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Cold EMR, hot EMR or ESD for large benign adenoma: not one size fits all 治疗大型良性腺瘤的冷电磁辐射、热电磁辐射或静电放电疗法:不能一刀切
IF 24.5 1区 医学
Gut Pub Date : 2024-09-17 DOI: 10.1136/gutjnl-2024-333490
Veronique Van der Voort, Cesare Hassan, Alessandro Repici, Romain Legros, Mathieu Pioche, Jérémie Jacques
{"title":"Cold EMR, hot EMR or ESD for large benign adenoma: not one size fits all","authors":"Veronique Van der Voort, Cesare Hassan, Alessandro Repici, Romain Legros, Mathieu Pioche, Jérémie Jacques","doi":"10.1136/gutjnl-2024-333490","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333490","url":null,"abstract":"We read with great interest the study by O’Sullivan et al ,1 examining the technical and procedural outcomes of Cold Endoscopic Mucosal Resection (C-EMR) versus Hot EMR (H-EMR). We congratulate the authors for conducting this important research, which adds valuable information to the body of knowledge guiding our choice of the optimal treatment modality for large, benign colorectal polyps. However, we would like to address several points. First, readers should be aware that this study focuses on a highly selected group of large non-pedunculated colon polyps (LNPCPs) as only 20% of referred lesions during the study period of 4 years met the inclusion criteria, being flat lesions of 15–50 mm, without macronodule, depressed area or optical suspicion of submucosal invasive cancer (SMIC). Despite this selection, 2.2% unrecognised SMIC was found, …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"29 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236841","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}
引用次数: 0
Metabolic reprogramming by mutant GNAS creates an actionable dependency in intraductal papillary mucinous neoplasms of the pancreas 突变型 GNAS 的代谢重编程在胰腺导管内乳头状粘液瘤中产生了可操作的依赖性
IF 24.5 1区 医学
Gut Pub Date : 2024-09-13 DOI: 10.1136/gutjnl-2024-332412
Yuki Makino, Kimal I Rajapakshe, Benson Chellakkan Selvanesan, Takashi Okumura, Kenjiro Date, Prasanta Dutta, Lotfi Abou-Elkacem, Akiko Sagara, Jimin Min, Marta Sans, Nathaniel Yee, Megan J Siemann, Jose Enriquez, Paytience Smith, Pratip Bhattacharya, Michael Kim, Merve Dede, Traver Hart, Anirban Maitra, Fredrik Ivar Thege
{"title":"Metabolic reprogramming by mutant GNAS creates an actionable dependency in intraductal papillary mucinous neoplasms of the pancreas","authors":"Yuki Makino, Kimal I Rajapakshe, Benson Chellakkan Selvanesan, Takashi Okumura, Kenjiro Date, Prasanta Dutta, Lotfi Abou-Elkacem, Akiko Sagara, Jimin Min, Marta Sans, Nathaniel Yee, Megan J Siemann, Jose Enriquez, Paytience Smith, Pratip Bhattacharya, Michael Kim, Merve Dede, Traver Hart, Anirban Maitra, Fredrik Ivar Thege","doi":"10.1136/gutjnl-2024-332412","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332412","url":null,"abstract":"Background Oncogenic ‘hotspot’ mutations of KRAS and GNAS are two major driver alterations in intraductal papillary mucinous neoplasms (IPMNs), which are bona fide precursors to pancreatic ductal adenocarcinoma. We previously reported that pancreas-specific Kras G12D and Gnas R201C co-expression in p48Cre; KrasLSL-G12D; Rosa26LSL-rtTA; Tg (TetO-GnasR201C) mice ( ‘Kras;Gnas ’ mice) caused development of cystic lesions recapitulating IPMNs. Objective We aim to unveil the consequences of mutant Gnas R201C expression on phenotype, transcriptomic profile and genomic dependencies. Design We performed multimodal transcriptional profiling (bulk RNA sequencing, single-cell RNA sequencing and spatial transcriptomics) in the ‘Kras;Gnas ’ autochthonous model and tumour-derived cell lines ( Kras;Gnas cells), where Gnas R201C expression is inducible. A genome-wide CRISPR/ Cas 9 screen was conducted to identify potential vulnerabilities in KrasG12D;GnasR201C co-expressing cells. Results Induction of Gnas R201C—and resulting G(s)alpha signalling—leads to the emergence of a gene signature of