Artificial intelligence (AI) for gastrointestinal endoscopy has shown remarkable performance in detecting and characterizing lesions. A randomized controlled trial reported that AI significantly reduced the miss rates for gastric neoplasms, but real-world implementation studies have shown inconsistent results. This discrepancy cannot be explained solely by technical limitations. Regardless of the AI capabilities, the visualization quality and systematic inspection remain fundamental prerequisites, and traditional apprenticeship training cannot be replaced by technology. This review examines AI implementation in endoscopy from a human-AI interaction perspective. Two cognitive phenomena are relevant: 'automation neglect,' where experienced endoscopists dismiss AI recommendations due to overconfidence or distrust, and 'automation bias,' where users over-rely on AI outputs, potentially missing unhighlighted lesions. Recent evidence raises concerns regarding deskilling, with studies showing decreased diagnostic performance after exposure to AI. A systematic analysis of 52 human-AI teaming studies showed that none achieved ideal complementarity, and collaboration sometimes decreased accuracy compared to humans alone. AI effectiveness varies according to operator expertise. High-performing endoscopists gain minimal benefit, while those with intermediate experience show the greatest improvement. Nevertheless, excessive false-positive alerts can negate benefits. Strategies to address these challenges include explainable AI, human-centered design, structured education, trust calibration, and expertise-tailored AI systems. Maintaining human expertise remains paramount. AI is a powerful tool, but clinicians must remain the final decision maker. Periodic AI-free practice may be necessary to preserve clinical competence.

Background:AI adoption in health care has accelerated rapidly, with ambient documentation tools, diagnostic imaging AI, and clinical decision support systems (CDSSs) entering routine practice. However, the cognitive demands placed on clinicians supervising these systems remain understudied. Specifically, the concept of verification burden requires closer examination. Consequently, institutional decision-makers lack a structured, certainty-graded evidence base regarding the true impact of AI on clinician workload and burnout. Objective:This study aimed to systematically review evidence on cognitive workload and burnout in health care professionals that use AI-powered clinical tools, quantify pooled effects under a conservative inferential framework, and assess certainty of evidence by AI category. Methods:The study was registered in PROSPERO (CRD420261284298) and reported per PRISMA 2020 and PRISMA-S guidelines. We searched MEDLINE, Embase, Web of Science, and Cochrane CENTRAL (January 2015-2026) for studies measuring cognitive workload or burnout using validated instruments (NASA Task Load Index [NASA-TLX] and Professional Fulfillment Index [PFI]) among health care professionals using clinical AI. Risk of bias was assessed using ROB 2.0 and ROBINS-I; certainty was rated using GRADE. Meta-analyses applied Hartung-Knapp-Sidik-Jonkman adjustment with restricted maximum likelihood estimation, incorporating prediction intervals (PIs). Results:We included 21 studies representing 2885 health care professionals across 7 countries. The synthesis demonstrated that the cognitive impact of clinical AI varies according to its specific application. Pooled analyses of ambient AI documentation showed statistically significant reductions in NASA-TLX temporal demand (SMD -1.46, 95% CI -2.81 to -0.11; k=2; I2=31.1%) and effort (SMD -1.29, 95% CI -2.16 to -0.42; k=2; I2=0%), PFI work exhaustion (MD -0.35, 95% CI -0.58 to -0.12; k=3; I2=0%; 95% PI -1.03 to 0.33), and burnout prevalence (OR 0.47, 95% CI 0.25-0.86; k=3; I2=0%; 95% PI 0.06-3.82). Two pools favored ambient AI but did not reach significance at k=2: NASA-TLX mental demand (SMD -1.29, 95% CI -3.64 to 1.07) and documentation time (SMD -0.24, 95% CI -1.10 to 0.61). Diagnostic imaging AI and CDSS showed mixed or paradoxically increased workload. GRADE certainty was moderate for cognitive workload reduction with ambient AI, low for burnout reduction with ambient AI, and very low for imaging AI and CDSS outcomes. Conclusions:This review combines validated workload instruments, meta-analysis, and PIs in health care AI, delivering a GRADE certainty assessment across 5 AI categories that prior accuracy- or efficiency-focused reviews have not provided. Ambient AI documentation was associated with reduced cognitive workload and burnout, but only in voluntary early-adopter cohorts and based on few studies; the conservative CIs were wide and, where estimable, PIs crossed the null. Findings inform institutional pilots with prospective workload measurement, regulatory human-factors evaluation of AI medical devices, and human-centered AI design. Net benefit on the health care workforce remains an open empirical question.

