Gastroenterology ReportPub Date : 2025-04-04eCollection Date: 2025-01-01DOI: 10.1093/gastro/goaf032
Toni Herta, Maik Schröder, Dominik Geisel, Cornelius Engelmann, Frank Tacke
{"title":"Management of IgG4-related cholangitis: diagnosis, therapy, and long-term surveillance.","authors":"Toni Herta, Maik Schröder, Dominik Geisel, Cornelius Engelmann, Frank Tacke","doi":"10.1093/gastro/goaf032","DOIUrl":"10.1093/gastro/goaf032","url":null,"abstract":"<p><p>IgG4-related cholangitis (IRC) is a chronic cholestatic liver disease that often occurs concomitantly with autoimmune pancreatitis type 1. Both conditions are manifestations of IgG4-related disease, a systemic autoimmune-mediated fibroinflammatory disorder. Patients often present with jaundice and weight loss, mimicking hepatobiliary malignancies, such as cholangiocarcinoma, primary sclerosing cholangitis, and pancreatic cancer. Accurate diagnosis is challenging due to the absence of pathognomonic findings but can be achieved using the HISORt criteria (histology, imaging, serology, other organ involvement, and response to immunosuppressive therapy). Early diagnosis is critical to avoid unnecessary surgery and prevent progression to liver fibrosis or cirrhosis. IRC responds well to corticosteroid therapy, though relapses are common, necessitating long-term immunosuppressive treatment in many cases. Steroid-sparing agents for remission induction and maintenance therapy comprise immunomodulators, such as azathioprine, as well as B-cell depletion therapies, such as rituximab. This review provides a structured clinical overview of the diagnosis, differential diagnosis, and therapy, including novel therapeutic options, such as inebilizumab, for this rare yet severe condition. A key focus is on long-term surveillance strategies, which include laboratory tests, imaging (contrast-enhanced magnetic resonance imaging/magnetic resonance cholangiopancreatography, ultrasound, endosonography), and, particularly in patients with fibrotic bile duct strictures, endoscopy (endoscopic retrograde cholangiopancreatography, cholangioscopy).</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf032"},"PeriodicalIF":3.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Latest possible timing for endoscopic-assisted intervention in capsule endoscopy.","authors":"Xinlong He, Yufeng Shen, Ye Feng, Zhifang Gao, Hanbing Xue, Huimin Chen","doi":"10.1093/gastro/goaf011","DOIUrl":"10.1093/gastro/goaf011","url":null,"abstract":"<p><strong>Background: </strong>Delayed upper gastrointestinal transit during small bowel capsule endoscopy (SBCE) can lead to incomplete or failed examinations but can be treated by endoscopic-assisted intervention (EAI). The aim of this study was to investigate the latest possible timing of EAI.</p><p><strong>Methods: </strong>Patients who underwent SBCE and received EAI between July 2007 and December 2020 were retrospectively reviewed. A novel T-value was developed that accounted for the varied battery life of different generations of PillCam when determining the latest possible timing of EAI, where T is calculated as EAI time/[minimum battery life of the PillCam minus small bowel transit time (6 h)] × 100%. Patients were divided into two groups based on the cut-off value of the receiver operating characteristic curve: early EAI (group A, T < 76.3%) and late EAI (group B, T ≥ 76.3%). The primary outcome was the completion rate (CR), and the secondary outcome was the detection rate. The latest possible timing of EAI (h) was calculated according to the T-value formula and further verified in our recent data set.</p><p><strong>Results: </strong>This study included 108 patients. The CR was significantly higher in group A than in group B (79.2% vs 58.2%; <i>P </i>=<i> </i>0.018). Late EAI was an independent predictor of incomplete SBCE (odds ratio = 2.900; 95% confidence interval, 1.193-7.053). The latest possible timing of EAI was 1.5 h and 4.6 h from the start of the examination for PillCam SB1 and PillCam SB2/3, respectively.</p><p><strong>Conclusions: </strong>Early EAI was associated with higher CR. The latest possible timing of EAI was 1.5 h for PillCam SB1 and 4.6 h for PillCam SB2/3 from the start of the examination.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf011"},"PeriodicalIF":3.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2025-03-26eCollection Date: 2025-01-01DOI: 10.1093/gastro/goaf024
Mandong Pan, Xianwei Huang, Xiaodong Huang, Xiong Liu, Jiyan Lin
