Pub Date : 2024-10-02DOI: 10.1136/gutjnl-2024-333827
Jiashu Han, Dan Shan
{"title":"Environmental and healthcare trade-offs between single-use and reusable gastroscopes.","authors":"Jiashu Han, Dan Shan","doi":"10.1136/gutjnl-2024-333827","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333827","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":23.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365060","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}
Background Enterically transmitted hepatitis viruses, such as hepatitis A virus (HAV) and hepatitis E virus (HEV), remain notable threats to public health. However, stable and reliable animal models of HAV and HEV infection are lacking. Objective This study aimed to establish HAV and HEV infections in multiple small animals by intravenously injecting lipid nanoparticle (LNP)-encapsulated full-length viral RNAs (LNP-vRNA). Design In vitro transcribed and capped full-length HAV RNA was encapsulated into LNP and was intravenously inoculated to Ifnar −/− mice, and HEV RNA to rabbits and gerbils. Virological parameters were determined by RT-qPCR, ELISA and immunohistochemistry. Liver histopathological changes were analysed by H&E staining. Antiviral drug and vaccine efficacy were further evaluated by using the LNP-vRNA-based animal model. Results On intravenous injection of LNP-vRNA, stable viral shedding was detected in the faeces and infectious HAV or HEV was recovered from the livers of the inoculated animals. Liver damage was observed in LNP-vRNA (HAV)-injected mice and LNP-vRNA (HEV)-injected rabbits. Mongolian gerbils were also susceptible to LNP-vRNA (HEV) injections. Finally, the antiviral countermeasures and in vivo function of HEV genome deletions were validated in the LNP-vRNA-based animal model. Conclusion This stable and standardised LNP-vRNA-based animal model provides a powerful platform to investigate the pathogenesis and evaluate countermeasures for enterically transmitted hepatitis viruses and can be further expanded to other viruses that are not easily cultured in vitro or in vivo. All data relevant to the study are included in the article or uploaded as online supplemental information.
{"title":"Establishment of enterically transmitted hepatitis virus animal models using lipid nanoparticle-based full-length viral genome RNA delivery system","authors":"Tianxu Liu, Jian Li, Xin Yin, Fengmin Lu, Hui Zhao, Lin Wang, Cheng-Feng Qin","doi":"10.1136/gutjnl-2024-332784","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332784","url":null,"abstract":"Background Enterically transmitted hepatitis viruses, such as hepatitis A virus (HAV) and hepatitis E virus (HEV), remain notable threats to public health. However, stable and reliable animal models of HAV and HEV infection are lacking. Objective This study aimed to establish HAV and HEV infections in multiple small animals by intravenously injecting lipid nanoparticle (LNP)-encapsulated full-length viral RNAs (LNP-vRNA). Design In vitro transcribed and capped full-length HAV RNA was encapsulated into LNP and was intravenously inoculated to Ifnar −/− mice, and HEV RNA to rabbits and gerbils. Virological parameters were determined by RT-qPCR, ELISA and immunohistochemistry. Liver histopathological changes were analysed by H&E staining. Antiviral drug and vaccine efficacy were further evaluated by using the LNP-vRNA-based animal model. Results On intravenous injection of LNP-vRNA, stable viral shedding was detected in the faeces and infectious HAV or HEV was recovered from the livers of the inoculated animals. Liver damage was observed in LNP-vRNA (HAV)-injected mice and LNP-vRNA (HEV)-injected rabbits. Mongolian gerbils were also susceptible to LNP-vRNA (HEV) injections. Finally, the antiviral countermeasures and in vivo function of HEV genome deletions were validated in the LNP-vRNA-based animal model. Conclusion This stable and standardised LNP-vRNA-based animal model provides a powerful platform to investigate the pathogenesis and evaluate countermeasures for enterically transmitted hepatitis viruses and can be further expanded to other viruses that are not easily cultured in vitro or in vivo. All data relevant to the study are included in the article or uploaded as online supplemental information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363064","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 : 2024-10-01DOI: 10.1136/gutjnl-2021-325564corr1
BMJ Publishing Group Ltd and British Society of Gastroenterology
Alonso-Nocelo M, Ruiz-Cañas L, Sancho P, et al . Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma. Gut 2023;72:345-59. The …
Alonso-Nocelo M, Ruiz-Cañas L, Sancho P, et al .巨噬细胞通过 LOXL2 介导的胰腺导管腺癌转移级联引导癌细胞。Gut 2023; 72:345-59..........
