BMJ Open Gastroenterology最新文献

{"title":"Parental perspectives on gluten immunogenic peptide urine testing in children with coeliac disease: a qualitative study on barriers, emotions and interest in point-of-care tools.","authors":"Aisling Fiuza, Alfonso Rodriguez-Herrera","doi":"10.1136/bmjgast-2026-002350","DOIUrl":"10.1136/bmjgast-2026-002350","url":null,"abstract":"","PeriodicalId":9235,"journal":{"name":"BMJ Open Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline characteristics of participants recruited into the COLO-COHORT study: a UK-wide resource for colorectal cancer prevention.","authors":"Yashvee Dunneram, Eleanor Hackney, Sarah Manning, Panayiotis Louca, Christopher J Stewart, Guy S Taylor, Sara Koo, Gregory R Young, Suparna Mitra, James S Hampton, Christina Dobson, Laura J Neilson, Caroline Addison, John Whelpton, Linda Sharp, Mark A Hull, Colin Rees","doi":"10.1136/bmjgast-2026-002421","DOIUrl":"10.1136/bmjgast-2026-002421","url":null,"abstract":"<p><strong>Objective: </strong>To describe the design, recruitment, and baseline characteristics of the first phase of COLO-COHORT and to establish this population as a resource for colorectal cancer (CRC) prevention research.</p><p><strong>Methods: </strong>COLO-COHORT is a prospective, multicentre observational study recruiting adults undergoing colonoscopy through screening and routine National Health Service referral pathways within a 32-site UK network. We present descriptive data from the first 4754 participants, recruited through 27 Phase 1 sites, including demographics, lifestyle factors, clinical characteristics, biospecimen availability and colonoscopy outcomes.</p><p><strong>Results: </strong>Participants had a median age of 64 years (IQR 57-70), and 54.3% were male. Overweight (38.0%) and obesity (30.5%) were common, and cardiometabolic comorbidities were prevalent (11.8% with type II diabetes; 39.4% with hypertension). Colorectal neoplasia was identified at colonoscopy in over half of participants (56.1%), with histologically characterised data available on polyp type, size, morphology and anatomical location. Core demographic and clinical variables were available for >95% of participants, with colonoscopy findings recorded for all. Linked blood and stool microbiome biospecimens were available for approximately 80% and 40% of participants, respectively.</p><p><strong>Conclusion: </strong>This paper establishes and characterises COLO-COHORT's Phase 1 study cohort as a well-phenotyped resource, representing a population of individuals undergoing colonoscopy via UK screening and routine clinical pathways. This cohort will support and underpin future collaborative clinical, epidemiological and translational research in CRC prevention.</p>","PeriodicalId":9235,"journal":{"name":"BMJ Open Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient outcomes and healthcare utilisation following implementation of an advanced therapy care pathway for inflammatory bowel disease: a multicentre, prospective quasi-experimental preimplementation/postimplementation study in the Netherlands.","authors":"Elyke H Visser, Martijn A Oude Voshaar, Reinier C A Van Linschoten, Jildou Hoekstra, Kristin Robbers, Vincent de Jonge, Edith Koehler, K Evelyne Verweij, Sanne van der Wiel, Daniëlle van der Horst, C Janneke van der Woude, Desiree van Noord, Rachel L West","doi":"10.1136/bmjgast-2026-002381","DOIUrl":"10.1136/bmjgast-2026-002381","url":null,"abstract":"<p><strong>Objective: </strong>Care pathways have the potential to decrease treatment variation and improve patient outcomes. This study aims to evaluate the effect of an advanced therapy care pathway (ACP) on patient outcomes, healthcare utilisation and treatment variation among patients with inflammatory bowel disease (IBD) in the Netherlands.</p><p><strong>Methods: </strong>A multicentre, prospective quasi-experimental preimplementation/postimplementation study was conducted, with a preimplementation (December 2020-December 2021) and postimplementation period (March 2022-March 2023). Outcomes were collected from electronic medical records and validated questionnaires according to the International Consortium for Health Outcomes Measurement standard set. The effect of the ACP was analysed using difference-in-differences (DiD) analysis.