{"title":"USP38 protects intestinal epithelial cells from ischemia/reperfusion injury by stabilizing BIRC5.","authors":"Mandong Pan, Xianwei Huang, Xiaodong Huang, Xiong Liu, Jiyan Lin","doi":"10.1093/gastro/goaf024","DOIUrl":"10.1093/gastro/goaf024","url":null,"abstract":"<p><strong>Background: </strong>Intestinal ischemia/reperfusion (II/R) is a severe condition with high mortality and limited treatment options. Extracellular vesicles that are derived from bone marrow mesenchymal stem cells (BM-MSC-EVs) exhibit therapeutic potential in alleviating II/R injury. However, the mechanism by which BM-MSC-EVs fulfill this function requires further characterization. The ubiquitin-proteasome system plays an essential role in II/R, but the functions of individual ubiquitination regulators such as ubiquitin-specific proteases (USPs) in this process remain incompletely understood.</p><p><strong>Methods: </strong>An II/R cellular model was established by using IEC-6 intestinal epithelial cells with oxygen-glucose deprivation/reperfusion (OGD/R) treatment. The expression of USPs was evaluated by using quantitative polymerase chain reaction and Western blot. The role of USP38 on the viability, apoptosis, migration, and reactive oxygen species (ROS) levels in OGD/R-treated IEC-6 cells were measured by using CCK-8, Annexin V/PI staining, transwell assay, and 2',7'-dichlorofluorescin diacetate (DCFDA) staining, respectively. The interaction between USP38 and BIRC5 was explored by using co-immunoprecipitation (Co-IP) and the ubiquitination level and stability of BIRC5 were examined by using Western blot. USP38-overexpressing BM-MSC-EVs were produced to treat OGD/R-treated IEC-6 cells.</p><p><strong>Results: </strong>USP38 expression was significantly downregulated in OGD/R-treated IEC-6 cells. Incubation of these cells with BM-MSC-EVs substantially elevated the USP38 expression, resulting in improved viability, reduced apoptosis, enhanced migration, and decreased ROS levels. Furthermore, overexpression of USP38 in BM-MSC-EVs further enhanced their protective effect on OGD/R-treated IEC-6 cells. At the molecular level, USP38 interacts with and stabilizes BIRC5 by decreasing its ubiquitination. Knock-down of BIRC5 abolished the protective effect of excessive USP38 on OGD/R-treated IEC-6 cells.</p><p><strong>Conclusion: </strong>USP38 protects intestinal epithelial cells from I/R injury by enhancing the stability of BIRC5.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf024"},"PeriodicalIF":3.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2025-03-18eCollection Date: 2025-01-01DOI: 10.1093/gastro/goaf021
Yi-Zhong Wu, Yao Xie, Lin Chen, Lei Ning, Xiao-Qi Hu, Xiao-Ping Xu
{"title":"Gasdermin E-mediated intestinal epithelial pyroptosis promotes chemically induced colitis in mice.","authors":"Yi-Zhong Wu, Yao Xie, Lin Chen, Lei Ning, Xiao-Qi Hu, Xiao-Ping Xu","doi":"10.1093/gastro/goaf021","DOIUrl":"10.1093/gastro/goaf021","url":null,"abstract":"<p><strong>Background: </strong>Gasdermin E (GSDME) is a newly identified pyroptosis executioner and is upregulated in the intestinal epithelial cell (IEC) of ulcerative colitis (UC) patients. However, the effects of epithelial GSDME on UC remain unknown.</p><p><strong>Methods: </strong>Bone marrow chimera experiments were performed to investigate the role of GSDME in nonhematopoietic cells, mainly including IECs. An FITC-dextran assay was used to assess the integrity of the intestinal epithelial barrier.</p><p><strong>Results: </strong><i>Gsdme<sup>-/-</sup></i> chimeras that were reconstituted with wild-type bone marrow cells exhibited lower weight loss, disease activity index, colon shortening, and histology scores than wild-type chimeras after treatment with dextran sulfate sodium (DSS). However, <i>Gsdme</i> <sup>+/+</sup> chimeras that were reconstituted with <i>Gsdme</i>-deficient bone marrow cells were not protected from DSS-induced colitis compared with wild-type chimeras. Importantly, DSS treatment activated Caspase-3 and cleaved GSDME to generate GSDME-N terminal fragments that are responsible for the induction of pyroptosis in IECs, but not in the intestinal lamina propria cell. Additionally, GSDME deficiency inhibited DSS-induced disruption of the intestinal epithelial barrier. Mechanistically, GSDME-mediated IEC pyroptosis is dependent on Caspase-3 activation, which is supported by the observation that the Caspase-3 inhibitor Z-DEVD-FMK inhibited DSS-induced GSDME cleavage in IECs.</p><p><strong>Conclusions: </strong>We show that GSDME-mediated epithelial pyroptosis contributes to the development of DSS-induced colitis by promoting intestinal inflammation and disrupting the intestinal epithelial barrier.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf021"},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2025-03-14eCollection Date: 2025-01-01DOI: 10.1093/gastro/goaf023