gastric (pyloric type) metaplasia in pancreatic neoplastic epithelial cells. CRISPR screening identified the synthetic essentiality of glycolysis-related genes Gpi1 and Slc2a1 in Kras G12D; Gnas R201C co-expressing cells. Real-time metabolic analyses in Kras;Gnas cells and autochthonous Kras;Gnas model confirmed enhanced glycolysis on Gnas R201C induction. Induction of Gnas R201C made Kras G12D expressing cells more dependent on glycolysis for their survival. Protein kinase A-dependent phosphorylation of the glycolytic intermediate enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) was a driver of increased glycolysis on Gnas R201C induction. Conclusion Multiple orthogonal approaches demonstrate that Kras G12D and Gnas R201C co-expression results in a gene signature of gastric pyloric metaplasia and glycolytic dependency during IPMN pathogenesis. The observed metabolic reprogramming may provide a potential target for therapeutics and interception of IPMNs. Data are available in a public, open access repository. Bulk RNA-seq, single-cell RNA-seq and spatial transcriptomic datasets generated in this study have been deposited in the NCBI Gene Expression Omnibus (GEO) database under accession number GSE275406.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"323 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231345","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}
引用次数: 0
Long-term hepatitis B surface antigen response after finite treatment of ARC-520 or JNJ-3989 ARC-520 或 JNJ-3989 有限治疗后的长期乙型肝炎表面抗原反应
IF 24.5 1区 医学
Gut Pub Date : 2024-09-12 DOI: 10.1136/gutjnl-2024-333026
Lung Yi Mak, Christine I Wooddell, Oliver Lenz, Thomas Schluep, James Hamilton, Heather L Davis, Xianhua Mao, Wai-Kay Seto, Michael Biermer, Man-Fung Yuen
{"title":"Long-term hepatitis B surface antigen response after finite treatment of ARC-520 or JNJ-3989","authors":"Lung Yi Mak, Christine I Wooddell, Oliver Lenz, Thomas Schluep, James Hamilton, Heather L Davis, Xianhua Mao, Wai-Kay Seto, Michael Biermer, Man-Fung Yuen","doi":"10.1136/gutjnl-2024-333026","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333026","url":null,"abstract":"Background and aims RNA interference has been extensively explored in patients with chronic hepatitis B (CHB) infection. We aimed to characterise the long-term efficacy of small interfering RNA (siRNA) on hepatitis B surface antigen (HBsAg) suppression. Methods We prospectively followed up participants with CHB who received siRNA, either ARC-520 or JNJ-73763989 (JNJ-3989), in combination with nucleoside analogue (NUC) in our centre. Participants enrolled included 15 receiving 4 monthly injections of ARC-520, 38 receiving 3 injections of JNJ-3989 at 1, 2 or 4 weekly intervals and 5 receiving placebo in previous clinical trials. Serial blood sampling was performed according to the original protocols and on completion every 24 weeks until last follow-up (LFU) with mean duration of 52.5 months. Results Among the 53 NUC+siRNA-treated participants (mean age 46.8, baseline HBsAg 3.08 log, 83% previously on NUC, 34% hepatitis B e antigen+), the proportion of patients achieving HBsAg seroclearance or <100 IU/mL at LFU was 1.9% and 32.1%, respectively, compared with 0% and 0% for placebo. Among siRNA-recipients, 48.5% and 5.0% of those with HBsAg <100 IU/mL and >100 IU/mL at nadir or ≤24 weeks from last dose could maintain or achieve HBsAg <100 IU/mL at LFU, respectively. Compared with placebo recipients, siRNA-recipients demonstrated faster overall annual decline of HBsAg (0.08 vs 0.21 log IU/mL/year) contributed predominantly by changes in the first year. Age was negatively correlated with HBsAg reduction at LFU (r=−0.427, p=0.001). Conclusion Short-duration siRNA treatment suppressed HBsAg expression with a prolonged effect for up to 6 years in some participants. All data relevant to the study are included in the article or uploaded as online supplemental information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"17 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174962","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}
