Pub Date : 2024-12-24DOI: 10.1053/j.gastro.2024.12.011
J.D. Windster, N.J.M. Kakiailatu, L.E. Kuil, A. Antanaviciute, A. Sacchetti, K.C. MacKenzie, J. Peulen-Zink, T.W. Kan, E. Bindels, E. de Pater, M. Doukas, T.P.P. van den Bosch, S. Yousefi, T.S. Barakat, C. Meeussen, C.E.J. Sloots, R.M.H. Wijnen, K. Parikh, W. Boesmans, V. Melotte, M.M. Alves
Background and Aims
The enteric nervous system (ENS), comprised of neurons and glia, regulates intestinal motility. Hirschsprung disease (HSCR) results from defects in ENS formation, yet while neuronal aspects have been extensively studied, enteric glia remain disregarded. This study aimed to explore enteric glia diversity in health and disease.
Methods
Full-thickness intestinal resection material from pediatric controls and HSCR patients was collected, dissociated and enriched for the ENS population through fluorescence-activated cell sorting. Single-cell RNA sequencing was performed to uncover the transcriptomic diversity of the ENS in HSCR patients and controls, as well as in wildtype and ret mutant zebrafish. Immunofluorescence and fluorescence in situ hybridization confirmed the presence of distinct subtypes.
Results
Two major enteric glial classes emerged in the pediatric intestine: Schwann-like enteric glia, reminiscent of Schwann cells, and Enteric glia, expressing classical glial markers. Comparative analysis with previously published datasets confirmed our classification and revealed that whilst classical enteric glia are predominant prenatally, Schwann-like enteric glia become more abundant postnatally. In HSCR, ganglionic segments mirrored controls, while aganglionic segments, only featured Schwann-like enteric glia. Leveraging the regenerative potential of Schwann cells, we explored therapeutic options using a ret mutant zebrafish. Prucalopride, a serotonin-receptor (5-HT) agonist, induced neurogenesis partially rescuing the HSCR phenotype in ret+/- mutants.
Conclusion
Two major enteric glial classes were identified in the pediatric intestine, highlighting the significant postnatal contribution of Schwann-like enteric glia to glial heterogeneity. Crucially, these glial subtypes persist in aganglionic segments of HSCR patients, offering a new target for their treatment using 5-HT agonists.
{"title":"Human enteric glia diversity in health and disease: new avenues for the treatment of Hirschsprung disease","authors":"J.D. Windster, N.J.M. Kakiailatu, L.E. Kuil, A. Antanaviciute, A. Sacchetti, K.C. MacKenzie, J. Peulen-Zink, T.W. Kan, E. Bindels, E. de Pater, M. Doukas, T.P.P. van den Bosch, S. Yousefi, T.S. Barakat, C. Meeussen, C.E.J. Sloots, R.M.H. Wijnen, K. Parikh, W. Boesmans, V. Melotte, M.M. Alves","doi":"10.1053/j.gastro.2024.12.011","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.12.011","url":null,"abstract":"<h3>Background and Aims</h3>The enteric nervous system (ENS), comprised of neurons and glia, regulates intestinal motility. Hirschsprung disease (HSCR) results from defects in ENS formation, yet while neuronal aspects have been extensively studied, enteric glia remain disregarded. This study aimed to explore enteric glia diversity in health and disease.<h3>Methods</h3>Full-thickness intestinal resection material from pediatric controls and HSCR patients was collected, dissociated and enriched for the ENS population through fluorescence-activated cell sorting. Single-cell RNA sequencing was performed to uncover the transcriptomic diversity of the ENS in HSCR patients and controls, as well as in wildtype and <em>ret</em> mutant zebrafish. Immunofluorescence and fluorescence <em>in situ</em> hybridization confirmed the presence of distinct subtypes.