Pub Date : 2025-12-22DOI: 10.1038/s41575-025-01166-5
Pierfrancesco Visaggi, Edoardo V. Savarino
Potassium-competitive acid blockers (P-CABs) overcome the limitations of proton pump inhibitors by providing faster, longer and stronger acid suppression without meal timing. Evidence shows that P-CABs are non-inferior for the management of mild erosive oesophagitis and superior for severe erosive oesophagitis, whereas data for non-erosive reflux disease remain conflicting.
{"title":"Potassium-competitive acid blockers for the management of gastroesophageal reflux disease","authors":"Pierfrancesco Visaggi, Edoardo V. Savarino","doi":"10.1038/s41575-025-01166-5","DOIUrl":"10.1038/s41575-025-01166-5","url":null,"abstract":"Potassium-competitive acid blockers (P-CABs) overcome the limitations of proton pump inhibitors by providing faster, longer and stronger acid suppression without meal timing. Evidence shows that P-CABs are non-inferior for the management of mild erosive oesophagitis and superior for severe erosive oesophagitis, whereas data for non-erosive reflux disease remain conflicting.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 3","pages":"205-206"},"PeriodicalIF":51.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807886","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 : 2025-12-18DOI: 10.1038/s41575-025-01165-6
Orla M. Fitzpatrick, Yelena Y. Janjigian
Gastric and gastroesophageal junction adenocarcinoma remains a major global health challenge, with a rising incidence among younger individuals worldwide despite advances in biomarker-directed targeted therapies and immunotherapy. Current breakthroughs include perioperative immunotherapy, HER2-directed therapy sequencing and a decisive shift towards biomarker-driven treatment.
{"title":"Redefining gastroesophageal junction cancer care with perioperative immunotherapy, minimal residual disease monitoring and new targets","authors":"Orla M. Fitzpatrick, Yelena Y. Janjigian","doi":"10.1038/s41575-025-01165-6","DOIUrl":"10.1038/s41575-025-01165-6","url":null,"abstract":"Gastric and gastroesophageal junction adenocarcinoma remains a major global health challenge, with a rising incidence among younger individuals worldwide despite advances in biomarker-directed targeted therapies and immunotherapy. Current breakthroughs include perioperative immunotherapy, HER2-directed therapy sequencing and a decisive shift towards biomarker-driven treatment.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 2","pages":"124-125"},"PeriodicalIF":51.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770800","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 : 2025-12-17DOI: 10.1038/s41575-025-01163-8
Lung-Yi Mak, Daniel Q. Huang
Chronic hepatitis B infection remains the dominant aetiology of liver-related complications and hepatocellular carcinoma. In 2025, key evidence emerged supporting the expansion of treatment criteria, confirming the feasibility of an RNA interference-based combination regimen to boost functional cure rate, and identifying low-risk individuals who might not require liver cancer surveillance.
