Lancet Gastroenterology & Hepatology最新文献

{"title":"Efficacy and safety of duvakitug in patients with Crohn's disease (RELIEVE UCCD): a phase 2b, randomised, placebo-controlled trial","authors":"Vipul Jairath, Jaroslaw Kierkuś, George Aaron Duvall, Silvio Danese, Bruce E Sands, Bogdan Ratiu-Duma, Rajendra Singh, Phillip Levine, Hadas Barkay, Nicholas Gross, Ken Abrams, Walter Reinisch","doi":"10.1016/s2468-1253(26)00119-6","DOIUrl":"https://doi.org/10.1016/s2468-1253(26)00119-6","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"35 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148461874","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":"Efficacy and safety of duvakitug in patients with ulcerative colitis (RELIEVE UCCD): a phase 2b, randomised, placebo-controlled trial","authors":"Walter Reinisch, David Stepek, Radoslaw Kempinski, Silvio Danese, Bruce E Sands, Bogdan Ratiu-Duma, Rajendra Singh, Phillip Levine, Hadas Barkay, Nicholas Gross, Ken Abrams, Vipul Jairath","doi":"10.1016/s2468-1253(26)00120-2","DOIUrl":"https://doi.org/10.1016/s2468-1253(26)00120-2","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"33 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148460018","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":"Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial","authors":"Robert Hüneburg, Querijn N E van Bokhorst, Maria Pellisé, Francesc Balaguer, Angelo Brunori, Thomas Rösch, Deepak B Vangala, Kien Vu Trung, Arne Kandulski, Britt B S L Houwen, Hanneke Beaumont, Dewkoemar Ramsoekh, Christian P Strassburg, Raf Bisschops, Alexander Link, Tim Marwitz, Jonas Rogee, Katrin van Beekum, Christoph Engel, Evelien Dekker, Jacob Nattermann, Anne-Sophie Layritz, Kristin Gehrmann, Sonja Haas, Rebecca Sturm, Antonia Schuler, Ronny Dathe, Maria Daca Alvarez, Oswaldo Ortiz, Liseth Rivero, Teresa Ocaña, Hardeep Kumari, Joaquin Andres Castillo, Manon van der Vlugt, Joep Grootjans, Barbara A.J. Bastiaansen, Dominik Heling, Dominik J Kaczmarek, Michael Pohl, Michael Steckstor, Josef Pospiech","doi":"10.1016/s2468-1253(26)00163-9","DOIUrl":"https://doi.org/10.1016/s2468-1253(26)00163-9","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"54 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459983","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":"Pathophysiology of irritable bowel syndrome","authors":"Yasmin Nasser, Andrea Shin, Alexander C Ford, Michael Camilleri, Christopher J Black","doi":"10.1016/s2468-1253(26)00148-2","DOIUrl":"https://doi.org/10.1016/s2468-1253(26)00148-2","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"32 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148460017","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":"Efficacy and safety of zalfermin co-administered with semaglutide in participants with fibrosis and cirrhosis due to metabolic dysfunction-associated steatohepatitis: a phase 2, dose-ranging, double-blind, randomised controlled trial.","authors":"Rohit Loomba,Jacob George,Laurent Castera,Sven Francque,Eric Lawitz,Ahsan Shoeb,Jesper Ole Clausen,Birgitte Andersen,Anna Bille Larsen,Lise Lotte Gluud","doi":"10.1016/s2468-1253(26)00123-8","DOIUrl":"https://doi.org/10.1016/s2468-1253(26)00123-8","url":null,"abstract":"BACKGROUNDThis phase 2 study evaluated once-weekly zalfermin and semaglutide for efficacy and safety in patients with metabolic dysfunction-associated steatohepatitis and clinically significant fibrosis, including patients with compensated cirrhosis (F4c).METHODSThis proof-of-concept, phase 2, dose-ranging, double-blind, randomised controlled trial was done in 187 clinical trial sites in Australia, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Greece, India, Italy, Japan, Malaysia, Poland, Portugal, Russia, Singapore, South Korea, Spain, Taiwan, Türkiye, and the USA. Eligible participants were aged 18 years or older with histological confirmation of steatohepatitis on liver biopsy (baseline or historical within 180 days). Eligible participants had clinically significant fibrosis (stage F2-F4c) in the absence of decompensation. Eligible participants were randomly assigned to receive subcutaneous zalfermin 7·5 mg plus subcutaneous semaglutide 2·4 mg, zalfermin 15 mg plus semaglutide 2·4 mg, zalfermin 30 mg plus semaglutide 2·4 mg, zalfermin 30 mg, semaglutide 2·4 mg, cagrilintide 2·4 mg plus semaglutide 2·4 mg, or placebo only once a week for 52 weeks. The primary endpoint was improvement in liver fibrosis on the NASH CRN fibrosis scale of at least one stage and no worsening of metabolic dysfunction-associated steatohepatitis at week 52. Efficacy was assessed in the full analysis set (all randomly assigned participants) and safety was analysed in all participants who were randomly assigned and received at least one dose of trial product or placebo. The trial is registered with ClinicalTrials.gov, NCT05016882, and is completed.FINDINGSBetween Aug 31, 2021, and March 14, 2025, 2420 people were screened for inclusion. 