</p><p><strong>Results: </strong>1173 patients were included; the majority was female (55%) with a median age of 45 years (IQR 33-58 years). Most patients had Crohn's disease (64%). Patients reported a high level of disease control and this did not change postimplementation (DiD-estimate: 0.12, 95% CI -0.74 to 1.01). Number of emergency room visits and hospital admissions decreased significantly 6 months postimplementation; however, the effect attributable to the ACP was only maintained for admissions (DiD-estimate visits: -0.05, 95% CI -0.10 to 0.01; DiD-estimate admissions: -0.06, 95% CI -0.11 to -0.03).</p><p><strong>Conclusion: </strong>Implementation of an ACP, in which a minimum of care is defined, can achieve outcomes comparable to standard practice, highlighting the value of prioritising structured care pathways, especially given the current burden of IBD on healthcare systems. An ACP can guide healthcare providers and policymakers in standardising treatment and improving quality of care in chronic disease management.</p><p><strong>Study registration: </strong>NL8276/NL-OMON21751 (https://onderzoekmetmensen.nl/en/trial/21751).</p>","PeriodicalId":9235,"journal":{"name":"BMJ Open Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of intestinal spirochaetosis in serrated polyposis syndrome compared with other colorectal polyp conditions: a case-control study in Japan.","authors":"Mizuki Honda, Kazuhiro Katada, Eiichi Konishi, Motohiro Kojima, Tetsuya Imura","doi":"10.1136/bmjgast-2026-002414","DOIUrl":"10.1136/bmjgast-2026-002414","url":null,"abstract":"<p><strong>Objective: </strong>Serrated polyposis syndrome (SPS) is the most common form of colorectal polyposis syndrome. Most SPS cases are sporadic, and the environmental factors underlying its pathogenesis remain poorly defined. Intestinal spirochaetosis (IS), an infection of the colonic epithelium by <i>Brachyspira</i> species, is frequently asymptomatic and its clinical relevance is uncertain. Here, we examined the potential association between IS and SPS.</p><p><strong>Methods: </strong>In this retrospective case-control study at two centres in Japan, IS prevalence was assessed in 64 patients with SPS and 382 non-SPS controls who underwent colonoscopic polypectomy. Controls were classified as having only conventional adenomas (Ctrl-CA) or serrated polyps not meeting the diagnostic criteria of SPS (Ctrl-SP).</p><p><strong>Results: </strong>Histologically confirmed IS was detected in 12/64 (18.8%) SPS cases and 6/382 (1.6%) controls (OR 14.5, 95% CI 5.2 to 40.2; p<0.001). IS prevalence increased stepwise across Ctrl-CA, Ctrl-SP and SPS groups (1/274 (0.4%), 5/108 (4.6%) and 12/64 (18.8%), respectively; OR 6.5, 95% CI 3.1 to 13.8; p for trend <0.001). Among the 12 IS-positive SPS cases, all had a history of cigarette smoking and altered bowel habits were common. Furthermore, IS detection rates did not differ based on anatomical locations of polyps, but considerable intraindividual variability was observed across serial colonoscopies, suggesting possible episodes of clearance and reinfection. Real-time PCR and sequencing analyses demonstrated that all IS-positive cases were attributable to <i>Brachyspira aalborgi</i>, a species commonly found in developed countries.</p><p><strong>Conclusions: </strong>This study reveals a novel association between IS and SPS with distinct clinical characteristics in Japan. Considering the retrospective design and small sample size from a single geographic region, further investigation is required to clarify the significance and generalisability of this association.</p>","PeriodicalId":9235,"journal":{"name":"BMJ Open Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic arteriovenous malformations as a manifestation of hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber disease): a systematic review.","authors":"Isabel de Jager, Ebba Asplund, Nikolaos Kartalis, Poya Ghorbani, Nina Bloch, Johannes Matthias Löhr, Miroslav Vujasinovic","doi":"10.1136/bmjgast-2026-002491","DOIUrl":"10.1136/bmjgast-2026-002491","url":null,"abstract":"<p><strong>Objectives: </strong>Limited data are available on pancreatic arteriovenous malformations (AVMs) in patients with hereditary haemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease. This systematic review aimed to identify all reported cases of pancreatic AVMs in patients with HHT and summarise patient demographics, clinical presentation, diagnostic modalities, treatment strategies and follow-up.</p><p><strong>Design: </strong>Systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.</p><p><strong>Data sources: </strong>Databases PubMed, Embase, Cochrane Library and Web of Science were systematically screened up to June 2025.