Erwan Guyot
{"title":"Heparan sulfate chains in hepatocellular carcinoma.","authors":"Erwan Guyot","doi":"10.1093/gastro/goaf023","DOIUrl":"https://doi.org/10.1093/gastro/goaf023","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) corresponds to the vast majority of liver cancer cases, with one of the highest mortality rates. Major advances have been made in this field both in the characterization of the molecular pathogenesis and in the development of systemic therapies. Despite these achievements, biomarkers and more efficient treatments are still needed to improve its management. Heparan sulfate (HS) chains are polysaccharides that are present at the cell surface or in the extracellular matrix that are able to bind various types of molecules, such as soluble factors, affecting their availability and thus their effects, or to contribute to interactions that position cells in their environments. Enzymes can modify HS chains after their synthesis, thus changing their properties. Numerous studies have shown HS-related proteins to be key actors that are associated with cellular effects, such as tumor growth, invasion, and metastasis, including in the context of liver carcinogenesis. The aim of this review is to provide a comprehensive overview of the biology of HS chains and their potential importance in HCC, from biological considerations to clinical development, and the identification of biomarkers, as well as therapeutic perspectives.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf023"},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2025-03-14eCollection Date: 2025-01-01DOI: 10.1093/gastro/goaf028
Fredrik Åberg, Ville Männistö
{"title":"Prediction of major liver-related events in the population using prognostic models.","authors":"Fredrik Åberg, Ville Männistö","doi":"10.1093/gastro/goaf028","DOIUrl":"https://doi.org/10.1093/gastro/goaf028","url":null,"abstract":"<p><p>Liver disease poses a significant global health burden, with steatotic liver disease related to metabolic dysfunction and/or alcohol use being the most prevalent type. Current risk stratification strategies emphasize detecting advanced fibrosis as a surrogate marker for liver-related events (LREs), such as hospitalization, liver cancer, or death. However, fibrosis alone does not adequately predict imminent outcomes, particularly in fast-progressing individuals without advanced fibrosis at evaluation. This underscores the need for models designed specifically to predict LREs, enabling timely interventions. The Chronic Liver Disease (CLivD) risk score, the dynamic aspartate aminotransferase-to-alanine aminotransferase ratio (dAAR), and the Cirrhosis Outcome Risk Estimator (CORE) were explicitly developed to predict LRE risk rather than detect fibrosis. Derived from general population cohorts, these models incorporate either standard liver enzymes (dAAR and CORE) or risk factors (CLivD), enabling broad application in primary care and population-based settings. They directly estimate the risk of future LREs, improving on traditional fibrosis-focused approaches. Conversely, widely used models like the Fibrosis-4 index and newer ones, such as the LiverRisk and LiverPRO scores, were initially developed to detect significant/advanced fibrosis or liver stiffness. While not designed for LRE prediction, they have later been analyzed for this purpose. Integrating fibrosis screening with LRE-focused models like CLivD, dAAR, and CORE can help healthcare systems adopt proactive, preventive care. This approach emphasizes identifying individuals at imminent risk of severe outcomes, potentially ensuring better resource allocation and personalized interventions.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf028"},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Los Angeles-B esophagitis is a conclusive diagnostic evidence for gastroesophageal reflux disease: the validation of Lyon Consensus 2.0.","authors":"Jing Chen, Peiwen Dong, Songfeng Chen, Qianjun Zhuang, Mengyu Zhang, Kaidi Sun, Feng Tang, Qiong Wang, Yinglian Xiao","doi":"10.1093/gastro/goaf004","DOIUrl":"10.1093/gastro/goaf004","url":null,"abstract":"<p><strong>Background and aims: </strong>Recently, Lyon Consensus 2.0 recommended Los Angeles (LA)-B esophagitis as conclusive evidence and LA-A esophagitis as borderline evidence for gastroesophageal reflux disease (GERD). This study aimed to investigate the diagnostic value of LA-B and LA-A esophagitis.