Alimentary Pharmacology & Therapeutics最新文献

{"title":"Letter: Methodological Gaps Undermine Conclusions on Electronic Nose Use for Colorectal Cancer Detection—Authors' Reply","authors":"Milou. L. M. van Riswijk, Peter D. Siersema","doi":"10.1111/apt.70243","DOIUrl":"10.1111/apt.70243","url":null,"abstract":"<p>Editors,</p><p>We appreciate the interest of Drs. Ding Shi and Buyuan Dong [<span>1</span>] in our recently published study investigating the diagnostic accuracy of an electronic nose (e-nose) in a large-scale study with external validation [<span>2</span>]. They raised important considerations regarding the use of volatile organic compounds (VOCs) in colorectal cancer (CRC) screening, which we are happy to address.</p><p>First, although identifying individual VOCs is of interest, our sensor-based e-nose approach focused on conductivity changes upon VOC interaction. This results in a breath profile that is analysed through a supervised machine learning model [<span>3</span>]. The diagnostic gold standard of colonoscopy with corresponding pathology results was used throughout. A stepwise validation process ensured robustness and decreased the risk of spurious correlations [<span>4</span>]. Moreover, this was followed by external validation. This process differs fundamentally from gas chromatography mass spectrometry (GCMS). However, both approaches may ultimately complement each other. Indeed, VOC profiles vary considerably across studies probably due to—among others—biological heterogeneity across tumour stages, genetic mutations and microbiological influences. These differences support the integration of complementary VOC detection strategies rather than positioning them as mutually exclusive.</p><p>Second, confounders such as medication use and comorbidities can influence VOCs. We included several known confounders [<span>5, 6</span>] in our dataset, as seen in our baseline characteristics. Unfortunately, due to the poor performance of the e-nose, formal confounder analyses were not feasible, as the predictions were nearly random. As noted in the discussion, the use of multiple devices may have contributed to the disappointing results. While the e-nose was designed for transferable calibration [<span>7</span>], and previously showed promising results in a pilot study [<span>8</span>], subsequent simulation studies revealed that a low cancer prevalence and use of multiple devices may negatively impact diagnostic performance [<span>9</span>]. Therefore, the low AUC probably reflects not only pathophysiological differences among early-stage CRC, but prevalence and inter-device variations could also have played a role, as addressed in the discussion.</p><p>Third, we did perform repeated testing in a subset of 750 patients, which revealed poor reproducibility. Nevertheless, root cause analysis was limited by the test's overall poor performance. Longitudinal assessment of VOC progression from non-advanced adenoma to CRC could be informative, but current clinical practice where polyps are removed precludes this. Furthermore, the evaluation of new screening modalities involves several steps [<span>10</span>]. While repeated testing may provide insights into test robustness, its necessity would limit clinical applicability in a screening context.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 3","pages":"374-375"},"PeriodicalIF":6.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295812","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":"Optimising Use of Stool Gluten Immunogenic Peptide Tests for Monitoring Adherence to Gluten‐Free Diet in Patients With Coeliac Disease","authors":"Juan P. Stefanolo, Roberto Puebla, Samantha Dodds, María P. Temprano, María E. Oregui, Edgardo Smecuol, Sonia I. Niveloni, Julio C. Bai","doi":"10.1111/apt.70242","DOIUrl":"https://doi.org/10.1111/apt.70242","url":null,"abstract":"Stool gluten immunogenic peptide (s‐GIP) measurement is an innovative tool for detecting voluntary and involuntary gluten exposure in patients with coeliac disease. However, the optimal strategy for its clinical use remains unclear. This longitudinal, prospective study evaluated stool sampling twice a week over 28 days, comparing average s‐GIP concentrations with reduced sampling strategies to optimise its clinical application. Testing stool twice within 7 days was practical and accurate for monitoring dietary adherence. This approach effectively balances patient convenience with diagnostic accuracy for routine clinical use.