Pub Date : 2026-02-23DOI: 10.1038/s41575-026-01184-x
Yasser Fouad, Ming-Lung Yu, Saeed Hamid, Robert G Gish, Mohammed Eslam
{"title":"Hepatitis C elimination: is it time to redefine the goals?","authors":"Yasser Fouad, Ming-Lung Yu, Saeed Hamid, Robert G Gish, Mohammed Eslam","doi":"10.1038/s41575-026-01184-x","DOIUrl":"https://doi.org/10.1038/s41575-026-01184-x","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":" ","pages":""},"PeriodicalIF":51.0,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276779","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 : 2026-02-19DOI: 10.1038/s41575-026-01179-8
David E. J. Jones, Robert Mitchell-Thain, Emma L. Culver, Jessica K. Dyson, Robert G. Gish, Bettina E. Hansen, Gideon M. Hirschfield, Kris V. Kowdley, Ana Lleo, Andreas E. Kremer, Marlyn J. Mayo, Mark G. Swain, Michael Trauner, Palak J. Trivedi, John M. Vierling, Martin Weltman, Andrew D. Yeoman, Cynthia Levy, Marco Carbone
{"title":"The ethics of unlicensed therapy use in primary biliary cholangitis: a counter view","authors":"David E. J. Jones, Robert Mitchell-Thain, Emma L. Culver, Jessica K. Dyson, Robert G. Gish, Bettina E. Hansen, Gideon M. Hirschfield, Kris V. Kowdley, Ana Lleo, Andreas E. Kremer, Marlyn J. Mayo, Mark G. Swain, Michael Trauner, Palak J. Trivedi, John M. Vierling, Martin Weltman, Andrew D. Yeoman, Cynthia Levy, Marco Carbone","doi":"10.1038/s41575-026-01179-8","DOIUrl":"https://doi.org/10.1038/s41575-026-01179-8","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"281 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146223157","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 : 2026-02-18DOI: 10.1038/s41575-026-01176-x
Maria L Marco, Marla Cunningham, Stephan C Bischoff, Gerard Clarke, Nathalie Delzenne, James D Lewis, Marlies Meisel, Daniel Merenstein, Paul W O'Toole, Heidi M Staudacher, Hania Szajewska, Jerry M Wells, Eamonn M M Quigley
The term 'gut health' is increasingly used as a catch-all phrase by many stakeholders, including scientists, health-care professionals, industry and the general public, to describe a wide range of health-related concepts. Despite its widespread use, particularly in relation to studies on diet, fermented foods, biotics and the gut microbiome, it remains unclear what the term gut health means. Therefore, an expert panel was convened by the International Scientific Association for Probiotics and Prebiotics to address the current state of scientific and clinical knowledge on the physiology, manifestation, application and measurement of the concept of gut health. The panel evaluated the term in the context of the central role of the gastrointestinal tract in health and overall well-being and proposed a definition of gut health as "a state of normal gastrointestinal function without active gastrointestinal disease and gut-related symptoms that affect quality of life". The definition was developed mindful of the functional, subjective and extrinsic domains that contribute to gut health. In this Consensus Statement, clinically relevant and accessible metrics to assess these domains are reviewed and a comprehensive approach to gut health is proposed that is relevant to clinical practice as well as to studies of dietary and biotic interventions.