{"title":"Novel insights into chronic HBV infection","authors":"Lung-Yi Mak, Daniel Q. Huang","doi":"10.1038/s41575-025-01163-8","DOIUrl":"10.1038/s41575-025-01163-8","url":null,"abstract":"Chronic hepatitis B infection remains the dominant aetiology of liver-related complications and hepatocellular carcinoma. In 2025, key evidence emerged supporting the expansion of treatment criteria, confirming the feasibility of an RNA interference-based combination regimen to boost functional cure rate, and identifying low-risk individuals who might not require liver cancer surveillance.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 2","pages":"122-123"},"PeriodicalIF":51.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770801","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 : 2025-12-10DOI: 10.1038/s41575-025-01153-w
Jesus M. Banales, Pedro M. Rodrigues, Silvia Affò, Jesper B. Andersen, Patricia Aspichueta, Luke Boulter, John Bridgewater, Diego F. Calvisi, Andres Cardenas, Vincenzo Cardinale, Guido Carpino, Cédric Coulouarn, Cristina Dopazo, Julien Edeline, Luca Fabris, Trine Folseraas, Alejandro Forner, Benjamin Goeppert, Mathias Heikenwalder, Timothy J. Kendall, Shahid A. Khan, Heinz-Josef Klümpen, Bas Groot Koerkamp, Angela Lamarca, Stacie Lindsey, Ana Lleo, Tom Luedde, Rocio I. R. Macias, Helen Morement, Jean-Charles Nault, Paula Olaizola, Maria J. Perugorria, Chiara Raggi, Lorenza Rimassa, Anna Saborowski, Juan W. Valle, Mathew Vithayathil, Arndt Vogel, Chiara Braconi, International CCA Consensus Consortium
Cholangiocarcinoma (CCA) is a cancer that originates within the bile ducts. Traditionally considered to be a rare neoplasm, increased awareness of CCA alongside advancements in diagnosis and the rising prevalence of certain risk factors have contributed to a global increase in incidence and mortality. CCAs are highly heterogeneous from the clinical, histomorphological and molecular perspectives but commonly share a poor prognosis. These tumours usually develop and progress silently; by the time they are detected, it is often too late for curative surgical intervention. In such cases, current therapeutic approaches offer modest survival improvements and are generally considered palliative. Although well-known risk factors predispose individuals to developing CCA, the majority of cases are considered sporadic, occurring without any identifiable underlying condition. Over the past decade, substantial collaborative efforts have been made to improve our understanding of the aetiopathogenesis of these tumours, aiming to identify novel biomarkers and therapeutic targets to develop more effective treatments. The ultimate goal is to improve patient outcomes and overall well-being. However, there are significant gaps in our understanding of the molecular mechanisms that drive cholangiocarcinogenesis. In this international Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we provide a critical overview of the latest advancements in the field of CCA. We highlight the key aspects of CCA aetiopathogenesis and clinical management and provide insights into promising new treatments. Finally, we provide a set of consensus recommendations and future research priorities for CCA based on a Delphi panel questionnaire involving international experts. In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.
{"title":"Cholangiocarcinoma 2026: status quo, unmet needs and priorities","authors":"Jesus M. Banales, Pedro M. Rodrigues, Silvia Affò, Jesper B. Andersen, Patricia Aspichueta, Luke Boulter, John Bridgewater, Diego F. Calvisi, Andres Cardenas, Vincenzo Cardinale, Guido Carpino, Cédric Coulouarn, Cristina Dopazo, Julien Edeline, Luca Fabris, Trine Folseraas, Alejandro Forner, Benjamin Goeppert, Mathias Heikenwalder, Timothy J. Kendall, Shahid A. Khan, Heinz-Josef Klümpen, Bas Groot Koerkamp, Angela Lamarca, Stacie Lindsey, Ana Lleo, Tom Luedde, Rocio I. R. Macias, Helen Morement, Jean-Charles Nault, Paula Olaizola, Maria J. Perugorria, Chiara Raggi, Lorenza Rimassa, Anna Saborowski, Juan W. Valle, Mathew Vithayathil, Arndt Vogel, Chiara Braconi, International CCA Consensus Consortium","doi":"10.1038/s41575-025-01153-w","DOIUrl":"10.1038/s41575-025-01153-w","url":null,"abstract":"Cholangiocarcinoma (CCA) is a cancer that originates within the bile ducts. Traditionally considered to be a rare neoplasm, increased awareness of CCA alongside advancements in diagnosis and the rising prevalence of certain risk factors have contributed to a global increase in incidence and mortality. CCAs are highly heterogeneous from the clinical, histomorphological and molecular perspectives but commonly share a poor prognosis. These tumours usually develop and progress silently; by the time they are detected, it is often too late for curative surgical intervention. In such cases, current therapeutic approaches offer modest survival improvements and are generally considered palliative. Although well-known risk factors predispose individuals to developing CCA, the majority of cases are considered sporadic, occurring without any