Alimentary Pharmacology & Therapeutics最新文献

{"title":"Meta‐Analysis: The Placebo Response in Modern Treatments for Cholestatic Pruritus: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials","authors":"Igor Boechat Silveira, Leonardo Corrêa Süffert, Gustavo André Pedral Diniz Leite, Milena Ramos Tomé, Sarah Quick Lourenço de Lima, Gabriel André Pedral Diniz Leite, Bernardo de Faria Moraes, Pedro Robson Costa Passos, Guilherme Grossi Lopes Cançado","doi":"10.1111/apt.70915","DOIUrl":"https://doi.org/10.1111/apt.70915","url":null,"abstract":"Background/Aims Cholestatic pruritus is a debilitating symptom with substantial placebo responses. We aimed to quantify this response and identify trial‐level moderators in randomized controlled trials of contemporary therapies. Methods We performed a systematic review and meta‐analysis of placebo‐controlled trials evaluating ileal bile acid transporter inhibitors or PPAR agonists (searched through March 2026, with a supplementary search on 11 July 2026). Primary outcomes included the standardized mean change (SMC) of pruritus intensity, placebo response rate and mean difference (MD) in Numerical Rating Scale (NRS) and Worst–Itch NRS (WI‐NRS) scores. Secondary outcomes included PBC‐40 and 5‐D Itch scores. We used random‐effects models with Hartung–Knapp adjustment and meta‐regression. Results Thirteen trials ( <jats:italic>n</jats:italic> = 548) were analysed. Across placebo groups, pruritus intensity decreased significantly from baseline during follow‐up periods of up to 52 weeks. The pooled SMC was −0.49 (95% CI, −0.72 to −0.27) overall, and −0.57 (95% CI, −0.81 to −0.33) for moderate‐to‐severe pruritus. Pooled response rates were 30.0% (overall) and 27.4% (moderate‐to‐severe). In moderate‐to‐severe patients, NRS showed a significant mean reduction of −1.62, whereas the WI‐NRS change (−0.65) was not statistically significant. Significant reductions occurred in the PBC‐40 itch domain (−2.02) and overall score (−9.13), while 5‐D Itch changes were non‐significant. None of the evaluated moderators were statistically significant. Conclusions The magnitude of placebo‐associated improvement differed across outcome instruments and may affect estimates and interpretation of treatment effects in cholestatic‐pruritus trials. These findings may inform endpoint selection and assumptions used in future trial design. Trial Registration PROSPERO registration number: CRD420261385974","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"10 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149033060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Sparse Mortality Events and the Apparent OS Benefit of TDF After HCC Resection","authors":"Nobuyuki Toshikuni","doi":"10.1111/apt.70879","DOIUrl":"10.1111/apt.70879","url":null,"abstract":"&lt;p&gt;I read with interest the study by Jeong et al., which compared entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) after curative resection of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) [&lt;span&gt;1&lt;/span&gt;]. Although recurrence-free survival (RFS) was comparable among the regimens, TDF was independently associated with better overall survival (OS) than ETV in the multivariable Cox model (adjusted hazard ratio [aHR], 0.48; 95% confidence interval [CI], 0.26–0.89). This unexpected OS–RFS discordance is clinically intriguing, but the limited number of mortality events warrants cautious interpretation.&lt;/p&gt;&lt;p&gt;Although the cohort included 902 patients, only 54 deaths occurred. The primary OS model estimated seven coefficients, including two antiviral-regimen indicators, while the TAF group contributed only one death. The precision and stability of Cox regression estimates are driven principally by the number of events rather than the total cohort size. Although rigid events-per-variable thresholds are not universally appropriate, sparse events can increase coefficient instability, exaggerate estimated associations, and make statistical significance sensitive to model specification [&lt;span&gt;2, 3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Indeed, the TDF estimate changed from a hazard ratio (HR) of 0.60 (95% CI, 0.33–1.07; &lt;i&gt;p&lt;/i&gt; = 0.083) in the univariable analysis to an aHR of 0.48 (95% CI, 0.26–0.89; &lt;i&gt;p&lt;/i&gt; = 0.021) after covariate adjustment. Moreover, neither the unweighted OS comparison nor the inverse probability of treatment weighting (IPTW)-adjusted comparison was statistically significant. In the IPTW analysis, the global &lt;i&gt;p&lt;/i&gt; value was 0.079, while the Holm-adjusted ETV–TDF comparison yielded &lt;i&gt;p&lt;/i&gt; = 0.088. The consistency in direction is noteworthy, but the emergence of statistical significance only after model-based adjustment makes demonstration of estimate stability particularly important.