Gut最新文献

{"title":"Eosinophilic gastritis: burden of disease, diagnostic challenges and unmet needs.","authors":"Marc E Rothenberg, Mirna Chehade, Evan S Dellon, Margaret Collins, Nicholas J Talley, Margee Louisias, Ashish Bansal","doi":"10.1136/gutjnl-2025-337900","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337900","url":null,"abstract":"<p><p>Eosinophilic gastritis (EoG) is a rare, chronic disease characterised by pathological eosinophilia of the stomach and gastrointestinal symptoms. Evidence suggests that pathophysiology is triggered by food antigens and driven by type 2 immune dysregulation, with upregulation of interleukins 4 and 13. Diagnosis is based on symptoms, endoscopic evaluation and abnormal gastric biopsies demonstrating dense eosinophilic infiltration, after exclusion of other potential causes of eosinophilia. There are currently no approved treatments for EoG, and existing therapeutic options-including dietary elimination and off-label systemic or topical corticosteroids-have suboptimal outcomes or are not appropriate for long-term use. Ongoing clinical studies of biologics in the field have the potential to impact clinical care.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":24.6,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001739","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":"Coordinated cellular programmes distinguish responses to neoadjuvant PD-L1 blockade and potentiate combinatorial immunotherapy in ESCC.","authors":"Si Li, Jiyu Guo, Jianqun Ma, Jiaxin Yang, Zuxiang Wang, Gang Xu, Yun Yu, Kang Xu, Yueying Gao, Weiwei Zhou, Can Zhang, Qinghua Jiang, Xiaoyuan Wang, Hang Yin, Yongsheng Li","doi":"10.1136/gutjnl-2026-339071","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-339071","url":null,"abstract":"<p><strong>Background: </strong>Programmed death ligand 1 (PD-L1) blockade offers new therapeutic options for oesophageal squamous cell carcinoma (ESCC); however, the underlying mechanisms and associated biomarkers that determine treatment response remain unclear.</p><p><strong>Objective: </strong>We delineate the mechanisms underlying the response and resistance, and elucidate the immune features that enhance neoadjuvant PD-L1 blockade efficacy in ESCC.</p><p><strong>Design: </strong>Here, we characterise the cellular dynamics following neoadjuvant PD-L1 blockade via analysing the single-cell transcriptomes of 210 978 cells and spatial transcriptomes of 20 tissue sections.</p><p><strong>Results: </strong>We identify coordinated cellular programmes centred on CXCL13⁺ CD8⁺ exhausted T cells, TNFRSF9⁺ CD4⁺ regulatory T cells, atypical memory B cells and APOE⁺ macrophages, which coordinate the responses to neoadjuvant PD-L1 blockade at baseline. In post-treatment non-responder ESCCs, the cellular programmes exhibit an immunosuppressive phenotype, leading to the failure of therapeutic benefits. Furthermore, we reveal that lymphocyte activation gene 3 serves as a potential target and can potentiate the response via perturbation of the coordinated cellular programmes.</p><p><strong>Conclusions: </strong>Overall, our findings unravel the coordinated cellular programmes associated with treatment response, providing insights for prioritising individualised immunotherapy strategies in ESCC.</p><p><strong>Trial registration number: </strong>ChiCTR2400083452.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":24.6,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001760","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":"A durably colonising engineered native symbiont enables sustained intestinal delivery for metabolic dysfunction and colitis.","authors":"Qixiang Zhao, Yong Ding, Sen Yan, Haohan Ma, Yicun Wang, Siqi Guo, Xi Luo, Yanli Pang, Changtao Jiang, Kai Wang","doi":"10.1136/gutjnl-2026-339637","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-339637","url":null,"abstract":"<p><strong>Background: </strong>Engineered bacterial therapeutics represent a promising strategy for sustained intestinal delivery of therapeutic molecules, but their efficacy is limited by inefficient colonisation, safety concerns and the need for repeated administration or auxiliary delivery systems.</p><p><strong>Objective: </strong>To develop a safety-optimised native bacterial chassis capable of long-term gut colonisation and sustained therapeutic delivery for intestinal inflammatory and metabolic diseases.