178 withdrew before random assignment and 1544 were disqualified. 698 participants were enrolled and randomly assigned to zalfermin 7·5 mg plus semaglutide 2·4 mg (n=99), zalfermin 15 mg plus semaglutide 2·4 mg (n=100), zalfermin 30 mg plus semaglutide 2·4 mg (n=99), zalfermin 30 mg (n=101), semaglutide 2·4 mg (n=100), cagrilintide 2·4 mg plus semaglutide 2·4 mg (n=99), or placebo (n=100). 441 (63%) of 698 participants were female and 257 (37%) were male. 484 (69%) of 698 participants were White and 172 (25%) were Asian. At week 52, the proportion of participants who had an improvement in liver fibrosis and no worsening of metabolic dysfunction-associated steatohepatitis with zalfermin 30 mg plus semaglutide 2·4 mg was not significantly greater than with placebo (24 [24%] of 99 participants in the combination group vs 16 [16%] of 100 participants in the placebo group; estimated difference in responder proportions [EDP] 7·98, 95% CI -3·82 to 19·79; p=0·19). A nominally significantly greater proportion of participants in the semaglutide 2·4 mg group achieved this endpoint than in the placebo group (30 [30%] of 100 participants in the semaglutide group; EDP 14·05, 95% CI 1·88 to 26·23; p=0·024), but not in the zalferm","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"11 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451437","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":"Aspirin for cancer prevention in individuals with Lynch syndrome: first results from the CaPP3 multicentre, randomised, double-blind, non-inferiority trial.","authors":"John Burn,Gillian M Borthwick,Faye Elliott,Finlay Macrae,Kai Ren Ong,Alison C Kraus,Nadir Arber,Jukka-Pekka Mecklin,Angel Alonso,Emma R Woodward,D Gareth Evans,Alex Murray,Katie Snape,Ruth E Cleaver,Adam Shaw,Huw J W Thomas,Ajith V Kumar,Dorothy Halliday,Lucy E Side,Rachel E Harrison,Rosemarie Davidson,Ruth Armstrong,Jackie Cook,Rachel Hart,Patrick J Morrison,Julian G Barwell,Alan Donaldson,Zoe Kemp,Jennie Murray,Zosia Miedzybrodzka,Caroline Pottinger,Jonathan Berg,Richard Gallon,D Timothy Bishop, ","doi":"10.1016/s2468-1253(26)00114-7","DOIUrl":"https://doi.org/10.1016/s2468-1253(26)00114-7","url":null,"abstract":"BACKGROUNDIn CAPP2, 600 mg aspirin daily significantly reduced the incidence of colorectal cancer and the incidence of all Lynch syndrome cancers among participants with Lynch syndrome. CaPP3 aimed to assess the efficacy of two lower doses of aspirin.METHODSCaPP3 was a multicentre, parallel-group, randomised, double-blind, dose non-inferiority trial that compared 100 mg or 300 mg daily aspirin with 600 mg daily aspirin in Lynch syndrome carriers aged older than 18 years; patients were recruited from clinical genetics centres in the UK, Australia, Finland, Israel, and Spain. The trial was double-blinded for 2 years, and open label on the same dose for three subsequent years with consent for cancer follow-up (except in the UK, where 75 mg aspirin replaced the 100 mg dose in the open phase). Participants from the five countries were randomly assigned by the Newcastle Clinical Trials Unit in a 3:3:4 ratio to receive daily doses of 100 mg, 300 mg, and 600 mg. Participants received blinded doses of aspirin, identically packaged so as not to indicate dose, every 6 months. Information on compliance was collected on a self-report basis. The dose was revealed at 2 years of recruitment; subsequently, aspirin was obtained via hospital prescriptions during this open-label phase. The primary outcome was the number of new primary mismatch repair-deficient cancers (referred to as Lynch syndrome cancers) developing in participants and diagnosed in the period from the start of the intervention for each participant. The safety outcome was the number of adverse events of interest in the first 2 years of blinded treatment. Aspirin-specific adverse events were recorded at regular participant interviews as a measure of harm during the blinded phase. A non-inferiority margin of 1·5 was chosen for each lower dose against 600 mg daily for the primary endpoint. The effects of the two lower doses (compared to 600 mg daily) were examined with Cox proportional hazards examining time to first Lynch syndrome cancer, with the effect being assessed by hazard ratios (HRs), while negative binomial regression examined the relative cancer burden assessed by incidence rate ratios (IRRs). Non-inferiority was proposed with either lower dose if the upper 95% CI of both the HR and IRR in comparison with 600 mg were below the non-inferiority boundary of 1·5. Participants were deemed per protocol if they had adhered to the protocol and continued taking aspirin into the unblinded phase (ie, they agreed to remain in the study at the 2-year review); non-inferiority required consistency of effects within both intention-to-treat and per-protocol populations and for both HR and IRR analyses. CaPP3 is registered on the ISRCTN registry (ISRCTN16261285) and ClinicalTrials.gov (NCT02497820), and was closed to recruitment in March 2019; this analysis was timed for when all