Metabolic dysfunction-associated steatotic liver disease (MASLD) is a rising global health burden linked to dyslipidemia, metabolic syndrome, and hepatic inflammation. Statins are widely prescribed in MASLD, but comparative evidence on their efficacy, safety, and cost-effectiveness remains limited. To evaluate and compare the clinical effectiveness and cost-efficiency of atorvastatin, rosuvastatin, and lovastatin–niacin fixed-dose combination [LN-FDC; commercially distributed as Linicor in Taiwan] (lovastatin plus niacin) in improving liver enzymes and lipid profiles in MASLD patients. This retrospective cohort study analyzed electronic medical records from a teaching hospital in southern Taiwan. Of 984 screened patients, 729 were included after 1:1 propensity score matching by age, sex, and baseline ALT. Patients received daily atorvastatin (20 mg), rosuvastatin (10 mg), or LN-FDC (20/500 mg) for six months. Primary outcomes were ALT and AST changes and treatment response (≥ 30

Mono-antibiotic therapy for Helicobacter pylori (H. pylori) infection minimizes unnecessary antibiotic exposure, reduces disruption of the gut microbiota, and lowers the risk of multidrug resistance. Although resistance of H. pylori to amoxicillin remains extremely low (<3%) worldwide, regular-dose amoxicillin monotherapy achieves eradication rates of less than 30%. Strategies to improve the efficacy of amoxicillin-based mono-antibiotic therapy include elevating intragastric pH with potent acid suppression, increasing the amoxicillin dose, and adding bismuth salts to the treatment regimen. This review evaluates the safety and effectiveness of six amoxicillin-based treatments for H. pylori. All regimens lasted 14 days and were studied in clinical trials published between 1 October 2014, and 1 October 2025. The pooled intention-to-treat and per-protocol eradication rates for each regimen were as follows: Regimen 1: Regular-dose amoxicillin + high-dose proton pump inhibitor (PPI): 84.7% (83/98) and 84.7% (83/98); Regimen 2: High-dose amoxicillin + high-dose PPI: 85.3% (3709/4347) and 89.9% (3692/4109); Regimen 3: Regular-dose amoxicillin + high-dose potassium-competitive acid blocker (PCAB): 86.0% (901/1048) and 91.2% (888/974); Regimen 4: High-dose amoxicillin + high-dose PCAB: 88.2% (1771/2009) and 93.5% (1720/1839); Regimen 5: Regular-dose amoxicillin + high-dose PCAB + bismuth: 84.9% (327/385) and 91.3% (327/358); Regimen 6: High-dose amoxicillin + high-dose PCAB + bismuth: 95.8% (115/120) and 98.4% (115/117). In conclusion, potent acid inhibition, escalation of amoxicillin dosage, and incorporation of bismuth can transform amoxicillin mono-antibiotic therapy from an ineffective approach into a highly effective eradication regimen for H. pylori infection.

BACKGROUND:The eradication rate of amoxicillin-vonoprazan (AV) dual therapy for Helicobacter pylori (H. pylori) infection varies by region and is below 90% in both the United States and Taiwan. We recently added bismuth to this regimen, and the resulting bismuth-amoxicillin-vonoprazan (BAV) triple therapy achieved eradication rates ≥ 95% in Taiwan. AIMS:To compare the efficacy and safety of 14-day BAV triple therapy with AV dual therapy and clarithromycin-amoxicillin-rabeprazole (CAR) standard triple therapy as first-line regimens for H. pylori eradication. METHODS:In this multicenter, randomized, open-label trial, adults with H. pylori infection were randomized (1:1:1) to receive one of the following 14-day regimens: BAV triple therapy (tripotassium dicitrato bismuthate 300 mg four times daily, amoxicillin 750 mg four times daily, and vonoprazan 20 mg twice daily), AV dual therapy (vonoprazan 20 mg twice daily and amoxicillin 750 mg four times daily), or CAR standard triple therapy (rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily). Eradication was assessed by the 13C-urea breath test. The primary endpoint was eradication in the intention-to-treat population. RESULTS:Between November 2023 and June 2025, 390 patients were enrolled. Intention-to-treat eradication rates were 93.8% with BAV therapy, 83.8% with AV therapy, and 83.1% with CAR therapy. BAV therapy was superior to both AV therapy (95% CI, 2.4%-17.6%; p = 0.010) and CAR therapy (95% CI, 3.0%-18.4%; p = 0.007). Per-protocol eradication rates were 97.5%, 88.3%, and 88.0%, respectively; BAV therapy remained superior to AP therapy (p = 0.010) and CAR therapy (p = 0.05). Overall adverse event rates (10.8%, 8.5%, and 13.8%) were comparable. Amoxicillin resistance and clarithromycin resistance were identified as risk factors for eradication failure with BAV and CAR therapies, respectively. CONCLUSIONS:BAV triple therapy demonstrates superior efficacy compared with AV dual therapy and CAR triple therapy as first-line treatment for H. pylori infection in Taiwan. This regimen represents a promising first-line option that may obviate the need for routine clarithromycin-resistance testing in regions where AV dual therapy yields suboptimal eradication rates.