<h3>Results</h3>Two major enteric glial classes emerged in the pediatric intestine: Schwann-like enteric glia, reminiscent of Schwann cells, and Enteric glia, expressing classical glial markers. Comparative analysis with previously published datasets confirmed our classification and revealed that whilst classical enteric glia are predominant prenatally, Schwann-like enteric glia become more abundant postnatally. In HSCR, ganglionic segments mirrored controls, while aganglionic segments, only featured Schwann-like enteric glia. Leveraging the regenerative potential of Schwann cells, we explored therapeutic options using a <em>ret</em> mutant zebrafish. Prucalopride, a serotonin-receptor (5-HT) agonist, induced neurogenesis partially rescuing the HSCR phenotype in <em>ret</em><sup>+/-</sup> mutants.<h3>Conclusion</h3>Two major enteric glial classes were identified in the pediatric intestine, highlighting the significant postnatal contribution of Schwann-like enteric glia to glial heterogeneity. Crucially, these glial subtypes persist in aganglionic segments of HSCR patients, offering a new target for their treatment using 5-HT agonists.","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"19 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879865","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}
Pub Date : 2024-12-24DOI: 10.1053/j.gastro.2024.12.013
Chengzi Huang, Yilian Zhong, Bin He, Xi Shao, Jun Li
No Abstract
没有抽象的
{"title":"Analysis of “Prevotella Is Associated With Sex-Based Differences in Irritable Bowel Syndrome”","authors":"Chengzi Huang, Yilian Zhong, Bin He, Xi Shao, Jun Li","doi":"10.1053/j.gastro.2024.12.013","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.12.013","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"8 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879830","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}
Pub Date : 2024-12-24DOI: 10.1053/j.gastro.2024.12.014
J.C. Coffey, L. Bai, F.F. Wu
No Abstract
没有抽象的
{"title":"Catching up with creeping fat - unravelling the mysteries of the mesentery in Crohn's disease","authors":"J.C. Coffey, L. Bai, F.F. Wu","doi":"10.1053/j.gastro.2024.12.014","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.12.014","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"24 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879829","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}
Pub Date : 2024-12-24DOI: 10.1053/j.gastro.2024.12.012
Sheré Paris, Xi Zhang, Daniel Davis, Anh D. Nguyen, Ahsen Ustaoglu, Robert M. Genta, Xuan Wang, Ishani Kale, Rebecca Ekeanyanwu, Steven Leeds, Marc Ward, Eitan Podgaetz, Qiuyang Zhang, Yan Chang, Zui Pan, Philip J. Woodland, Daniel Sifrim, Stuart Jon Spechler, Rhonda F. Souza
BACKGROUND & AIMS
Dilated intercellular space (DIS) in esophageal epithelium, a sign of impaired barrier function, is a characteristic finding of GERD that also is found in obese patients without GERD. We have explored molecular mechanisms whereby adipose tissue products might impair esophageal barrier integrity.
METHODS
We established cultures of visceral fat obtained during foregut surgery from obese and non-obese patients. Monolayer and air-liquid interface (ALI) cultures of human esophageal cells were grown with conditioned medium (CM) from fat cultures. RNA sequencing, ELISA, western blot, immunostaining, histology, and analyses of barrier function were performed; inhibitors of HIF-2α (PT2385), caspase-1 (AC-YVAD-CHO), myosin light chain (MLC) kinase (PIK), and MLC phosphatase (PIP250) were applied; blebbistatin was used to disrupt actin-myosin interactions; NAC was used to scavenge reactive oxygen species (ROS).
RESULTS
CM from EGJ fat of obese patients (EGJ-CM-Obese) caused DIS with impaired barrier function in esophageal ALI cultures; these effects were blocked by PT2385. EGJ-CM-Obese induced ROS production that activated HIF-2α in esophageal cells. RNA sequencing analyses linked EGJ-CM-Obese-induced HIF-2α increases with innate immune response pathways. Cross-talk between HIF-2α and caspase-1 in esophageal cells led to IL-1β secretion, and IL-1β/IL-1R1 signaling caused DIS with impaired esophageal barrier function via actin-myosin interactions induced by MLC phosphorylation.
