Nature Reviews Gastroenterology &Hepatology最新文献

{"title":"Bezafibrate for primary biliary cholangitis: time to act on the evidence","authors":"Christophe Corpechot, Maria-Carlota Londoño, Alejandra Villamil, Henriette Ytting, Atsushi Tanaka, Ulrich Beuers","doi":"10.1038/s41575-025-01135-y","DOIUrl":"10.1038/s41575-025-01135-y","url":null,"abstract":"After the regulatory rejection of obeticholic acid, peroxisome proliferator-activated receptor (PPAR) agonists have emerged as the leading second-line candidates for primary biliary cholangitis, pending definitive approval. Of these, only bezafibrate — a low-cost, widely available generic — has demonstrated long-term efficacy, a fact largely disregarded.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 12","pages":"805-807"},"PeriodicalIF":51.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261134","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}

{"title":"WNT–β-catenin signalling in hepatocellular carcinoma: from bench to clinical trials","authors":"Brandon M. Lehrich, Satdarshan P. Monga","doi":"10.1038/s41575-025-01127-y","DOIUrl":"10.1038/s41575-025-01127-y","url":null,"abstract":"WNT–β-catenin activation is observed in around 50% of all patients with hepatocellular carcinoma (HCC), through either gain-of-function mutations in CTNNB1 (which encodes β-catenin) or loss-of-function mutations in AXIN1 or APC. Currently, first-line therapies for HCC are immune checkpoint inhibitor (ICI) combinations, and β-catenin-active HCCs have garnered increased attention due to their unique tumour immune microenvironment (TIME). This pathway is known to drive an immune-excluded TIME, but clinical investigations have provided a more nuanced perspective, with the emergence of a new ‘immune-like’ subclass of HCC that is paradoxically enriched for CTNNB1 mutations and has high levels of T cell infiltration. As such, patients and animal models with β-catenin activation treated with ICIs exhibit heterogeneous responses. Additionally, these tumours exhibit higher fatty acid oxidation to fuel tumour growth owing to a unique metabolic milieu shaped by zone 3 metabolism, which is a physiological function of WNT–β-catenin signalling in the liver lobule. Biomarkers to detect molecular subclasses of patients for targeted therapies are being developed. In this Review, we discuss advances in our understanding of the TIME and metabolism of β-catenin-active HCC, driven by in vitro and in vivo models and single-cell and spatial sequencing, and their implications for the treatment of a subset of HCCs using precision therapies against WNT–β-catenin signalling. WNT–β-catenin activation is common in hepatocellular carcinoma (HCC). In this Review, the authors summarize our understanding of the role of WNT–β-catenin activation in HCC — based on results from in vitro and in vivo models — and implications for precision treatment of HCC via targeting β-catenin.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 3","pages":"246-263"},"PeriodicalIF":51.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254586","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}

{"title":"Nivolumab and ipilimumab as neoadjuvant therapy for potentially resectable HCC","authors":"Jordan Hindson","doi":"10.1038/s41575-025-01136-x","DOIUrl":"10.1038/s41575-025-01136-x","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 11","pages":"739-739"},"PeriodicalIF":51.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235944","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}

{"title":"Aspirin and recurrence of PI3K-mutated CRC","authors":"Jordan Hindson","doi":"10.1038/s41575-025-01137-w","DOIUrl":"10.1038/s41575-025-01137-w","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 11","pages":"739-739"},"PeriodicalIF":51.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235943","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}

{"title":"Submucosal electronics for long-term in situ diagnosis and therapeutics of gastrointestinal diseases","authors":"Chong Zhang \u0000 (, ), Kai Fung Chan \u0000 (, ), Chengfeng Pan \u0000 (, ), Xianfeng Xia \u0000 (, ), Philip Wai Yan Chiu \u0000 (, )","doi":"10.1038/s41575-025-01130-3","DOIUrl":"10.1038/s41575-025-01130-3","url":null,"abstract":"Submucosal endoscopy creates a new space to implant bioelectronics in a ‘scarless’ way, establishing a reliable interface between device and tissue that remains stable for months in the gastrointestinal tract. Submucosal bioelectronics, combining diagnostic and therapeutic functions, hold great promise as powerful tools to advance both fundamental understanding and clinical management of gastrointestinal disease.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 12","pages":"808-810"},"PeriodicalIF":51.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235945","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}

{"title":"A neurobiotic sense curbs feeding: a new frontier in gut–brain communication","authors":"Rajan Singh","doi":"10.1038/s41575-025-01126-z","DOIUrl":"10.1038/s41575-025-01126-z","url":null,"abstract":"In a new study by Liu and colleagues, researchers demonstrated a novel neuroepithelial circuit in colonic neuropod cells through which a molecular pattern from resident microorganisms was relayed to the brain — a ‘neurobiotic sense’ by which the host adjusted its feeding behaviour by monitoring a gut microbial pattern.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 12","pages":"812-813"},"PeriodicalIF":51.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209058","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}