&lt;/p&gt;&lt;p&gt;The exploratory post-recurrence analysis does not fully explain the finding. Of the 54 deaths, 47 occurred after recurrence—33 in the ETV group, 13 in the TDF group, and one in the TAF group. However, post-recurrence survival did not differ significantly between TDF and ETV (HR, 0.58; 95% CI, 0.31–1.11; &lt;i&gt;p&lt;/i&gt; = 0.099). After adjustment for year of recurrence, the estimate moved towards the null (aHR, 0.69; 95% CI, 0.35–1.37; &lt;i&gt;p&lt;/i&gt; = 0.292). Thus, the analysis identified the period during which most deaths occurred, but did not demonstrate a statistically supported TDF effect after recurrence.&lt;/p&gt;&lt;p&gt;Additional analyses could clarify the robustness of the association. These might include an omnibus likelihood-ratio test for antiviral regimen in the Cox model, an IPTW-adjusted Cox model with robust variance estimation, a focused ETV–TDF analysis excluding the extremely sparse TAF group, and penalised or bootstrap sensitivity analyses. Until the association is reproduced with substantially more mortality events, ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"64 8","pages":"1173-1174"},"PeriodicalIF":6.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70879","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiviral Therapy and Post-Resection Outcomes in Patients With Hepatitis B Virus-Related Hepatocellular Carcinoma","authors":"Jaehong Jeong,&nbsp;Jung Pyo Hong,&nbsp;Dong Yun Kim,&nbsp;Jae Seung Lee,&nbsp;Mi Na Kim,&nbsp;Seung Up Kim,&nbsp;Beom Kyung Kim,&nbsp;Jun Yong Park,&nbsp;Do Young Kim,&nbsp;Sang Hoon Ahn,&nbsp;Hye Won Lee","doi":"10.1111/apt.70850","DOIUrl":"10.1111/apt.70850","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>The comparative outcomes of entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection remain unclear. This study aimed to evaluate the survival benefits of these antiviral regimens in a large real-world cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed 902 patients with BCLC stage 0 or A HBV-related HCC who underwent curative resection between September 2001 and August 2025. Patients received ETV (<i>n</i> = 474), TDF (<i>n</i> = 363), or TAF (<i>n</i> = 65) as first-line therapy within 3 months post-resection. Inverse probability of treatment weighting (IPTW) was implemented to balance baseline covariates. The primary and secondary endpoints were overall survival (OS) and recurrence-free survival (RFS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The IPTW-adjusted 5-year OS rates for ETV, TDF, and TAF were 90.7%, 95.2%, and 97.1%, respectively (global <i>p</i> = 0.079). The 5-year RFS rates were comparable for ETV, TDF, and TAF (57.4% vs. 61.0% vs. 69.4%; global <i>p</i> = 0.533). In multivariable Cox regression analysis, however, TDF was independently associated with a significantly lower risk of death compared with ETV (aHR 0.48; 95% CI, 0.26–0.89; <i>p</i> = 0.021). TAF showed higher survival rates compared to ETV, although the difference did not reach statistical significance (aHR 0.34; 95% CI, 0.04–2.55; <i>p</i> = 0.292).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The choice of antiviral regimen was not associated with RFS after curative resection for HBV-related HCC, whereas TDF was independently associated with improved OS compared with ETV. Further large-scale studies are warranted to validate the long-term prognostic impact of TAF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"64 8","pages":"1123-1134"},"PeriodicalIF":6.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148415751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elobixibat Versus Prucalopride in Functional Constipation: A Prospective Comparative Effectiveness Study","authors":"Omesh Goyal,&nbsp;Manjeet Kumar Goyal,&nbsp;Bhupinder Singh,&nbsp;Rajdeep Singh,&nbsp;Prerna Goyal,&nbsp;Varun Mehta,&nbsp;Sandeep Kaushal,&nbsp;Ajit Sood","doi":"10.1111/apt.70828","DOIUrl":"10.1111/apt.70828","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The choice of second-line therapy in functional constipation (FC) is often empirical, owing to the lack of direct comparisons between agents with distinct mechanisms of action. Elobixibat, an ileal bile acid transporter inhibitor, and prucalopride, a selective 5-HT₄ receptor agonist, represent two different therapeutic approaches targeting intestinal secretion and colonic motility. This study aimed to directly compare the efficacy of elobixibat and prucalopride in patients with FC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this multicentre, prospective, pragmatic study with blinded outcome assessment, adults meeting Rome IV criteria for FC and refractory to first-line treatment were enrolled after a standardized run-in period. Participants received either elobixibat or prucalopride for 8 weeks. The primary endpoint was a sustained complete spontaneous bowel movement (CSBM) response, defined as ≥ 3 CSBMs per week and an increase of ≥ 1 CSBM from baseline for at least 6 of 8 weeks. Secondary outcomes included changes in stool consistency, associated symptoms and quality of life (QoL).