identifiable underlying condition. Over the past decade, substantial collaborative efforts have been made to improve our understanding of the aetiopathogenesis of these tumours, aiming to identify novel biomarkers and therapeutic targets to develop more effective treatments. The ultimate goal is to improve patient outcomes and overall well-being. However, there are significant gaps in our understanding of the molecular mechanisms that drive cholangiocarcinogenesis. In this international Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we provide a critical overview of the latest advancements in the field of CCA. We highlight the key aspects of CCA aetiopathogenesis and clinical management and provide insights into promising new treatments. Finally, we provide a set of consensus recommendations and future research priorities for CCA based on a Delphi panel questionnaire involving international experts. In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 1","pages":"65-96"},"PeriodicalIF":51.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41575-025-01153-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717624","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}
Pub Date : 2025-12-03DOI: 10.1038/s41575-025-01139-8
Manon Defaye, Yasmin Nasser, Christophe Altier
Chronic abdominal pain is prevalent among individuals with inflammatory bowel disease (IBD). Substantial progress has been made in the past few decades in understanding how pain signals travel from the gut to the brain. Preclinical studies have greatly contributed to uncovering the mechanisms of chronic pain in IBD. However, practical applications in clinical settings are still lacking. In this Review, we present the current understanding of the pathological mechanisms of chronic pain in IBD. We explore the neuroplastic changes that occur along the afferent pain pathway from the nerve endings in the colonic mucosa to the brain. We explore the importance of new variables in chronic IBD pain, including the influence of host–microbe interactions during disease, and the effect of comorbid psychological factors, including stress and anxiety, in triggering pain. Finally, we discuss gaps in treatment strategies while proposing new directions for research to identify novel priorities that could pave the way for effective pain therapies. In this Review, Altier and colleagues describe the mechanisms of chronic abdominal pain in inflammatory bowel disease (IBD). In addition, they discuss implications for IBD treatment and identify directions for future research.
{"title":"Mechanisms of chronic abdominal pain in inflammatory bowel disease and implications for treatment","authors":"Manon Defaye, Yasmin Nasser, Christophe Altier","doi":"10.1038/s41575-025-01139-8","DOIUrl":"10.1038/s41575-025-01139-8","url":null,"abstract":"Chronic abdominal pain is prevalent among individuals with inflammatory bowel disease (IBD). Substantial progress has been made in the past few decades in understanding how pain signals travel from the gut to the brain. Preclinical studies have greatly contributed to uncovering the mechanisms of chronic pain in IBD. However, practical applications in clinical settings are still lacking. In this Review, we present the current understanding of the pathological mechanisms of chronic pain in IBD. We explore the neuroplastic changes that occur along the afferent pain pathway from the nerve endings in the colonic mucosa to the brain. We explore the importance of new variables in chronic IBD pain, including the influence of host–microbe interactions during disease, and the effect of comorbid psychological factors, including stress and anxiety, in triggering pain. Finally, we discuss gaps in treatment strategies while proposing new directions for research to identify novel priorities that could pave the way for effective pain therapies. In this Review, Altier and colleagues describe the mechanisms of chronic abdominal pain in inflammatory bowel disease (IBD). In addition, they discuss implications for IBD treatment and identify directions for future research.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 3","pages":"227-245"},"PeriodicalIF":51.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664279","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 : 2025-11-28DOI: 10.1038/s41575-025-01157-6
Rupa Banerjee
The year 2025 has seen a pivotal shift in inflammatory bowel disease research, from therapeutic management to prevention. Emerging evidence emphasizes the ‘3 Ps’ shaping future care — prevention, pre-diagnosis and participation — focusing on dietary risk modification, early biomarker detection and multisectoral engagement to advance proactive, population-level inflammatory bowel disease prevention. In summary, 2025 has seen a shift in focus from pure therapeutic management to active disease prevention. The message is unambiguous. The next breakthrough in IBD will not emerge solely from new drugs or biologics, but from reimagining how we live, eat and engage with the microbial ecosystems that define our health.
