Alimentary Pharmacology & Therapeutics最新文献

{"title":"Long-Term Dynamic Changes of Alanine Aminotransferase Levels Are Associated With Liver-Related Events in Nucleos(t)ide Analogue-Treated Chronic Hepatitis B Patients in China.","authors":"Rong Fan,Ning Yu,Jimmy Che-To Lai,Vicki Wing-Ki Hui,Jie Peng,Yongpeng Chen,Zhihong Liu,Xieer Liang,Henry Lik-Yuen Chan,Junhua Yin,Vincent Wai-Sun Wong,Chunxiu Zhong,Grace Lai-Hung Wong,Jian Sun,Terry Cheuk-Fung Yip,Jinlin Hou","doi":"10.1111/apt.70195","DOIUrl":"https://doi.org/10.1111/apt.70195","url":null,"abstract":"BACKGROUNDThe role of alanine aminotransferase (ALT) dynamics during nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB) is unclear. We aimed to evaluate the correlation between ALT dynamics and liver-related events (LRE), and explore the optimal threshold of ALT during NA treatment.METHODSWe enrolled 18,129 NA-treated patients, comprising 3104 patients from the Search-B study (NCT02167503) and 15,025 patients from a real-world cohort in Hong Kong. Latent-class mixed model (LCMM) was adopted to identify trajectory patterns of ALT during treatment. ALT value at the 95th percentile of the trajectory group with the lowest LRE risk was obtained as the optimal threshold.RESULTSDuring a median follow-up of 53.3 months, 1164 patients developed LRE with a 7-year cumulative incidence of 9.9%. In the Search-B cohort, LCMM recognised 3 trajectory groups with progressively increasing ALT levels, which were positively associated with LRE risk. Subsequently, the optimal thresholds for ALT were obtained as 23 U/L for men and 16 U/L for women. The 7-year cumulative incidence of LRE was 5.5% for ALT ≤ 23 or 16 U/L, significantly lower than that for ALT > 23 or 16 U/L but ≤ 40 U/L (10.8%; aHR = 2.0, p < 0.001), and ALT > 40 U/L (15.1%; aHR = 3.4, p < 0.001). Similarly, in the Hong Kong cohort, ALT > 23 or 16 U/L but < 40 U/L and ALT > 40 U/L also increased the LRE risk, with aHRs of 2.0 (p = 0.003) and 6.1 (p < 0.001), respectively.CONCLUSIONOn-treatment ALT levels were significantly correlated with the prognosis of CHB. ALT ≤ 23 U/L for men and ≤ 16 U/L for women were identified as the optimal thresholds during NA treatment, suggesting that CHB patients should strive for a lower ALT level beyond the traditional normal range.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"234 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087746","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":"Real-World Effectiveness of Budesonide Orodispersible Tablets for Eosinophilic Oesophagitis: The Importance of Patience and Education.","authors":"Sarah Taylor,Emily Barwick,Varan Perananthan,Nikita Parkash,Sarah Lucas,Ayushi Chauhan,Catherine Yu,Katrina Tan,Gloria Sepe,Mani Suleiman,Diana Lewis,Chamara Basnayake,Hamish Philpott,Sanjay Nandurkar,Rebecca Burgell,Mayur Garg","doi":"10.1111/apt.70197","DOIUrl":"https://doi.org/10.1111/apt.70197","url":null,"abstract":"Budesonide orodispersible tablets (BOT) have been shown to be efficacious for eosinophilic oesophagitis (EoE) in clinical trials. This study evaluated the real-world effectiveness of BOT in a retrospective cohort of 94 patients across six tertiary centres. 61% of patients achieved histological remission and 39% clinicohistological remission following induction therapy. Adverse events were reported by 16% of patients and 17% were noted to have incorrect technique of administration. BOT was demonstrated to have lower rates of clinicohistological remission in real-world practice than reported in clinical trials, largely due to incorrect technique and cessation due to adverse events.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"35 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945461","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":"Anthropometric Measures and Mortality Risk in Individuals With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Population-Based Cohort Study.","authors":"Yee Hui Yeo,Yixuan Zhu,Jingli Gao,Shanghao Liu,Wenjing Ni,Fajuan Rui,Xue Bai,Nan Geng,Rui Jin,Elizabeth K Speliotes,Chao Wu,Junping Shi,Xiaolong Qi,Vincent L Chen,Philip N Newsome,Jie Li","doi":"10.1111/apt.70174","DOIUrl":"https://doi.org/10.1111/apt.70174","url":null,"abstract":"BACKGROUND/AIMSAs the primary anthropometric measure in metabolic dysfunction-associated steatotic liver disease (MASLD), waist circumference (WC) may more accurately reflect the visceral fat distribution than body mass index (BMI). This study aimed to compare the prognostic value