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 214 patients were included (elobixibat, <i>n</i> = 108; prucalopride, <i>n</i> = 106), with a mean age of 50.8 ± 17.4 years and 62.6% males. Elobixibat resulted in a significantly higher sustained CSBM response compared to prucalopride (55.6% vs. 33.9%; <i>p</i> = 0.024), indicating a clinically meaningful benefit. Both treatments significantly improved CSBM frequency and stool consistency; however, elobixibat showed greater improvement in key symptom domains, including straining (<i>p</i> &lt; 0.001), abdominal discomfort (<i>p</i> = 0.005), bloating (<i>p</i> = 0.011) and QoL (<i>p</i> = 0.009). Both drugs were well tolerated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This head-to-head comparative study demonstrates that elobixibat provides superior overall symptomatic relief and quality-of-life improvement compared with prucalopride, potentially due to its dual mechanism of action. These findings support the consideration of IBAT inhibition as a second-line treatment option in patients with FC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>Clinical Trials Registry of India: CTRI/2025/04/085075</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"64 8","pages":"1071-1082"},"PeriodicalIF":6.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148365152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Safety and Efficacy of Obeticholic Acid in Patients With Primary Biliary Cholangitis: Final Results of the POISE Long-Term Safety Extension","authors":"Christopher L. Bowlus,&nbsp;Frederik Nevens,&nbsp;Kris V. Kowdley,&nbsp;Alan Bonder,&nbsp;Thomas Capozza,&nbsp;Jing Li,&nbsp;Radhika Nair,&nbsp;Michael Trauner,&nbsp;David E. Jones","doi":"10.1111/apt.70832","DOIUrl":"10.1111/apt.70832","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Obeticholic acid (OCA) has been evaluated in patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to ursodeoxycholic acid (UDCA) in the 12-month, double-blind, phase 3 POISE trial. A 3-year interim analysis of the open-label extension (OLE) demonstrated a favourable safety profile with sustained improvements in liver biochemistries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To present the final long-term safety and efficacy data from the 5-year POISE OLE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All patients who entered the OLE (<i>N</i> = 193) were started on OCA 5 mg daily for a minimum of 3 months, after which the dose could be increased. Safety and efficacy were evaluated in the overall OLE population. Additional analyses censored data points following OCA titration &gt; 10 mg to align with the prescribing label.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>POISE was terminated after it was determined that the OLE had achieved its study objectives of sustained efficacy with no unexpected safety findings. With censoring of data points following OCA titration to &gt; 10 mg, the most common treatment-emergent adverse event (TEAE) was pruritus (70%); serious hepatic-related TEAEs were reported in five patients (3%). The serious hepatic-related TEAEs and deaths (<i>n</i> = 2, 1%) were assessed by the Investigators as unrelated to OCA. Liver biochemistries improved throughout the OLE; the response rate for the POISE primary endpoint was 63% at Month 72. Liver stiffness, as measured by transient elastography, was stable over the study duration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Findings from the POISE OLE support the safety and efficacy profile of long-term OCA treatment for patients with PBC with inadequate response or intolerance to UDCA (NCT01473524).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>Phase 3 study of obeticholic acid in patients with primary biliary cirrhosis (POISE) ClinicalTrials.gov identifier: NCT01473524</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"64 8","pages":"1083-1096"},"PeriodicalIF":6.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70832","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogen‐Specific Bloodstream Infections Associated With Tumour Necrosis Factor‐α Inhibitors, Vedolizumab and Ustekinumab in Inflammatory Bowel Disease: A Danish Nationwide Case‐Control Study 2010–2024","authors":"Cæcilie Leding, Alessandra Meddis, Jon Gitz Holler, Johan Burisch, Thomas Benfield","doi":"10.1111/apt.70999","DOIUrl":"https://doi.org/10.1111/apt.70999","url":null,"abstract":"Background Biologic drugs have substantially expanded treatment options for inflammatory bowel disease (IBD), but infection risk during exposure remains a concern. Aims To investigate the association between current use of tumour necrosis factor‐α inhibitors (TNFi), vedolizumab and ustekinumab and bloodstream infection (BSI) in individuals with IBD. Methods Nationwide, registry‐based case‐control study including all individuals with a first‐time microbiologically confirmed BSI from 2010 to 2024 and an IBD diagnosis (cases). Each case