Background/Aims:Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes and obesity. Gastrointestinal adverse events are common; however, the association with gastroesophageal reflux disease (GERD) has not been validated across diverse populations. We aimed to assess GERD signals associated with GLP-1 RAs using disproportionality analysis across three national adverse event reporting systems. Methods:We analyzed FAERS, JADER, and Canada Vigilance. GLP-1 RAs were compared against dipeptidyl peptidase-4 inhibitors as active comparators. GERD was identified using MedDRA preferred terms. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by drug, age, and sex. Results:Among 260,417 GLP-1 RA reports, significant GERD signals were detected across all databases: FAERS (ROR, 2.83; 95% CI, 2.39 to 3.35; 9,245 vs 139), JADER (4.76; 95% CI, 2.45 to 9.27; 19 vs 16), and Canada Vigilance (2.91; 95% CI, 1.97 to 4.31; 206 vs 29). All signals met both ROR and proportional reporting ratio detection criteria. Drug-specific analyses revealed the strongest signals for semaglutide across all databases (3.44 to 6.93), followed by liraglutide (2.36 to 5.90), tirzepatide (2.76 to 5.77), and dulaglutide (2.35 to 3.32). Exenatide showed an inverse association in FAERS (ROR, 0.60; 95% CI, 0.46 to 0.77). Age-stratified analysis demonstrated increasing signal strength with age (≥65 years: ROR, 3.01; p-trend=0.028). Sensitivity analysis confirmed consistent signal directions. Conclusions:This first multi-database pharmacovigilance analysis confirms consistent GERD signals for GLP-1 RAs across Western and Asian populations, demonstrating approximately 2- to 5-fold higher reporting. Clinicians need to monitor for reflux symptoms during GLP-1 RA therapy, particularly in elderly patients.

BACKGROUND:Clostridioides difficile infection (CDI) remains a significant public health challenge, with variable diagnostic and treatment practices. This study evaluated current clinical practices for CDI diagnosis and management in Korean physicians through a nationwide survey. METHODS:An online survey was conducted among physicians treating CDI, including gastroenterologists and infectious disease specialists. The survey covered diagnostic approaches, treatment regimens, and management strategies, including differentiation based on disease severity and recurrence. RESULTS:A total of 300 physicians responded. The most commonly reported indication for CDI testing was the occurrence of three or more diarrheal episodes within a 24-hour period. The majority of physicians (69.7%) preferred multiple diagnostic tests, favoring simultaneous testing (90.4%) over a stepwise approach. Preferred tests included nucleic acid amplification test (NAAT) (69%), glutamate dehydrogenase+toxin A/B combined assay (56%) and toxin enzyme immunoassay (EIA) (48%). Single-test users preferred toxin EIA (37.4%) and NAAT (29.7%). Treatment was primarily tailored to severity by 84.1% of physicians. For non-severe CDI, oral vancomycin (50.7%) and metronidazole (29%) were the main treatments, with 88% not recommending hospitalization. Severe CDI was treated with oral vancomycin (45.3%) or intravenous metronidazole in combination (44.9%), often for ≥ 14 days. For the first recurrence, 69.3% used oral vancomycin, with 22.6% opting for a tapered/pulsed regimen. Fecal microbiota transplantation use increased from 0.3% initially to 17.6% for multiple recurrences. In CDI with ileus, 64% preferred combination therapy, and 48% used vancomycin enemas. In inflammatory bowel disease patients, 99% underwent CDI testing for worsening diarrhea. Immunomodulators and biologics were continued in 79% and 73% of non-severe cases, respectively, but often paused during severe CDI. CONCLUSION:Korean physicians generally follow the recently developed Korean guideline for CDI practice, but certain gaps and inconsistencies in choices were observed in clinical situations. Further efforts are needed to monitor guideline implementation and to analyze gaps between guideline recommendations and real-world clinical practice to optimize CDI management in Korea.