{"title":"Correction: Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma","authors":"BMJ Publishing Group Ltd and British Society of Gastroenterology","doi":"10.1136/gutjnl-2021-325564corr1","DOIUrl":"https://doi.org/10.1136/gutjnl-2021-325564corr1","url":null,"abstract":"Alonso-Nocelo M, Ruiz-Cañas L, Sancho P, et al . Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma. Gut 2023;72:345-59. The …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158817","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 : 2024-10-01DOI: 10.1136/gutjnl-2024-332095
Guodong Lian, Ermanno Malagola, Chengguo Wei, Qiongyu Shi, Junfei Zhao, Masahiro Hata, Hiroki Kobayashi, Yosuke Ochiai, Biyun Zheng, Xiaofei Zhi, Feijing Wu, Ruhong Tu, Osmel Companioni Nápoles, Wenjing Su, Leping Li, Changqing Jing, Man Chen, Leah Zamechek, Richard Friedman, Karol Nowicki-Osuch, Michael Quante, Jianwen Que, Timothy C Wang
Background While p53 mutations occur early in Barrett’s oesophagus (BE) progression to oesophageal adenocarcinoma (EAC), their role in gastric cardia stem cells remains unclear. Objective This study investigates the impact of p53 mutation on the fate and function of cardia progenitor cells in BE to EAC progression, particularly under the duress of chronic injury. Design We used a BE mouse model (L2-IL1β) harbouring a Trp53 mutation (R172H) to study the effects of p53 on Cck2r+ cardia progenitor cells. We employed lineage tracing, pathological analysis, organoid cultures, single-cell RNA sequencing (scRNA-seq) and computational analyses to investigate changes in progenitor cell behaviour, differentiation patterns and tumour progression. Additionally, we performed orthotopic transplantation of sorted metaplastic and mutant progenitor cells to assess their tumourigenic potential in vivo. Results The p53 mutation acts as a switch to expand progenitor cells and inhibit their differentiation towards metaplasia, but only amidst chronic injury. In L2-IL1β mice, p53 mutation increased progenitors expansion and lineage-tracing with a shift from metaplasia to dysplasia. scRNA-seq revealed dysplastic cells arise directly from mutant progenitors rather than progressing through metaplasia. In vitro, p53 mutation enhanced BE progenitors’ organoid-forming efficiency, growth, DNA damage resistance and progression to aneuploidy. Sorted metaplastic cells grew poorly with no progression to dysplasia, while mutant progenitors gave rise to dysplasia in orthotopic transplantation. Computational analyses indicated that p53 mutation inhibited stem cell differentiation through Notch activation. Conclusions p53 mutation contributes to BE progression by increasing expansion and fitness of undifferentiated cardia progenitors and preventing their differentiation towards metaplasia. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information.
{"title":"p53 mutation biases squamocolumnar junction progenitor cells towards dysplasia rather than metaplasia in Barrett’s oesophagus","authors":"Guodong Lian, Ermanno Malagola, Chengguo Wei, Qiongyu Shi, Junfei Zhao, Masahiro Hata, Hiroki Kobayashi, Yosuke Ochiai, Biyun Zheng, Xiaofei Zhi, Feijing Wu, Ruhong Tu, Osmel Companioni Nápoles, Wenjing Su, Leping Li, Changqing Jing, Man Chen, Leah Zamechek, Richard Friedman, Karol Nowicki-Osuch, Michael Quante, Jianwen Que, Timothy C Wang","doi":"10.1136/gutjnl-2024-332095","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332095","url":null,"abstract":"Background While p53 mutations occur early in Barrett’s oesophagus (BE) progression to oesophageal adenocarcinoma (EAC), their role in gastric cardia stem cells remains unclear. Objective This study investigates the impact of p53 mutation on the fate and function of cardia progenitor cells