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"113 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289861","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":"Safety and Tolerability of Injectable Extended‐Release Naltrexone for the Management of Alcohol Use Disorder in Advanced Alcohol‐Associated Liver Disease","authors":"Luis Antonio Díaz, Summer Collier, Jeffrey Yin, Rohit Loomba","doi":"10.1111/apt.70237","DOIUrl":"https://doi.org/10.1111/apt.70237","url":null,"abstract":"BackgroundPharmacologic treatment of alcohol use disorder (AUD) in patients with advanced alcohol‐associated liver disease (ALD) remains underutilised due to concerns regarding hepatotoxicity. Injectable extended‐release naltrexone (XR‐NTX) may offer a safer alternative by avoiding first‐pass hepatic metabolism, but data on its safety and effectiveness in patients with advanced ALD are limited.AimTo describe the clinical experience with XR‐NTX in individuals with advanced ALD, evaluating its safety, tolerability and impact on liver function and alcohol use.MethodsRetrospective case series of adults with ALD who received at least one dose of XR‐NTX 380 mg IM at a tertiary care centre between 2023 and March 2025. Clinical data and laboratory tests were extracted from electronic health records over a minimum follow‐up of 12 weeks. Safety was assessed based on adverse events and liver biochemistry. Alcohol use was evaluated using phosphatidylethanol (PEth) levels.ResultsFourteen individuals with ALD were included (2 had F3 and 9 cirrhosis Child A–B). The median age was 51 [44–65] years, 64% were male, and median follow‐up was 127 days. Four patients (29%) experienced mild adverse effects (injection site pain, nausea and vomiting, fatigue and sexual side effects); none had hepatotoxicity or hepatic decompensation. No significant changes in liver function tests or MELD/Child‐Pugh scores were observed during the follow‐up period. Eight participants (57%) had a decrease in alcohol consumption, with a non‐significant decline in PEth levels.ConclusionIn this case series, XR‐NTX was well tolerated in patients with advanced ALD, without evidence of hepatotoxicity or liver decompensation.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"42 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289858","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":"Review: Human Intestinal Barrier—Optimal Measurement and Effects of Diet in the Absence of Overt Inflammation or Ulceration","authors":"Michael Camilleri","doi":"10.1111/apt.70225","DOIUrl":"10.1111/apt.70225","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The intestinal barrier protects humans from potentially deleterious ingested material. It consists of several components: commensal organisms, mucus, and transepithelial pathways, and immune functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To review, with major focus on human studies, the methods to measure intestinal barrier function in vivo and the impaired intestinal barrier function in non-inflammatory conditions, and the deleterious or beneficial effects of dietary components on the intestinal barrier.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PUBMED literature search was intentionally focused, when possible, on human studies conducted in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Although many gastrointestinal, rheumatological, and degenerative neurological diseases are attributed to impaired intestinal barrier function, often termed “leaky gut,” methods of accurate measurement of intestinal barrier function in vivo in humans are still being developed. In vivo measurements provide an overall assessment of barrier function at a whole organ level, whereas ex vivo or in vitro measurements using mucosal biopsies address mechanistic information at the cellular level. Several dietary components are detrimental to the barrier, including ethanol, fat, sugars, gliadin, food additives, emulsifiers, and microbial transglutaminase. Conversely, dietary components improving barrier function include fibre and metabolites such as short-chain fatty acids, anthocyanins, polyphenols, vitamins (such as A and D), zinc, specific amino acids (such as glutamine) and probiotics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Currently, data are not exclusively from human studies, and research is needed to corroborate observations in animals or further validate in humans. There are several practical dietary approaches that can be instituted for restoration of the intestinal barrier in humans.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 2","pages":"128-145"},"PeriodicalIF":6.