CONCLUSIONS
We have elucidated molecular mechanisms whereby visceral fat of obese patients can impair esophageal barrier integrity by secreting substances that generate ROS, which activate HIF-2α in esophageal epithelial cells. These mechanisms could render the esophagus of obese individuals vulnerable to damage by acid and other noxious agents.
背景,目的食管上皮细胞间隙扩大（DIS）是胃食管反流的特征性表现，也可在无胃食管反流的肥胖患者中发现。我们已经探索了脂肪组织产物可能损害食管屏障完整性的分子机制。方法对肥胖和非肥胖患者在前肠手术中获得的内脏脂肪进行培养。用脂肪培养的条件培养基（CM）培养人食管细胞的单层和气液界面（ALI）培养。进行RNA测序、ELISA、western blot、免疫染色、组织学和屏障功能分析；应用HIF-2α (PT2385)、caspase-1 （AC-YVAD-CHO）、肌球蛋白轻链（MLC）激酶（PIK）和MLC磷酸酶（PIP250）抑制剂；Blebbistatin用于破坏肌动蛋白-肌球蛋白的相互作用；NAC用于清除活性氧（ROS）。结果肥胖患者EGJ脂肪（EGJ- cm - obese）致食管ALI培养物DIS伴屏障功能受损；这些效应被PT2385阻断。egj - cm -肥胖诱导ROS产生，激活食管细胞HIF-2α。RNA测序分析将egj - cm -肥胖诱导的HIF-2α增加与先天免疫反应途径联系起来。食管细胞中HIF-2α和caspase-1的相互作用导致IL-1β分泌，IL-1β/IL-1R1信号通过MLC磷酸化诱导肌动蛋白-肌球蛋白相互作用导致食管屏障功能受损。结论我们已经阐明了肥胖患者内脏脂肪通过分泌产生ROS的物质破坏食管屏障完整性的分子机制，ROS可激活食管上皮细胞中的HIF-2α。这些机制可能使肥胖个体的食道容易受到酸和其他有害物质的损害。
{"title":"In Obesity, Esophagogastric Junction Fat Impairs Esophageal Barrier Function and Dilates Intercellular Spaces via HIF-2α","authors":"Sheré Paris, Xi Zhang, Daniel Davis, Anh D. Nguyen, Ahsen Ustaoglu, Robert M. Genta, Xuan Wang, Ishani Kale, Rebecca Ekeanyanwu, Steven Leeds, Marc Ward, Eitan Podgaetz, Qiuyang Zhang, Yan Chang, Zui Pan, Philip J. Woodland, Daniel Sifrim, Stuart Jon Spechler, Rhonda F. Souza","doi":"10.1053/j.gastro.2024.12.012","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.12.012","url":null,"abstract":"<h3>BACKGROUND & AIMS</h3>Dilated intercellular space (DIS) in esophageal epithelium, a sign of impaired barrier function, is a characteristic finding of GERD that also is found in obese patients without GERD. We have explored molecular mechanisms whereby adipose tissue products might impair esophageal barrier integrity.<h3>METHODS</h3>We established cultures of visceral fat obtained during foregut surgery from obese and non-obese patients. Monolayer and air-liquid interface (ALI) cultures of human esophageal cells were grown with conditioned medium (CM) from fat cultures. RNA sequencing, ELISA, western blot, immunostaining, histology, and analyses of barrier function were performed; inhibitors of HIF-2α (PT2385), caspase-1 (AC-YVAD-CHO), myosin light chain (MLC) kinase (PIK), and MLC phosphatase (PIP250) were applied; blebbistatin was used to disrupt actin-myosin interactions; NAC was used to scavenge reactive oxygen species (ROS).<h3>RESULTS</h3>CM from EGJ fat of obese patients (EGJ-CM-Obese) caused DIS with impaired barrier function in esophageal ALI cultures; these effects were blocked by PT2385. EGJ-CM-Obese induced ROS production that activated HIF-2α in esophageal cells. RNA sequencing analyses linked EGJ-CM-Obese-induced HIF-2α increases with innate immune response pathways. Cross-talk between HIF-2α and caspase-1 in esophageal cells led to IL-1β secretion, and IL-1β/IL-1R1 signaling caused DIS with impaired esophageal barrier function via actin-myosin interactions induced by MLC phosphorylation.<h3>CONCLUSIONS</h3>We have elucidated molecular mechanisms whereby visceral fat of obese patients can impair esophageal barrier integrity by secreting substances that generate ROS, which activate HIF-2α in esophageal epithelial cells. These mechanisms could render the esophagus of obese individuals vulnerable to damage by acid and other noxious agents.","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"130 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884104","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}
Pub Date : 2024-12-23DOI: 10.1053/j.gastro.2024.11.001
Shailja C. Shah, Andrew Y. Wang, Michael B. Wallace, Joo Ha Hwang