in BE to EAC progression, particularly under the duress of chronic injury. Design We used a BE mouse model (L2-IL1β) harbouring a Trp53 mutation (R172H) to study the effects of p53 on Cck2r+ cardia progenitor cells. We employed lineage tracing, pathological analysis, organoid cultures, single-cell RNA sequencing (scRNA-seq) and computational analyses to investigate changes in progenitor cell behaviour, differentiation patterns and tumour progression. Additionally, we performed orthotopic transplantation of sorted metaplastic and mutant progenitor cells to assess their tumourigenic potential in vivo. Results The p53 mutation acts as a switch to expand progenitor cells and inhibit their differentiation towards metaplasia, but only amidst chronic injury. In L2-IL1β mice, p53 mutation increased progenitors expansion and lineage-tracing with a shift from metaplasia to dysplasia. scRNA-seq revealed dysplastic cells arise directly from mutant progenitors rather than progressing through metaplasia. In vitro, p53 mutation enhanced BE progenitors’ organoid-forming efficiency, growth, DNA damage resistance and progression to aneuploidy. Sorted metaplastic cells grew poorly with no progression to dysplasia, while mutant progenitors gave rise to dysplasia in orthotopic transplantation. Computational analyses indicated that p53 mutation inhibited stem cell differentiation through Notch activation. Conclusions p53 mutation contributes to BE progression by increasing expansion and fitness of undifferentiated cardia progenitors and preventing their differentiation towards metaplasia. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363095","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 : 2024-09-30DOI: 10.1136/gutjnl-2024-332907
Timothy O'Sullivan, Francesco Vito Mandarino, Julia L Gauci, Anthony M Whitfield, Clarence Kerrison, James Elhindi, Catarina Neto do Nascimento, Sunil Gupta, Oliver Cronin, Anthony Sakiris, Juan Francisco Prieto Aparicio, Sophie Arndtz, Gregor Brown, Spiro Raftopoulos, David Tate, Eric Y Lee, Stephen J Williams, Nicholas Burgess, Michael J Bourke
Background and aims: The efficacy of colorectal endoscopic mucosal resection (EMR) is limited by recurrence and the necessity for conservative surveillance. Margin thermal ablation (MTA) after EMR has reduced the incidence of recurrence at the first surveillance colonoscopy at 6 months (SC1). Whether this effect is durable to second surveillance colonoscopy (SC2) is unknown. We evaluated long-term surveillance outcomes in a cohort of LNPCPs that have undergone MTA.
Methods: LNPCPs undergoing EMR and MTA from four academic endoscopy centres were prospectively recruited. EMR scars were evaluated at SC1 and in the absence of recurrence, SC2 colonoscopy was conducted in a further 12 months. A historical control arm was generated from LNPCPs that underwent EMR without MTA. The primary outcome was recurrence at SC2 in all LNPCPs with a recurrence-free scar at SC1.
Results: 1152 LNPCPs underwent EMR with complete MTA over 90 months until October 2022. 854 LNPCPs underwent SC1 with 29/854 (3.4%) LNPCPs demonstrating recurrence. 472 LNPCPs free of recurrence at SC1 underwent SC2. 260 LNPCPs with complete SC2 follow-up formed the control arm from January 2012 to May 2016. Recurrence at SC2 was significantly less in the MTA arm versus controls (1/472 (0.2%) vs 9/260 (3.5%); p<0.001)).
Conclusion: LNPCPs that have undergone successful EMR with MTA and are free of recurrence at SC1 are unlikely to develop recurrence in subsequent surveillance out to 2 years. Provided the colon is cleared of synchronous neoplasia, the next surveillance can be potentially extended to 3-5 years. Such an approach would reduce costs and enhance patient compliance.