OBJECTIVE:To convene a global consensus on Helicobacter pylori (H pylori) screening and eradication strategies for gastric cancer prevention, identify key knowledge gaps and outline future research directions. METHODS:32 experts from 12 countries developed and refined consensus statements on H pylori management, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess evidence and the Delphi method to achieve ≥80% agreement. RESULTS:Consensus was achieved on 28 statements. Eradication of H pylori, the primary cause of gastric cancer, reduces the risk of gastric cancer across all age groups, with the greatest risk reduction before the onset of premalignant conditions. H pylori eradication also promotes ulcer healing, prevents ulcer recurrence and reduces the risk of NSAID/aspirin related ulcers. H pylori transmission primarily occurs within families, making family based approaches promising for reducing spread and improving treatment outcomes. H pylori screening should prioritise high risk populations. 13C-urea breath test or monoclonal stool antigen tests are preferred. Validated serological testing is a feasible alternative in low prevalence settings when followed by confirmatory non-serological testing. Integrating H pylori screening into existing health programmes may optimise patient adherence and resource utilisation. Empiric eradication treatment, especially bismuth quadruple therapy, is recommended in regions with high H pylori antibiotic resistance for conventional antibiotics. Potassium competitive acid blocker based regimens are alternatives. Confirmatory testing is strongly recommended to ensure H pylori eradication. Endoscopy is suggested for H pylori infected individuals with a high risk of gastric cancer and/or alarm features. H pylori eradication does not increase the risk of reflux oesophageal adenocarcinoma. Long term disruptions to the microbiota and resistome, as well as the environmental impact of increased antibiotic use, warrant further investigation. The development of an H pylori vaccine remains an unmet need, as does the establishment of a risk stratified approach informed by advanced genetic research. CONCLUSION:H pylori eradication is an effective prevention strategy for gastric cancer that should be offered to all infected adult individuals. Future research should prioritise determining the optimal timing for screening, evaluating long term individual and population outcomes, as well as identifying more precise risk stratification parameters.

Introduction: Patients with advanced-stage or intermediate-stage hepatocellular carcinoma (HCC) unsuitable for transarterial chemoembolization (TACE) had poor prognoses. Recent advancements in hepatic arterial infusion chemotherapy (HAIC) and immune checkpoint inhibitors (ICIs) have demonstrated higher tumor response rates, which improved overall survival (OS). HAIC achieves an OS rate of approximately 14.5-15.3 months with a 39.1-42.5% tumor response rate. In comparison, ICIs have a 12-14 month OS rate with a 26-33% tumor response rate. Given these promising responses, this study evaluates the efficacy of conversion therapy with curative intent following HAIC or ICIs, focusing on survival outcomes. Methods: We retrospectively analyzed 80 patients with advanced or TACE-unsuitable intermediate HCC. Patients completed two HAIC or four ICI cycles, followed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria imaging. Based on demographics, cirrhosis status, Barcelona Clinic Liver Cancer classification (BCLC) stage, treatment responses, and treatment modality, survival impacts were analyzed. OS was compared between HAIC and immunotherapy groups. The effect of conversion therapy with curative intent on survival outcomes was analyzed using a Cox regression model. Results: Among the 80 patients, 26 achieved positive response (CR/PR) with HAIC or ICIs, and 9 of them subsequently underwent conversion therapy with curative intent. Key prognostic factors included Child-Pugh stage B versus A (HR = 2.21, p = 0.041), BCLC stage C versus B (HR = 4.38, p = 0.011), and elevated alpha-fetoprotein levels (HR = 5.02, p < 0.001). Positive responders saw substantial survival benefits (HR = 0.26, p = 0.001). Patients undergoing conversion therapy exhibited significantly enhanced survival. Median OS was 13.58 months with standard therapy, while the curative intent surgery group did not reach the median OS (p = 0.002). For CR/PR patients, 48-month survival was 75.0% for the curative surgery group versus 38.0% for standard treatment. Conclusion: Conversion therapy with curative intent following HAIC or ICIs might enhance survival in patients with advanced or TACE-unsuitable intermediate-stage HCC.

