Nature Reviews Gastroenterology &Hepatology最新文献_第6页

Ammonia-induced stress response in liver disease progression and hepatic encephalopathy 肝病进展和肝性脑病中氨诱导的应激反应

IF 45.9 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-09-09 DOI: 10.1038/s41575-024-00970-9

Rocío Gallego-Durán, Anna Hadjihambi, Javier Ampuero, Christopher F. Rose, Rajiv Jalan, Manuel Romero-Gómez

{"title":"Ammonia-induced stress response in liver disease progression and hepatic encephalopathy","authors":"Rocío Gallego-Durán, Anna Hadjihambi, Javier Ampuero, Christopher F. Rose, Rajiv Jalan, Manuel Romero-Gómez","doi":"10.1038/s41575-024-00970-9","DOIUrl":"10.1038/s41575-024-00970-9","url":null,"abstract":"Ammonia levels are orchestrated by a series of complex interrelated pathways in which the urea cycle has a central role. Liver dysfunction leads to an accumulation of ammonia, which is toxic and is strongly associated with disruption of potassium homeostasis, mitochondrial dysfunction, oxidative stress, inflammation, hypoxaemia and dysregulation of neurotransmission. Hyperammonaemia is a hallmark of hepatic encephalopathy and has been strongly associated with liver-related outcomes in patients with cirrhosis and liver failure. In addition to the established role of ammonia as a neurotoxin in the pathogenesis of hepatic encephalopathy, an increasing number of studies suggest that it can lead to hepatic fibrosis progression, sarcopenia, immune dysfunction and cancer. However, elevated systemic ammonia levels are uncommon in patients with metabolic dysfunction-associated steatotic liver disease. A clear causal relationship between ammonia-induced immune dysfunction and risk of infection has not yet been definitively proven. In this Review, we discuss the mechanisms by which ammonia produces its diverse deleterious effects and their clinical relevance in liver diseases, the importance of measuring ammonia levels for the diagnosis of hepatic encephalopathy, the prognosis of patients with cirrhosis and liver failure, and how our knowledge of inter-organ ammonia metabolism is leading to the development of novel therapeutic approaches. This Review describes inter-organ ammonia metabolism in liver disease and mechanisms underlying the pathogenic effect of hyperammonaemia in hepatic encephalopathy, liver disease progression in metabolic dysfunction-associated steatotic liver disease, immune dysfunction and hepatocellular carcinoma. It also addresses the principles of treating hyperammonaemia.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 11","pages":"774-791"},"PeriodicalIF":45.9,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158949","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

GLP1 agonists: current and future landscape of clinical trials for patients with metabolic dysfunction GLP1 激动剂：针对代谢功能障碍患者的临床试验现状与未来展望

IF 45.9 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-09-06 DOI: 10.1038/s41575-024-00977-2

Jonathan Goldney, Melanie J. Davies

引用次数: 0

AI-based tool for scoring MASH histology 基于人工智能的 MASH 组织学评分工具

IF 45.9 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-09-06 DOI: 10.1038/s41575-024-00987-0

Jordan Hindson

引用次数: 0

Hepatic immune regulation and sex disparities 肝脏免疫调节与性别差异

IF 45.9 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-09-05 DOI: 10.1038/s41575-024-00974-5

Patrizia Burra, Alberto Zanetto, Bernd Schnabl, Thomas Reiberger, Aldo J. Montano-Loza, Rosanna Asselta, Tom Hemming Karlsen, Frank Tacke

