IF 13.5 1区医学

Hepatology Pub Date : 2025-10-02 DOI: 10.1097/hep.0000000000001545

Mirko Minini,Giulio Avveduto,Sonia Becharef,Marie Meunier-Thaens,Bouchra Lekbaby,Maria Perez-Lazon,Alice Machado,Thomas Guilbert,Julie Lesieur,Gilles Renault,Sara Ceccacci,Ida Chiara Guerrera,Christophe Klein,Jérémy Augustin,Rana Bazzi,Stephane Roux,Jonathan Pol,Emmanuel Donnadieu,Florence Gazeau,Laura Fouassier

{"title":"Laser-activated nanoparticles rewire tumor microenvironment enhancing PD-1 blockade and T cell response in cholangiocarcinoma.","authors":"Mirko Minini,Giulio Avveduto,Sonia Becharef,Marie Meunier-Thaens,Bouchra Lekbaby,Maria Perez-Lazon,Alice Machado,Thomas Guilbert,Julie Lesieur,Gilles Renault,Sara Ceccacci,Ida Chiara Guerrera,Christophe Klein,Jérémy Augustin,Rana Bazzi,Stephane Roux,Jonathan Pol,Emmanuel Donnadieu,Florence Gazeau,Laura Fouassier","doi":"10.1097/hep.0000000000001545","DOIUrl":"https://doi.org/10.1097/hep.0000000000001545","url":null,"abstract":"BACKGROUND AND AIMSImmunotherapy has continued to revolutionize cancer treatment, achieving remarkable progress over the past decade. However, in most solid tumors, its effectiveness is often impaired because of immune resistance driven by the tumor microenvironment (TME). In fibrotic cancers, such as cholangiocarcinoma (CCA), the extracellular matrix (ECM) and cancer-associated fibroblasts (CAFs) form a dense, rigid stroma that hinders immune cell infiltration and promotes immunosuppression. Overcoming these physical and biological barriers is crucial for fully unleashing the potential of immunotherapeutic approaches.APPROACH RESULTSWe developed a dual-action strategy combining photothermal therapy (PTT) using gold-decorated iron oxide nanoflowers (GIONFs) and PD-1 immune checkpoint blockade. This approach was evaluated in preclinical models of CCA to assess its impact on ECM remodeling, CAF modulation, immune cell activation, and tumor growth.The combinatorial strategy effectively reduced ECM stiffness, reprogrammed CAF subsets, and enhanced cytotoxic T-cell infiltration. In preclinical CCA models, treated tumors shift from immune-cold to immune-hot states. This combination amplifies anti-tumor immune responses, decreases immunosuppressive stromal signatures, and improves tumor control.CONCLUSIONSOur findings emphasize the therapeutic potential of combining nanotechnology and immunotherapy to reshape the TME and overcome immunotherapy resistance in fibrotic tumors, such as CCA. Targeting both ECM and immune checkpoints has emerged as a promising and versatile strategy to enhance the efficacy of immunotherapy against desmoplastic cancers.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"114 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209159","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}

引用次数: 0

Reply to the letter to the editor: Dropout dynamics in RT+LT vs LR for pCCA-An overlooked variable? 回复给编辑的信：pcca的RT+LT vs LR的退学动态-一个被忽视的变量？

IF 13.5 1区医学

Hepatology Pub Date : 2025-10-02 DOI: 10.1097/hep.0000000000001556

Yawen Dong,Zhihao Li,Gregory J Gores,Julie K Heimbach,Rory L Smoot,Timucin Taner,Patrick P Starlinger

引用次数: 0

Multi-omics and machine learning in cholangiocarcinoma: A paradigm shift toward molecular subtyping and precision therapy. 胆管癌的多组学和机器学习：向分子分型和精确治疗的范式转变。

IF 13.5 1区医学

Hepatology Pub Date : 2025-10-02 DOI: 10.1097/hep.0000000000001560

Meng Xu,Lee Ju-Seog

引用次数: 0

Reply: Clarifying LSM cutoff validation, statistical power, and subgroup applicability in predicting liver- related events in chronic hepatitis B. 答复：澄清LSM截止验证、统计效力和预测慢性乙型肝炎肝脏相关事件的亚组适用性。

IF 13.5 1区医学

Hepatology Pub Date : 2025-10-02 DOI: 10.1097/hep.0000000000001559

Yameng Sun,Shuyan Chen,Xinyu Zhao,Hong You

引用次数: 0

Pioneering precision: The evolution of immunotherapy for hepatocellular carcinoma. 开创性的精确性：肝细胞癌免疫治疗的发展。