Artificial intelligence (AI) has emerged as a transformative tool in gastrointestinal (GI) endoscopy, addressing challenges in detection, diagnosis, and decision-making. In upper GI endoscopy, AI supports blind spot monitoring, Helicobacter pylori diagnosis, and the identification of premalignant and malignant lesions, with high accuracy and reduced miss rates. In lower GI endoscopy, computer-aided detection improves adenoma detection, whereas computer-aided diagnosis supports "resect-and-discard" and "diagnose-and-leave" strategies. However, real-world benefits remain modest, with concerns regarding overdetection and variable performance across lesion types and colon segments. In inflammatory bowel disease, AI standardizes endoscopic and histologic scoring, reduces interobserver variability, and accelerates capsule endoscopy interpretation, including high diagnostic accuracy for Crohn's disease. Pancreatobiliary applications, including endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, and cholangioscopy, demonstrate strong performance in differentiating pancreatic masses and biliary strictures and in predicting postprocedural complications. Despite expert-level performance across multiple domains, most studies remain single-center or retrospective, and explainability, workflow integration, medicolegal responsibility, and cost-effectiveness continue to limit adoption. Emerging solutions, including explainable AI and AI-generated common data model-compatible reports, may bridge these gaps. With rigorous multicenter validation and real-world implementation, AI can evolve from an experimental adjunct into a core component of routine endoscopic practice.

Background: Large Language Models (LLMs) are reshaping medical research workflows. Objective: This narrative review synthesizes evidence on LLM applications across systematic reviews, scientific writing, and clinical research. Methods: We reviewed literature from 2023-2025 examining LLM applications in medical research, identified through PubMed, Scopus, Web of Science, arXiv, medRxiv, and Google Scholar. Studies reporting empirical findings, methodological evaluations, or systematic analyses of LLM applications were included; editorials and commentaries without empirical data were excluded. Results: In systematic reviews, LLMs achieve 80-94% data extraction accuracy and 40% reduction in screening workload, but show only slight-to-moderate agreement (κ = 0.16-0.43) in risk-of-bias assessment. In scientific writing, hallucination rates of 47-55% for fabricated references and over 90% prevalence of demographic bias require rigorous verification. For clinical research, LLMs assist with statistical coding and protocol development but require human validation. Critically, excessive reliance on automated tools may cause cognitive offloading that compromises analytical capabilities. Conclusions: LLMs are powerful but unstable tools requiring constant verification. Success depends on maintaining human-in-the-loop approaches that preserve critical thinking while leveraging AI efficiency.

Since the 2020 Korean guidelines for Helicobacter pylori treatment, clarithromycin resistance rates have risen from 17.8% to 33.3%, dual-priming oligonucleotide-based polymerase chain reaction-guided tailored therapy has been adopted, and potassium-competitive acid blockers (P-CABs) have become available. This fourth revision addressed these changes. Nine key questions were addressed through systematic review and meta-analysis. Thirteen recommendations were evaluated using a modified Delphi process involving 64 experts. Twelve recommendations achieved a first-round consensus; one required revision and achieved 73.9% agreement. Key changes included: 1) a dual-pillar strategy of tailored therapy and empirical quadruple therapy; 2) restricted use of empirical clarithromycin-based triple therapy under specific conditions; 3) removal of sequential therapy; 4) use of P-CABs as alternatives to proton pump inhibitors; 5) expansion of eradication indications to include gastric cancer prevention in H. pylori gastritis and regression of hyperplastic polyps ≤10 mm; and 6) positioning of bismuth quadruple therapy as a conditionally recommended first-line empirical option, with preference for reservation as salvage therapy, and introduction of modified bismuth quadruple therapy (addition of bismuth to conventional regimens) as an additional first-line empirical option. The revised guidelines provide updated evidence-based recommendations for the diagnosis and treatment of H. pylori infection, reflecting the rapidly changing antibiotic resistance landscape and the introduction of new diagnostic and therapeutic tools in Korea. These guidelines aim to assist clinicians, patients, policymakers, and medical educators in optimizing H. pylori management. They may differ from the current medical insurance standards and will be further revised based on emerging evidence.