引用次数: 0
Targeting TL1A and DR3: the new frontier of anti-cytokine therapy in IBD 靶向 TL1A 和 DR3:IBD 抗细胞因子疗法的新领域
IF 24.5 1区 医学
Gut Pub Date : 2024-09-11 DOI: 10.1136/gutjnl-2024-332504
Giorgos Bamias, Paola Menghini, Theresa T Pizarro, Fabio Cominelli
{"title":"Targeting TL1A and DR3: the new frontier of anti-cytokine therapy in IBD","authors":"Giorgos Bamias, Paola Menghini, Theresa T Pizarro, Fabio Cominelli","doi":"10.1136/gutjnl-2024-332504","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332504","url":null,"abstract":"TNF-like cytokine 1A (TL1A) and its functional receptor, death-domain receptor 3 (DR3), are members of the TNF and TNFR superfamilies, respectively, with recognised roles in regulating innate and adaptive immune responses; additional existence of a decoy receptor, DcR3, indicates a tightly regulated cytokine system. The significance of TL1A:DR3 signalling in the pathogenesis of inflammatory bowel disease (IBD) is supported by several converging lines of evidence.To provide a comprehensive understanding of what is currently known regarding the TL1A/DR3 system in the context of IBD.TL1A and DR3 are expressed by cellular subsets with important roles for the initiation and maintenance of intestinal inflammation, serving as potent universal costimulators of effector immune responses, indicating their participation in the pathogenesis of IBD. Recent evidence also supports a homoeostatic role for TL1A:DR3 via regulation of Tregs and innate lymphoid cells. TL1A and DR3 are also expressed by stromal cells and may contribute to inflammation-induced or inflammation-independent intestinal fibrogenesis. Finally, discovery of genetic polymorphisms with functional consequences may allow for patient stratification, including differential responses to TL1A-targeted therapeutics.TL1A:DR3 signalling plays a central and multifaceted role in the immunological pathways that underlie intestinal inflammation, such as that observed in IBD. Such evidence provides the foundation for developing pharmaceutical approaches targeting this ligand-receptor pair in IBD.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"16 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170852","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}
引用次数: 0
Extending inflamed-class signature to predict immune checkpoint inhibitor-based combination therapy in hepatocellular carcinoma 扩展炎症类特征,预测肝细胞癌中基于免疫检查点抑制剂的联合疗法
IF 24.5 1区 医学
Gut Pub Date : 2024-09-11 DOI: 10.1136/gutjnl-2024-333375
Wenhua You, Chupeng Hu, Mengya Zhao, Yuhan Zhang, Jinying Lu, Yedi Huang, Ling Li, Yun Chen
{"title":"Extending inflamed-class signature to predict immune checkpoint inhibitor-based combination therapy in hepatocellular carcinoma","authors":"Wenhua You, Chupeng Hu, Mengya Zhao, Yuhan Zhang, Jinying Lu, Yedi Huang, Ling Li, Yun Chen","doi":"10.1136/gutjnl-2024-333375","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333375","url":null,"abstract":"Recently, we were intrigued by a recent study by Montironi et al ,1 in which they discovered that an inflamed subclass in hepatocellular carcinoma (HCC) patients is associated with a response to immunotherapy. The authors used a 20-gene signature to distinguish these patients and further found different immune infiltration between inflamed and non-inflamed class at the bulk level. We commend the authors for undertaking this study, which holds significant clinical implications. We also observed that Li et al 2 have validated the predictive value of inflamed class in two additional RNA-seq datasets from patients who received anti-PD1 therapy. However, the use of combination immunotherapy, which includes dual immune checkpoint inhibitors or is combined with anti-VEGF agents, has become a growing trend in HCC.3–6 