<h3>Description</h3>Gastric cancer (GC) is a leading cause of preventable cancer and mortality in certain US populations. The most impactful way to reduce GC mortality is via primary prevention, namely <em>Helicobacter pylori</em> eradication, and secondary prevention, namely endoscopic screening and surveillance of precancerous conditions, such as gastric intestinal metaplasia (GIM). An emerging body of evidence supports the possible impact of these strategies on GC incidence and mortality in identifiable high-risk populations in the United States. Accordingly, the primary objective of this American Gastroenterological Association (AGA) Clinical Practice Update (CPU) Expert Review is to provide best practice advice for primary and secondary prevention of GC in the context of current clinical practice and evidence in the United States.<h3>Methods</h3>This CPU Expert Review was commissioned and approved by the AGA Institute CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of <em>Gastroenterology.</em> These best practice advice statements were drawn from a review of the published literature and expert opinion. Because systematic reviews were not performed, these best practice advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations.<strong>Best Practice Advice Statements</strong><h3>Best Practice Advice 1</h3>There are identifiable high-risk groups in the United States who should be considered for GC screening. These include first-generation immigrants from high-incidence GC regions and possibly other non-White racial and ethnic groups, those with a family history of GC in a first-degree relative, and individuals with certain hereditary gastrointestinal polyposis or hereditary cancer syndromes.<h3>Best Practice Advice 2</h3>Endoscopy is the best test for screening or surveillance in individuals at increased risk for GC. Endoscopy enables direct visualization to endoscopically stage the mucosa and identify areas concerning for neoplasia, as well as enables biopsies for further histologic examination and mucosal staging. Both endoscopic and histologic staging are key for risk stratification and determining whether ongoing surveillance is indicated and at what interval.<h3>Best Practice Advice 3</h3>High-quality upper endoscopy for the detection of premalignant and malignant gastric lesions should include the use of a high-definition white-light endoscopy system with image enhancement, gastric mucosal cleansing, and insufflation to achieve optimal mucosal visualization, in addition to adequate visual inspection time, photodocumentation, and use of a systematic biopsy protocol for mucosal staging when appropriate.<h3>Best Practice Advice 4</h3><em>H pylori</em> eradication is essential and serves a
{"title":"AGA Clinical Practice Update on Screening and Surveillance in Individuals at Increased Risk for Gastric Cancer in the United States: Expert Review","authors":"Shailja C. Shah, Andrew Y. Wang, Michael B. Wallace, Joo Ha Hwang","doi":"10.1053/j.gastro.2024.11.001","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.11.001","url":null,"abstract":"<h3>Description</h3>Gastric cancer (GC) is a leading cause of preventable cancer and mortality in certain US populations. The most impactful way to reduce GC mortality is via primary prevention, namely <em>Helicobacter pylori</em> eradication, and secondary prevention, namely endoscopic screening and surveillance of precancerous conditions, such as gastric intestinal metaplasia (GIM). An emerging body of evidence supports the possible impact of these strategies on GC incidence and mortality in identifiable high-risk populations in the United States. Accordingly, the primary objective of this American Gastroenterological Association (AGA) Clinical Practice Update (CPU) Expert Review is to provide best practice advice for primary and secondary prevention of GC in the context of current clinical practice and evidence in the United States.<h3>Methods</h3>This CPU Expert Review was commissioned and approved by the AGA Institute CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of <em>Gastroenterology.</em> These best practice advice statements were drawn from a review of the published literature and expert opinion. Because systematic reviews were not performed, these best practice advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations.<strong>Best Practice Advice Statements</strong><h3>Best Practice Advice 1</h3>There are identifiable high-risk groups in the United States who should be considered for GC screening. These include first-generation immigrants from high-incidence GC regions and possibly other non-White racial and ethnic groups, those with a family history of GC in a first-degree relative, and individuals with certain hereditary gastrointestinal polyposis or hereditary cancer syndromes.