Recurrence of reflux symptoms following discontinuing proton pump inhibitor therapy is a common problem in the treatment of gastroesophageal reflux disease. We aim (1) to examine the cumulative 12-week incidence of symptom relapse following 8-week proton pump inhibitor therapy in patients with Los Angeles grade A/B erosive esophagitis and (2) to search the risk factors predicting symptom relapse in the treatment of erosive esophagitis. From June 2010 to May 2019, patients with Los Angeles Grade A/B erosive esophagitis receiving esomeprazole therapy (40 mg qd) for 8 weeks followed by complete symptom resolution were included in this study. Subjects received on-demand esomeprazole treatment for 12 weeks and underwent prospective follow-up for reflux symptoms. 12-week cumulative incidence of symptom relapse was assessed, and predictive risk factors for symptom relapse were determined by multivariate analysis. 219 patients with Los Angeles Grade A/B erosive esophagitis who achieved complete symptom resolution following 8-week esomeprazole therapy were enrolled. During the 12-week follow-up period, 110 patients (50.2%) developed symptom relapse. Univariate analysis showed that symptom relapse was significantly associated with advanced age, smoking, and the presence of heartburn (p = .003, .015, and .042, respectively). Multivariate analysis with stepwise logistic regression showed that only advanced age (95% confidence interval [CI]: 1.45-5.15) and smoking (95% CI: 1.30-6.58) were independent factors predicting symptom relapse with odds ratios of 2.74 and 2.92, respectively. The 12-week cumulative incidence of symptom relapse following initial proton pump inhibitor treatment in patients with Los Angeles grade A/B erosive esophagitis is 50.2%. Advanced age and smoking are independent risk factors predicting symptom relapse following treatment in patients with mild erosive esophagitis.

Background T cell receptor (TCR) signaling and T cell activation are tightly regulated by gatekeepers to maintain immune tolerance and avoid autoimmunity. The TRAIL receptor (TRAIL-R) is a TNF-family death receptor that transduces apoptotic signals to induce cell death. Recent studies have indicated that TRAIL-R regulates T cell-mediated immune responses by directly inhibiting T cell activation without inducing apoptosis; however, the distinct signaling pathway that regulates T cell activation remains unclear. In this study, we screened for intracellular TRAIL-R-binding proteins within T cells to explore the novel signaling pathway transduced by TRAIL-R that directly inhibits T cell activation. Methods Whole-transcriptome RNA sequencing was used to identify gene expression signatures associated with TRAIL-R signaling during T cell activation. High-throughput screening with mass spectrometry was used to identify the novel TRAIL-R binding proteins within T cells. Co-immunoprecipitation, lipid raft isolation, and confocal microscopic analyses were conducted to verify the association between TRAIL-R and the identified binding proteins within T cells. Results TRAIL engagement downregulated gene signatures in TCR signaling pathways and profoundly suppressed phosphorylation of TCR proximal tyrosine kinases without inducing cell death. The tyrosine phosphatase SHP-1 was identified as the major TRAIL-R binding protein within T cells, using high throughput mass spectrometry-based proteomics analysis. Furthermore, Lck was co-immunoprecipitated with the TRAIL-R/SHP-1 complex in the activated T cells. TRAIL engagement profoundly inhibited phosphorylation of Lck (Y394) and suppressed the recruitment of Lck into lipid rafts in the activated T cells, leading to the interruption of proximal TCR signaling and subsequent T cell activation. Conclusions TRAIL-R associates with phosphatase SHP-1 and transduces a unique and distinct immune gatekeeper signal to repress TCR signaling and T cell activation via inactivating Lck. Thus, our results define TRAIL-R as a new class of immune checkpoint receptors for restraining T cell activation, and TRAIL-R/SHP-1 axis can serve as a potential therapeutic target for immune-mediated diseases.