{"title":"Impact of margin thermal ablation after endoscopic mucosal resection of large (≥20 mm) non-pedunculated colonic polyps on long-term recurrence.","authors":"Timothy O'Sullivan, Francesco Vito Mandarino, Julia L Gauci, Anthony M Whitfield, Clarence Kerrison, James Elhindi, Catarina Neto do Nascimento, Sunil Gupta, Oliver Cronin, Anthony Sakiris, Juan Francisco Prieto Aparicio, Sophie Arndtz, Gregor Brown, Spiro Raftopoulos, David Tate, Eric Y Lee, Stephen J Williams, Nicholas Burgess, Michael J Bourke","doi":"10.1136/gutjnl-2024-332907","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332907","url":null,"abstract":"<p><strong>Background and aims: </strong>The efficacy of colorectal endoscopic mucosal resection (EMR) is limited by recurrence and the necessity for conservative surveillance. Margin thermal ablation (MTA) after EMR has reduced the incidence of recurrence at the first surveillance colonoscopy at 6 months (SC1). Whether this effect is durable to second surveillance colonoscopy (SC2) is unknown. We evaluated long-term surveillance outcomes in a cohort of LNPCPs that have undergone MTA.</p><p><strong>Methods: </strong>LNPCPs undergoing EMR and MTA from four academic endoscopy centres were prospectively recruited. EMR scars were evaluated at SC1 and in the absence of recurrence, SC2 colonoscopy was conducted in a further 12 months. A historical control arm was generated from LNPCPs that underwent EMR without MTA. The primary outcome was recurrence at SC2 in all LNPCPs with a recurrence-free scar at SC1.</p><p><strong>Results: </strong>1152 LNPCPs underwent EMR with complete MTA over 90 months until October 2022. 854 LNPCPs underwent SC1 with 29/854 (3.4%) LNPCPs demonstrating recurrence. 472 LNPCPs free of recurrence at SC1 underwent SC2. 260 LNPCPs with complete SC2 follow-up formed the control arm from January 2012 to May 2016. Recurrence at SC2 was significantly less in the MTA arm versus controls (1/472 (0.2%) vs 9/260 (3.5%); p<0.001)).</p><p><strong>Conclusion: </strong>LNPCPs that have undergone successful EMR with MTA and are free of recurrence at SC1 are unlikely to develop recurrence in subsequent surveillance out to 2 years. Provided the colon is cleared of synchronous neoplasia, the next surveillance can be potentially extended to 3-5 years. Such an approach would reduce costs and enhance patient compliance.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":23.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345114","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 : 2024-09-25DOI: 10.1136/gutjnl-2024-333643
Philip D J Dunne, Ewan H Forrest, Adrian J Stanley
We extend our congratulations to Tevethia et al for their recently published ‘CAVARLY trial’, which suggests the combination of variceal band ligation (VBL) and carvedilol is superior to VBL or carvedilol alone in the reduction of the first episode of oesophageal variceal bleeding (OVB) in patients with high-risk varices.1 This is the first primary prophylaxis randomised control trial to examine combination therapy and provides some interesting results which require further thought. Despite significantly lower rates of OVB and mortality in the combination therapy group, other indicators of disease severity such as; progression of ascites, …
{"title":"Variceal band ligation and carvedilol: together forever, or not?","authors":"Philip D J Dunne, Ewan H Forrest, Adrian J Stanley","doi":"10.1136/gutjnl-2024-333643","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333643","url":null,"abstract":"We extend our congratulations to Tevethia et al for their recently published ‘CAVARLY trial’, which suggests the combination of variceal band ligation (VBL) and carvedilol is superior to VBL or carvedilol alone in the reduction of the first episode of oesophageal variceal bleeding (OVB) in patients with high-risk varices.1 This is the first primary prophylaxis randomised control trial to examine combination therapy and provides some interesting results which require further thought. Despite significantly lower rates of OVB and mortality in the combination therapy group, other indicators of disease severity such as; progression of ascites, …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321531","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 : 2024-09-25DOI: 10.1136/gutjnl-2024-333378
Matthias Van Hul, Patrice D Cani, Camille Petifils, Willem M De Vos, Herbert Tilg, Emad M El Omar
The understanding that changes in microbiome composition can influence chronic human diseases and the efficiency of therapies has driven efforts to develop microbiota-centred therapies such as first and next generation probiotics, prebiotics and postbiotics, microbiota editing and faecal microbiota transplantation. Central to microbiome research is understanding how disease impacts microbiome composition and vice versa, yet there is a problematic issue with the term ‘dysbiosis’, which broadly links microbial imbalances to various chronic illnesses without precision or definition. Another significant issue in microbiome discussions is defining ‘healthy individuals’ to ascertain what characterises a healthy microbiome. This involves questioning who represents the healthiest segment of our population—whether it is those free from illnesses, athletes at peak performance, individuals living healthily through regular exercise and good nutrition or even elderly adults or centenarians who have been tested by time and achieved remarkable healthy longevity. This review advocates for delineating ‘what defines a healthy microbiome?’ by considering a broader range of factors related to human health and environmental influences on the microbiota. A healthy microbiome is undoubtedly linked to gut health. Nevertheless, it is very difficult to pinpoint a universally accepted definition of ‘gut health’ due to the complexities of measuring gut functionality besides the microbiota composition. We must take into account individual variabilities, the influence of diet, lifestyle, host and environmental factors. Moreover, the challenge in distinguishing causation from correlation between gut microbiome and overall health is presented. The review also highlights the resource-heavy nature of comprehensive gut health assessments, which hinders their practicality and broad application. Finally, we call for continued research and a nuanced approach to better understand the intricate and evolving concept of gut health, emphasising the need for more precise and inclusive definitions and methodologies in studying the microbiome.
