eGastroenterology最新文献

{"title":"Drug-target Mendelian randomisation applied to metabolic dysfunction-associated steatotic liver disease: opportunities and challenges.","authors":"Shan Luo, Ming-Hua Zheng, Vincent Wai-Sun Wong, Shiu Lun Au Yeung","doi":"10.1136/egastro-2024-100114","DOIUrl":"10.1136/egastro-2024-100114","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent cause of chronic liver disease worldwide affecting over one-third of the adult population. Despite the recent evolution of new nomenclature and diagnostic criteria for MASLD, progress in drug development for this condition remains limited. This review highlights the potential of drug-target Mendelian randomisation (MR), a study design that leverages human genetics and genomics, for the discovery, repositioning and safety assessment of drug targets in MASLD. We summarised key aspects of designing and appraising a drug-target MR study, discussing its inherent assumptions and considerations for instrument selection. Furthermore, we presented real-world examples from studies in MASLD which focused on opportunities and challenges in identifying novel drug targets, repositing existing drug targets, informing adjunctive treatments and addressing issues in paediatric MASLD.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 4","pages":"e100114"},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411979","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":"New dimension in viral hepatitis research.","authors":"Massimiliano Cocca, Barbara Testoni","doi":"10.1136/egastro-2024-100136","DOIUrl":"10.1136/egastro-2024-100136","url":null,"abstract":"<p><p>Chronic hepatitis B is the leading cause of hepatocellular carcinoma and a significant global health issue, affecting over 296 million people worldwide, with 15 million people coinfected with hepatitis delta virus (HDV) suffering accelerated disease progression. Recent advances in single-cell sequencing and spatial transcriptomics offer promising insights to improve the understanding of the liver's immune responses and hepatitis B virus (HBV)-infected cell distribution, with the final goal being the achievement of an HBV 'functional cure'. In this issue of <i>eGastroenterology</i>, Cross <i>et al</i> used the GeoMx nanostring digital spatial profiling (DSP) technology to study gene expression in the liver tissues of three patients (one HBV-monoinfected, one HBV/HDV coinfected and one HBV/human immunodeficiency virus (HIV) coinfected). Unlike other spatial transcriptomics techniques, GeoMx DSP allows targeted selection of specific tissue regions (regions of interest) for analysis, enabling precise gene expression mapping. The study revealed spatially distinct transcriptomic signatures related to immune features and viral burden, identifying a component of underinvestigated immune cells. Despite the small sample size, this proof-of-concept study demonstrates the feasibility of spatial transcriptomics in analysing HBV infections. Future advances, such as integrating viral proteins and nucleic acids, will enhance the understanding of spatial viral replication. Challenges in tissue processing, data analysis and costs remain before spatial transcriptomics can be applied as a diagnostic tool, but ongoing multiomics approaches offer promise for improved diagnosis and therapy.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":"e100136"},"PeriodicalIF":0.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411975","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":"Evidence-based incorporation of key parameters into MELD score for acute-on-chronic liver failure.","authors":"Xia Yu, Ruoqi Zhou, Wenting Tan, Xiaobo Wang, Xin Zheng, Yan Huang, Jinjun Chen, Beiling Li, Xinxin Liu, Zhiwei Li, Zhongji Meng, Yanhang Gao, Zhiping Qian, Feng Liu, Xiaobo Lu, Jia Shang, Huadong Yan, Yubao Zheng, Weituo Zhang, Shan Yin, Wenyi Gu, Guohong Deng, Xiaomei Xiang, Yi Zhou, Yixin Hou, Qun Zhang, Shue Xiong, Jing Liu, Ruochan Chen, Liyuan Long, Xiuhua Jiang, Sen Luo, Yuanyuan Chen, Chang Jiang, Jinming Zhao, Liujuan Ji, Xue Mei, Jing Li, Tao Li, Rongjiong Zheng, Xinyi Zhou, Qun Cai, Hai Li, Jifang Sheng, Yu Shi","doi":"10.1136/egastro-2024-100101","DOIUrl":"10.1136/egastro-2024-100101","url":null,"abstract":"<p><strong>Background: </strong>The model for end-stage liver disease (MELD) score is widely used for the prognostication in end-stage liver disease but has limited performance in acute-on-chronic liver failure (ACLF). In this study, we identified additional predictive parameters and reformed the MELD score to predict ACLF more accurately.</p><p><strong>Methods: </strong>A meta-analysis was performed on relevant studies to identify the predictive factors of 28-day/90-day outcomes of ACLF, which were validated in two large prospective cohorts. A prognostic score was developed by incorporating predictive parameters into the MELD score. The model was evaluated with a focus on discrimination and calibration.