of BMI, WC and WC-related indices including waist-hip ratio (WHR), body shape index (BSI) and weight-adjusted-waist index (WWI) in individuals with MASLD.METHODSThe study population was derived from four large-scale cohorts: the National Health and Nutrition Examination Survey (NHANES 2017-2020 and NHANES III), the Kailuan Cohort and the UK Biobank Cohort. We evaluated the mortality risk across these measures using multivariate Cox proportional hazards regression and restrictive cubic spline.RESULTSThe Pearson correlation coefficient of WC with hepatic steatosis and fibrosis was better than that of BMI. WC [Quartile 4 vs. Quartile 1: HR (hazard ratio) = 1.48 (95% confidence interval (CI) 1.13-1.93)] and WC-related indices [Quartile 4 vs. Quartile 1: WHR HR = 3.21 (95% CI 2.36-4.37); BSI HR = 3.22 (95% CI 2.48-4.17); WWI HR = 4.72 (95% CI 3.36-6.62)], but not BMI [obesity vs. lean: HR = 0.90 (95% CI 0.72-1.12)], indicated a significant mortality risk gradient among individuals with MASLD. The finding was consistent across sex and racial/ethnic subgroups, with external validation supporting the WC-related indices. MASLD and fibrosis prevalence showed a dose-dependent pattern across WC-related index quartiles. Notably, low BMI and high WC-related indices portended the highest mortality risk.CONCLUSIONSWC and WC-related indices are better parameters in prognosticating MASLD than BMI. The BMI-related 'obesity paradox' may be a misnomer resulting from the use of an incorrect metric. WC should be measured more routinely among individuals with MASLD.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"30 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945460","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 Article: GLP-1 Receptor Agonists and Glucagon/GIP/GLP-1 Receptor Dual or Triple Agonists-Mechanism of Action and Emerging Therapeutic Landscape in MASLD.","authors":"Maryam Zafer,Federica Tavaglione,Manuel Romero-Gómez,Rohit Loomba","doi":"10.1111/apt.70196","DOIUrl":"https://doi.org/10.1111/apt.70196","url":null,"abstract":"BACKGROUNDMetabolic dysfunction-associated steatotic liver disease (MASLD) is primarily managed through diet and lifestyle modifications. However, these behavioural interventions alone may not achieve disease regression or remission, and maintaining long-term adherence is challenging. Incretin mimetics and other gastrointestinal hormones targeting the pleiotropic pathophysiological pathways underlying MASLD have now emerged as promising disease-modifying therapies.AIMSThis is a comprehensive review summarising the role of glucagon-like peptide-1 (GLP-1) receptor agonists and glucagon/glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor dual or triple agonists in the treatment of metabolic dysfunction-associated steatohepatitis (MASH).METHODSOnly clinical trials with endpoints assessed by liver histology were included for a robust evaluation of therapeutic efficacy.RESULTSRecent evidence from phase 2 clinical trials for MASH demonstrated that pharmacological agents based on GLP-1 receptor agonism are effective in improving disease activity. Additionally, tirzepatide and survodutide showed potential clinical benefits in reducing fibrosis. Other cardiometabolic benefits observed include weight loss and improvements in glycaemic control and lipid profile. Adherence to treatment may be limited by gastrointestinal side effects, though they were found to be generally mild to moderate in severity. An interim analysis of the semaglutide phase 3 trial confirmed its efficacy in improving steatohepatitis and demonstrated its potential to improve fibrosis.CONCLUSIONSGLP-1 receptor agonists, alone or in combination with GIP and/or glucagon receptor agonists, represent promising, effective pharmacotherapies for the treatment of MASLD/MASH. Larger and longer-duration clinical trials are needed to further evaluate the efficacy and safety of GIP receptor and glucagon receptor agonism.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"32 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945465","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":"Some Risks of Gastrointestinal Adverse Events Associated With Glucagon-Like PEPTIDE-1 Receptor Agonists Are Likely Explained by BMI.","authors":"Benjamin Douglas Liu,Donovan Veccia,Yan Sun,Gengqing Song","doi":"10.1111/apt.70190","DOIUrl":"https://doi.org/10.1111/apt.70190","url":null,"abstract":"We performed a re-analysis of the gastrointestinal risks of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in obese US adult patients without diabetes using the TriNetX database (GLP-1 RA n = 8792; Bupropion-naltrexone n = 8792) after accounting for initial BMI. GLP-1 RA users had higher risks of gastroparesis (aHR 2.30; 95% CI 1.19-4.46) and biliary disease (aHR 1.27; 95% CI 0.96-1.39) but did not have a conclusively elevated risk of acute pancreatitis or obstruction. Not matching for BMI suggested an elevated pancreatitis risk (aHR 1.75; 95% CI 1.13-2.70). Semaglutide conferred superior weight loss but increased biliary risk.