{"title":"The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of gut health.","authors":"Maria L Marco, Marla Cunningham, Stephan C Bischoff, Gerard Clarke, Nathalie Delzenne, James D Lewis, Marlies Meisel, Daniel Merenstein, Paul W O'Toole, Heidi M Staudacher, Hania Szajewska, Jerry M Wells, Eamonn M M Quigley","doi":"10.1038/s41575-026-01176-x","DOIUrl":"10.1038/s41575-026-01176-x","url":null,"abstract":"<p><p>The term 'gut health' is increasingly used as a catch-all phrase by many stakeholders, including scientists, health-care professionals, industry and the general public, to describe a wide range of health-related concepts. Despite its widespread use, particularly in relation to studies on diet, fermented foods, biotics and the gut microbiome, it remains unclear what the term gut health means. Therefore, an expert panel was convened by the International Scientific Association for Probiotics and Prebiotics to address the current state of scientific and clinical knowledge on the physiology, manifestation, application and measurement of the concept of gut health. The panel evaluated the term in the context of the central role of the gastrointestinal tract in health and overall well-being and proposed a definition of gut health as \"a state of normal gastrointestinal function without active gastrointestinal disease and gut-related symptoms that affect quality of life\". The definition was developed mindful of the functional, subjective and extrinsic domains that contribute to gut health. In this Consensus Statement, clinically relevant and accessible metrics to assess these domains are reviewed and a comprehensive approach to gut health is proposed that is relevant to clinical practice as well as to studies of dietary and biotic interventions.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":" ","pages":""},"PeriodicalIF":51.0,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146219130","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 : 2026-02-12DOI: 10.1038/s41575-026-01175-y
Eric Trépo, Jessica Zucman-Rossi, Jean-Charles Nault
Steatotic liver diseases, encompassing metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease, affect nearly one-third of the global population and are a leading cause of cirrhosis and hepatocellular carcinoma. The substantial interindividual variation in disease progression indicates important genetic contributions beyond environmental factors. Genome-wide association studies have identified multiple common variants predominantly affecting lipid metabolism, with PNPLA3 I148M representing the strongest genetic determinant across the disease spectrum. The shared genetic architecture across metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease supports convergent pathogenic mechanisms. Discoveries of somatic mosaicism in adult liver tissues have revealed convergent mutations in metabolic genes such as FOXO1, GPAM and CIDEB, conferring adaptive advantages against lipotoxicity. Also, clonal haematopoiesis of indeterminate potential is associated with the risk of chronic liver diseases, metabolic dysfunction-associated steatohepatitis and its related liver cancer risk. Inherited and somatic variants can influence hepatocellular carcinoma risk through direct effects on chronic liver disease progression and/or through specific cancer-promoting pathways involving telomere maintenance and WNT signalling. Although polygenic risk scores represent a promising approach for risk stratification, current implementations face important limitations that must be addressed before achieving their full clinical potential.
{"title":"Germline mutations and somatic mosaicism in steatotic liver diseases and related liver carcinogenesis.","authors":"Eric Trépo, Jessica Zucman-Rossi, Jean-Charles Nault","doi":"10.1038/s41575-026-01175-y","DOIUrl":"https://doi.org/10.1038/s41575-026-01175-y","url":null,"abstract":"<p><p>Steatotic liver diseases, encompassing metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease, affect nearly one-third of the global population and are a leading cause of cirrhosis and hepatocellular carcinoma. The substantial interindividual variation in disease progression indicates important genetic contributions beyond environmental factors. Genome-wide association studies have identified multiple common variants predominantly affecting lipid metabolism, with PNPLA3 I148M representing the strongest genetic determinant across the disease spectrum. The shared genetic architecture across metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease supports convergent pathogenic mechanisms. Discoveries of somatic mosaicism in adult liver tissues have revealed convergent mutations in metabolic genes such as FOXO1, GPAM and CIDEB, conferring adaptive advantages against lipotoxicity. Also, clonal haematopoiesis of indeterminate potential is associated with the risk of chronic liver diseases, metabolic dysfunction-associated steatohepatitis and its related liver cancer risk. Inherited and somatic variants can influence hepatocellular carcinoma risk through direct effects on chronic liver disease progression and/or through specific cancer-promoting pathways involving telomere maintenance and WNT signalling. Although polygenic risk scores represent a promising approach for risk stratification, current implementations face important limitations that must be addressed before achieving their full clinical potential.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":" ","pages":""},"PeriodicalIF":51.0,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181180","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 : 2026-02-11DOI: 10.1038/s41575-026-01182-z