We read the Maastricht VI/Florence consensus report for the management of Helicobacter pylori (H. pylori) infection by Malfertheiner et al published in the Gut with great interest. The experts addressed that the goal of any antimicrobial therapy is to cure reliably H. pylori infection in the majority (eg, ≥90%) of patients. The goal of cure rate ≥90% meets the expectation of patients in the realworld expectation survey of AsiaPacific patients for H. pylori eradication therapy, which showed 91% of accepted minimal eradication rate expected by H. pyloriinfected patients. In the consensus report, clarithromycin triple therapy is recommended as firstline empirical treatment in areas of low clarithromycin resistance, and low clarithromycin resistance is defined as clarithromycin resistance rate <15%. However, a recent systemic review for randomised controlled trials published between 1 January 2011 and 1 January 2022 showed that the perprotocol eradication rates of 14day clarithromycin triple therapy for clarithromycinsusceptible strains and clarithromycinresistant H. pylori strains were 90.2% and 46.2%, respectively. The corresponding eradication rates of 7day clarithromycin triple therapy were 92.5% and 42.9%. According to efficacy prediction model, perprotocol eradication rates of 7day and 14day clarithromycin triple therapies fall below 90% when clarithromycin resistance rate is greater than 5%. In fact, all the prospective studies in that systemic review demonstrated that perprotocol eradication rates of 7day and 14day clarithromycin triple therapies fell below 90% in areas with clarithromycin resistance between 7% and 14%. 5 The data suggest that 5% of clarithromycin resistance rate is a more logical cutoff value than 15% for the application of clarithromycin triple therapy in clinical practice. Accordingly, 7day and 14day clarithromycin triple therapies are only recommended as the firstline anti-H. pylori treatment in areas with very low (<5%) clarithromycin resistance (eg, Sweden, Myanmar and Bhutan). In the consensus report, bismuth quadruple therapy is recommended as firstline empirical treatment in areas of high (>15%) clarithromycin resistance. If it is not available, nonbismuth concomitant quadruple therapy may be considered. In choosing a nonbismuth quadruple therapy, concomitant therapy (proton pump inhibitor (PPI), amoxicillin, clarithromycin and a nitroimidazole administered concurrently) should be the preferred choice given its proven reproducible effectiveness and less complexity compared with sequential and hybrid therapies. We agree with the experts’ comments that sequential and hybrid therapy are more complex than concomitant therapy. Nonetheless, reverse hybrid therapy is a simple regimen in the firstline treatment of H. pylori infection. It has a comparable eradication rate as standard hybrid therapy. Fourteenday reverse hybrid therapy achieves a higher eradication rate than 7day concomitant therapy, and has comparable eradication rate as 14day concomitant therapy. Additionally, 14day reverse hybrid therapy has fewer adverse events and is cheaper than 14day concomitant therapy. The novel therapy consists of a quadruple regimen with a PPI, amoxicillin, clarithromycin and metronidazole for 7 days followed by a dual regimen with a PPI and amoxicillin for 7 days. In fact, it is a modified 14day concomitant therapy without clarithromycin and metronidazole in the final 7 days. It is quite simple, and a recent realworld practice survey showed that 14day reverse hybrid therapy was the third most commonly used anti-H. pylori regimen in Taiwan in 2020. Therefore, reverse hybrid therapy can be a recommended empirical treatment in areas of high or unknown clarithromycin resistance.

Autoimmune disease is characterized by the proliferation of harmful immune cells, inducing tissue inflammation and ultimately causing organ damage. Current treatments often lack specificity, necessitating high doses, prolonged usage, and high recurrence rates. Therefore, the identification of innovative and safe therapeutic strategies is urgently required. Recent preclinical studies and clinical trials on inflammatory and autoimmune diseases have evidenced the immunosuppressive properties of mesenchymal stromal cells (MSCs). Studies have demonstrated that extracellular vesicles (EV) derived from MSCs can mitigate abnormal autoinflammation while maintaining safety within the diseased microenvironment. This study conducted a systematic review to elucidate the crucial role of MSC-EVs in alleviating autoimmune diseases, particularly focusing on their impact on the underlying mechanisms of autoimmune conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD). By specifically examining the regulatory functions of microRNAs (miRNAs) derived from MSC-EVs, the comprehensive study aimed to enhance the understanding related to disease mechanisms and identify potential diagnostic markers and therapeutic targets for these diseases.