{"title":"What defines a healthy gut microbiome?","authors":"Matthias Van Hul, Patrice D Cani, Camille Petifils, Willem M De Vos, Herbert Tilg, Emad M El Omar","doi":"10.1136/gutjnl-2024-333378","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333378","url":null,"abstract":"The understanding that changes in microbiome composition can influence chronic human diseases and the efficiency of therapies has driven efforts to develop microbiota-centred therapies such as first and next generation probiotics, prebiotics and postbiotics, microbiota editing and faecal microbiota transplantation. Central to microbiome research is understanding how disease impacts microbiome composition and vice versa, yet there is a problematic issue with the term ‘dysbiosis’, which broadly links microbial imbalances to various chronic illnesses without precision or definition. Another significant issue in microbiome discussions is defining ‘healthy individuals’ to ascertain what characterises a healthy microbiome. This involves questioning who represents the healthiest segment of our population—whether it is those free from illnesses, athletes at peak performance, individuals living healthily through regular exercise and good nutrition or even elderly adults or centenarians who have been tested by time and achieved remarkable healthy longevity. This review advocates for delineating ‘what defines a healthy microbiome?’ by considering a broader range of factors related to human health and environmental influences on the microbiota. A healthy microbiome is undoubtedly linked to gut health. Nevertheless, it is very difficult to pinpoint a universally accepted definition of ‘gut health’ due to the complexities of measuring gut functionality besides the microbiota composition. We must take into account individual variabilities, the influence of diet, lifestyle, host and environmental factors. Moreover, the challenge in distinguishing causation from correlation between gut microbiome and overall health is presented. The review also highlights the resource-heavy nature of comprehensive gut health assessments, which hinders their practicality and broad application. Finally, we call for continued research and a nuanced approach to better understand the intricate and evolving concept of gut health, emphasising the need for more precise and inclusive definitions and methodologies in studying the microbiome.","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321532","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 : 2024-09-24DOI: 10.1136/gutjnl-2024-333222
Maximilian Joseph Brol, Ali Canbay, Jonel Trebicka
Alcohol-associated hepatitis (AH) is the acute deterioration of alcohol-related liver disease (ArLD) with rapid onset or worsening of jaundice, which, in severe cases, may transition to acute-on-chronic liver failure (ACLF) with extremely high short-term mortality, increasing with the number and severity of hepatic and extra-hepatic organ dysfunction. Systemic inflammation is a hallmark, driving acute decompensation (AD) towards ACLF. Diagnosis and treatment are insufficient and challenging, especially due to the complex, multifactorial and as yet not fully understood pathogenesis. In patients with AH, this inflammation is characterised by increased levels of circulating and hepatic neutrophils, which are essential immune cells responsible for pathogen defence. However, the exact role of neutrophils in AH remains controversial, with ongoing debate over whether their hyperactivation exacerbates liver damage or helps to resolve the disease. Current treatment for AH primarily relies on steroids, but their use is restricted in cases of bacterial infections. Consequently, there is a clinical need to better understand the mechanisms underlying AH and the associated organ dysfunction. Moreover, early detection and treatment of bacterial infections are critical to improve patient outcomes. These challenges, coupled with its rising prevalence in Germany and other Western countries, highlight a significant gap in patient care.1 Chronic alcohol consumption is associated with gut dysbiosis, leading to alterations in the composition of bacteria, viruses and fungi. Several bacterial metabolites were identified to foster liver disease progression. Among them, cytolysin, an endotoxin secreted by Enterococcus faecalis, is associated with higher hepatic inflammation and higher short-term mortality in patients with AH.2 …
{"title":"Alcohol-associated hepatitis: a neutrophile disease?","authors":"Maximilian Joseph Brol, Ali Canbay, Jonel Trebicka","doi":"10.1136/gutjnl-2024-333222","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333222","url":null,"abstract":"Alcohol-associated hepatitis (AH) is the acute deterioration of alcohol-related liver disease (ArLD) with rapid onset or worsening of jaundice, which, in severe cases, may transition to acute-on-chronic liver failure (ACLF) with extremely high short-term mortality, increasing with the number and severity of hepatic and extra-hepatic organ dysfunction. Systemic inflammation is a hallmark, driving acute decompensation (AD) towards ACLF. Diagnosis and treatment are insufficient and challenging, especially due to the complex, multifactorial and as yet not fully understood pathogenesis. In