{"title":"The 3 Ps of IBD today — prevention, pre-diagnosis and participation","authors":"Rupa Banerjee","doi":"10.1038/s41575-025-01157-6","DOIUrl":"10.1038/s41575-025-01157-6","url":null,"abstract":"The year 2025 has seen a pivotal shift in inflammatory bowel disease research, from therapeutic management to prevention. Emerging evidence emphasizes the ‘3 Ps’ shaping future care — prevention, pre-diagnosis and participation — focusing on dietary risk modification, early biomarker detection and multisectoral engagement to advance proactive, population-level inflammatory bowel disease prevention. In summary, 2025 has seen a shift in focus from pure therapeutic management to active disease prevention. The message is unambiguous. The next breakthrough in IBD will not emerge solely from new drugs or biologics, but from reimagining how we live, eat and engage with the microbial ecosystems that define our health.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 2","pages":"119-121"},"PeriodicalIF":51.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611396","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 : 2025-11-24DOI: 10.1038/s41575-025-01147-8
Mihael Vucur, Vangelis Kondylis, Petr Broz, Tom Luedde
{"title":"Regulated necrosis at the crossroads of liver inflammation and cancer development","authors":"Mihael Vucur, Vangelis Kondylis, Petr Broz, Tom Luedde","doi":"10.1038/s41575-025-01147-8","DOIUrl":"https://doi.org/10.1038/s41575-025-01147-8","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"107 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583190","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 : 2025-11-24DOI: 10.1038/s41575-025-01149-6
Frances Lee, Meena B. Bansal
As persons living with human immunodeficiency virus (HIV) infection are living longer, non-AIDS-related mortality continues to rise, with liver disease being one of the most common causes. This Review provides a synopsis of the current burden of liver diseases, ranging from viral hepatitis to metabolic dysfunction-associated steatotic liver disease to liver cancer, and discusses the barriers and challenges to screening and treatment as well as cofactors contributing to increasing disease burden. A brief insight is provided on the potential molecular mechanisms driving hepatic inflammation and fibrosis in persons living with HIV. Given the effect of direct-acting antivirals on hepatitis C virus infection and suppressive treatment for hepatitis B virus infection, special attention is drawn to the emergence of metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis in this population, focusing on factors related to the increasing prevalence of relevant comorbidities, the role of antiretroviral therapy, and HIV-specific factors in driving liver fibrosis progression. Individuals living with human immunodeficiency virus infection are experiencing an increase in liver disease burden. This Review summarizes current knowledge on the burden of liver diseases in this population and provides insights into clinical management and future directions.
{"title":"Liver disease in people living with HIV infection: a changing landscape","authors":"Frances Lee, Meena B. Bansal","doi":"10.1038/s41575-025-01149-6","DOIUrl":"10.1038/s41575-025-01149-6","url":null,"abstract":"As persons living with human immunodeficiency virus (HIV) infection are living longer, non-AIDS-related mortality continues to rise, with liver disease being one of the most common causes. This Review provides a synopsis of the current burden of liver diseases, ranging from viral hepatitis to metabolic dysfunction-associated steatotic liver disease to liver cancer, and discusses the barriers and challenges to screening and treatment as well as cofactors contributing to increasing disease burden. A brief insight is provided on the potential molecular mechanisms driving hepatic inflammation and fibrosis in persons living with HIV. Given the effect of direct-acting antivirals on hepatitis C virus infection and suppressive treatment for hepatitis B virus infection, special attention is drawn to the emergence of metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis in this population, focusing on factors related to the increasing prevalence of relevant comorbidities, the role of antiretroviral therapy, and HIV-specific factors in driving liver fibrosis progression. Individuals living with human immunodeficiency virus infection are experiencing an increase in liver disease burden. This Review summarizes current knowledge on the burden of liver diseases in this population and provides insights into clinical management and future directions.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 3","pages":"264-280"},"PeriodicalIF":51.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583188","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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