</p><p><strong>Design: </strong>Native murine <i>Escherichia coli</i> isolates were screened for antibiotic susceptibility, genetic tractability and long-term intestinal colonisation. The selected strain, MEc30, was further optimised by deleting the putative virulence-associated <i>clb</i> and <i>irp</i> loci. MEc30 was then engineered to produce nicotinic acid (MEc30-NA) or deliver murine interleukin-10 (MEc30-mIL-10), and therapeutic efficacy was evaluated in a high-fat diet-induced metabolic dysfunction model as well as <i>Il10</i> ^-/- and dextran sulphate sodium (DSS)-induced colitis models.</p><p><strong>Results: </strong>MEc30 achieved stable lifelong colonisation of the murine intestine after a single oral administration, without antibiotic preconditioning or auxiliary delivery systems and did not detectably disturb host physiology or gut microbial ecology. Deletion of <i>clb</i> and <i>irp</i> abolished potential colibactin- and yersiniabactin-associated biosafety risks while preserving bacterial growth and colonisation capacity. MEc30-NA continuously produced nicotinic acid in the gut, activated epithelial GPR109a-associated barrier signalling, improved glucose and lipid metabolism, reduced systemic inflammation and avoided the sharp peak exposure associated with conventional nicotinic acid administration. MEc30-mIL-10 enabled sustained intestinal interleukin-10 delivery, suppressed inflammatory macrophage activation, improved barrier integrity and alleviated colitis in both <i>Il10^-</i> ^/ <i>^-</i> and DSS-induced mouse models.</p><p><strong>Conclusion: </strong>This study identifies MEc30 as a durable and safety-optimised native <i>E. coli</i> chassis for sustained intestinal therapeutic delivery. Engineered native symbionts may provide a long-acting live biotherapeutic strategy for metabolic diseases and chronic intestinal inflammation.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":24.6,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001747","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":"HBV induces immunosuppressive macrophages via metabolic and epigenetic reprogramming to facilitate the establishment of chronic persistent infection.","authors":"Zhengmin Wang, Nan Liu, Yongqi Li, Tianyang Li, Licong Ma, Zhongfeng Wang, Xinyang Li, Yun Dai, Tong Zhang, Zhiheng Guo, Yao Zhi, Faxiang Ma, Juan Lv, Yanhang Gao, Junqi Niu, Yang Yang, Zhengkun Tu","doi":"10.1136/gutjnl-2025-337367","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337367","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis B virus (HBV) induces hepatic immunosuppressive macrophages to facilitate chronic infection but the mechanisms remain unclear. Metabolic and epigenetic reprogramming during monocyte differentiation into macrophages has also been observed in bacterial infection and Bacillus Calmette-Guerin (BCG) vaccination, shaping tolerant or trained macrophages.</p><p><strong>Objective: </strong>To investigate whether HBV modulates monocyte-to-macrophage differentiation via metabolic-epigenetic reprogramming.</p><p><strong>Design: </strong>Monocytes from chronic HBV-infected patients, healthy controls and cord blood were differentiated into macrophages (monocyte-derived macrophages and cord blood monocyte-derived macrophages). Cytokine expression and secretion, metabolic and epigenetic changes and immunomodulatory functions were characterised by qRT-PCR, ELISA, Western blotting, immunofluorescence, multiplexed immunohistochemistry, immunoprecipitation, metabolite measurements, ChIP-seq, ChIP-qPCR assay, plasmid transfection, reanalysed scRNA-seq and flow cytometry.</p><p><strong>Results: </strong>MDMs from CHB patients showed higher IL-10 and lower TNF-α than healthy donors ex vivo. HBV employed its surface antigen (HBsAg) to strongly influence cord blood but not adult monocyte differentiation into such an immunosuppressive macrophage in vitro. This occurred via post-translational modification of histone H3 on residue K18 (H3K18). HBsAg-pyruvate kinase M2 (PKM2) dimer interaction promoted PKM2/LDHA-driven lactate production, enhancing H3K18 lactylation at the IL-10 promoter and increasing IL-10 secretion. Meanwhile, phosphorylation of STAT1 is shifted with increased serine 727-phosphate but decreased tyrosine 701-phosphate via the p38/AKT pathway. It triggers the CD38/NAD⁺/SIRT1 axis, reducing H3K18 acetylation at the TNF-α promoter and suppressing TNF-α synthesis. Moreover, HBV-educated immunosuppressive macrophages inhibited NK cell IFN-γ production and promoted HBV replication in hepatocytes.