Pub Date : 2024-07-22DOI: 10.1038/s41575-024-00950-z
Yannick Brüggemann, Mara Klöhn, Heiner Wedemeyer, Eike Steinmann
Hepatitis E virus (HEV) infections are a major cause of acute viral hepatitis in humans worldwide. In immunocompetent individuals, the majority of HEV infections remain asymptomatic and lead to spontaneous clearance of the virus, and only a minority of individuals with infection (5–16%) experience symptoms of acute viral hepatitis. However, HEV infections can cause up to 30% mortality in pregnant women, become chronic in immunocompromised patients and cause extrahepatic manifestations. A growing body of evidence suggests that the host immune response to infection with different HEV genotypes is a critical determinant of distinct HEV infection outcomes. In this Review, we summarize key components of the innate and adaptive immune responses to HEV, including the underlying immunological mechanisms of HEV associated with acute and chronic liver failure and interactions between T cell and B cell responses. In addition, we discuss the current status of vaccines against HEV and raise outstanding questions regarding the immune responses induced by HEV and treatment of the disease, highlighting areas for future investigation. Many aspects of the biology and pathogenesis of hepatitis E virus (HEV) infection remain underexplored. In this Review, Steinmann and colleagues summarize the role of the innate and adaptive immune systems in HEV infection.
戊型肝炎病毒（HEV）感染是全球人类急性病毒性肝炎的主要病因。在免疫功能正常的个体中，大多数 HEV 感染都没有症状，病毒会自发清除，只有少数感染者（5-16%）会出现急性病毒性肝炎的症状。然而，HEV 感染可导致孕妇高达 30% 的死亡率，在免疫力低下的患者中会转为慢性，并引起肝外表现。越来越多的证据表明，宿主对不同 HEV 基因型感染的免疫反应是决定不同 HEV 感染结果的关键因素。在本综述中，我们总结了针对 HEV 的先天性和适应性免疫反应的关键组成部分，包括 HEV 与急性和慢性肝功能衰竭相关的潜在免疫机制以及 T 细胞和 B 细胞反应之间的相互作用。此外，我们还讨论了针对 HEV 的疫苗的现状，并提出了有关 HEV 诱导的免疫反应和疾病治疗的悬而未决的问题，强调了未来的研究领域。
{"title":"Hepatitis E virus: from innate sensing to adaptive immune responses","authors":"Yannick Brüggemann, Mara Klöhn, Heiner Wedemeyer, Eike Steinmann","doi":"10.1038/s41575-024-00950-z","DOIUrl":"10.1038/s41575-024-00950-z","url":null,"abstract":"Hepatitis E virus (HEV) infections are a major cause of acute viral hepatitis in humans worldwide. In immunocompetent individuals, the majority of HEV infections remain asymptomatic and lead to spontaneous clearance of the virus, and only a minority of individuals with infection (5–16%) experience symptoms of acute viral hepatitis. However, HEV infections can cause up to 30% mortality in pregnant women, become chronic in immunocompromised patients and cause extrahepatic manifestations. A growing body of evidence suggests that the host immune response to infection with different HEV genotypes is a critical determinant of distinct HEV infection outcomes. In this Review, we summarize key components of the innate and adaptive immune responses to HEV, including the underlying immunological mechanisms of HEV associated with acute and chronic liver failure and interactions between T cell and B cell responses. In addition, we discuss the current status of vaccines against HEV and raise outstanding questions regarding the immune responses induced by HEV and treatment of the disease, highlighting areas for future investigation. Many aspects of the biology and pathogenesis of hepatitis E virus (HEV) infection remain underexplored. In this Review, Steinmann and colleagues summarize the role of the innate and adaptive immune systems in HEV infection.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 10","pages":"710-725"},"PeriodicalIF":45.9,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736891","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 : 2024-07-17DOI: 10.1038/s41575-024-00955-8
Juan M. Pericàs, Quentin M. Anstee, Salvador Augustin, Ramón Bataller, Annalisa Berzigotti, Andreea Ciudin, Sven Francque, Juan G. Abraldes, Virginia Hernández-Gea, Mònica Pons, Thomas Reiberger, Ian A. Rowe, Peter Rydqvist, Elmer Schabel, Frank Tacke, Emmanuel A. Tsochatzis, Joan Genescà
Although metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of cirrhosis worldwide, therapeutic options are limited and the number of clinical trials in MASH-related compensated cirrhosis is low as compared to those conducted in earlier disease stages. Moreover, designing clinical trials in MASH cirrhosis presents a series of challenges regarding the understanding and conceptualization of the natural history, regulatory considerations, inclusion criteria, recruitment, end points and trial duration, among others. The first international workshop on the state of the art and future direction of clinical trials in MASH-related compensated cirrhosis was held in April 2023 at Vall d’Hebron University Hospital in Barcelona (Spain) and was attended by a group of international experts on clinical trials from academia, regulatory agencies and industry, encompassing expertise in MASH, cirrhosis, portal hypertension, and regulatory affairs. The presented Roadmap summarizes important content of the workshop on current status, regulatory requirements and end points in MASH-related compensated cirrhosis clinical trials, exploring alternative study designs and highlighting the challenges that should be considered for upcoming studies on MASH cirrhosis. Metabolic dysfunction-associated steatohepatitis (MASH), a primary cause of chronic liver disease (CLD), often leads to advanced CLD stages such as cirrhosis. This Roadmap summarizes the current landscape and challenges of MASH-related compensated cirrhosis clinical trials and explores a way forward for future studies.