{"title":"Hepatic immune regulation and sex disparities","authors":"Patrizia Burra, Alberto Zanetto, Bernd Schnabl, Thomas Reiberger, Aldo J. Montano-Loza, Rosanna Asselta, Tom Hemming Karlsen, Frank Tacke","doi":"10.1038/s41575-024-00974-5","DOIUrl":"10.1038/s41575-024-00974-5","url":null,"abstract":"Chronic liver disease is a major cause of morbidity and mortality worldwide. Epidemiology, clinical phenotype and response to therapies for gastrointestinal and liver diseases are commonly different between women and men due to sex-specific hormonal, genetic and immune-related factors. The hepatic immune system has unique regulatory functions that promote the induction of intrahepatic tolerance, which is key for maintaining liver health and homeostasis. In liver diseases, hepatic immune alterations are increasingly recognized as a main cofactor responsible for the development and progression of chronic liver injury and fibrosis. In this Review, we discuss the basic mechanisms of sex disparity in hepatic immune regulation and how these mechanisms influence and modify the development of autoimmune liver diseases, genetic liver diseases, portal hypertension and inflammation in chronic liver disease. Alterations in gut microbiota and their crosstalk with the hepatic immune system might affect the progression of liver disease in a sex-specific manner, creating potential opportunities for novel diagnostic and therapeutic approaches to be evaluated in clinical trials. Finally, we identify and propose areas for future basic, translational and clinical research that will advance our understanding of sex disparities in hepatic immunity and liver disease. Immune dysregulation is a main feature of chronic liver disease, whose burden increases worldwide. This Review discusses the influence of biological sex in hepatic immune mechanisms in the context of liver disease and identifies sex disparities in research and therapeutics.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 12","pages":"869-884"},"PeriodicalIF":45.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138029","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

Consequences of bathroom restriction on transgender individuals with gastrointestinal conditions in the United States 浴室限制对美国患有肠胃疾病的变性人的影响

IF 45.9 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-09-02 DOI: 10.1038/s41575-024-00975-4

Cass D. Condray, Kira L. Newman, Victor G. Chedid

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Intestinal organ chips for disease modelling and personalized medicine 用于疾病建模和个性化医疗的肠道器官芯片。

IF 45.9 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-08-27 DOI: 10.1038/s41575-024-00968-3

Alican Özkan, Nina Teresa LoGrande, Jessica F. Feitor, Girija Goyal, Donald E. Ingber

{"title":"Intestinal organ chips for disease modelling and personalized medicine","authors":"Alican Özkan, Nina Teresa LoGrande, Jessica F. Feitor, Girija Goyal, Donald E. Ingber","doi":"10.1038/s41575-024-00968-3","DOIUrl":"10.1038/s41575-024-00968-3","url":null,"abstract":"Alterations in intestinal structure, mechanics and physiology underlie acute and chronic intestinal conditions, many of which are influenced by dysregulation of microbiome, peristalsis, stroma or immune responses. Studying human intestinal physiology or pathophysiology is difficult in preclinical animal models because their microbiomes and immune systems differ from those of humans. Although advances in organoid culture partially overcome this challenge, intestinal organoids still lack crucial features that are necessary to study functions central to intestinal health and disease, such as digestion or fluid flow, as well as contributions from long-term effects of living microbiome, peristalsis and immune cells. Here, we review developments in organ-on-a-chip (organ chip) microfluidic culture models of the human intestine that are lined by epithelial cells and interfaced with other tissues (such as stroma or endothelium), which can experience both fluid flow and peristalsis-like motions. Organ chips offer powerful ways to model intestinal physiology and disease states for various human populations and individual patients, and can be used to gain new insight into underlying molecular and biophysical mechanisms of disease. They can also be used as preclinical tools to discover new drugs and then validate their therapeutic efficacy and safety in the same human-relevant model. Studying human physiology and pathophysiology in preclinical animal models has drawbacks. Developments in organ-on-a-chip (organ chip) technology have opened up new ways to model human intestinal physiology. This Review discusses intestinal organ chips as disease models and preclinical tools and their potential for personalized medicine.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 11","pages":"751-773"},"PeriodicalIF":45.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41575-024-00968-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080907","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

Mapping neuroimmune interactions in the gut 绘制肠道神经免疫相互作用图

IF 45.9 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-08-22 DOI: 10.1038/s41575-024-00982-5

Katrina Ray

引用次数: 0

Liver diseases and hepatocellular carcinoma in the Asia-Pacific region: burden, trends, challenges and future directions 亚太地区的肝病和肝细胞癌：负担、趋势、挑战和未来方向

IF 45.9 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-08-15 DOI: 10.1038/s41575-024-00967-4

Lung-Yi Mak, Ken Liu, Sakkarin Chirapongsathorn, Kuo Chao Yew, Nobuharu Tamaki, Ruveena Bhavani Rajaram, Mara Teresa Panlilio, Rashid Lui, Hye Won Lee, Jimmy Che-To Lai, Anand V. Kulkarni, Madhumita Premkumar, Cosmas Rinaldi Adithya Lesmana, Yao Chun Hsu, Daniel Q. Huang