participants reached 5 years past recruitment. Further follow-up is planned until all participants reach 10 years past recruitment","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"18 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416158","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":"Low-dose aspirin: effective cancer chemoprevention in Lynch syndrome.","authors":"Kevin J Monahan","doi":"10.1016/s2468-1253(26)00124-x","DOIUrl":"https://doi.org/10.1016/s2468-1253(26)00124-x","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"9 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416155","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":"Research in Brief","authors":"Holly Baker","doi":"10.1016/s2468-1253(26)00190-1","DOIUrl":"https://doi.org/10.1016/s2468-1253(26)00190-1","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"68 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148538340","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":"Barrier restoration as a therapeutic strategy for disorders of gut-brain interaction.","authors":"Timmie A Britton,Madhusudan Grover","doi":"10.1016/s2468-1253(26)00081-6","DOIUrl":"https://doi.org/10.1016/s2468-1253(26)00081-6","url":null,"abstract":"Disorders of gut-brain interaction, such as irritable bowel syndrome and functional dyspepsia, are increasingly linked to defects in gut barrier function. Mucosal disruption, encompassing alterations in the epithelial and mucus layers, leads to enhanced intestinal permeability, microbial translocation, and aberrant immune and neuronal signalling, potentially contributing to symptom severity. Despite growing recognition of barrier dysfunction in disorders of gut-brain interaction, clinical interventions remain largely symptom-based, with few therapies designed to directly restore epithelial integrity. In this Review, we examine the cellular and molecular pathways underpinning gut barrier function and highlight evidence supporting the role of diet, microbiome-targeted interventions, stress modulation, and pharmacological agents in maintaining or restoring intestinal permeability. Mechanistic insights reveal that short-chain fatty acids, amino acids (glutamine and tryptophan), and targeted probiotics can enhance tight junction integrity and mucin secretion, whereas psychological stress, low-fibre diets, and high-fat diets disrupt these pathways. We also discuss novel therapeutics, including antihistamines, mast cell stabilisers, protease inhibitors, secretagogues, and guanylate cyclase C agonists, and emerging technologies, such as vagal nerve stimulation and barrier-protective hydrogel delivery systems. Although promising, these strategies require validation in well designed clinical trials with targeted endpoints, and patient stratification based on microbial and immune phenotypes. By integrating advances in molecular biology with translational therapeutics, interventions targeting intestinal permeability could shift the treatment paradigm for disorders of gut-brain interaction from general symptom management to personalised disease modification.","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"79 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400887","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":"Bowel endometriosis: from pathogenesis to clinical management.","authors":"Fabio Barra,Edoardo Giovanni Giannini,Maria Grazia Centurioni,Claudio Gustavino,Franco Alessandri,Simone Ferrero","doi":"10.1016/s2468-1253(26)00117-2","DOIUrl":"https://doi.org/10.1016/s2468-1253(26)00117-2","url":null,"abstract":"Bowel involvement is a severe manifestation of deep endometriosis that affects approximately 8-12% of women with endometriosis. Bowel endometriosis is most commonly localised in the rectosigmoid colon and frequently coexists with other pelvic lesions. The pathogenesis of bowel endometriosis is multifactorial, involving hormonal, inflammatory, immune, genetic, and anatomical factors. Clinical presentation ranges from asymptomatic disease to severe gastrointestinal and pelvic symptoms, which can mimic other digestive disorders such as irritable bowel syndrome and inflammatory bowel disease. Diagnostic delays frequently exceed 7-10 years. Transvaginal ultrasound and MRI are the main non-invasive tools for the diagnosis and preoperative assessment of rectosigmoid endometriosis. First-line medical therapy with combined oral contraceptives or progestogens might provide symptom control but is not curative, whereas surgery is reserved for bowel obstruction or severe or refractory symptoms, with surgical approach tailored to disease characteristics and patient needs. Fertility outcomes remain uncertain, and the complexity of long-term management, including the rare risk of malignant transformation, supports the need for multidisciplinary follow-up.","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"204 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379623","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}