INTRODUCTION:REBYOTA and VOWST are the first FDA-approved live biotherapeutic products for recurrent Clostridioides difficile infection (CDI). Previous FDA safety alerts (2019-2020) regarding invasive infections from investigational fecal microbiota transplantation underscore the need for postmarketing surveillance of these novel products. The aims of this study were to characterize the real-world safety profiles of REBYOTA and VOWST using the FDA Adverse Event Reporting System and compare them against established CDI therapeutics. METHODS:We performed a disproportionality analysis of FDA Adverse Event Reporting System data (Q1; 2020-Q4; 2025). REBYOTA and VOWST were identified as primary suspect drugs using Biologics License Application numbers and drug name matching. Comparators included fidaxomicin, bezlotoxumab, and vancomycin (CDI-filtered). Four methods were applied: reporting odds ratio (ROR), proportional reporting ratio, information component, and empirical Bayes geometric mean. Signals required ≥2 methods agreement. RESULTS:We identified 231 REBYOTA and 813 VOWST primary suspect reports, yielding 18 and 54 disproportionality signals, respectively. Both products' signals were consistent with known gastrointestinal adverse events. No signals were detected for bacteremia, septic shock, or anaphylaxis. Death was reported at lower-than-expected frequency for VOWST (ROR 0.29; 95% confidence interval 0.15-0.53). A VOWST-specific urinary tract infection (UTI) cluster (Klebsiella UTI ROR 405.73; Pseudomonal UTI ROR 168.54) was identified; head-to-head comparison showed no significant UTI difference vs REBYOTA (ROR 1.39, not significant), suggesting stimulated reporting bias rather than a biological signal. Route-dependent adverse event profiles differed between oral VOWST and rectal REBYOTA. DISCUSSION:FDA-approved live biotherapeutic products demonstrate reassuring postmarketing safety profiles without transmitted infection signals. The extreme VOWST UTI signal is likely attributable to FDA-mandated expedited reporting obligations rather than a causal drug effect.

Background/Aims:Peptic ulcer disease (PUD) exhibits sex-based differences in epidemiology and treatment that shift across the lifespan; however, there are no sex-specific recommendations in the current guidelines. For this scoping review, sex and gender differences in PUD were mapped to inform guideline development. Methods:Following the PRISMA-ScR guidelines, we searched PubMed, Embase, the Cochrane Library, and KoreaMed through October 2025. Two reviewers independently screened articles and extracted data on epidemiology, hormonal factors, treatment responses, and outcomes. Results:Of the 940 identified records (895 from databases and 45 from manual searching), 68 studies met the inclusion criteria. Key findings were organized into three thematic domains-Epidemiology: the male-to-female PUD ratio has narrowed from 2:1 to near parity, with elderly females (≥70 years) demonstrating elevated bleeding and mortality risk, particularly with concurrent nonsteroidal anti-inflammatory drug or aspirin use; Hormonal factors: both natural and surgical menopause were consistently associated with increased PUD risk, with a stronger association for surgical menopause. Postmenopausal females had higher perforation and mortality rates; and Treatment response and pharmacology: females experienced twice as many adverse events during Helicobacter pylori therapy despite similar eradication rates and had higher H. pylori recurrence rates. Females showed approximately 30% higher plasma proton pump inhibitor (PPI) concentrations, suggesting pharmacokinetic differences. An exploratory quantitative synthesis suggested a sex-specific benefit of PPI gastroprotection in anticoagulated females, requiring confirmation. Conclusions:Substantial sex-based differences in PUD epidemiology, hormonal factors, and treatment response remain unaddressed in current guidelines. In the future, those developing guidelines should consider incorporating postmenopausal status into risk stratification, gastroprotection measures for elderly females on antithrombotic therapy, and sex-specific pharmacokinetic differences in PPI dosing.