</p><p><strong>Methods: </strong>Patients with typical reflux symptoms who underwent endoscopy examination and received acid-suppressive therapy from two tertiary hospitals [the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, P. R. China) and the Third People's Hospital of Chengdu (Chengdu, P. R. China)] were retrospectively included. Acid-suppression response rates, endoscopy results, motility, and reflux parameters were compared between patients with different grades of esophagitis.</p><p><strong>Results: </strong>In total, 401 patients were enrolled, among whom 254 were without reflux esophagitis (RE), 51 had LA-A esophagitis, 44 had LA-B esophagitis, and 52 had LA-C/D esophagitis. Patients with LA-B esophagitis and LA-C/D esophagitis had significantly higher acid-suppressive response rates than non-RE patients (<i>P </i><<i> </i>0.05), whereas no significant difference was found between patients with LA-A esophagitis and non-RE patients (non-RE vs LA-A vs LA-B vs LA-C/D: 52.4% vs 70.6% vs 75.0% vs 82.7%). Among patients with LA-A esophagitis, those with a number of reflux episodes that exceeded 80 per day (90.0% vs 52.4%, <i>P </i>=<i> </i>0.044) or hypotensive esophagogastric junction (72.4% vs 52.4%, <i>P </i>=<i> </i>0.040) had significantly higher acid-suppressive response rates than non-RE patients.</p><p><strong>Conclusions: </strong>LA-B esophagitis can be regarded as conclusive evidence for GERD and initiate acid-suppressive therapy. LA-A esophagitis did not establish a definite GERD diagnosis alone. When combined with adjunctive or supportive evidence, the acid-suppressive therapy response rate of LA-A esophagitis improved.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf004"},"PeriodicalIF":3.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2025-03-10eCollection Date: 2025-01-01DOI: 10.1093/gastro/goaf022
Cheng Chen, Yanghui Bi, Bangtao Chen, Song He
{"title":"Nedd4L signaling contributes to carbon tetrachloride-induced liver fibrosis in female mice and is associated with enteric dysbacteriosis.","authors":"Cheng Chen, Yanghui Bi, Bangtao Chen, Song He","doi":"10.1093/gastro/goaf022","DOIUrl":"10.1093/gastro/goaf022","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis is characterized by hepatic stellate cell (HSC) activation and collagen overproduction, but its pathogenesis remains largely unknown. This study aimed to uncover the role of neural precursor cell expressed developmentally downregulated 4-like (Nedd4L) signaling in liver fibrosis and its relationship with gut microbiota.</p><p><strong>Methods: </strong>Intraperitoneal injection of carbon tetrachloride (CCl<sub>4</sub>) was used to induce liver fibrosis in 8-week-old female C57BL/6J mice with <i>Nedd4L</i> knockout or administration of the Nedd4L protein phosphorylation inhibitor EMD638683. HSCs isolated from mice were activated with transforming growth factor-beta 1 (TGFβ1) with or without EMD638683.</p><p><strong>Results: </strong>An approximately 3-fold elevation in <i>Nedd4L</i> mRNA was observed in hepatocytes and liver tissues, and significantly higher hepatic Nedd4L phosphorylation was observed in fibrotic mice than in non-fibrotic mice. <i>Nedd4L</i> mRNA level in HSCs isolated from fibrotic livers and Nedd4L protein level in TGFβ1-stimulated HSCs from wild-type livers remained unchanged. In isolated HSCs, TGFβ1-induced Nedd4L phosphorylation and cell activation were suppressed with EMD638683. In CCl<sub>4</sub>-treated mice, EMD638683 alleviated liver fibrosis and induced a relative increase in fecal <i>Bacteroides</i>, <i>Parabacteroides</i>, <i>Erysipelatoclostridium</i>, <i>Blautia</i>, and <i>Klebsiella</i>, whereas Nedd4L deficiency predisposed mice to liver injury and liver fibrosis with a remarkable reduction in fecal <i>Lactobacillus</i>, <i>Enterorhabdus</i>, and <i>Bacteroides</i>.</p><p><strong>Conclusion: </strong>Hepatic Nedd4L signaling contributes to CCl<sub>4</sub>-induced liver fibrosis in female mice, which is associated with alterations in the gut microbiota, and Nedd4L phosphorylation is involved in TGFβ1-mediated HSC activation.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf022"},"PeriodicalIF":3.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}