Here, we first performed unsupervised clustering on the RNA-seq data from 289 patients enrolled in the GO30140 Ph1b and IMbrave150 PhIII trials who received a combination of anti-PD-L1 and anti-VEGF therapy7 (figure 1). The results indicated that the subclass (C1), which exhibited high expression of genes associated with B/plasma cells and fibroblasts, had a higher inflamed-class score and better therapeutic efficacy (figure 1B–D). The performance of inflamed-class gene signature in predicting combination therapy response showed anarea under …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"58 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170853","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}
引用次数: 0
Identification of PRMT5 as a therapeutic target in cholangiocarcinoma 确定 PRMT5 为胆管癌的治疗靶点
IF 24.5 1区 医学
Gut Pub Date : 2024-09-11 DOI: 10.1136/gutjnl-2024-332998
Jasmin Elurbide, Leticia Colyn, Maria U Latasa, Iker Uriarte, Stefano Mariani, Amaya Lopez-Pascual, Emiliana Valbuena, Borja Castello-Uribe, Robert Arnes-Benito, Elena Adan-Villaescusa, Luz A Martinez-Perez, Mikel Azkargorta, Felix Elortza, Hanghang Wu, Marcin Krawczyk, Kai Markus Schneider, Bruno Sangro, Luca Aldrighetti, Francesca Ratti, Andrea Casadei Gardini, Jose J G Marin, Irene Amat, Jesus M Urman, Maria Arechederra, Maria Luz Martinez-Chantar, Christian Trautwein, Meritxell Huch, Francisco Javier Cubero, Carmen Berasain, Maite G Fernandez-Barrena, Matias A Avila
{"title":"Identification of PRMT5 as a therapeutic target in cholangiocarcinoma","authors":"Jasmin Elurbide, Leticia Colyn, Maria U Latasa, Iker Uriarte, Stefano Mariani, Amaya Lopez-Pascual, Emiliana Valbuena, Borja Castello-Uribe, Robert Arnes-Benito, Elena Adan-Villaescusa, Luz A Martinez-Perez, Mikel Azkargorta, Felix Elortza, Hanghang Wu, Marcin Krawczyk, Kai Markus Schneider, Bruno Sangro, Luca Aldrighetti, Francesca Ratti, Andrea Casadei Gardini, Jose J G Marin, Irene Amat, Jesus M Urman, Maria Arechederra, Maria Luz Martinez-Chantar, Christian Trautwein, Meritxell Huch, Francisco Javier Cubero, Carmen Berasain, Maite G Fernandez-Barrena, Matias A Avila","doi":"10.1136/gutjnl-2024-332998","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332998","url":null,"abstract":"Background Cholangiocarcinoma (CCA) is a very difficult-to-treat cancer. Chemotherapies are little effective and response to immune checkpoint inhibitors is limited. Therefore, new therapeutic strategies need to be identified. Objective We characterised the enzyme protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in CCA. Design We evaluated the expression of PRMT5, its functional partner MEP50 and methylthioadenosine phosphorylase (MTAP)—an enzyme that modulates the sensitivity of PRMT5 to pharmacological inhibitors—in human CCA tissues. PRMT5-targeting drugs, currently tested in clinical trials for other malignancies, were assessed in human CCA cell lines and organoids, as well as in two immunocompetent CCA mouse models. Transcriptomic, proteomic and functional analyses were performed to explore the underlying antitumoural mechanisms. Results PRMT5 and MEP50 proteins were correlatively overexpressed in most CCA tissues. MTAP was absent in 25% of intrahepatic CCA. PRMT5-targeting drugs markedly inhibited CCA cell proliferation, synergising with cisplatin and gemcitabine and hindered the growth of cholangiocarcinoma organoids. PRMT5 inhibition blunted the expression of oncogenic genes involved in chromatin remodelling and DNA repair, consistently inducing the formation of RNA loops and promoting DNA damage. Treatment with PRMT5-targeting drugs significantly restrained the growth of experimental CCA without adverse effects and concomitantly induced the recruitment of CD4 and CD8 T cells to shrinking tumourous lesions. Conclusion PRMT5 and MEP50 are frequently upregulated in human CCA, and PRMT5-targeting drugs have significant antitumoural efficacy in clinically relevant CCA models. Our findings support the evaluation of PRMT5 inhibitors in clinical trials, including their combination with cytotoxic and immune therapies. Data are available on reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"50 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170854","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}