was matched with five controls with IBD using risk‐set sampling. Current biologic use was defined as recorded use of either TNFi, vedolizumab or ustekinumab within 180 days before the index date. Adjusted incidence rate ratios (aIRR) with 95% confidence intervals (CIs) were estimated using conditional logistic regression. Results We included 4503 cases and 22,473 controls. TNFi use was associated with higher BSI rates compared with no current biologic use (aIRR 1.73, 95% CI 1.49–2.00), whereas vedolizumab (aIRR 0.85, 95% CI 0.61–1.20) and ustekinumab (aIRR 0.68, 95% CI 0.38–1.23) use was not. In pathogen‐specific analyses, TNFi use was associated with higher rates of BSI caused by <jats:styled-content style=\"fixed-case\"> <jats:italic>Escherichia coli</jats:italic> </jats:styled-content> and <jats:styled-content style=\"fixed-case\"> <jats:italic>Staphylococcus aureus</jats:italic> </jats:styled-content> , while vedolizumab use was associated with higher rates of <jats:styled-content style=\"fixed-case\"> <jats:italic>Enterococcus faecium</jats:italic> </jats:styled-content> BSI. Concomitant glucocorticoid use was associated with increased BSI rates among TNFi and vedolizumab users compared with monotherapy. Conclusions TNFi use was associated with increased BSI rates in patients with IBD, whereas vedolizumab and ustekinumab use was not. Overall, the findings suggest potential differences in infection risk across biologic therapies and in pathogen‐specific susceptibility.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"80 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Comparative Effectiveness in Chronic Constipation—Interpreting Real-World Evidence","authors":"Andrea Shin","doi":"10.1111/apt.70871","DOIUrl":"10.1111/apt.70871","url":null,"abstract":"&lt;p&gt;Chronic constipation (CC), previously termed functional constipation, is a common disorder of gut-brain interaction affecting approximately 10%–15% of the global population [&lt;span&gt;1, 2&lt;/span&gt;]. Although diverse pathophysiological disturbances contribute to CC, pharmacological management remains largely empiric and symptom-directed [&lt;span&gt;3&lt;/span&gt;]. First-line therapies include osmotic and stimulant laxatives, while second-line options include intestinal secretagogues, ion transport inhibitors, ileal bile acid transporter (IBAT) inhibitors and serotonergic agents [&lt;span&gt;4&lt;/span&gt;]. Despite the wide range of treatments available, there is little evidence to guide the selection of one second-line pharmacological treatment over another. In practice, therapies are often chosen based on availability or accessibility rather than their comparative efficacy or factors that predict treatment response. In the absence of head-to-head trials, comparative efficacy has largely been inferred from network meta-analyses, which suggest linaclotide may be most effective for irritable bowel syndrome with constipation [&lt;span&gt;5&lt;/span&gt;] and that stimulant laxatives or prucalopride may provide the greatest benefit for CC [&lt;span&gt;6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Goyal et al. [&lt;span&gt;7&lt;/span&gt;] report results from an open-label, real-world trial comparing elobixibat and prucalopride in patients with CC. Elobixibat, an IBAT inhibitor approved for the treatment of CC in Japan [&lt;span&gt;8&lt;/span&gt;], was associated with higher sustained complete spontaneous bowel movement response rates and greater improvements in bloating, straining, discomfort and quality of life than prucalopride. Authors propose the enhanced efficacy of elobixibat could be due to its dual effects on intestinal secretion and motility. Study strengths include the large sample size, multicenter design, well-characterized patient population, comprehensive clinical assessments and blinded outcome assessments. As the first head-to-head comparison of two second-line therapies for CC, the study has important implications for clinical practice. However, several points should be considered when interpreting the results.&lt;/p&gt;&lt;p&gt;Although elobixibat was associated with greater efficacy, treatment allocation was not randomized but determined by physician discretion, consistent with the study's pragmatic intent. However, randomization is typically preserved in pragmatic trials, with pragmaticism reflected through other elements such as participant recruitment, intervention delivery, follow-up and outcomes asessments [&lt;span&gt;9&lt;/span&gt;]. While physician-selected treatment responses provide valuable real-world evidence, non-random treatment allocation introduces the potential for confounding by indication or channelling biases that could influence observed outcomes [&lt;span&gt;10&lt;/span&gt;]. Additionally, despite the use of a non-randomized design, treatment groups were well balanced with respect to participant numbers and clinical characteristics. Further","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"64 8","pages":"1160-1161"},"PeriodicalIF":6.