</p><p><strong>Eligibility criteria: </strong>All English-language, full-text studies reporting pancreatic AVMs in patients with HHT. Only patients with definite diagnoses of HHT and pancreatic AVM were included.</p><p><strong>Data extraction and synthesis: </strong>All identified articles were independently screened by two reviewers. Data regarding patient demographics, clinical presentation, diagnostic modalities, treatment strategies and follow-up were collected. The mean AVM size was calculated when individual AVM size and number of AVMs were reported.</p><p><strong>Results: </strong>Of 429 screened records, 46 articles underwent full-text assessment. Nineteen patients from 13 studies met the inclusion criteria. Most patients were female (58%), with a mean age of 52 years, presenting asymptomatically (50%) without laboratory findings (73%). CT was the most frequently used diagnostic modality (56%), and the mean AVM size was 7.1 mm. Most patients were treated conservatively (69%). Prognosis was frequently unavailable (79%). Differential diagnoses consisted mostly of neuroendocrine tumours (75%).</p><p><strong>Conclusions: </strong>Pancreatic AVMs in patients with HHT appear to be smaller and are more frequently asymptomatic compared with the general population. Severe complications, such as portal hypertension and gastrointestinal bleeding, were less frequent. Conservative management was most common. Additional studies are needed to better characterise prognosis and treatment outcomes, particularly in symptomatic patients.</p><p><strong>Prospero registration number: </strong>CRD420251077109.</p>","PeriodicalId":9235,"journal":{"name":"BMJ Open Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastric varices: a contemporary review of vascular anatomy and therapeutic strategies.","authors":"Sagnik Biswas, Sanchita Gupta, Mukesh Kumar Ranjan, Shivanand Gamanagatti, Shalimar","doi":"10.1136/bmjgast-2026-002476","DOIUrl":"10.1136/bmjgast-2026-002476","url":null,"abstract":"<p><p>Gastric varices (GV) are found in 20% of patients with portal hypertension and bleed infrequently, but are associated with greater blood loss, higher transfusion requirements and mortality than oesophageal varices. The vascular anatomy of GV is characterised by different afferent and efferent pathways, which vary depending on its anatomical location. Contemporary radiological classification systems complement traditional endoscopic systems and assist in selection of the optimal treatment modality in an individual patient. Endoscopic cyanoacrylate injection remains the standard therapy for acute GV bleeding and achieves high rates of primary haemostasis, but is limited by incomplete obliteration, recurrent bleeding and risk of systemic embolisation. Endovascular interventions, including transjugular intrahepatic portosystemic shunt and retrograde transvenous obliteration (RTO), have demonstrated superior long-term bleeding control in recent randomised clinical trials, although each has distinct indications and adverse-event profiles (ascites, aggravation of oesophageal varices and hepatic encephalopathy). Endoscopic ultrasound (EUS)-guided interventions enable real-time visualisation of vascular anatomy and targeted treatment with coils, glue or thrombin, resulting in improved obliteration rates and lower recurrence. However, there are limited direct comparisons between these modalities in present literature. The availability of multiple treatment modalities has resulted in the evolution of the management of GV from conventional endoscopic therapy towards individualised, anatomy-driven treatment strategies incorporating EUS-guided and endovascular interventions. This review summarises the contemporary understanding of GV anatomy, pathophysiology and therapeutic strategies.</p>","PeriodicalId":9235,"journal":{"name":"BMJ Open Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using a mobile unit to deliver capsule sponge testing for Barrett's oesophagus in the community in England through GP invitation and self-referral: an implementation study.","authors":"Rebecca Landy, Jo Waller, Irene Debiram-Beecham, Abigail Kerridge, James Booth, Peter Holloway, James Morrow, Fiona M Walter, Mimi McCord, Peter D Sasieni, Rebecca C Fitzgerald, Oliver Stovin","doi":"10.1136/bmjgast-2026-002496","DOIUrl":"10.1136/bmjgast-2026-002496","url":null,"abstract":"<p><strong>Objective: </strong>Offering individuals with gastro-oesophageal reflux a non-endoscopic capsule sponge test increased detection of Barrett's oesophagus (BO), a precursor to oesophageal adenocarcinoma. However, only 24% of individuals identified through general practitioner (GP) records participated. We therefore performed an implementation study to assess the feasibility of screening on a mobile unit and screening uptake among GP-invited and self-referred individuals.