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288295","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: Endomysial Antibodies for a No-Biopsy Diagnosis of Coeliac Disease—The Jury Is Still Out","authors":"Mohamed G. Shiha,&nbsp;Hugo A. Penny","doi":"10.1111/apt.70191","DOIUrl":"10.1111/apt.70191","url":null,"abstract":"&lt;p&gt;Studies in children and adults have shown that immunoglobulin (Ig)A anti-tissue transglutaminase (tTG) antibody levels ≥ 10× upper limit of normal are highly specific for a diagnosis of coeliac disease and may obviate the need for histological confirmation in approximately 30% of patients [&lt;span&gt;1, 2&lt;/span&gt;]. Given that many patients prefer to avoid endoscopy [&lt;span&gt;3&lt;/span&gt;], the ‘no-biopsy’ approach to diagnosis is an area of interest with the potential to improve patient experience and reduce associated healthcare costs.&lt;/p&gt;&lt;p&gt;In this issue of &lt;i&gt;Alimentary Pharmacology &amp; Therapeutics&lt;/i&gt;, Maimaris and colleagues present the findings of a retrospective/prospective study evaluating the accuracy of endomysial antibodies (EMA) in combination with clinical risk stratification to support a no-biopsy diagnosis of adult coeliac disease [&lt;span&gt;4&lt;/span&gt;]. A positive EMA test had a specificity and a positive predictive value (PPV) of 100% for a diagnosis of coeliac disease, suggesting that this may be a suitable alternative to IgA-tTG testing in this no-biopsy approach. However, EMAs are typically identified in serum using indirect immunofluorescence, which is more costly and labour-intensive than conventional tTG-based immunoassays; this methodology is also subject to inter-observer variability. Importantly, the EMA test also lacks a quantitative readout, which is a central tenet of the no-biopsy approach, as low titre IgA-tTG levels (i.e.,1-5× upper limit of normal) confer less specificity for the duodenal inflammation typical of coeliac disease than high titre levels (i.e., ≥ 10× upper limit of normal) [&lt;span&gt;5&lt;/span&gt;], despite both being identified as a positive result.&lt;/p&gt;&lt;p&gt;Notably, all patients with a positive EMA result were diagnosed with coeliac disease in this study. However, patients with potential coeliac disease—defined by positive serology without duodenal villous atrophy—were included within this group. If these individuals were re-classified as false positives, the specificity would fall from 100% to 93.7%, and the PPV would fall from 100% to 87.4%, based on a disease prevalence/pre-test probability of 31%. On the one hand, does this matter if the end goal is a gluten-free diet? On the other hand, serology will normalise in up to a third of patients with potential coeliac disease despite ongoing gluten exposure [&lt;span&gt;6&lt;/span&gt;]. Therefore, it is important not to blur the lines between the two conditions. Indeed, this is one of the limitations of the no-biopsy approach, which should be balanced against the shortcomings of the serology-biopsy pathway before either is considered for diagnosis.&lt;/p&gt;&lt;p&gt;Beyond this, the study provides reassuring data on the safety of avoiding upper gastrointestinal endoscopy in patients with positive coeliac serology, as no major concomitant pathology was identified among those with a positive EMA regardless of their age or the presence of alarm symptoms. Conversely, most non-coeliac enteropathies were ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 2","pages":"220-221"},"PeriodicalIF":6.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278703","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":"Editorial: Patient Reported Outcomes Provide Insight Into Disease Severity for People Living With Primary Sclerosing Cholangitis","authors":"Aisha Alawi,&nbsp;Gideon M. Hirschfield","doi":"10.1111/apt.70223","DOIUrl":"10.1111/apt.70223","url":null,"abstract":"&lt;p&gt;Primary sclerosing cholangitis (PSC) is a rare autoimmune liver disease (AILD) of unknown aetiology. It is a progressive disease that leads to cirrhosis and liver failure with no curative therapy other than liver transplantation [&lt;span&gt;1&lt;/span&gt;]. The physical burden and uncertainty associated with PSC have a significant impact on patient quality of life (QOL) [&lt;span&gt;2, 3&lt;/span&gt;]. However, insufficient studies have investigated this [&lt;span&gt;4, 5&lt;/span&gt;]. Tan et al. sought to characterise the impact of the disease on QOL in PSC patients living in Australia and investigate the relationship between demographics, disease, and patient reported outcomes (PROs).