<h3>Best Practice Advice 2</h3>Endoscopy is the best test for screening or surveillance in individuals at increased risk for GC. Endoscopy enables direct visualization to endoscopically stage the mucosa and identify areas concerning for neoplasia, as well as enables biopsies for further histologic examination and mucosal staging. Both endoscopic and histologic staging are key for risk stratification and determining whether ongoing surveillance is indicated and at what interval.<h3>Best Practice Advice 3</h3>High-quality upper endoscopy for the detection of premalignant and malignant gastric lesions should include the use of a high-definition white-light endoscopy system with image enhancement, gastric mucosal cleansing, and insufflation to achieve optimal mucosal visualization, in addition to adequate visual inspection time, photodocumentation, and use of a systematic biopsy protocol for mucosal staging when appropriate.<h3>Best Practice Advice 4</h3><em>H pylori</em> eradication is essential and serves a","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874644","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}
Pub Date : 2024-12-21DOI: 10.1053/j.gastro.2024.12.008
Jonas J. Rudbæk, Tine Jess
No Abstract
没有抽象的
{"title":"Reply to Shao et al, Yang et al, and Li","authors":"Jonas J. Rudbæk, Tine Jess","doi":"10.1053/j.gastro.2024.12.008","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.12.008","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"33 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867308","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}
Pub Date : 2024-12-20DOI: 10.1053/j.gastro.2024.07.049
Liqi Li
No Abstract
没有抽象的
{"title":"Comments on “Inflammatory markers at birth and risk of early onset inflammatory bowel disease”","authors":"Liqi Li","doi":"10.1053/j.gastro.2024.07.049","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.07.049","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"15 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867311","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}
Pub Date : 2024-12-20DOI: 10.1053/j.gastro.2024.12.009
Tien S. Dong, Lin Chang
No Abstract
没有抽象的
{"title":"Reply to Huang et al","authors":"Tien S. Dong, Lin Chang","doi":"10.1053/j.gastro.2024.12.009","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.12.009","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"31 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867307","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}
Pub Date : 2024-12-20DOI: 10.1053/j.gastro.2024.10.038
Jessica P.E. Davis, Joseph K. Lim, Fadi F. Francis, Joseph Ahn
<h3>Description</h3>Portal vein thromboses (PVTs) are common in patients with cirrhosis and are associated with advanced portal hypertension and mortality. The treatment of PVTs remains a clinical challenge due to limited evidence and competing risks of PVT-associated complications vs bleeding risk of anticoagulation. Significant heterogeneity in PVT phenotype based on anatomic, host, and disease characteristics, and an emerging spectrum of therapeutic options further complicate PVT management. This Clinical Practice Update (CPU) aims to provide best practice advice for the evaluation and management of PVT in cirrhosis, including the role of direct oral anticoagulants and endovascular interventions.<h3>methods</h3>This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of <em>Gastroenterology.</em> These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations.<strong>Best Practice Advice Statements</strong><h3>Best Practice Advice 1</h3>Asymptomatic patients with compensated cirrhosis do not require routine screening for PVT.<h3>Best Practice Advice 2</h3>Patients with cirrhosis with PVTs identified on Doppler ultrasound should undergo cross-sectional imaging with computed tomography or magnetic resonance imaging to confirm the diagnosis, evaluate for malignancy, and document the degree of lumen occlusion, clot extent, and chronicity.