</p><p><strong>Results: </strong>The meta-analysis incorporated 32 cohort studies with a total of 13 939 patients, of which 13 risk factors were identified, and 3 risk factors (age, neutrophil count and hepatic encephalopathy (HE) grade) besides MELD score were validated in 751 patients with ACLF derived from two prospective cohorts. A new model (Chinese Acute-on-Chronic Liver Failure Consortium (CATCH-LIFE)-MELD score) was developed as follows: 0.028×age+0.3×HE grade+0.039×neutrophil count+0.079×MELD score. CATCH-LIFE-MELD score achieved a concordance index of 0.791/0.788 for 28-day/90-day outcomes, which is superior to other traditional scores. Other discrimination indices, including net reclassification improvement, integrated discrimination improvement and probability density function, and calibration including Nagelkerke's R² and Brier scores confirmed its superiority. Moreover, the accuracy of CATCH-LIFE-MELD score remained stable. It was highest in patients with or without hepatitis B virus infection, cirrhosis, liver failure or under the Chinese Group on the Study of Severe Hepatitis B (COSSH) criteria or European Association for the Study of the Liver (EASL) criteria. All results were substantiated by an evaluation using an external cohort.</p><p><strong>Conclusions: </strong>CATCH-LIFE-MELD score, a modified MELD score exhibited improved accuracy in predicting the short-term prognosis of ACLF than other traditional scores.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":"e100101"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411974","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":"Lysosomal physiology and pancreatic lysosomal stress in diabetes mellitus.","authors":"Meihua Hao, Sara C Sebag, Qingwen Qian, Ling Yang","doi":"10.1136/egastro-2024-100096","DOIUrl":"10.1136/egastro-2024-100096","url":null,"abstract":"<p><p>Endocrine and exocrine functions of the pancreas control nutritional absorption, utilisation and systemic metabolic homeostasis. Under basal conditions, the lysosome is pivotal in regulating intracellular organelles and metabolite turnover. In response to acute or chronic stress, the lysosome senses metabolic flux and inflammatory challenges, thereby initiating the adaptive programme to re-establish cellular homeostasis. A growing body of evidence has demonstrated the pathophysiological relevance of the lysosomal stress response in metabolic diseases in diverse sets of tissues/organs, such as the liver and the heart. In this review, we discuss the pathological relevance of pancreatic lysosome stress in diabetes mellitus. We begin by summarising lysosomal biology, followed by exploring the immune and metabolic functions of lysosomes and finally discussing the interplay between lysosomal stress and the pathogenesis of pancreatic diseases. Ultimately, our review aims to enhance our understanding of lysosomal stress in disease pathogenesis, which could potentially lead to the discovery of innovative treatment methods for these conditions.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607719","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":"Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease.","authors":"Hui Gao, Yanchao Jiang, Ge Zeng, Nazmul Huda, Themis Thoudam, Zhihong Yang, Suthat Liangpunsakul, Jing Ma","doi":"10.1136/egastro-2024-100104","DOIUrl":"10.1136/egastro-2024-100104","url":null,"abstract":"<p><p>Alcohol-associated liver disease (ALD) is a growing global health concern and its prevalence and severity are increasing steadily. While bacterial endotoxin translocation into the portal circulation is a well-established key factor, recent evidence highlights the critical role of sterile inflammation, triggered by diverse stimuli, in alcohol-induced liver injury. This review provides a comprehensive analysis of the complex interactions within the hepatic microenvironment in ALD. It examines the contributions of both parenchymal cells, like hepatocytes, and non-parenchymal cells, such as hepatic stellate cells, Kupffer cells, neutrophils, and liver sinusoidal endothelial cells, in driving the progression of the disease. Additionally, we explored the involvement of key mediators, including cytokines, chemokines and inflammasomes, which regulate inflammatory responses and promote liver injury and fibrosis. A particular focus has been placed on extracellular vesicles (EVs) as essential mediators of intercellular communication both within and beyond the liver. These vesicles facilitate the transfer of signalling molecules, such as microRNAs and proteins, which modulate immune responses, fibrogenesis and lipid metabolism, thereby influencing disease progression. Moreover, we underscore the importance of organ-to-organ crosstalk, particularly in the gut-liver axis, where dysbiosis and increased intestinal permeability lead to microbial translocation, exacerbating hepatic inflammation. The adipose-liver axis is also highlighted, particularly the impact of adipokines and free fatty acids from adipose tissue on hepatic steatosis and inflammation in the context of alcohol consumption.