&lt;/p&gt;&lt;p&gt;The group conducted a prospective observational cohort study with patients from nine tertiary liver centres in Australia. In total, 55 adult patients with PSC were recruited. Each participant was provided with a baseline PSC QOL questionnaire. Those with concomitant IBD also completed an IBD questionnaire. Clinical data was collected for all patients [&lt;span&gt;6&lt;/span&gt;] (Figure 1).&lt;/p&gt;&lt;p&gt;Results showed that fatigue was the most commonly reported symptom. Overall scores for the PSC PRO were low and IBD questionnaire high, indicating disease did not have a significant impact on QOL in this cohort. A positive correlation was found between PSC and IBD symptoms in patients. Decompensated cirrhosis and a history of cholangitis were associated with lower QOL. This is the first study to find an association with the latter [&lt;span&gt;6&lt;/span&gt;]. Unlike in previous studies, older age was protective, and both sex and PSC phenotype were not associated with QOL [&lt;span&gt;4-6&lt;/span&gt;]. However, the fact that concomitant IBD did not affect QOL, while cirrhosis was found to have a negative impact, is in line with previous work [&lt;span&gt;4, 5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Several limitations affect this study's generalisability. To begin with, the small cohort mainly consists of patients with less severe disease. In addition, patients from tertiary centers typically differ in their clinical characteristics when compared to other patients [&lt;span&gt;7&lt;/span&gt;]. The study also strictly enrolled English-speaking individuals, meaning results do not represent the experience of marginalised groups. The cross-sectional nature of this study also fails to account for the variable experience of PSC.&lt;/p&gt;&lt;p&gt;Future research should focus on collecting longitudinal data from larger, diverse, prospective cohorts. Studies could administer additional questionnaires that look at specific symptoms (e.g., fatigue) and allow for comparison of QOL scores (e.g., Chronic Liver Disease Questionnaire (CLDQ)). Having a control group of patients with a similar disease (e.g., PBC) complete disease-specific QOL questionnaires (e.g., PBC-40) would also help substantiate results.&lt;/p&gt;&lt;p&gt;As it takes many years for outcomes to occur in PSC patients, there is a need for surrogate endpoints in clinical trials [&lt;span&gt;2&lt;/span&gt;]. This study points towards associations between PRO","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 3","pages":"362-363"},"PeriodicalIF":6.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278433","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":"Editorial: Endomysial Antibodies for a No-Biopsy Diagnosis of Coeliac Disease—The Jury Is Still out. Authors' Reply","authors":"Stiliano Maimaris,&nbsp;Annalisa Schiepatti,&nbsp;Federico Biagi","doi":"10.1111/apt.70234","DOIUrl":"10.1111/apt.70234","url":null,"abstract":"&lt;p&gt;We appreciate the editorial by Drs Shiha and Penny [&lt;span&gt;1&lt;/span&gt;] on our study [&lt;span&gt;2&lt;/span&gt;] concerning endomysial antibodies and clinical risk stratification for biopsy-sparing coeliac disease diagnosis. We acknowledge that endomysial antibodies present some drawbacks, including higher cost and need for trained personnel, potentially limiting their use. Our study's excellent endomysial antibody results [&lt;span&gt;2&lt;/span&gt;] reflect extensive experience with this assay and may not generalise to less experienced centres. However, endomysial antibodies offer some advantages over tissue transglutaminase antibodies. First, endomysial antibodies exhibited 99.7% specificity for coeliac disease in a meta-analysis of 34 studies [&lt;span&gt;3&lt;/span&gt;]. Second, while requiring skilled interpretation, endomysial antibodies are an objective measure, unlike tissue transglutaminase antibodies, which show significant inter-assay variability [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We agree that managing potential coeliac disease within a biopsy-sparing framework remains an open question depending on patients' clinical features. A meta-analysis of 17 studies found that nearly 90% of potential coeliac disease patients improve on a gluten-free diet [&lt;span&gt;5&lt;/span&gt;]. Thus, in symptomatic, endomysial antibody-positive patients, a gluten-free diet is warranted, so distinguishing symptomatic potential coeliac disease from conventional coeliac disease is of limited importance. For the minority of asymptomatic adult potential coeliac disease patients identified via screening, the decision for a gluten-free diet versus monitoring on a gluten-containing diet remains case-by-case. However, in our experience, most adopt a gluten-free diet due to associated autoimmune conditions or family environment. Patients also generally prefer a gluten-free diet over endoscopic follow-up, rarely maintaining a gluten-containing diet long-term.