Bismuth quadruple therapy is recommended as the choice treatment for Helicobacter pylori (H. pylori) infection in areas of either low or high clarithromycin resistance in the Maastricht VI/Florence Consensus Report. However, the optimal treatment duration and drug dosages of bismuth quadruple therapy remain unclear. The study aimed to search the independent risk factors predicting eradication failure of standard bismuth quadruple therapy in the first-line treatment of H. pylori infection. From July 2014 to June 2022, 274 H. pylori-infected patients who received 10-day or 14-day bismuth quadruple therapy containing a proton pump inhibitor, bismuth, tetracycline and metronidazole were included for the study. Post-treatment H. pylori status was assessed at least 4 weeks after completion of treatment. The relationships between eradication rate and 13 clinical parameters were analyzed by univariate and multivariate analyses. The eradication rates of standard bismuth quadruple therapy were 93.8% and 94.2% by intention-to-treat and per-protocol analyses, respectively. Univariate analysis revealed that patients harboring metronidazole-resistant strains had a lower eradication rate than those harboring metronidazole-susceptible strains (88.7% [55/62] vs. 96.7% [148/153]). The other factors including smoking, treatment duration and drug adherence were not significantly associated with cure rate. Multivariate analysis revealed that metronidazole resistance of H. pylori was the only independent risk factors related to eradication failure of standard bismuth quadruple therapy with an odds ratio of 3.8 (95% CI: 1.2-12.4). In conclusion, metronidazole resistance is an independent risk factor predicting eradication failure of standard bismuth quadruple therapy in the first-line treatment of H. pylori infection. There is no difference in eradication efficacy between 10-day and 14-day bismuth quadruple therapies in Taiwan.

Helicobacter pylori (H. pylori) infection is the principal cause of chronic gastritis, gastric ulcers, duodenal ulcers, and gastric cancer. In clinical practice, diagnosis of H. pylori infection by a gastroenterologists' impression of endoscopic images is inaccurate and cannot be used for the management of gastrointestinal diseases. The aim of this study was to develop an artificial intelligence classification system for the diagnosis of H. pylori infection by pre-processing endoscopic images and machine learning methods. Endoscopic images of the gastric body and antrum from 302 patients receiving endoscopy with confirmation of H. pylori status by a rapid urease test at An Nan Hospital were obtained for the derivation and validation of an artificial intelligence classification system. The H. pylori status was interpreted as positive or negative by Convolutional Neural Network (CNN) and Concurrent Spatial and Channel Squeeze and Excitation (scSE) network, combined with different classification models for deep learning of gastric images. The comprehensive assessment for H. pylori status by scSE-CatBoost classification models for both body and antrum images from same patients achieved an accuracy of 0.90, sensitivity of 1.00, specificity of 0.81, positive predictive value of 0.82, negative predicted value of 1.00, and area under the curve of 0.88. The data suggest that an artificial intelligence classification model using scSE-CatBoost deep learning for gastric endoscopic images can distinguish H. pylori status with good performance and is useful for the survey or diagnosis of H. pylori infection in clinical practice.

A standard bismuth quadruple therapy, a fluoroquinolone-containing triple (or quadruple) therapy or a proton pump inhibitor (PPI)-amoxicillin high-dose dual therapy has been recommended as a second-line treatment for Helicobacter pylori infection by the Maastricht VI/Florence Consensus Report. The major shortcoming of levofloxacin-amoxicillin triple therapy is low cure rate for eradicating levofloxacin-resistant strains. With the rising prevalence of levofloxacin-resistant strains, levofloxacin-amoxicillin triple therapy cannot reliably achieve a high eradication rate for second-line treatment of H. pylori infection in most countries now. The present article aims to review current second-line eradication regimens with a per-protocol eradication rate exceeding 85% in most geographic areas. Recently, a novel tetracycline-levofloxacin quadruple therapy consisting of a PPI, bismuth, tetracycline, and levofloxacin for rescue treatment of H. pylori infection has been developed. The new therapy achieved a higher per-protocol eradication rate than levofloxacin-amoxicillin triple treatment in a randomized controlled trial (98% versus 69%). Additionally, the tetracycline-levofloxacin quadruple therapy also exhibits a higher eradication rate than amoxicillin-levofloxacin quadruple therapy. High-dose dual PPI-amoxicillin therapy is another novel second-line treatment for H. pylori infection. The new therapy can achieve an eradication rate of 89% by per-protocol analysis for the second-line treatment in Taiwan. Recently, levofloxacin-based sequential quadruple therapy and potassium-competitive acid blocker have also been applied in the second-line treatment of H. pylori infection. A meta-analysis revealed that a vonoprazan-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. In conclusion, the eradication rate of levofloxacin-amoxicillin triple therapy is suboptimal in the second-line treatment of H. pylori infection now. Currently, a standard bismuth quadruple therapy (tetracycline-metronidazole quadruple therapy), a tetracycline-levofloxacin quadruple therapy, an amoxicillin-levofloxacin quadruple therapy, a levofloxacin-based sequential quadruple therapy or a high-dose PPI-amoxicillin dual therapy is recommended for the second-line treatment of H. pylori infection.

