Pub Date : 2026-01-09DOI: 10.1038/s41575-026-01172-1
Eleni Kotsiliti
{"title":"Drug approvals in 2025 in gastroenterology and hepatology","authors":"Eleni Kotsiliti","doi":"10.1038/s41575-026-01172-1","DOIUrl":"10.1038/s41575-026-01172-1","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 2","pages":"111-111"},"PeriodicalIF":51.0,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937617","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 : 2026-01-09DOI: 10.1038/s41575-025-01168-3
Yoshio Yamauchi,Laura J Sharpe,Andrew J Brown
Increasingly, cholesterol is implicated in diseases beyond the cardiovascular system. Major diseases of the gastrointestinal tract and liver are a case in point and are a focus of this Review. Particularly active in whole-body cholesterol metabolism, the gut and liver are the major organs that produce and secrete plasma lipoproteins, specifically chylomicrons, very-low-density lipoprotein and high-density lipoprotein. In addition, the liver is the only organ in which cholesterol is converted into bile acids. In this Review, we summarize how the liver and gut handle cholesterol to achieve homeostasis. A multitude of diverse and elaborate mechanisms strictly regulate whole-body cholesterol homeostasis by maintaining crucial liver and gut functions, notably cholesterol biosynthesis, absorption, metabolism, transport and excretion. Perturbation of cholesterol homeostasis is associated with liver and gut diseases, including metabolic dysfunction-associated steatotic liver disease, hepatocellular carcinoma and colorectal cancer. Therefore, the molecular machinery involved in cholesterol regulation is of great therapeutic interest. We provide an overview of how cholesterol balance is normally maintained, how its dysregulation can contribute to liver and gut diseases, and how cholesterol homeostasis is targetable to combat these diseases.
{"title":"Balancing cholesterol metabolism in the liver and gut: perspectives in health and disease.","authors":"Yoshio Yamauchi,Laura J Sharpe,Andrew J Brown","doi":"10.1038/s41575-025-01168-3","DOIUrl":"https://doi.org/10.1038/s41575-025-01168-3","url":null,"abstract":"Increasingly, cholesterol is implicated in diseases beyond the cardiovascular system. Major diseases of the gastrointestinal tract and liver are a case in point and are a focus of this Review. Particularly active in whole-body cholesterol metabolism, the gut and liver are the major organs that produce and secrete plasma lipoproteins, specifically chylomicrons, very-low-density lipoprotein and high-density lipoprotein. In addition, the liver is the only organ in which cholesterol is converted into bile acids. In this Review, we summarize how the liver and gut handle cholesterol to achieve homeostasis. A multitude of diverse and elaborate mechanisms strictly regulate whole-body cholesterol homeostasis by maintaining crucial liver and gut functions, notably cholesterol biosynthesis, absorption, metabolism, transport and excretion. Perturbation of cholesterol homeostasis is associated with liver and gut diseases, including metabolic dysfunction-associated steatotic liver disease, hepatocellular carcinoma and colorectal cancer. Therefore, the molecular machinery involved in cholesterol regulation is of great therapeutic interest. We provide an overview of how cholesterol balance is normally maintained, how its dysregulation can contribute to liver and gut diseases, and how cholesterol homeostasis is targetable to combat these diseases.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"57 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937615","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 : 2026-01-08DOI: 10.1038/s41575-025-01167-4
Mohamed El-Kassas, Zobair M Younossi
{"title":"Preventive hepatology for MASLD in the MENA region: reframing care from late-stage treatment to early intervention.","authors":"Mohamed El-Kassas, Zobair M Younossi","doi":"10.1038/s41575-025-01167-4","DOIUrl":"https://doi.org/10.1038/s41575-025-01167-4","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":" ","pages":""},"PeriodicalIF":51.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934304","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 : 2026-01-05DOI: 10.1038/s41575-025-01159-4
S K Sarin,Ashok Choudhury,Anupam Kumar,Nadim Mahmud,G H Lee,Qin Ning,Soek-Siam Tan,Kessarin Thanapirom,Vinod Arora,Nobuaki Nakayama,Jun Li,Constantine J Karvellas
Acute-on-chronic liver failure (ACLF) is a complex syndrome characterized by acute hepatic decompensation superimposed on pre-existing chronic liver disease or cirrhosis that is associated with acute worsening of portal hypertension, increased risk of infection, organ dysfunction and high short-term mortality. This Review provides a comprehensive update on definitions, pathophysiological mechanisms, clinical presentation and management of ACLF. The severe hepatic injury in ACLF triggers systemic inflammation, which is driven by damage-associated molecular patterns, gut-derived microbial products, and immunometabolic and functional dysregulation. Immune dysfunction can range from hyperinflammation and hypercytokinaemia to immune paresis, which in turn predisposes patients to infection and organ failure. The principles of ACLF management prioritize ameliorating the acute hepatic insult, managing portal hypertension, preventing organ failure and optimizing patients who are eligible for liver transplantation. Emerging options include novel therapies targeting immune modulation and liver regeneration, therapeutic plasma exchange and artificial liver support systems. Well-defined criteria for prompt interventions and selection of patients for transplantation within the first week after diagnosis - the 'golden window' - have improved outcomes of liver transplantation in patients with ACLF. The Kyoto ACLF Consensus reflects global efforts on unifying definitions, simplifying treatment end points, refining prediction tools, and filling the void of targeted non-transplantation interventions to improve outcomes in patients with ACLF; however, large knowledge gaps remain and further research is needed.