</p><p><strong>Conclusions: </strong>HBV controls monocyte-to-macrophage fate via HBsAg-mediated metabolic-epigenetic-immune cascades to facilitate chronic persistent infection. These metabolic-epigenetic axes represent potential therapeutic targets.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":24.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982513","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":"Impact of non-enteric-coated pancreatic enzyme replacement therapy (NEPERT) on pain in patients with chronic pancreatitis: a double-blind, parallel-group, placebo-controlled, randomised trial.","authors":"Rupjyoti Talukdar, Abdul Rasheed, Misbah Unnisa, Chandana Vuyyala, Rajesh Goud, Manohar Reddy, Jahangeer Basha, Chandan Peddapulla, Manu Tandan, Nageshwar D Reddy","doi":"10.1136/gutjnl-2026-338802","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338802","url":null,"abstract":"<p><strong>Background: </strong>Pain in chronic pancreatitis (CP) is multifactorial. Efficacy of pancreatic enzyme replacement therapy (PERT) for pain remains uncertain.</p><p><strong>Objective: </strong>To assess the effect of non-enteric-coated PERT (NEPERT) on pain in CP.</p><p><strong>Design: </strong>In this 24-week, double-blind, placebo-controlled, randomised trial, we enrolled adults aged 18-60 years with CP (Mayo Clinic criteria) and chronic abdominal pain at two academic centres. Participants were randomised to NEPERT (protease 30 000U, lipase 25 000U, amylase 8000U per capsule) or placebo for 12 weeks. Outcomes were measured at 12 and 24 weeks. Primary outcome was between-group differences in change in Izbicki pain score from baseline to 12 weeks. Secondary outcomes were Izbicki and Visual Analogue Scale (for pain) at 24 weeks, painful days, analgesic/hospitalisation requirements, patient's global impression of change and quality of life at 12 and 24 weeks. The reason for secondary outcomes assessment at 24 weeks was to evaluate carry-over effects after NEPERT. Primary analysis used repeated-measures mixed-effects models.</p><p><strong>Results: </strong>107 patients (mean (SD) age 34.4 (11.4) years; 71% men; 66% idiopathic) were randomised (53 placebo; 54 NEPERT). On intention-to-treat analysis, there were no significant between-group differences in pain improvement at 12 weeks (Izbicki -2.5 (95% CI -9.3 to 4.2), p=0.49). Findings were similar at 24 weeks. Secondary outcomes were also similar at 12 and 24 weeks, except for a higher proportion of participants reporting painful days at 12 weeks in the NEPERT group (mean group differences (95% CI) of -14.5 (-26.0 to -3.0); p=0.02). Adverse events were mild, self-limiting and comparable between groups.</p><p><strong>Conclusions: </strong>In adults with painful CP, NEPERT did not improve pain compared with placebo.</p><p><strong>Trial registration number: </strong>NCT05042284.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":24.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982583","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":"Divergent microbial preludes to necrotising enterocolitis defined by gut phages and bacterial resistomes.","authors":"Kailun Zhang, Mark G Gorelik, Janice E Sullivan, Paula Radmacher, Marilyn Escobedo, Barbara B Warner, Phillip I Tarr, Gautam Dantas","doi":"10.1136/gutjnl-2026-338976","DOIUrl":"10.1136/gutjnl-2026-338976","url":null,"abstract":"<p><strong>Background: </strong>Translating microbiome correlations into robust predictive features for complex gut disorders remains elusive, partly due to oversimplified models of pathogenesis and neglect of the virome, a key player in microbial ecosystems. Necrotising enterocolitis (NEC), a devastating disease of preterm infants with no reliable clinical predictors, exemplifies this challenge.</p><p><strong>Objective: </strong>To determine the predictive potential of the gut prophageome and polymicrobial aetiologies for NEC.</p><p><strong>Design: </strong>We applied integrated metagenomic and metatranscriptomic analyses and machine learning to 1825 longitudinal stool samples from 43 preterm infants who later developed NEC and 86 gestational age-matched and birthweight-matched controls across three US hospitals. We characterised gut prophageome acquisitions and their association with clinical exposures, including antibiotics, diet and pharmacotherapies. To predict NEC risk, we integrated pre-onset prophageome, antibacterial resistome and bacteriome profiles with neonatal pathology, stratifying the cohort by disease onset timing (early: ≤40 days; late: >40 days) for separate analysis.