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"96 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945150","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":"Clearance of Hepatitis C Viremia During Direct-Acting Antiviral Therapy Leads to Rapid Changes in Lipid and Lipoprotein Metabolism.","authors":"Zahra Sarrafan-Chaharsoughi,Varun Takyar,Sungyoung Auh,Gavin Nee,Ahmad Alawad,Brent S Abel,Devika Kapuria,Colleen Byrnes,Anna Wolska,David E Kleiner,Robert Shamburek,Alan T Remaley,Marc G Ghany","doi":"10.1111/apt.70130","DOIUrl":"https://doi.org/10.1111/apt.70130","url":null,"abstract":"BACKGROUND AND AIMSChronic hepatitis C virus (HCV) infection is associated with hypolipidemia. HCV eradication may, therefore, result in hyperlipidemia and increase cardiovascular disease (CVD) risk. We investigated the impact of HCV eradication on serum lipid and lipoprotein profiles and CVD risk during and following direct-acting antiviral (DAA) therapy.APPROACH AND RESULTSWe retrospectively analysed stored sera and plasma from 60 DAA-naïve patients, genotypes 1-4, treated with 12 weeks of sofosbuvir-velpatasvir. Serum lipids, apolipoproteins (apo), and a systemic inflammatory marker, GlycA, were measured serially beginning early on treatment and off treatment. Additionally, NMR LipoProfile analysis was performed on plasma samples. Expression of genes regulating lipid metabolism was assessed from paired liver biopsies obtained before and on treatment. Linear mixed models were used to examine changes in lipid and inflammatory markers; Framingham and ASCVD CVD risk scores were assessed before and after treatment. Decline in HCV viremia was associated with a rapid, significant increase in TChol, HDL-C, LDL-C, ApoA-1 and ApoB, and GlycA, improvement in ALT, hepatic inflammation, and steatosis but no change in glycemic control (HOMA-IR and HbA1c). Increase in TChol, LDL-C, and ApoB was associated with an increased SREBP1expression. Both ASCVD and Framingham risk scores were significantly increased at week 24 post treatment after adjusting for age (p < 0.0001).CONCLUSIONSerum lipids and lipoproteins rapidly increase with inhibition of viral replication during DAA therapy, an effect that may be mediated by genes affecting hepatic de novo lipogenesis. Based on lipid changes, HCV eradication may increase CVD risk, but this needs to be investigated prospectively.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"35 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945466","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: Different Risk of Acute Variceal Bleeding According to the Liver Disease Aetiology in Decompensated Cirrhosis Patients Receiving Carvedilol‐Based Primary Prophylaxis—May Insulin Resistance Unloose This Gordian Knot?","authors":"Mario Romeo, Fiammetta Di Nardo, Carmine Napolitano, Paolo Vaia, Alessandro Federico, Marcello Dallio","doi":"10.1111/apt.70192","DOIUrl":"https://doi.org/10.1111/apt.70192","url":null,"abstract":"&lt;p&gt;&lt;i&gt;Editors&lt;/i&gt;.&lt;/p&gt;\u0000&lt;p&gt;We enthusiastically read the brilliant research by Villanueva et al. which, by systematically reviewing randomised clinical trials (RCTs) comparing non-selective beta-blocker (NSBB) versus variceal band ligation (VBL) for primary acute variceal bleeding (AVB) prevention in cirrhotic patients presenting high-risk varices, revealed NSBBs significantly improved survival versus VBL, with no additional benefit noted of the combination strategy, exclusively in patients with compensated advanced chronic liver disease (cACLD), reporting, in contrast, a similar survival with both therapies in decompensated (dACLD) individuals [&lt;span&gt;1&lt;/span&gt;]. These findings remarked on a crucial need for personalised AVB-primary prophylaxis by adapting treatment to the clinical stage of cirrhosis [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;More recently, the “&lt;i&gt;CAVARLY trial&lt;/i&gt;” has demonstrated the superiority