{"title":"Acute-on-chronic liver failure: pathophysiological mechanisms and clinical management.","authors":"S K Sarin,Ashok Choudhury,Anupam Kumar,Nadim Mahmud,G H Lee,Qin Ning,Soek-Siam Tan,Kessarin Thanapirom,Vinod Arora,Nobuaki Nakayama,Jun Li,Constantine J Karvellas","doi":"10.1038/s41575-025-01159-4","DOIUrl":"https://doi.org/10.1038/s41575-025-01159-4","url":null,"abstract":"Acute-on-chronic liver failure (ACLF) is a complex syndrome characterized by acute hepatic decompensation superimposed on pre-existing chronic liver disease or cirrhosis that is associated with acute worsening of portal hypertension, increased risk of infection, organ dysfunction and high short-term mortality. This Review provides a comprehensive update on definitions, pathophysiological mechanisms, clinical presentation and management of ACLF. The severe hepatic injury in ACLF triggers systemic inflammation, which is driven by damage-associated molecular patterns, gut-derived microbial products, and immunometabolic and functional dysregulation. Immune dysfunction can range from hyperinflammation and hypercytokinaemia to immune paresis, which in turn predisposes patients to infection and organ failure. The principles of ACLF management prioritize ameliorating the acute hepatic insult, managing portal hypertension, preventing organ failure and optimizing patients who are eligible for liver transplantation. Emerging options include novel therapies targeting immune modulation and liver regeneration, therapeutic plasma exchange and artificial liver support systems. Well-defined criteria for prompt interventions and selection of patients for transplantation within the first week after diagnosis - the 'golden window' - have improved outcomes of liver transplantation in patients with ACLF. The Kyoto ACLF Consensus reflects global efforts on unifying definitions, simplifying treatment end points, refining prediction tools, and filling the void of targeted non-transplantation interventions to improve outcomes in patients with ACLF; however, large knowledge gaps remain and further research is needed.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"18 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897512","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 : 2026-01-02DOI: 10.1038/s41575-025-01164-7
Salomé S Pinho, Joana Torres, Jean-Frederic Colombel
Glycans are essential components of homeostatic networks, acting as fine tuners of immunological responses, and are therefore promising targets for manipulating immune tolerance. Glycans shield the entire gut mucosa surface, contributing to epithelial barrier integrity. Moreover, most microorganisms expose glycoconjugates on their surfaces, making glycans essential molecules in the crosstalk between host immune response and the gut microbiota. The vast amount of biological information encoded by mucosal glycans is deciphered by a variety of glycan-binding proteins that translate glycan recognition into either pro-inflammatory or anti-inflammatory responses. Current evidence from inflammatory bowel disease (IBD) has highlighted the prominent role of glycans in establishing and regulating key cellular and molecular pathways underlying the transition from health to intestinal inflammation, with implications for understanding IBD immunopathogenesis and for IBD prediction and prevention. In this Review, we discuss current advances, emerging challenges and future prospects in exploiting the power of the mucosal glycocalyx and the glycome as master coordinators of the immunoregulatory networks in IBD from the preclinical phase to established diagnosis. We discuss the clinical utility of the glycome as a serological biomarker with diagnostic, prognostic and predictive value, and as a potential new target for preventive intervention strategies in IBD.
{"title":"Mucosal glycans: key drivers of the development of inflammatory bowel disease and a potential new therapeutic target.","authors":"Salomé S Pinho, Joana Torres, Jean-Frederic Colombel","doi":"10.1038/s41575-025-01164-7","DOIUrl":"https://doi.org/10.1038/s41575-025-01164-7","url":null,"abstract":"<p><p>Glycans are essential components of homeostatic networks, acting as fine tuners of immunological responses, and are therefore promising targets for manipulating immune tolerance. Glycans shield the entire gut mucosa surface, contributing to epithelial barrier integrity. Moreover, most microorganisms expose glycoconjugates on their surfaces, making glycans essential molecules in the crosstalk between host immune response and the gut microbiota. The vast amount of biological information encoded by mucosal glycans is deciphered by a variety of glycan-binding proteins that translate glycan recognition into either pro-inflammatory or anti-inflammatory responses. Current evidence from inflammatory bowel disease (IBD) has highlighted the prominent role of glycans in establishing and regulating key cellular and molecular pathways underlying the transition from health to intestinal inflammation, with implications for understanding IBD immunopathogenesis and for IBD prediction and prevention. In this Review, we discuss current advances, emerging challenges and future prospects in exploiting the power of the mucosal glycocalyx and the glycome as master coordinators of the immunoregulatory networks in IBD from the preclinical phase to established diagnosis. We discuss the clinical utility of the glycome as a serological biomarker with diagnostic, prognostic and predictive value, and as a potential new target for preventive intervention strategies in IBD.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":" ","pages":""},"PeriodicalIF":51.0,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889634","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 : 2025-12-22DOI: 10.1038/s41575-025-01166-5
Pierfrancesco Visaggi,Edoardo V Savarino
{"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":"https://doi.org/10.1038/s41575-025-01166-5","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"29 1","pages":""},"PeriodicalIF":65.1,"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}
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