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904275","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":"New therapeutic target for alcohol-associated hepatitis (AH): AH-associated IL-8⁺ neutrophils.","authors":"Yukun Guan, Dechun Feng, Luca Maccioni, Yang Wang, Bin Gao","doi":"10.1136/egastro-2024-100166","DOIUrl":"10.1136/egastro-2024-100166","url":null,"abstract":"","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916467","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":"Goblet cells: guardians of gut immunity and their role in gastrointestinal diseases.","authors":"Fernanda Raya Tonetti, Alvaro Eguileor, Cristina Llorente","doi":"10.1136/egastro-2024-100098","DOIUrl":"10.1136/egastro-2024-100098","url":null,"abstract":"<p><p>Goblet cells (GCs) are specialised guardians lining the intestine. They play a critical role in gut defence and immune regulation. GCs continuously secrete mucus creating a physical barrier to protect from pathogens while harbouring symbiotic gut bacteria adapted to live within the mucus. GCs also form specialised GC-associated passages in a dynamic and regulated manner to deliver luminal antigens to immune cells, promoting gut tolerance and preventing inflammation. The composition of gut bacteria directly influences GC function, highlighting the intricate interplay between these components of a healthy gut. Indeed, imbalances in the gut microbiome can disrupt GC function, contributing to various gastrointestinal diseases like colorectal cancer, inflammatory bowel disease, cystic fibrosis, pathogen infections and liver diseases. This review explores the interplay between GCs and the immune system. We delve into the underlying mechanisms by which GC dysfunction contributes to the development and progression of gastrointestinal diseases. Finally, we examine current and potential treatments that target GCs and represent promising avenues for further investigation.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634002","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":"Rare cause of recurrent acute pancreatitis in teenage man.","authors":"Yamin Lai, Jiachun Pan, Kaixin Peng, Dong Wu, Li Wen","doi":"10.1136/egastro-2024-100105","DOIUrl":"10.1136/egastro-2024-100105","url":null,"abstract":"","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":"e100105"},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411977","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":"Causal role of the gut microbiome in certain human diseases: a narrative review.","authors":"Connor Prosty, Khaled Katergi, Jesse Papenburg, Alexander Lawandi, Todd C Lee, Hao Shi, Philip Burnham, Lee Swem, Bertrand Routy, Cedric P Yansouni, Matthew P Cheng","doi":"10.1136/egastro-2024-100086","DOIUrl":"10.1136/egastro-2024-100086","url":null,"abstract":"<p><p>Composed of an elaborate ecosystem of bacteria, fungi, viruses and protozoa residing in the human digestive tract, the gut microbiome influences metabolism, immune modulation, bile acid homeostasis and host defence. Through observational and preclinical data, the gut microbiome has been implicated in the pathogenesis of a spectrum of chronic diseases ranging from psychiatric to gastrointestinal in nature. Until recently, the lack of unequivocal evidence supporting a causal link between gut microbiome and human health outcomes incited controversy regarding its significance. However, recent randomised controlled trial (RCT) evidence in conditions, such as <i>Clostridioides difficile</i> infection<i>,</i> cancer immunotherapy and ulcerative colitis, has supported a causal relationship and has underscored the potential of the microbiome as a therapeutic target. This review delineates the RCT evidence substantiating the potential for a causal relationship between the gut microbiome and human health outcomes, the seminal observational evidence that preceded these RCTs and the remaining knowledge gaps.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":"e100086"},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411960","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 incidentaloma: incidental findings from history towards the era of liquid biopsy.","authors":"J-Matthias Löhr, Miroslav Vujasinovic, Nikolaos Kartalis, Philipp Osten","doi":"10.1136/egastro-2024-100082","DOIUrl":"10.1136/egastro-2024-100082","url":null,"abstract":"<p><p>This report provides an overview of the most common diagnostic methods that bring to light incidental findings of pancreatic cancer. It reviews the impact of medical imaging and genetic assessment on the definitions of incidental findings and incidentaloma of the pancreas. For different diagnostic approaches (eg, MRI and CT) and for different affections (cysts/intraductal papillary mucinous neoplasia, solid lesions), specific guidelines have been proposed and some are established. Based on this, we summarise the differences between the traditional methods with those applied in the PANCAID project. Biomarkers, genetic predispositions, mutations and circulating tumour cells give rise to different levels of concern. The final part of the report discusses the risks and the opportunities associated with further diagnostic procedures and surgical interventions. From the ethical perspective, the most urging question is, can a screening based on liquid biopsy and blood samples open a gateway for the prevention of pancreatic cancer-even if morbidity and lethality of today's surgical interventions is still very high?</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":"e100082"},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411976","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}