</p><p><strong>Results: </strong>NEC cases exhibited distinct viral diversity trajectories before disease onset. Early-onset NEC was best predicted by phage-bacterial interaction signatures (75% accuracy, 81% sensitivity). Metatranscriptomics revealed increased phage DNA abundance with low gene expression, suggesting a lysogenic lifestyle that may stabilise pathobionts. These phages encode metabolic genes potentially enhancing pathobiont resilience. Late-onset NEC was best predicted by antibacterial resistome profiles (83% accuracy).</p><p><strong>Conclusion: </strong>The gut prophageome serves as both a source of pre-symptomatic predictive signals and an active modulator of NEC pathogenesis, with distinct microbial mechanisms driving early-onset and late-onset disease. These polymicrobial etiologies inform strategies for early detection, risk stratification and the development of microbiome-targeted preventive and therapeutic interventions.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":24.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982546","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":"Longitudinal gut microbiome dynamics during immunotherapy identify microbial features of clinical benefit in advanced primary liver cancer.","authors":"Zhenwei Qian, Jie Han, Beile Lyu, Aizier Ainiwaer, Qiancheng Zhao, Shuai Wang, Jiamin Cheng, Yinyin Li, Ying Sun, Xiannian Zhang, Yinying Lu","doi":"10.1136/gutjnl-2026-339115","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-339115","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiome has been linked to immune checkpoint inhibitor (ICI) outcomes, but the temporal dynamics of microbial communities during treatment remain poorly characterised.</p><p><strong>Objective: </strong>To characterise gut microbiome trajectories during ICI therapy and evaluate whether on-treatment microbial states improve the identification and generalisability of pretreatment biomarker signatures.</p><p><strong>Design: </strong>We performed a large prospective longitudinal shotgun metagenomic study of 315 patients with advanced primary liver cancer receiving ICI-based therapy, profiling 777 serial stool metagenomes collected at baseline and at approximately 3-month intervals on treatment. Responders (durable clinical benefit ≥6 months) contributed extended follow-up beyond 18 months. On-treatment windows were used for feature discovery; baseline-trained models were evaluated across all nine public ICI cohorts (n=1204).</p><p><strong>Results: </strong>Responders showed higher baseline alpha diversity and distinct community structure. Longitudinal profiling revealed marked ecological remodelling during therapy in both response groups, characterised by reduced network connectivity, increased modularity and strong time point specificity of discriminatory species. Using the on-treatment contrast at ~6 months (T2) as a discovery window, we identified a 16-species panel. A baseline model built from this panel outperformed models based on baseline-only feature discovery and generalised across nine public ICI studies. The resulting gut microbiome-derived immunotherapy outcome score stratified overall and progression-free survival in the discovery cohort (HRs 0.49 and 0.44) and across multiple external datasets, including stable-disease subsets.</p><p><strong>Conclusion: </strong>The gut microbiome undergoes structured ecological remodelling during ICI therapy; on-treatment longitudinal windows improve pretreatment signature portability and support microbiome-guided stratification in immuno-oncology.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":24.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982521","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":"Global epidemiology of disorders of gut-brain interaction: new insights with Rome V.","authors":"Christopher J Black, Kee-Huat Chuah","doi":"10.1136/gutjnl-2026-340229","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-340229","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":24.