引用次数: 0
AlphaMissense versus laboratory-based pathogenicity prediction of 13 novel missense CPA1 variants from pancreatitis cases 胰腺炎病例中13个新型错义CPA1变异的AlphaMissense与基于实验室的致病性预测比较
IF 24.5 1区 医学
Gut Pub Date : 2024-09-10 DOI: 10.1136/gutjnl-2024-333697
Máté Sándor, Isabelle Scheers, Atsushi Masamune, Heiko Witt, Jessica LaRusch, Jian-Min Chen, Balázs Csaba Németh, Andrea Geisz, Aliye Uc, Miklós Sahin-Tóth
{"title":"AlphaMissense versus laboratory-based pathogenicity prediction of 13 novel missense CPA1 variants from pancreatitis cases","authors":"Máté Sándor, Isabelle Scheers, Atsushi Masamune, Heiko Witt, Jessica LaRusch, Jian-Min Chen, Balázs Csaba Németh, Andrea Geisz, Aliye Uc, Miklós Sahin-Tóth","doi":"10.1136/gutjnl-2024-333697","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333697","url":null,"abstract":"We have read with great interest the study by Wang et al 1 in which the authors evaluated the utility of the AlphaMissense prediction programme2 (https://alphamissense.hegelab.org) in the classification of missense CPA1 variants with respect to pathogenicity in chronic pancreatitis. While the AI-driven prediction performed relatively well, the authors highlighted potential shortcomings that can limit its value in clinical practice. Defining the pathogenic potential of CPA1 variants detected in pancreatitis cases can be challenging because the mechanistic basis of disease risk is unrelated to loss of CPA1 function and seems to be determined by mutation-induced misfolding and the ensuing endoplasmic reticulum (ER) stress.3–5 Recently, we used transiently transfected HEK 293T cells to measure the secretion efficiency and induction of BiP mRNA expression, a marker of ER stress, for 50 missense CPA1 variants from pancreatitis cases and healthy controls.6 We found that the best predictor of pathogenicity was loss of secretion (<10% of wild type) irrespective of BiP levels. This data set can serve as a reference for the assignment of clinical significance of novel CPA1 variants. In the present study, we set out to examine what fraction of novel CPA1 variants detected in real-world genetic testing can be classified as pathogenic and whether AlphaMissense can replace …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"15 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166206","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}
引用次数: 0
High accuracy model for HBsAg loss based on longitudinal trajectories of serum qHBsAg throughout long-term antiviral therapy. 基于长期抗病毒治疗过程中血清 qHBsAg 纵向轨迹的 HBsAg 消失高精度模型。
IF 23 1区 医学
Gut Pub Date : 2024-09-09 DOI: 10.1136/gutjnl-2024-332182
Rong Fan, Siru Zhao, Junqi Niu, Hong Ma, Qing Xie, Song Yang, Jianping Xie, Xiaoguang Dou, Jia Shang, Huiying Rao, Qi Xia, Yali Liu, Yongfeng Yang, Hongbo Gao, Aimin Sun, Xieer Liang, Xueru Yin, Yongfang Jiang, Yanyan Yu, Jian Sun, Nikolai V Naoumov, Jinlin Hou
{"title":"High accuracy model for HBsAg loss based on longitudinal trajectories of serum qHBsAg throughout long-term antiviral therapy.","authors":"Rong Fan, Siru Zhao, Junqi Niu, Hong Ma, Qing Xie, Song Yang, Jianping Xie, Xiaoguang Dou, Jia Shang, Huiying Rao, Qi Xia, Yali Liu, Yongfeng Yang, Hongbo Gao, Aimin Sun, Xieer Liang, Xueru Yin, Yongfang Jiang, Yanyan Yu, Jian Sun, Nikolai V Naoumov, Jinlin Hou","doi":"10.1136/gutjnl-2024-332182","DOIUrl":"10.1136/gutjnl-2024-332182","url":null,"abstract":"<p><strong>Objective: </strong>Hepatitis B surface antigen (HBsAg) loss is the optimal outcome for patients with chronic hepatitis B (CHB) but this rarely occurs with currently approved therapies. We aimed to develop and validate a prognostic model for HBsAg loss on treatment using longitudinal data from a large, prospectively followed, nationwide cohort.