&lt;/p&gt;&lt;p&gt;The issue is further complicated by ultra-short coeliac disease, which requires bulb biopsies to differentiate from potential coeliac disease [&lt;span&gt;6&lt;/span&gt;]. However, bulb biopsies are not routinely performed, and obtaining ≥ 4 biopsies can already be considered an achievement [&lt;span&gt;7&lt;/span&gt;]. A meta-analysis estimated ultra-short coeliac disease prevalence at 9.2% among coeliac disease patients, increasing with the number of bulb biopsies taken [&lt;span&gt;8&lt;/span&gt;]. A large portion of ultra-short coeliac disease patients may be misdiagnosed as potential coeliac disease if only the second portion of the duodenum is biopsied. Collectively, these render distinguishing between potential coeliac disease, ultra-short coeliac disease, and other coeliac disease forms of questionable clinical significance.&lt;/p&gt;&lt;p&gt;Our findings on the safety of a biopsy-sparing approach are perhaps most crucial and generalise beyond specific serological tests. The lack of major concomitant pathology in coeliac disease patients diagnosed in our study [&lt;span&gt;2&lt;/span&gt;] is reassuring, supportin","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 2","pages":"222-223"},"PeriodicalIF":6.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70234","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278434","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":"Predicting Hepatic Decompensation in Patients With Metabolic Dysfunction Associated Steatotic Liver Disease-Related Cirrhosis: The ABID-LSM Model.","authors":"Luis Calzadilla Bertot, Anna Sòria, Alba Jimenez-Masip, Isabel Serra, Teresa Broquetas, Mercedes Vergara, Adrià Rodriguez, Carles Aracil, Cautar El Maimouni, Sergio Muñoz-Martinez, Jose A Carrión, Albert Pardo, Juan M Pericàs, Isabel Graupera, Leon A Adams","doi":"10.1111/apt.70215","DOIUrl":"https://doi.org/10.1111/apt.70215","url":null,"abstract":"<p><strong>Background & aims: </strong>Predicting the risk of hepatic decompensation guides prognostication and therapy; however, it is challenging in patients with cirrhosis due to metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to improve a previously developed predictive tool of hepatic decompensation in MASLD cirrhosis (ABIDE) by incorporating liver stiffness measurement (LSM).</p><p><strong>Methods: </strong>A multi-centre retrospective cohort of patients with compensated cirrhosis due to MASLD was identified, with decompensation incidence assessed using competing risk regression. The prognostic accuracy of a modified ABIDE model incorporating LSM (ABID-LSM) was assessed using time-dependent AUC (tAUC) and compared with other predictive models.</p><p><strong>Results: </strong>Out of 388 patients, 273 (70.4%) had available LSM. Hepatic decompensation occurred in 54 (20%) patients during follow-up (median 31 months, range: 20-60). The predictive accuracy at 5 years of ABID-LSM (tAUC 0.80) was better than ABIDE (tAUC 0.75, p = 0.03) and LSM (tAUC 0.63, p < 0.001). The ABID-LSM model calibrated well (slope 0.99) with excellent overall performance (Integrated Brier Score 0.15). A cut-off of 8.1 separated those at high and low risk of hepatic decompensation at 5 years (24% vs. 5%, respectively, sHR = 4.8, p < 0.001). The ABID-LSM model had better predictive ability at 5 years than ALBI, FIB-4, NAFLD Decompensation Risk Score and ANTICIPATE models (all p < 0.001) as well as hepatic vein pressure gradient measurement (tAUC 0.78 vs. 0.71, p < 0.001, n = 60).</p><p><strong>Conclusions: </strong>The ABID-LSM model has greater accuracy in predicting hepatic decompensation in patients with cirrhosis due to MASLD than existing predictive models. If externally validated, ABID-LSM may identify those who benefit from pharmacotherapy and close monitoring.