of the combination therapy (VBL-NSBB) to either strategy alone in preventing the first AVB in dACLD patients with high-risk varices [&lt;span&gt;2&lt;/span&gt;]. Interestingly, an elevated rate of events in the carvedilol arm (33.6%) was reported, and, notably, over half of the patients did not show a haemodynamic NSBB response [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;Unlike previous historical research [&lt;span&gt;3&lt;/span&gt;], in this trial, a significant proportion (~50%) of enrolled patients presented Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD)-related cirrhosis, providing an updated snapshot of the current chronic liver disease (CLD) epidemiology.&lt;/p&gt;\u0000&lt;p&gt;Relevantly, type 2 diabetes mellitus (T2DM) and obesity have already been demonstrated to impair the haemodynamic response to NSBB, thus predisposing to overall hepatic decompensation [&lt;span&gt;4, 5&lt;/span&gt;]. However, the impact of CLD aetiology on first AVB remains unexplored in dACLD patients.&lt;/p&gt;\u0000&lt;p&gt;From July 2022 to April 2024, we consecutively enrolled and followed over 12 months, 76 (35 viral-related and 41 MASD-related) dACLD individuals presenting high-risk varices (IRB-prot0021377/i). Patients received carvedilol-based primary prophylaxis (32 MASLD; 28 viral-related), reserving VBL for NSBB-intolerant subjects (9 MASLD; 7 viral-related) [&lt;span&gt;6&lt;/span&gt;]. As in “&lt;i&gt;CAVARLY&lt;/i&gt;”, NSBB compliance was self-monitored by arterial pressure measurements and a diary.&lt;/p&gt;\u0000&lt;p&gt;A significantly higher rate of AVB was observed in MASLD compared to the viral-related group (HR: 2.806, &lt;i&gt;p&lt;/i&gt;: 0.027), specifically in the carvedilol-receiving patients. Interestingly, the Cox regression analysis (adjusted for sex, age, Child-Pugh, BMI, and endoscopic varices features) revealed T2DM (aHR: 2.541, &lt;i&gt;p&lt;/i&gt;: 0.001), Homeostasis Model Assessment for Insulin Resistance (aHR: 2.112, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), obesity (aHR: 1.781, &lt;i&gt;p&lt;/i&gt;: 0.002), and C-reactive protein (aHR: 1.72, &lt;i&gt;p&lt;/i&gt;: 0.001) as the variables significantly associated with this outcome (Figure 1).&lt;/p&gt;\u0000&lt;figure&gt;&lt;picture&gt;\u0000&lt;source media=\"(min-width: 1650px)\" srcset=\"/cms","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"10 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940265","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: Selective FGFR1c/KLB Activation in MASH—A Mechanistic Dilemma?","authors":"Cuiyun Tao, Ye Liang, Jianghui Zeng","doi":"10.1111/apt.70166","DOIUrl":"https://doi.org/10.1111/apt.70166","url":null,"abstract":"<p>The Phase 2b trial of MK-3655 (NCT04583423) provides critical insights into fibroblast growth factor 21 (FGF21) pathway modulation, yet raises fundamental questions about therapeutic targeting strategies [<span>1</span>]. While the reported 26.1% placebo-adjusted liver fat reduction at 300 mg (<i>p</i> &lt; 0.05) aligns with early-phase FGF21 analogs [<span>2</span>], it falls substantially below the ≥ 40% reductions seen with efruxifermin [<span>3</span>] and pegozafermin [<span>4</span>] in comparable populations. This discrepancy underscores a key mechanistic consideration: does selective FGFR1c/KLB activation sufficiently replicate FGF21's pleiotropic effects?</p>\u0000<p>The trial's early termination limits histological interpretation, but the 17.6% MASH resolution rate at 300 mg versus 5.9% placebo (<i>p</i> = NS) suggests partial biological activity. However, the modest efficacy contrasts with dual FGFR1c/2c/3c activators showing 24%–26% MASH resolution rates [<span>3, 4</span>]. Preclinical models indicate FGFR1 primarily mediates metabolic effects through adipose tissue [<span>5</span>], but human data now suggest broader receptor engagement may be necessary for optimal hepatoprotection. This aligns with the 48% greater LFC reduction seen with pan-FGFR activator pegozafermin [<span>3</span>] versus MK-3655.</p>\u0000<p>The safety profile merits attention. While MK-3655 showed fewer gastrointestinal events than FGF21 analogs [<span>3, 4</span>], its 2.2%–4.3% blood pressure elevation mirrors class effects observed in SYMMETRY trial [<span>6</span>]. Paradoxical weight gain (+1.2 kg vs. placebo) contrasts with FGF21's catabolic profile, potentially reflecting incomplete β-Klotho receptor engagement or compensatory mechanisms.