patients with AH, this inflammation is characterised by increased levels of circulating and hepatic neutrophils, which are essential immune cells responsible for pathogen defence. However, the exact role of neutrophils in AH remains controversial, with ongoing debate over whether their hyperactivation exacerbates liver damage or helps to resolve the disease. Current treatment for AH primarily relies on steroids, but their use is restricted in cases of bacterial infections. Consequently, there is a clinical need to better understand the mechanisms underlying AH and the associated organ dysfunction. Moreover, early detection and treatment of bacterial infections are critical to improve patient outcomes. These challenges, coupled with its rising prevalence in Germany and other Western countries, highlight a significant gap in patient care.1 Chronic alcohol consumption is associated with gut dysbiosis, leading to alterations in the composition of bacteria, viruses and fungi. Several bacterial metabolites were identified to foster liver disease progression. Among them, cytolysin, an endotoxin secreted by Enterococcus faecalis, is associated with higher hepatic inflammation and higher short-term mortality in patients with AH.2 …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317592","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 : 2024-09-19DOI: 10.1136/gutjnl-2024-333773
Duc Trong Quach,Toru Hiyama,Gwang Ha Kim,Takuji Gotoda,Kentaro Sugano
{"title":"Rethinking routine mapping biopsies in gastric intestinal metaplasia: justification for endoscopic stratification.","authors":"Duc Trong Quach,Toru Hiyama,Gwang Ha Kim,Takuji Gotoda,Kentaro Sugano","doi":"10.1136/gutjnl-2024-333773","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333773","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275218","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 : 2024-09-18DOI: 10.1136/gutjnl-2024-333426
Jaime Bosch
I read with pleasure the paper by Zhou et al 1 analysing the long-term clinical outcomes and changes in liver elastography associated with statin usage in patients with metabolic-associated steatotic liver disease (MASLD). This is a population-based study of 7988 patients selected from a total of 17 849 MASLD patients seen in 16 centres in Europe, America and Asia and who had also transient elastography measurements of liver stiffness (LSM). The final cohort included patients >18 years that had at least two LSM, a controlled attenuation parameter denoting steatosis (over ≥248 dB/m), a prolonged follow-up (over 1 year, median 4.6 years), and no other cause of liver disease or excessive alcohol intake. Usage of statins was defined as the consistent use of statins on most days for more than 1 month within a year, which occurred in 3233 patients (40.4%). Patients were considered to have compensated advanced chronic liver disease (cACLD) if the first LSM was >10 kPa, which occurred in 17.2%. The primary outcome was a composite of all-cause death and liver-related events (LREs) (developing cirrhosis decompensation, hepatocellular carcinoma (HCC) or liver-related mortality). In addition, a secondary outcome was the change in LSM, categorised as progression, regression or stable based on observing or not changes in LSM of at least 20% or crossing the threshold of 10 kPa. The authors did Cox regression analysis for examining the association between statin …
{"title":"Statins for MAFLD/MASH: another brick in the wall while waiting for final answers","authors":"Jaime Bosch","doi":"10.1136/gutjnl-2024-333426","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333426","url":null,"abstract":"I read with pleasure the paper by Zhou et al 1 analysing the long-term clinical outcomes and changes in liver elastography associated with statin usage in patients with metabolic-associated steatotic liver disease (MASLD). This is a population-based study of 7988 patients selected from a total of 17 849 MASLD patients seen in 16 centres in Europe, America and Asia and who had also transient elastography measurements of liver stiffness (LSM). The final cohort included patients >18 years that had at least two LSM, a controlled attenuation parameter denoting steatosis (over ≥248 dB/m), a prolonged follow-up (over 1 year, median 4.6 years), and no other cause of liver disease or excessive alcohol intake. Usage of statins was defined as the consistent use of statins on most days for more than 1 month within a year, which occurred in 3233 patients (40.4%). Patients were considered to have compensated advanced chronic liver disease (cACLD) if the first LSM was >10 kPa, which occurred in 17.2%. The primary outcome was a composite of all-cause death and liver-related events (LREs) (developing cirrhosis decompensation, hepatocellular carcinoma (HCC) or liver-related mortality). In addition, a secondary outcome was the change in LSM, categorised as progression, regression or stable based on observing or not changes in LSM of at least 20% or crossing the threshold of 10 kPa. The authors did Cox regression analysis for examining the association between statin …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245449","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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