</p><p><strong>Methods: </strong>In this implementation study, 3293 individuals aged ≥50 with a repeat proton pump inhibitor prescription were invited to participate by their GPs across three GP practices in the East of England between June 2021 and January 2023. Additionally, we advertised the study and allowed self-referrals. Eligibility was assessed based on age and reflux history. Eligible individuals were invited to an appointment. Acceptability was assessed after the appointment. Individuals with a positive capsule sponge test were referred for endoscopy.</p><p><strong>Results: </strong>Half of the GP-invited individuals responded, of whom 59.6% (n=952/1598) were interested. Among interested individuals who could be contacted, 66.3% (n=574/866) were eligible, and 532 participated. Of these, 502 (94%) successfully swallowed a capsule sponge, representing 15% of those invited and 87.5% of eligible individuals. Among 468 individuals who self-referred and could be contacted, 48.5% (n=227) were eligible, 217 participated, and 208 (96%) successfully swallowed a capsule sponge (39.6% of self-referred, 91.6% of eligible individuals). 9.4% (n=47/502) of GP-invited and 12.0% (n=25/208) of self-referred individuals were referred for endoscopy, with 4.2% (n=21/502) and 3.4% (n=7/208), respectively, diagnosed with BO (positive predictive value of endoscopy referral=42.4%), including three with dysplasia. Over 99% of participants said the capsule sponge test was acceptable.</p><p><strong>Conclusion: </strong>Screening on a mobile unit is feasible. Identifying individuals at increased risk of BO from GP records is feasible, and encouraging self-referrals increases uptake. BO prevalence was similar among eligible participants who self-referred and those identified through GP records.</p><p><strong>Trial registration number: </strong>ISRCTN91655550.</p>","PeriodicalId":9235,"journal":{"name":"BMJ Open Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimising clinical trial design choices in inflammatory bowel disease.","authors":"Peter Bossuyt, Katarzyna Moscicka, Kremena Stoyanova, Jennifer Zalud, Luke M Shelton","doi":"10.1136/bmjgast-2026-002489","DOIUrl":"10.1136/bmjgast-2026-002489","url":null,"abstract":"<p><p>The success of inflammatory bowel disease (IBD) clinical trials is strongly influenced by study design and disease-specific operational challenges. Over the past decade, however, IBD clinical trials face slow enrolment, poor retention, accumulating costs and limited representativeness. Trials are further constrained by protocol and operational complexity, financial pressures and regulatory requirements. Carefully selected and optimised trial designs may address the inherent challenges of IBD research and should take into account the patient profiles under investigation, mode of action and speed of onset of effect of the investigational product, among other factors. This narrative review discusses four key study design strategies for IBD clinical trials, including treat-through maintenance, responder re-randomisation, Master Protocol approaches (basket, umbrella and platform trials) and Bayesian methodologies. Treat-through maintenance designs are effective at evaluating sustained efficacy and real-world durability, whereas responder re-randomisation approaches are widely used in drug registration programmes to distinguish induction and maintenance effects for regulator clarity. Master Protocol designs may improve efficiency and reduce placebo exposure, while trials using Bayesian methodologies can strengthen interpretation of efficacy and safety outcomes, particularly in early-phase or complex studies. Key considerations within protocols include the use of co-primary endpoints, selection of secondary/exploratory endpoints, control group design and integrating digital health technologies, among others. Strategic application of innovative methodologies can improve trial delivery and enhance data robustness and interpretability, thus supporting more efficient development of effective therapies for patients with IBD.