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70871","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-Analysis: Prevalence of Non-Helicobacter pylori, Non-NSAID Peptic Ulcer Disease","authors":"Jun Watanabe,&nbsp;Hiromi Sekiguchi,&nbsp;Takeshi Kanno,&nbsp;Keigo Misawa,&nbsp;Satoshi Sato,&nbsp;Yuhong Yuan,&nbsp;Paul Moayyedi,&nbsp;Tomonori Yano,&nbsp;Atsushi Masamune,&nbsp;Tomoari Kamada","doi":"10.1111/apt.70906","DOIUrl":"10.1111/apt.70906","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Non-<i>Helicobacter pylori</i> (<i>H. pylori</i>), non-nonsteroidal anti-inflammatory drug (NSAID) peptic ulcer disease (PUD) is increasingly recognized as a distinct subgroup, but its proportion across clinical presentations remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We aimed to estimate this proportion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched MEDLINE, Embase and CENTRAL from their inception to March 2026 for observational studies. The primary outcome was the proportion of non-<i>H. pylori</i>, non-NSAID PUD among adults with overall, bleeding and perforated PUD. Random-effects meta-analysis of logit-transformed proportions was performed using restricted maximum likelihood. Meta-regression assessed associations with study year, country-level <i>H. pylori</i> prevalence and region. Protocol registered in PROSPERO (CRD420251174202).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 92 studies (60,816 patients) from 32 countries were included. The pooled proportions of non-<i>H. pylori</i>, non-NSAID PUD cases were 13.0% (95% confidence interval [CI], 10.4–16.2) in overall PUD, 11.3% (95% CI, 8.8–14.4) in bleeding PUD, and 22.0% (95% CI, 13.1%–34.7%) in perforated PUD. In univariable meta-regression, a more recent study year was associated with a higher proportion of bleeding PUD (<i>β</i> = 0.076; 95% CI, 0.031–0.120). This association remained statistically significant after adjustment for country-level <i>H. pylori</i> prevalence (<i>β</i> = 0.070; 95% CI, 0.026–0.113). Lower <i>H. pylori</i> prevalence was also associated with a higher proportion after further adjustment for region (<i>β</i> = −0.025; 95% CI, −0.046 to −0.005).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Non-<i>H. pylori</i>, non-NSAID PUD represents a non-negligible but heterogeneous component of PUD. In bleeding PUD, exploratory ecological analyses suggest a temporal increase, potentially reflecting evolving etiologic patterns beyond <i>H. pylori</i> infection and NSAID exposure.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"64 8","pages":"1034-1045"},"PeriodicalIF":6.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70906","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Major Adverse Outcomes in Steatotic Liver Disease Subtypes—From Etiological Classification to Biological Phenotyping: Authors' Reply","authors":"Takao Miwa,&nbsp;Bernd Schnabl","doi":"10.1111/apt.70900","DOIUrl":"10.1111/apt.70900","url":null,"abstract":"&lt;p&gt;We sincerely thank Cespiati and Schattenberg for their thoughtful letter and constructive comments regarding our article on subtype differences in outcomes among patients with steatotic liver disease (SLD) [&lt;span&gt;1, 2&lt;/span&gt;]. They raise several important points, and we appreciate the opportunity to further discuss the implications of our findings.&lt;/p&gt;&lt;p&gt;First, they question whether etiological classification alone is sufficient for precision risk stratification. We believe this is an important perspective. In our study, metabolic dysfunction-associated SLD (MASLD) and metabolic dysfunction and alcohol-associated liver disease (MetALD) differed with respect to liver-related outcomes, whereas the differences in cardiovascular outcomes were relatively modest. The principal distinction between these two subtypes is the presence of moderate alcohol consumption. While even moderate alcohol consumption has been associated with adverse liver-related outcomes [&lt;span&gt;3&lt;/span&gt;], its influence on cardiovascular outcomes may be less pronounced. Historically, moderate alcohol consumption was hypothesized to be cardioprotective, although this concept has been increasingly challenged by more recent evidence [&lt;span&gt;4, 5&lt;/span&gt;]. Taken together, our findings may suggest that, for cardiovascular risk stratification, greater emphasis should be placed on well-established cardiovascular risk factors, such as hypertension, diabetes mellitus and dyslipidemia, rather than moderate alcohol consumption alone. We also agree that incorporating biological factors, including genetic susceptibility, into future risk stratification models represents an important direction for precision hepatology.