</p>\u0000<p>This study crucially demonstrates that isolated FGFR1c activation achieves a partial therapeutic effect, challenging the sufficiency of ‘adipose-first’ strategies in MASH. Future development should explore whether multi-receptor agonists or combination therapies can optimise metabolic-liver crosstalk while maintaining favourable safety profiles.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"39 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926637","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: Crohn's Disease With Latent Tuberculosis Infection or Intestinal Tuberculosis: Rapid Discrimination by Targeted Next-Generation Sequencing","authors":"Maryam Irshad, Shahzeen Irshad","doi":"10.1111/apt.70152","DOIUrl":"https://doi.org/10.1111/apt.70152","url":null,"abstract":"&lt;p&gt;We read with interest the study by Ye et al. [&lt;span&gt;1&lt;/span&gt;]. The authors demonstrated that targeted next-generation sequencing (tNGS) has high sensitivity (83%) and 100% specificity for detecting &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt; from fresh ulcer base biopsy samples, offering an alternative to conventional methods like acid-fast bacillus staining, TB-PCR, and histopathological examination. Given the diagnostic challenges in tuberculosis-endemic regions, this represents a potentially significant advancement in clinical gastroenterology.&lt;/p&gt;\u0000&lt;p&gt;The novelty of the study represents promising findings, but there are limitations.&lt;/p&gt;\u0000&lt;p&gt;First, the study was restricted to patients with positive Interferon Gamma Release Assay (IGRA) results. Since IGRA can yield false-negative results, especially in immunocompromised patients, this selection criterion may have excluded some patients with intestinal tuberculosis (ITB), thereby limiting generalizability [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;Second, the test missed 17% of true ITB cases. The authors attributed this to a low bacterial load in biopsy samples. However, particular patient-based factors such as immune suppression, prior antibiotic use, and variation in granuloma formation might also have played a role in the lower detection rate.&lt;/p&gt;\u0000&lt;p&gt;Third, the study was performed at a single institution and the sample size was small. These restrict the generalisability of the results as the specificity and sensitivity of a diagnosis may vary with respect to population, healthcare setting and endemic region. These factors may significantly influence the performance of tNGS, including variation of TB strain types, host immune responses and healthcare infrastructure. To establish such results prior to impulsive concretising of clinical use, a multicentre validation study with diverse patient cohorts and under diverse laboratory conditions would be necessary.&lt;/p&gt;\u0000&lt;p&gt;Although tNGS performs better than some conventional tests, the absence of the gold standard of TB culture limits direct comparison [&lt;span&gt;3&lt;/span&gt;]. Its real-life benefits are unknown without head-to-head assessments against diagnostics such as Xpert MTB/RIF (Xpert &lt;i&gt;M. tuberculosis&lt;/i&gt;/rifampicin) assay, a nucleic acid amplification test endorsed by the World Health Organization for detecting &lt;i&gt;M. tuberculosis&lt;/i&gt; complex and resistance to rifampicin in under 2 h [&lt;span&gt;4&lt;/span&gt;]. Moreover, histopathological data would be nullable, if based on biopsies performed on ulcer bases, which are very much subject to sampling error given the variable distribution of pathogens and difficulties in obtaining fresh tissue. Additional studies are needed to investigate whether larger numbers of biopsy sites or broader approaches to molecular techniques would increase sensitivity and feasibility.&lt;/p&gt;\u0000&lt;p&gt;In summary, while Ye et al. have provided meaningful insights into the potential of tNGS for rapidly distinguishing ITB from Crohn's disease with latent tuberculosis inf","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"7 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926635","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: Are Antispasmodics Truly Ineffective in IBD? Considerations on Nuanced Interpretation and Stratified Analysis","authors":"Haoxun Mao, Sheng Li","doi":"10.1111/apt.70168","DOIUrl":"https://doi.org/10.1111/apt.70168","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"228 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920320","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}