{"title":"Maternal gut microbiome in early pregnancy: predictor of preterm birth?","authors":"Katrina Ray","doi":"10.1038/s41575-025-01131-2","DOIUrl":"10.1038/s41575-025-01131-2","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 11","pages":"739-739"},"PeriodicalIF":51.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189379","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}

{"title":"Interaction of inflammation and portal hypertension in cirrhosis progression","authors":"Dalila Costa, Jonel Trebicka, Cristina Ripoll, Richard Moreau, Rajiv Jalan, Thomas Reiberger","doi":"10.1038/s41575-025-01107-2","DOIUrl":"10.1038/s41575-025-01107-2","url":null,"abstract":"Decompensated cirrhosis describes an advanced clinical stage with clinical complications, such as ascites, variceal bleeding or hepatic encephalopathy, associated with considerable mortality. Portal hypertension is the main risk factor for developing decompensation in patients with compensated cirrhosis, whereas systemic inflammation is the key driving force for organ failure, that is, for acute-on-chronic liver failure in later stages of cirrhosis. As portal hypertension and systemic inflammation coexist in patients with cirrhosis, an improved understanding of their interaction and dynamic role in distinct stages of cirrhosis is an important step forward towards the development of urgently needed therapeutic interventions. Based on emerging evidence from clinical and translational studies, a novel concept of different predominant pathomechanisms of decompensated cirrhosis is presented, which includes portal hypertension-predominant, systemic inflammmation-predominant and mixed portal hypertension–systemic inflammation phenotypes. A comprehensive set of biomarkers and surrogates of portal hypertension and systemic inflammation might assist clinicians in identifying a predominance of one over the other cirrhosis phenotype. As survival rates of patients with decompensated cirrhosis have remained detrimental without liver transplantation over the past decades, future studies should build on this knowledge to develop effective portal hypertension and systemic inflammation-directed therapies for this underserved population. Portal hypertension and systemic inflammation are key factors driving decompensation and organ failure in cirrhosis. This Review examines those two factors and, based on their mechanistic interaction, proposes a new concept of the clinical phenotypes in decompensated cirrhosis.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 12","pages":"846-865"},"PeriodicalIF":51.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189489","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}

{"title":"Clinical trial design, biomarkers and end points in metabolic and alcohol-related liver disease","authors":"Luis Antonio Diaz, Maja Thiele, Alexandre Louvet, Brian P. Lee, Veeral Ajmera, Federica Tavaglione, Cynthia L. Hsu, Daniel Q. Huang, Elisa Pose, Ramon Bataller, Craig McClain, Jessica Mellinger, Monica Tincopa, Mack C. Mitchell, Vlad Ratziu, Mary E. Rinella, Shiv K. Sarin, Vijay H. Shah, Gyongyi Szabo, Vincent Wai-Sun Wong, Meena B. Bansal, Lorenzo Leggio, Patrick S. Kamath, Aleksander Krag, Arun J. Sanyal, Marco Arrese, Juan Pablo Arab, Quentin M. Anstee, Philippe Mathurin, Rohit Loomba","doi":"10.1038/s41575-025-01120-5","DOIUrl":"10.1038/s41575-025-01120-5","url":null,"abstract":"Metabolic and alcohol-related liver disease (MetALD) is a newly defined entity within the spectrum of steatotic liver disease, characterized by the interplay of cardiometabolic risk factors and alcohol consumption. The evolving epidemiology and complex pathophysiology of MetALD present unique challenges and opportunities for clinical trial design. Inclusion criteria should require simultaneous evidence of metabolic dysfunction (at least two cardiometabolic features) and verified quantifiable alcohol exposure recorded over the preceding 3–6 months. Traditional histological end points are limited by invasiveness, sampling error and interpretative variability. Thus, imaging modalities, serum-based fibrosis biomarkers and quantitative measures of alcohol intake are gaining relevance as non-invasive, reproducible and patient-centric end points aiming to improve trial feasibility. Furthermore, incorporating alcohol biomarkers, stratifying patients by metabolic risk factor burden, and using adaptive designs of trials might enhance the precision and generalizability of MetALD clinical trials. Although uncertainties remain regarding optimal patient selection criteria, event rates and the dynamic interplay between metabolic dysfunction and alcohol intake, ongoing research efforts aim to refine diagnostic criteria, standardize methodologies and validate novel end points. These advances will ultimately accelerate drug development, improve trial efficiency and foster interventions to treat MetALD. Metabolic and alcohol-related liver disease presents challenges in clinical trials due to complex pathophysiology. This Review discusses noninvasive imaging, serum biomarkers and adaptive designs as modalities to enhance patient-centric end points, aiming to refine diagnostics and improve drug development.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 12","pages":"866-884"},"PeriodicalIF":51.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153420","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}

{"title":"NeuroGASTRO 2025","authors":"Katrina Ray","doi":"10.1038/s41575-025-01128-x","DOIUrl":"10.1038/s41575-025-01128-x","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 11","pages":"739-739"},"PeriodicalIF":51.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125112","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}