A standard bismuth quadruple therapy, a fluoroquinolone-containing triple (or quadruple) therapy or a proton pump inhibitor (PPI)-amoxicillin high-dose dual therapy has been recommended as a second-line treatment for Helicobacter pylori infection by the Maastricht VI/Florence Consensus Report. The major shortcoming of levofloxacin-amoxicillin triple therapy is low cure rate for eradicating levofloxacin-resistant strains. With the rising prevalence of levofloxacin-resistant strains, levofloxacin-amoxicillin triple therapy cannot reliably achieve a high eradication rate for second-line treatment of H. pylori infection in most countries now. The present article aims to review current second-line eradication regimens with a per-protocol eradication rate exceeding 85% in most geographic areas. Recently, a novel tetracycline-levofloxacin quadruple therapy consisting of a PPI, bismuth, tetracycline, and levofloxacin for rescue treatment of H. pylori infection has been developed. The new therapy achieved a higher per-protocol eradication rate than levofloxacin-amoxicillin triple treatment in a randomized controlled trial (98% versus 69%). Additionally, the tetracycline-levofloxacin quadruple therapy also exhibits a higher eradication rate than amoxicillin-levofloxacin quadruple therapy. High-dose dual PPI-amoxicillin therapy is another novel second-line treatment for H. pylori infection. The new therapy can achieve an eradication rate of 89% by per-protocol analysis for the second-line treatment in Taiwan. Recently, levofloxacin-based sequential quadruple therapy and potassium-competitive acid blocker have also been applied in the second-line treatment of H. pylori infection. A meta-analysis revealed that a vonoprazan-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. In conclusion, the eradication rate of levofloxacin-amoxicillin triple therapy is suboptimal in the second-line treatment of H. pylori infection now. Currently, a standard bismuth quadruple therapy (tetracycline-metronidazole quadruple therapy), a tetracycline-levofloxacin quadruple therapy, an amoxicillin-levofloxacin quadruple therapy, a levofloxacin-based sequential quadruple therapy or a high-dose PPI-amoxicillin dual therapy is recommended for the second-line treatment of H. pylori infection.

INTRODUCTION:The study aimed to compare the efficacies and safety of 14-day hybrid therapy, 14-day high-dose dual therapy, and 10-day bismuth quadruple therapy in the first-line treatment of Helicobacter pylori infections. METHODS:In this multicenter, open-label, randomized trial, we recruited adult H. pylori -infected patients from 9 centers in Taiwan. Subjects were randomly assigned (1:1:1) to 14-day hybrid therapy, 14-day high-dose dual therapy, or 10-day bismuth quadruple therapy. Eradication status was determined by the 13 C-urea breath test. The primary outcome was the eradication rate of H. pylori assessed in the intention-to-treat population. RESULTS:Between August 1, 2018, and December 2021, 918 patients were randomly assigned in this study. The intention-to-treat eradication rates were 91.5% (280/306; 95% confidence interval [CI] 88.4%-94.6%) for 14-day hybrid therapy, 83.3% (255/306; 95% CI 87.8%-95.0%) for 14-day high-dose dual therapy, and 90.2% (276/306; 95% CI 87.8%-95.0%) for 10-day bismuth quadruple therapy. Both hybrid therapy (difference 8.2%; 95% CI 4.5%-11.9%; P = 0.002) and bismuth quadruple therapy (difference 6.9%; 95% CI 1.6%-12.2%; P = 0.012) were superior to high-dose dual therapy and were similar to one another. The frequency of adverse events was 27% (81/303) with 14-day hybrid therapy, 13% (40/305) with 14-day high-dose dual therapy, and 32% (96/303) with 10-day bismuth quadruple therapy. Patients receiving high-dose dual therapy had the fewest adverse events (both P < 0.001). DISCUSSION:Fourteen-day hybrid therapy and 10-day bismuth quadruple therapy are more effective than 14-day high-dose dual therapy in the first-line treatment of H. pylori infection in Taiwan. However, high-dose dual therapy has fewer adverse effects than hybrid bismuth quadruple therapies.