Background: Mirikizumab, a first-in-class interleukin-23p19 antagonist, was approved for ulcerative colitis (2023) and Crohn’s disease (2025). The US Food and Drug Administration (FDA) identified a hepatotoxicity signal during pre-approval review, mandating post-marketing surveillance. No independent pharmacovigilance analysis has been published. Aims: To characterise the post-marketing safety profile of mirikizumab using multi-database pharmacovigilance, with a focus on hepatotoxicity and IL-23 inhibitor class comparison. Methods: Disproportionality analysis of the FDA Adverse Event Reporting System (FAERS; Q4 2023–Q4 2025) and Japanese Adverse Drug Event Report database (JADER) was performed using four algorithms (reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, empirical Bayesian geometric mean). Signals of disproportionate reporting were defined by concordance of all four methods. Active comparator analysis against risankizumab, guselkumab and ustekinumab, Weibull time-to-onset modelling and hepatotoxicity case characterisation were conducted. Reporting followed READUS-PV guidelines. Results: We identified 564 mirikizumab reports in FAERS and 123 in JADER. Nine signals met all four criteria in FAERS, including spontaneous abortion (Reporting odds ratio (ROR) 10.16, 95% CI 5.16–20.02), pulmonary embolism (ROR 5.56, 2.93–10.56) and injection site reactions. Hepatotoxicity showed no disproportionate reporting in either FAERS (ROR 1.19, 0.74–1.92; n = 17) or JADER (ROR 0.24, 0.05–1.19; n = 1). Comparator analysis identified cytomegalovirus infection and interstitial lung disease as mirikizumab-specific versus the IL-23 class. Weibull analysis (β = 0.65) indicated early-onset adverse event clustering. Discussion: This first multi-database pharmacovigilance study of mirikizumab did not confirm the FDA-flagged hepatotoxicity signal. Potential signals warranting further investigation include thromboembolic events and pulmonary toxicity.

The efficacy of clarithromycin-containing triple therapy (TT) against Helicobacter pylori has declined in Korea, with recent first-line eradication rates falling below 70%. Clarithromycin resistance exceeded 30%, undermining the standard regimen for H. pylori. These trends necessitate a change in the treatment strategy. This review analyzed the shift proposed in the draft of the 2025 Korean H. pylori guidelines. We examined the rationale for abandoning TT as a first-line empirical therapy and the establishment of a new dual-pillar strategy: 1) the declining role of clarithromycin-containing TT as a first-line treatment and 2) polymerase chain reaction (PCR)-based tailored therapy as the recommended precision approach. We explored the 1) emergence of new empirical regimen options, 2) application of tailored therapy, and 3) adoption of potassium-competitive acid blockers (P-CABs). Empirical regimens have shifted toward four-drug combinations to achieve higher cure rates. Concomitant therapy (proton-pump inhibitor [PPI] or P-CAB+amoxicillin+clarithromycin+metronidazole) offers high efficacy but raises concerns about antibiotic overuse. As a compromise, bismuth-augmented triple regimens (adding bismuth to TT) are now recommended; these modified quadruple therapies (e.g., PACB: PPI+amoxicillin+clarithromycin+bismuth, or PAMB: PPI+amoxicillin+metronidazole+bismuth) significantly improve eradication rates without requiring a third antibiotic class. Regarding tailored therapy, PCR-based domestic clinical research data consistently achieves ≥90% cure rates in first-line treatment-markedly higher than empirical TT in Korea. Economic analyses supported the cost-effectiveness of this approach. The guideline algorithm for salvage therapy was clarified. Bismuth quadruple therapy has been confirmed as the standard second-line treatment. For third-line therapy, we analyzed the efficacy of levofloxacin-based regimens, rifabutin-based therapy, and bismuth add-on therapy with two previously unused antibiotics. The 2025 Korean guidelines establish quadruple therapies as the new standard through a dual strategy: pragmatic empirical treatment and PCR-guided tailored therapy, with P-CABs and bismuth-based regimens as key components.