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976714","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":"Patient-level predictors of safety and recurrence after cold versus hot snare resection of large, non-pedunculated colorectal polyps: an individual patient data meta-analysis of four randomised-controlled trials.","authors":"Ingo Steinbrück, Timothy O'Sullivan, Oscar Nogales, Douglas K Rex, Viktor Rempel, Cyrus R Piraka, Oliver Cronin, Sheyla Montori, Christian Wiessner, Thomas Rösch, Eduardo Albéniz, Michael J Bourke, Heiko Pohl","doi":"10.1136/gutjnl-2026-339233","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-339233","url":null,"abstract":"<p><strong>Background: </strong>Cold resection is standard for small colorectal polyps and sessile serrated lesions (SSLs). For large (≥20 mm) non-pedunculated adenomas, it appears safer than hot snare endoscopic mucosal resection (EMR) but is associated with higher rates of residual/recurrent adenoma (RRA).</p><p><strong>Objective: </strong>To pool individual patient data from all available randomised controlled trials (RCTs) and determine whether RRA differs across polyp subgroups.</p><p><strong>Design: </strong>International, multicentre post hoc individual patient data meta-analysis of four RCTs. Primary outcomes were rates of major adverse events (AE) (AE=deep mural injury III-V/perforation and/or delayed bleeding) and RRA. Subgroup analyses assessed outcomes by location, size, morphology and histology.</p><p><strong>Results: </strong>1509 polyps in 1423 patients (mean age 66.1 years; mean size 31.3 mm) from 50 centres were included. Major AE occurred in 1.7% of cold versus 5.9% of hot snare resections (OR 0.26; p<0.001). Cold snare was the only factor to reduce major AE in multivariate analysis (OR 0.21; 95% CI 0.07 to 0.60; p=0.004). RRA was higher after cold resection (26.5% vs 12.8%; OR 2.61; p<0.001), with a significant interaction by lesion diameter (p=0.035). By histology, differences were the smallest in SSLs (15.0% vs 8.1%; OR 2.13; p=0.053) and greatest in adenomas with high-grade dysplasia (40.8% vs 18.0%; OR 2.88; p=0.002).</p><p><strong>Conclusions: </strong>Cold resection is safer than hot EMR but results in more than double the RRA in all adenoma subgroups, especially those with high-grade dysplasia. It may be appropriate for SSLs between 2 cm and 4 cm and selected cases under anticoagulant/antiplatelet therapy or multimorbid patients, for which further studies are needed.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":24.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976664","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":"International expert panel review for the use of resmetirom and semaglutide in the management of MASH-related fibrosis: clinical practice update","authors":"Maria Mironova,Vlad Ratziu,Mary E Rinella,Meena B Bansal,Mazen Noureddin,Naim Alkhouri,Quentin M Anstee,Philip N Newsome,Jörn M Schattenberg,Arun J Sanyal,Rohit Loomba","doi":"10.1136/gutjnl-2026-340031","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-340031","url":null,"abstract":"The recent conditional US Food and Drug Administration (FDA) approval of two therapies, resmetirom (Rezdiffra) and semaglutide (Wegovy), marks the first time clinicians have pharmacological therapy for metabolic dysfunction-associated steatohepatitis (MASH) with significant fibrosis (F2–F3) without cirrhosis, a disease that previously had no available pharmacological treatment. The two agents act through complementary mechanisms: resmetirom as a liver-directed thyroid hormone receptor-beta agonist and semaglutide as a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a broad spectrum of metabolic effects. In this international expert panel review, we consolidate data from phase III trials, FDA labels and emerging clinical experience into a single resource. It covers the entire care pathway: non-invasive test-based diagnosis of MASH with significant fibrosis, treatment selection and initiation, on-treatment monitoring and response assessment. We offer practical recommendations for individualising therapy by patient phenotype, managing patients already receiving GLP-1 RAs and defining response, non-response and criteria for switching or combining agents. The proposed framework is intended to evolve as long-term outcomes data emerge and additional MASH therapies become available.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"6 1","pages":"gutjnl-2026-340031"},"PeriodicalIF":24.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148933644","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}