{"title":"A roadmap for clinical trials in MASH-related compensated cirrhosis","authors":"Juan M. Pericàs, Quentin M. Anstee, Salvador Augustin, Ramón Bataller, Annalisa Berzigotti, Andreea Ciudin, Sven Francque, Juan G. Abraldes, Virginia Hernández-Gea, Mònica Pons, Thomas Reiberger, Ian A. Rowe, Peter Rydqvist, Elmer Schabel, Frank Tacke, Emmanuel A. Tsochatzis, Joan Genescà","doi":"10.1038/s41575-024-00955-8","DOIUrl":"10.1038/s41575-024-00955-8","url":null,"abstract":"Although metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of cirrhosis worldwide, therapeutic options are limited and the number of clinical trials in MASH-related compensated cirrhosis is low as compared to those conducted in earlier disease stages. Moreover, designing clinical trials in MASH cirrhosis presents a series of challenges regarding the understanding and conceptualization of the natural history, regulatory considerations, inclusion criteria, recruitment, end points and trial duration, among others. The first international workshop on the state of the art and future direction of clinical trials in MASH-related compensated cirrhosis was held in April 2023 at Vall d’Hebron University Hospital in Barcelona (Spain) and was attended by a group of international experts on clinical trials from academia, regulatory agencies and industry, encompassing expertise in MASH, cirrhosis, portal hypertension, and regulatory affairs. The presented Roadmap summarizes important content of the workshop on current status, regulatory requirements and end points in MASH-related compensated cirrhosis clinical trials, exploring alternative study designs and highlighting the challenges that should be considered for upcoming studies on MASH cirrhosis. Metabolic dysfunction-associated steatohepatitis (MASH), a primary cause of chronic liver disease (CLD), often leads to advanced CLD stages such as cirrhosis. This Roadmap summarizes the current landscape and challenges of MASH-related compensated cirrhosis clinical trials and explores a way forward for future studies.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 11","pages":"809-823"},"PeriodicalIF":45.9,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141631321","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 : 2024-07-15DOI: 10.1038/s41575-024-00958-5
Hannah Kuper, Tom Shakespeare
Globally, one in six people have a disability, and individuals with disabilities often experience a narrow margin of health, less financial security and health disparities. We call for action to improve access to health care for people with disabilities and show how this plan might be achieved.
{"title":"Disability inclusion in research and health care","authors":"Hannah Kuper, Tom Shakespeare","doi":"10.1038/s41575-024-00958-5","DOIUrl":"10.1038/s41575-024-00958-5","url":null,"abstract":"Globally, one in six people have a disability, and individuals with disabilities often experience a narrow margin of health, less financial security and health disparities. We call for action to improve access to health care for people with disabilities and show how this plan might be achieved.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 9","pages":"601-602"},"PeriodicalIF":45.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618351","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 : 2024-07-08DOI: 10.1038/s41575-024-00957-6
Stuart Cantrill
After decades of institutional deceit, deflection, defensiveness and delay, publication of the final report of the Infected Blood Inquiry lays bare the failings of the British state and its National Health Service. Now, it is time for justice, accountability and a change in patient safety culture.
{"title":"A bloody disgrace — time to change patient safety culture","authors":"Stuart Cantrill","doi":"10.1038/s41575-024-00957-6","DOIUrl":"10.1038/s41575-024-00957-6","url":null,"abstract":"After decades of institutional deceit, deflection, defensiveness and delay, publication of the final report of the Infected Blood Inquiry lays bare the failings of the British state and its National Health Service. Now, it is time for justice, accountability and a change in patient safety culture.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 8","pages":"530-530"},"PeriodicalIF":45.9,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556765","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 : 2024-06-14DOI: 10.1038/s41575-024-00952-x
Haitao Liu, Siheng Sean You, Zhigang Gao, Ning Hu, Yunlong Zhao
This Comment reviews the evolution from early electrophysiological studies to advanced diagnostic tools, highlighting the challenges and innovations shaping the future of gastrointestinal diagnostics.
这篇评论回顾了从早期电生理研究到先进诊断工具的演变过程，强调了塑造胃肠道诊断未来的挑战和创新。
{"title":"Next generation of gastrointestinal electrophysiology devices","authors":"Haitao Liu, Siheng Sean You, Zhigang Gao, Ning Hu, Yunlong Zhao","doi":"10.1038/s41575-024-00952-x","DOIUrl":"10.1038/s41575-024-00952-x","url":null,"abstract":"This Comment reviews the evolution from early electrophysiological studies to advanced diagnostic tools, highlighting the challenges and innovations shaping the future of gastrointestinal diagnostics.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 7","pages":"457-458"},"PeriodicalIF":45.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319913","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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