The management of peptic ulcer disease (PUD) in patients receiving antithrombotic therapy requires balancing bleeding and thrombotic risk. The shift from Helicobacter pylori-dominant to drug-induced PUD combined with increasing antithrombotic use has created a new high-risk population that demands particular attention. In this review, we synthesize the current evidence from Korean and international guidelines, focusing on practical management strategies for the acute treatment and long-term prevention of PUD. Key recommendations include individualized risk assessment of bleeding and thrombotic risks, timely resumption of antithrombotic agents following successful hemostasis, and mandatory proton pump inhibitor co-therapy for high-risk patients. Multidisciplinary collaboration and evidence-based approaches are necessary to optimize patient outcomes while minimizing gastrointestinal and cardiovascular complications.

BACKGROUND:Helicobacter pylori infection is epidemiologically linked to Parkinson's disease (PD), though findings remain inconsistent. This study aimed to determine whether patients with PD have a higher prevalence of H. pylori infection than controls through an updated systematic review and meta-analysis and to explore heterogeneity through subgroup analyses. METHODS:A comprehensive literature search of relevant studies published till October 2024 was performed using PubMed, EMBASE and Cochrane Library databases. Studies examining the prevalence of H. pylori infection in patients with PD were included. Pooled odds ratios (OR) with 95% confidence intervals (CI) and pooled prevalence rates were calculated. Subgroup analyses were conducted based on geographical region, H. pylori detection methods and exclusion of individuals with prior eradication therapy. Sensitivity analyses and publication bias assessments were also performed. RESULTS:Twenty-three studies involving 7205 patients with PD and 41,937 controls were included in meta-analysis. Among studies reporting prevalence, the pooled prevalence of H. pylori infection in patients with PD was 39.0% (95% CI 26.5%-53.1%). In 13 studies comparing the prevalence of H. pylori infection between patients with PD and controls, H. pylori infection was found to be associated with PD (OR 1.328, 95% CI 1.165-1.514). Subgroup analyses showed consistent results and sensitivity analyses confirmed the robustness of the findings. Furthermore, no publication bias was observed. CONCLUSIONS:Patients with PD exhibit a higher prevalence of H. pylori infection than controls. These findings support a potential role of H. pylori infection in PD pathogenesis, although causality cannot be established.