&lt;/p&gt;&lt;p&gt;Second, the authors point out that body mass index (BMI) alone is insufficient to capture the biological heterogeneity of SLD. We fully agree with this view. Accumulating evidence has demonstrated that skeletal muscle mass, visceral adiposity and subcutaneous adiposity are closely associated with clinical outcomes in patients with SLD and advanced liver disease [&lt;span&gt;6, 7&lt;/span&gt;]. However, implementing comprehensive body composition assessment in routine clinical practice remains challenging because of limitations in equipment availability, cost and accessibility. Similarly, although genetic risk scores have shown considerable promise, universal implementation for all patients is currently impractical from both economic and logistical perspectives [&lt;span&gt;8&lt;/span&gt;]. Consequently, a key challenge for future research will be to identify the populations most likely to benefit from detailed body composition assessment and genetic profiling and to establish practical strategies for incorporating these approaches into clinical risk assessment. In addition, collaboration among academia, industry and healthcare systems will be essential to facilitate their successful implementation in routine practice. From our perspective as medical researchers, one of our most important responsibil","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"64 8","pages":"1171-1172"},"PeriodicalIF":6.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70900","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148662942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Non-Invasive Tests After Semaglutide in MASH as Disease-Activity Readouts Rather Than Response Biomarkers. Authors' Reply","authors":"Louise M. Nitze,&nbsp;Quentin M. Anstee","doi":"10.1111/apt.70897","DOIUrl":"10.1111/apt.70897","url":null,"abstract":"&lt;p&gt;We thank Drs. Mao and Lan for their thoughtful comments regarding our analysis of non-invasive tests (NITs) in people with metabolic dysfunction-associated steatohepatitis (MASH) treated with semaglutide [&lt;span&gt;1&lt;/span&gt;]. Their letter highlights important considerations regarding the interpretation of NIT changes and the distinction between different contexts of use: treatment monitoring vs. pharmacodynamic effects, as well as the issue of biomarker qualification [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We agree that NITs should be interpreted according to their biological context and current level of validation. As acknowledged in our article, no NIT is currently validated as a treatment-response biomarker in MASH, and our study was intended as an exploratory analysis of a broad panel of NITs within a well-characterised phase 2b trial dataset. We would, however, point out that liver histology is itself an imperfect reference standard that is subject to sampling error and both inter- and intra-observer variation in interpretation, even with expert hepatopathologists [&lt;span&gt;3-5&lt;/span&gt;]. The corollary of this is that, when histological and NIT assessment of treatment response diverge, it is inappropriate to assume that histology necessarily provides a more reliable measure of the underlying biological response to treatment.&lt;/p&gt;&lt;p&gt;Our objective was to explore how NITs capture treatment-associated changes and the extent to which those changes align with histological outcomes observed in the phase 2b trial. We address the absence of a single “perfect” test in our study by exploring the concordance of different NITs with histology at the individual patient level. This exploratory approach is founded on the hypothesis that concordance of complementary NITs assessing different aspects of disease biology (e.g., elastography as a measure of liver stiffness and the Enhanced Liver Fibrosis [ELF] score as a marker of extracellular matrix turnover) may provide a more comprehensive assessment of treatment-related changes. Consistent with this objective, we highlighted several limitations, including the completer population, pooled semaglutide dose groups and the absence of adjustment for multiple comparisons. Ultimately, we concluded that, whilst our findings support the value of NIT strategies to measure treatment response in MASH and the utility of test concordance analysis, further validation is required. In this regard, larger datasets, including those from the phase 3 ESSENCE trial of semaglutide in patients with MASH, provide an important opportunity to further evaluate the relationship between changes in NITs, liver histology and outcomes indicative of clinically meaningful treatment benefit.&lt;/p&gt;&lt;p&gt;We appreciate the opportunity to further discuss these important issues and share Drs. Mao and Lan's view that continued efforts towards robust, outcome-anchored non-invasive assessment strategies are essential for advancing MASH clinical care.&lt;/p&gt;&lt;p&gt;The authors' declaratio","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"64 8","pages":"1166-1167"},"PeriodicalIF":6.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70897","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}