{"title":"Liver diseases and hepatocellular carcinoma in the Asia-Pacific region: burden, trends, challenges and future directions","authors":"Lung-Yi Mak, Ken Liu, Sakkarin Chirapongsathorn, Kuo Chao Yew, Nobuharu Tamaki, Ruveena Bhavani Rajaram, Mara Teresa Panlilio, Rashid Lui, Hye Won Lee, Jimmy Che-To Lai, Anand V. Kulkarni, Madhumita Premkumar, Cosmas Rinaldi Adithya Lesmana, Yao Chun Hsu, Daniel Q. Huang","doi":"10.1038/s41575-024-00967-4","DOIUrl":"10.1038/s41575-024-00967-4","url":null,"abstract":"Globally, nearly half of deaths from cirrhosis and chronic liver diseases (CLD) and three-quarters of deaths from hepatocellular carcinoma (HCC) occur in the Asia-Pacific region. Chronic hepatitis B is responsible for the vast majority of liver-related deaths in the region. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common form of CLD, affecting an estimated 30% of the adult population. Compared with people of European descent, people from the Asia-Pacific region carry more genetic variants associated with MASLD and its progression. Alcohol is a fast-growing cause of CLD and HCC in Asia as a result of the rising per-capita consumption of alcohol. Drug-induced liver injury is under-recognized and probably has a high prevalence in this region. The epidemiological and outcome data of acute-on-chronic liver failure are heterogeneous, and non-unified definitions across regions contribute to this heterogeneity. CLDs are severely underdiagnosed, and effective treatments and vaccinations are underutilized. In this Review, we highlight trends in the burden of CLD and HCC in the Asia-Pacific region and discuss the rapidly changing aetiologies of liver disease. We examine the multiple gaps in the care cascade and propose mitigating strategies and future directions. Mortality related to liver diseases and liver cancer is high and on the rise in the Asia-Pacific region. This Review summarizes the current epidemiological data and discusses the changing landscape of burden and aetiology of liver disease and liver cancer in the Asia-Pacific region.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 12","pages":"834-851"},"PeriodicalIF":45.9,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986364","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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EPC 2024 EPC 2024。

IF 45.9 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-08-12 DOI: 10.1038/s41575-024-00979-0

Jordan Hindson

引用次数: 0

Cellular and molecular basis of proximal small intestine disorders 近端小肠疾病的细胞和分子基础

IF 45.9 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-08-08 DOI: 10.1038/s41575-024-00962-9

Tania Bildstein, Fabienne Charbit-Henrion, Aline Azabdaftari, Nadine Cerf-Bensussan, Holm H. Uhlig

{"title":"Cellular and molecular basis of proximal small intestine disorders","authors":"Tania Bildstein, Fabienne Charbit-Henrion, Aline Azabdaftari, Nadine Cerf-Bensussan, Holm H. Uhlig","doi":"10.1038/s41575-024-00962-9","DOIUrl":"10.1038/s41575-024-00962-9","url":null,"abstract":"The proximal part of the small intestine, including duodenum and jejunum, is not only dedicated to nutrient digestion and absorption but is also a highly regulated immune site exposed to environmental factors. Host-protective responses against pathogens and tolerance to food antigens are essential functions in the small intestine. The cellular ecology and molecular pathways to maintain those functions are complex. Maladaptation is highlighted by common immune-mediated diseases such as coeliac disease, environmental enteric dysfunction or duodenal Crohn’s disease. An expanding spectrum of more than 100 rare monogenic disorders inform on causative molecular mechanisms of nutrient absorption, epithelial homeostasis and barrier function, as well as inflammatory immune responses and immune regulation. Here, after summarizing the architectural and cellular traits that underlie the functions of the proximal intestine, we discuss how the integration of tissue immunopathology and molecular mechanisms can contribute towards our understanding of disease and guide diagnosis. We propose an integrated mechanism-based taxonomy and discuss the latest experimental approaches to gain new mechanistic insight into these disorders with large disease burden worldwide as well as implications for therapeutic interventions. The proximal small intestine is key for nutrition, metabolism and immune responses, and can be affected by a wide range of disorders. This Review describes the cellular and molecular bases of diseases of the proximal small intestine (including rare monogenic disorders), proposing a mechanism-based taxonomy.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 10","pages":"687-709"},"PeriodicalIF":45.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904647","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