The efficacy of clarithromycin-containing triple therapy (TT) against Helicobacter pylori has declined in Korea, with recent first-line eradication rates falling below 70%. Clarithromycin resistance exceeded 30%, undermining the standard regimen for H. pylori. These trends necessitate a change in the treatment strategy. This review analyzed the shift proposed in the draft of the 2025 Korean H. pylori guidelines. We examined the rationale for abandoning TT as a first-line empirical therapy and the establishment of a new dual-pillar strategy: 1) the declining role of clarithromycin-containing TT as a first-line treatment and 2) polymerase chain reaction (PCR)-based tailored therapy as the recommended precision approach. We explored the 1) emergence of new empirical regimen options, 2) application of tailored therapy, and 3) adoption of potassium-competitive acid blockers (P-CABs). Empirical regimens have shifted toward four-drug combinations to achieve higher cure rates. Concomitant therapy (proton-pump inhibitor [PPI] or P-CAB+amoxicillin+clarithromycin+metronidazole) offers high efficacy but raises concerns about antibiotic overuse. As a compromise, bismuth-augmented triple regimens (adding bismuth to TT) are now recommended; these modified quadruple therapies (e.g., PACB: PPI+amoxicillin+clarithromycin+bismuth, or PAMB: PPI+amoxicillin+metronidazole+bismuth) significantly improve eradication rates without requiring a third antibiotic class. Regarding tailored therapy, PCR-based domestic clinical research data consistently achieves ≥90% cure rates in first-line treatment—markedly higher than empirical TT in Korea. Economic analyses supported the cost-effectiveness of this approach. The guideline algorithm for salvage therapy was clarified. Bismuth quadruple therapy has been confirmed as the standard second-line treatment. For third-line therapy, we analyzed the efficacy of levofloxacin-based regimens, rifabutin-based therapy, and bismuth add-on therapy with two previously unused antibiotics. The 2025 Korean guidelines establish quadruple therapies as the new standard through a dual strategy: pragmatic empirical treatment and PCR-guided tailored therapy, with P-CABs and bismuth-based regimens as key components.

Subepithelial lesions (SELs) of the upper gastrointestinal tract are commonly detected during endoscopic examinations and encompass a broad spectrum of benign and potentially malignant tumors. Although most SELs are asymptomatic and found incidentally, accurate diagnosis remains challenging owing to their subepithelial location, necessitating advanced imaging and tissue acquisition techniques. Endoscopic ultrasonography plays a crucial role in differentiating SELs, although its diagnostic accuracy remains limited. The Korean College of Helicobacter and Upper Gastrointestinal Research has developed evidence-based practice guidelines for the diagnosis and endoscopic treatment of SELs to address the need for standardized clinical management. These guidelines were established through a systematic review of existing literature and expert consensus, resulting in 11 key recommendations for addressing diagnostic strategies, surveillance intervals, biopsy techniques, and indications for endoscopic or surgical resection.

Background & Aims: Vonoprazan consistently demonstrates superior H. pylori eradication (HPE) rates compared to other P-CABs, yet the pharmacological basis for this heterogeneity remains unclear. We hypothesized that acid dissociation constant (pKa)—which determines acid stability and parietal cell accumulation—may explain differential efficacy among individual P-CABs. This study aims to examine whether pKa values predict clinical efficacy of P-CABs for HPE and erosive esophagitis (EE) healing. Methods: SR and network meta-analysis was conducted. RCTs comparing P-CABs with PPIs were identified from core databases (~January 2026). Risk of bias was assessed using RoB 2.0 and certainty of evidence using GRADE. Results: Thirty RCTs (7639 patients) were included for HPE. High-pKa P-CABs (vonoprazan 9.06, keverprazan 9.12) achieved 82–84% eradication in clarithromycin-resistant infections versus 32-40% with PPIs, while low-pKa P-CAB achieved only 47.8% (NS vs PPI). For EE (10 RCTs; 4,196 patients), high-pKa zastaprazan (9.95) achieved 100% LA Grade C/D healing versus 83.3% with esomeprazole, whereas low-pKa P-CABs showed inferior outcomes. Spearman correlation analysis revealed a positive association between pKa and efficacy (ρ=0.80). However, fexuprazan (pKa 9.04) showed PPI-equivalent outcomes despite high pKa, highlighting pKa as necessary but not sufficient for clinical efficacy. Network ranking confirmed high-pKa P-CABs as top-ranked agents. No publication bias was detected. Conclusion: P-CAB efficacy may not be uniform across the class. High-pKa P-CABs (≥9.0) were associated with higher eradication rates in clarithromycin-resistant infections and superior healing in severe esophagitis, whereas low-pKa P-CABs showed limited advantages over PPIs. pKa may serve as a hypothesis-generating pharmacological parameter, though all P-CAB comparisons were indirect and prospective validation is needed.