<h3>Best Practice Advice 3</h3>Patients with cirrhosis and PVT do not require a hypercoagulable workup in the absence of additional thromboemboli or laboratory abnormalities or family history suggestive of thrombophilia.<h3>Best Practice Advice 4</h3>Patients with cirrhosis and PVT with evidence of intestinal ischemia require urgent anticoagulation to minimize ischemic injury. If available, these patients should be managed by a multidisciplinary team, including gastroenterology and hepatology, interventional radiology, hematology, and surgery.<h3>Best Practice Advice 5</h3>Consider observation, with repeat imaging every 3 months until clot regression, in patients with cirrhosis without intestinal ischemia and recent (<6 months) thrombosis involving the intrahepatic portal vein branches or when there is <50% occlusion of the main portal vein, splenic vein, or mesenteric veins.<h3>Best Practice Advice 6</h3>Anticoagulation should be considered in patients with cirrhosis without intestinal ischemia who develop recent (<6 months) PVT that is >50% occlusive or involves the main
{"title":"AGA Clinical Practice Update on Management of Portal Vein Thrombosis in Patients With Cirrhosis: Expert Review","authors":"Jessica P.E. Davis, Joseph K. Lim, Fadi F. Francis, Joseph Ahn","doi":"10.1053/j.gastro.2024.10.038","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.10.038","url":null,"abstract":"<h3>Description</h3>Portal vein thromboses (PVTs) are common in patients with cirrhosis and are associated with advanced portal hypertension and mortality. The treatment of PVTs remains a clinical challenge due to limited evidence and competing risks of PVT-associated complications vs bleeding risk of anticoagulation. Significant heterogeneity in PVT phenotype based on anatomic, host, and disease characteristics, and an emerging spectrum of therapeutic options further complicate PVT management. This Clinical Practice Update (CPU) aims to provide best practice advice for the evaluation and management of PVT in cirrhosis, including the role of direct oral anticoagulants and endovascular interventions.<h3>methods</h3>This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of <em>Gastroenterology.</em> These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations.<strong>Best Practice Advice Statements</strong><h3>Best Practice Advice 1</h3>Asymptomatic patients with compensated cirrhosis do not require routine screening for PVT.<h3>Best Practice Advice 2</h3>Patients with cirrhosis with PVTs identified on Doppler ultrasound should undergo cross-sectional imaging with computed tomography or magnetic resonance imaging to confirm the diagnosis, evaluate for malignancy, and document the degree of lumen occlusion, clot extent, and chronicity.<h3>Best Practice Advice 3</h3>Patients with cirrhosis and PVT do not require a hypercoagulable workup in the absence of additional thromboemboli or laboratory abnormalities or family history suggestive of thrombophilia.<h3>Best Practice Advice 4</h3>Patients with cirrhosis and PVT with evidence of intestinal ischemia require urgent anticoagulation to minimize ischemic injury. If available, these patients should be managed by a multidisciplinary team, including gastroenterology and hepatology, interventional radiology, hematology, and surgery.<h3>Best Practice Advice 5</h3>Consider observation, with repeat imaging every 3 months until clot regression, in patients with cirrhosis without intestinal ischemia and recent (<6 months) thrombosis involving the intrahepatic portal vein branches or when there is <50% occlusion of the main portal vein, splenic vein, or mesenteric veins.<h3>Best Practice Advice 6</h3>Anticoagulation should be considered in patients with cirrhosis without intestinal ischemia who develop recent (<6 months) PVT that is >50% occlusive or involves the main ","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"24 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867310","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}
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