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256834","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":"Effects of Screening Colonoscopy on Colorectal Cancer Mortality: Lessons From Comparative Analyses of Randomised Trials.","authors":"Hermann Brenner, Dmitry Sergeev, Thomas Heisser, Michael Hoffmeister","doi":"10.1111/apt.70231","DOIUrl":"https://doi.org/10.1111/apt.70231","url":null,"abstract":"<p><p>NordICC, the first randomised trial on long-term effects of screening colonoscopy, failed to demonstrate a significant reduction in colorectal cancer (CRC) mortality. We compared reported 10-year CRC mortality results from NordICC with those of NORCCAP, a similarly designed pragmatic sigmoidoscopy trial. In NORCCAP, differences in CRC mortality only began to emerge after 9.5 years of follow-up, rapidly increased thereafter and were approximately 4-fold as high after 12 years than after 10 years. Other sigmoidoscopy trials yielded similar 11- to 12-year results. Our analysis suggests that the apparent negative CRC mortality results of NordICC primarily reflect insufficient follow-up time.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256833","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: Time to EXIT? When Less Is More in IBD Management. Authors' Reply","authors":"María José Casanova,&nbsp;María Chaparro,&nbsp;Javier P. Gisbert","doi":"10.1111/apt.70230","DOIUrl":"10.1111/apt.70230","url":null,"abstract":"&lt;p&gt;We thank Drs. Asonuma and Kobayashi [&lt;span&gt;1&lt;/span&gt;] for highlighting our publication on long-term outcomes following anti-TNF withdrawal in patients with inflammatory bowel disease in remission [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;As they noted, our randomised controlled trial (EXIT) and its extended follow-up study found no significant differences in relapse rates at 1 year and over the longer term between patients who discontinued or continued anti-TNF therapy [&lt;span&gt;2, 3&lt;/span&gt;]. We acknowledge that these results contrast with previous randomised trials such as HAYABUSA, STOP-IT, and SPARE, which reported higher relapse rates following anti-TNF withdrawal [&lt;span&gt;4-6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Several key differences distinguish EXIT from these earlier trials. Primarily, EXIT included only highly selected patients who had maintained deep, stable remission for at least 6 months on standard-dose anti-TNF combined with immunomodulators, without prior risk factors such as intestinal resection or significant endoscopic lesions [&lt;span&gt;2&lt;/span&gt;]. Conversely, the cohorts of HAYABUSA, STOP-IT, and SPARE enrolled more heterogeneous patient populations, had shorter anti-TNF exposure times, did not uniformly include concomitant immunomodulator therapy, and only STOP-IT was double-blinded [&lt;span&gt;4-6&lt;/span&gt;]. Moreover, all participants in EXIT continued stable immunomodulator therapy before and after randomisation. While retrospective studies have suggested a protective role for immunomodulators post-withdrawal of a biologic, prospective randomised data are limited [&lt;span&gt;2, 4-8&lt;/span&gt;]. In EXIT and EXIT long-term, the consistent use of immunomodulators potentially mitigated post-withdrawal flares, thereby minimising differences in relapse rates between treatment arms.&lt;/p&gt;&lt;p&gt;Our findings suggest that a carefully monitored anti-TNF discontinuation strategy, with planned treatment resumption upon relapse, is effective in carefully selected patients. This aligns with real-world evidence, which also reported high remission recapture rates after treatment resumption [&lt;span&gt;9, 10&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We agree with Drs. Asonuma and Kobayashi that future research should focus on identifying optimal candidates for anti-TNF withdrawal and retreatment. Planned anti-TNF withdrawal may be safe in highly selected patients in stable, deep remission on combined therapy, provided rigorous biomarker monitoring (faecal calprotectin and C-reactive protein) is conducted, especially during the first year after discontinuation. Moreover, rapid access to anti-TNF therapy upon relapse is crucial to successfully recapturing remission. This strategy should not be routinely applied but should rather be individualised, carefully weighing patient preferences, risk profiles, and commitment to frequent monitoring.&lt;/p&gt;&lt;p&gt;Crucially, this “exit” strategy should be reserved for motivated patients willing to undergo stringent monitoring. However, for broader IBD populations—especially those with previous surgeries, anti-","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 2","pages":"226-227"},"PeriodicalIF":6.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70230","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237863","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}