancer-related deaths globally. In Latin America, a region significantly impacted by high mortality and incidence of GC, chronic H. pylori infection remains the primary cause of GC, with an overall prevalence of around 42.5% from 2015 to 2022. Asian countries have developed innovative strategies for primary and secondary prevention. Among the most notable primary and secondary screening programs were endoscopy-based screening in Japan and South Korea; a nationwide population-based H. pylori eradication program in Bhutan; mass H. pylori eradication in the Matsu Islands of Taiwan; and a recently developed family-based H. pylori eradication strategy in China. In this Opinion Review, we discuss the opportunities and pitfalls of implementing an individual-and family-screening-based H. pylori eradication strategy for GC prevention in Latin American intermediate- and high-risk areas.