</p>","PeriodicalId":9235,"journal":{"name":"BMJ Open Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the predictive value of multiple rounds of faecal haemoglobin measurement for the prediction of advanced neoplasia and colorectal cancer: an analysis of data from the Dutch national colorectal cancer screening programme.","authors":"Lucy Wairimu Mwangi, Chiara Brück, Alexandra Katsara, Esther Toes-Zoutendijk, Anneke van Vuuren, Marc Thelen, Iris Nagetaal, Evelien Dekker, Manon Spaander, Monique van Leerdam, Iris Lansdorp Vogelaar","doi":"10.1136/bmjgast-2026-002286","DOIUrl":"10.1136/bmjgast-2026-002286","url":null,"abstract":"<p><strong>Objective: </strong>Faecal haemoglobin (f-Hb) concentrations from two screening rounds improve colorectal cancer (CRC) risk prediction, but the value of longer longitudinal data remains uncertain. This study aimed to assess whether incorporating f-Hb data from three prior screening rounds improves risk stratification for CRC and advanced neoplasia (AN).</p><p><strong>Methods: </strong>Using data from four rounds of the Dutch national CRC screening programme (1 January 2014 and 31 December 2022), prognostic models combining age, sex, and f-Hb concentrations were developed to predict CRC and AN. Multiple representations of longitudinal f-Hb were evaluated. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration, and information criteria. Risk reclassification was quantified using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). The policy impact of risk-based referral, expressed as additional colonoscopies, was examined. External validation used data from a Dutch faecal immunochemical test pilot study.</p><p><strong>Results: </strong>Among 1 171 070 participants included, 2357 (0.2%) had CRC and 14 543 (1.2%) had AN. Models incorporating categorised f-Hb values from three prior rounds, age, and sex achieved the highest discrimination (AUC: AN 0.76 (0.75-0.77); CRC 0.73 (0.72-0.74)) and significantly improved reclassification (NRI and IDI, p<0.001). Participants in the highest 15% predicted risk had a 6.8-fold (95% CI 6.4 to 6.9) increased risk of AN and a 5.9-fold (95% CI 5.4 to 6.6) increased risk of CRC. Risk-based referral enabled earlier detection with minimal additional colonoscopy for both CRC and AN.</p><p><strong>Conclusion: </strong>Including f-Hb data from three prior screening rounds improves CRC and AN risk prediction. Targeted referral of the highest risk individuals enables earlier detection with limited impact on colonoscopy capacity, supporting personalised CRC screening strategies.</p>","PeriodicalId":9235,"journal":{"name":"BMJ Open Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>SAE1</i> knockdown attenuates hepatic fibrosis by promoting ubiquitination and proteasomal degradation of TGF-β receptors.","authors":"Tong Liu, Mengru Wang, Guoliang Zheng, Yuying Wu, Jiankun Shen, Xueqing Dong, Qikai Sun, Yanfei Zhang, Wenfang Tian","doi":"10.1136/bmjgast-2026-002413","DOIUrl":"10.1136/bmjgast-2026-002413","url":null,"abstract":"<p><strong>Objective: </strong>Liver fibrosis is characterised by excessive accumulation of extracellular matrix and can ultimately progress to cirrhosis and malignant transformation. Activation of hepatic stellate cells (HSCs), largely driven by transforming growth factor-beta (TGF-β) signalling, is a central event in fibrogenesis. SAE1 is a subunit of the small ubiquitin-like modifier-activating enzyme E1; its role in liver fibrosis and HSC activation remains unclear. This study aimed to investigate the regulatory function and underlying mechanism of SAE1 in hepatic fibrogenesis.</p><p><strong>Methods: </strong>A carbon tetrachloride (CCl₄)-induced mouse model of liver fibrosis was established to assess SAE1 expression in vivo. SAE1 was silenced using an adeno-associated virus serotype 6-mediated approach. In vitro, primary HSCs and TGF-β-treated LX-2 cells were used to evaluate the effects of <i>SAE1</i> knockdown on HSC activation and profibrotic gene expression. The activity of the TGF-β/SMAD signalling pathway and the stability of TGF-β receptors were also examined.</p><p><strong>Results: </strong>SAE1 expression was significantly increased in fibrotic livers. <i>SAE1</i> knockdown attenuated HSC activation and downregulated profibrotic genes. Mechanistically, <i>SAE1</i> silencing promoted ubiquitin-proteasome-dependent degradation of TGF-β receptor I/II, thereby reducing SMAD2/3 phosphorylation. In vivo, <i>Sae1</i> knockdown alleviated CCl₄-induced liver fibrosis.</p><p><strong>Conclusion: </strong>SAE1 contributes to liver fibrosis by maintaining TGF-β receptor stability and enhancing TGF-β/SMAD-driven HSC activation. These results highlight SAE1 as a potential target for antifibrotic therapy.</p>","PeriodicalId":9235,"journal":{"name":"BMJ Open Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}