</p><p><strong>Design: </strong>CHB patients receiving nucleos(t)ide analogues as antiviral treatment were enrolled from 50 centres in China. Quantitative HBsAg (qHBsAg) testing was prospectively performed biannually per protocol. Longitudinal discriminant analysis algorithm was used to estimate the incidence of HBsAg loss, by integrating clinical data of each patient collected during follow-up.</p><p><strong>Results: </strong>In total, 6792 CHB patients who had initiated antiviral treatment 41.3 (IQR 7.6-107.6) months before enrolment and had median qHBsAg 2.9 (IQR 2.3-3.3) log<sub>10</sub>IU/mL at entry were analysed. With a median follow-up of 65.6 (IQR 51.5-84.7) months, the 5-year cumulative incidence of HBsAg loss was 2.4%. A prediction model integrating all qHBsAg values of each patient during follow-up, designated GOLDEN model, was developed and validated. The AUCs of GOLDEN model were 0.981 (95% CI 0.974 to 0.987) and 0.979 (95% CI 0.974 to 0.983) in the training and external validation sets, respectively, and were significantly better than those of a single qHBsAg measurement. GOLDEN model identified 8.5%-10.4% of patients with a high probability of HBsAg loss (5-year cumulative incidence: 17.0%-29.1%) and was able to exclude 89.6%-91.5% of patients whose incidence of HBsAg loss is 0. Moreover, the GOLDEN model consistently showed excellent performance among various subgroups.</p><p><strong>Conclusion: </strong>The novel GOLDEN model, based on longitudinal qHBsAg data, accurately predicts HBsAg clearance, provides reliable estimates of functional hepatitis B virus (HBV) cure and may have the potential to stratify different subsets of patients for novel anti-HBV therapies.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1725-1736"},"PeriodicalIF":23.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431835","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}
引用次数: 0
Positive effects of diet-induced microbiome modification on GDM in mice following human faecal transfer. 人类粪便转移后,饮食诱导的微生物群改变对小鼠 GDM 有积极影响。
IF 23 1区 医学
Gut Pub Date : 2024-09-09 DOI: 10.1136/gutjnl-2023-331456
Sigal Frishman, Meital Nuriel-Ohayon, Sondra Turjeman, Yishay Pinto, Or Yariv, Kinneret Tenenbaum-Gavish, Yoav Peled, Eran Poran, Joseph Pardo, Rony Chen, Efrat Muller, Elhanan Borenstein, Moshe Hod, Yoram Louzoun, Betty Schwartz, Eran Hadar, Maria Carmen Collado, Omry Koren
{"title":"Positive effects of diet-induced microbiome modification on GDM in mice following human faecal transfer.","authors":"Sigal Frishman, Meital Nuriel-Ohayon, Sondra Turjeman, Yishay Pinto, Or Yariv, Kinneret Tenenbaum-Gavish, Yoav Peled, Eran Poran, Joseph Pardo, Rony Chen, Efrat Muller, Elhanan Borenstein, Moshe Hod, Yoram Louzoun, Betty Schwartz, Eran Hadar, Maria Carmen Collado, Omry Koren","doi":"10.1136/gutjnl-2023-331456","DOIUrl":"10.1136/gutjnl-2023-331456","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e17"},"PeriodicalIF":23.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139106094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of OLGA and OLGIM as predictors of gastric cancer in a Latin American population: the ECHOS Study. 比较 OLGA 和 OLGIM 对拉丁美洲人群胃癌的预测作用:ECHOS 研究。
IF 23 1区 医学
Gut Pub Date : 2024-09-09 DOI: 10.1136/gutjnl-2023-331059
Gonzalo Latorre, Felipe Silva, Isabella Montero, Miguel Bustamante, Eitan Dukes, Javier Uribe, Oscar Corsi Sotelo, Diego Reyes, Eduardo Fuentes-López, Margarita Pizarro, Patricio Medel, Javiera Torres, Juan Carlos Roa, Sebastián Pizarro, Pablo Achurra, Andrés Donoso, Ignacio Wichmann, Alejandro H Corvalán, Javier Chahuan, Roberto Candia, Carlos Agüero, Robinson Gonzalez, Jose Ignacio Vargas, Alberto Espino, M Constanza Camargo, Shailja C Shah, Arnoldo Riquelme
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