Jordan Hindson
{"title":"ENPP1 as a contributor to chronic pancreatitis-related PDAC","authors":"Jordan Hindson","doi":"10.1038/s41575-026-01182-z","DOIUrl":"10.1038/s41575-026-01182-z","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 3","pages":"207-207"},"PeriodicalIF":51.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166008","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 : 2026-01-30DOI: 10.1038/s41575-026-01174-z
Jeffrey V Lazarus,Christopher J Kopka,Aina Nicolàs,Safura Abdool Karim,Meena B Bansal,Michael Betel,John F Dillon,Pere Gines,Aleksander Krag,Veronica Miller,Cynthia A Moylan,Alisa Pedrana,Paula Petrone,Jörn M Schattenberg,Sunil S Solomon,Norah Terrault,Ellie Dow,Maja Thiele
Liver diseases account for 1 in 25 deaths worldwide. Owing to the asymptomatic nature across the dynamic spectrum of steatotic liver disease (SLD) and the absence of targeted screening programmes, individuals at risk of progression to cirrhosis or hepatocellular carcinoma (HCC) are unlikely to pursue liver disease testing. Historically, hepatitis B and C were the leading causes of liver injury that can progress to cirrhosis or HCC. Global efforts to implement screening and vaccination programmes, expand testing and treatment, and encourage active viral hepatitis case finding followed the widespread availability of curative treatment for hepatitis C and effective suppressive therapy and vaccines for hepatitis B, further supported by changes in law, regulation and public policy. With encouraging declines in new viral hepatitis infections in many countries, greater attention should turn to SLD, now the leading global indicator for cirrhosis and HCC. Screening and active case finding for SLD lag far behind its increasing prevalence, leaving most people undiagnosed. This Expert Recommendation draws on lessons learned from legal, regulatory and policy changes required to combat the viral hepatitis public health threat. Our recommendations can contribute to a concerted shift in legal frameworks and policies to enhance screening programmes, increase testing and improve health outcomes.
{"title":"Lessons learned from viral hepatitis testing that inform law and policy responses to steatotic liver disease.","authors":"Jeffrey V Lazarus,Christopher J Kopka,Aina Nicolàs,Safura Abdool Karim,Meena B Bansal,Michael Betel,John F Dillon,Pere Gines,Aleksander Krag,Veronica Miller,Cynthia A Moylan,Alisa Pedrana,Paula Petrone,Jörn M Schattenberg,Sunil S Solomon,Norah Terrault,Ellie Dow,Maja Thiele","doi":"10.1038/s41575-026-01174-z","DOIUrl":"https://doi.org/10.1038/s41575-026-01174-z","url":null,"abstract":"Liver diseases account for 1 in 25 deaths worldwide. Owing to the asymptomatic nature across the dynamic spectrum of steatotic liver disease (SLD) and the absence of targeted screening programmes, individuals at risk of progression to cirrhosis or hepatocellular carcinoma (HCC) are unlikely to pursue liver disease testing. Historically, hepatitis B and C were the leading causes of liver injury that can progress to cirrhosis or HCC. Global efforts to implement screening and vaccination programmes, expand testing and treatment, and encourage active viral hepatitis case finding followed the widespread availability of curative treatment for hepatitis C and effective suppressive therapy and vaccines for hepatitis B, further supported by changes in law, regulation and public policy. With encouraging declines in new viral hepatitis infections in many countries, greater attention should turn to SLD, now the leading global indicator for cirrhosis and HCC. Screening and active case finding for SLD lag far behind its increasing prevalence, leaving most people undiagnosed. This Expert Recommendation draws on lessons learned from legal, regulatory and policy changes required to combat the viral hepatitis public health threat. Our recommendations can contribute to a concerted shift in legal frameworks and policies to enhance screening programmes, increase testing and improve health outcomes.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"16 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089141","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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