IF 13.5 1区医学

Hepatology Pub Date : 2025-10-02 DOI: 10.1097/hep.0000000000001554

Friedrich Foerster,Lucas Wiesmann,Paula Bark,Peter Robert Galle

{"title":"Pioneering precision: The evolution of immunotherapy for hepatocellular carcinoma.","authors":"Friedrich Foerster,Lucas Wiesmann,Paula Bark,Peter Robert Galle","doi":"10.1097/hep.0000000000001554","DOIUrl":"https://doi.org/10.1097/hep.0000000000001554","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality. Systemic treatment is a central pillar for the clinical management of HCC which has been transformed by the arrival of immunotherapy in recent years. The established targets of today's immunotherapeutic options are PD-1, PD-L1, CTLA-4 and VEGF. Combinations of antibodies inhibiting PD-1/PD-L1 + VEGF and PD-1/PD-L1 + CTLA-4, respectively, have received approval and represent the current standard-of-care in the first-line setting. Immunotherapy for HCC has so far been confined to the advanced stage but is currently being evaluated in earlier stages, too. Molecular biomarkers and classifications have been developed to guide treatment selection but have not yet been adopted in routine clinical practice. In addition, several novel immunotherapeutic targets have been identified and treatments exploiting those targets are currently at early as well as late stages of clinical development. Herein, we review this evolution of immunotherapy for HCC which holds the potential for increasing therapeutic precision and thus for maximizing the benefit of patients while simultaneously reducing their risk of harm.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"99 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209068","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}

引用次数: 0

Identifying a therapeutic window of opportunity for people living with primary sclerosing cholangitis: Embryology and the overlap of inflammatory bowel disease with immune-mediated liver injury. 为原发性硬化性胆管炎患者寻找治疗机会之窗：胚胎学和炎症性肠病与免疫介导的肝损伤的重叠。

IF 15.8 1区医学

Hepatology Pub Date : 2025-10-01 Epub Date: 2024-05-14 DOI: 10.1097/HEP.0000000000000926

Richard Kellermayer, Marco Carbone, Thomas D Horvath, Reka G Szigeti, Cynthia Buness, Gideon M Hirschfield, Peter J Lewindon

{"title":"Identifying a therapeutic window of opportunity for people living with primary sclerosing cholangitis: Embryology and the overlap of inflammatory bowel disease with immune-mediated liver injury.","authors":"Richard Kellermayer, Marco Carbone, Thomas D Horvath, Reka G Szigeti, Cynthia Buness, Gideon M Hirschfield, Peter J Lewindon","doi":"10.1097/HEP.0000000000000926","DOIUrl":"10.1097/HEP.0000000000000926","url":null,"abstract":"Primary sclerosing cholangitis (PSC) is a variably progressive, fibrosis-causing autoimmune disorder of the intrahepatic and extrahepatic bile ducts of unclear etiology. PSC is commonly (in 60%-90% of cases) associated with an inflammatory bowel disease (IBD) like PSC-IBD and less commonly with an autoimmune hepatitis (AIH) like PSC-AIH or AIH-overlap disorder. Hepatologists and Gastroenterologists often consider these combined conditions as distinctly different from the classical forms in isolation. Here, we review recent epidemiologic observations and highlight that PSC-IBD and PSC-AIH overlap appear to represent aspects of a common PSC clinico-pathological pathway and manifest in an age-of-presentation-dependent manner. Particularly from the pediatric experience, we hypothesize that all cases of PSC likely originate from a complex \"Early PSC\"-\"IBD\"-\"AIH\" overlap in which PSC defines the uniquely and variably associated \"AIH\" and \"IBD\" components along an individualized lifetime continuum. We speculate that a distinctly unique, \"diverticular autoimmunity\" against the embryonic cecal- and hepatic diverticulum-derived tissues may be the origin of this combined syndrome, where \"AIH\" and \"IBD\" variably commence then variably fade while PSC progresses with age. Our hypothesis provides an explanation for the age-dependent variation in the presentation and progression of PSC. This is critical for the optimal targeting of studies into PSC etiopathogenesis and emphasizes the concept of a \"developmental window of opportunity for therapeutic mitigation\" in what is currently recognized as an irreversible disease process. The discovery of such a window would be critically important for the targeting of interventions, both the administration of current therapies and therapeutic trial planning.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"949-959"},"PeriodicalIF":15.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920804","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}

引用次数: 0

IBAT inhibitors in pediatric cholestatic liver diseases: Transformation on the horizon? IBAT 抑制剂在小儿胆汁淤积性肝病中的应用：转型在即？

IF 15.8 1区医学

Hepatology Pub Date : 2025-10-01 Epub Date: 2024-07-25 DOI: 10.1097/HEP.0000000000001032

Harry Sutton, Ronald J Sokol, Binita M Kamath

{"title":"IBAT inhibitors in pediatric cholestatic liver diseases: Transformation on the horizon?","authors":"Harry Sutton, Ronald J Sokol, Binita M Kamath","doi":"10.1097/HEP.0000000000001032","DOIUrl":"10.1097/HEP.0000000000001032","url":null,"abstract":"Historically, the therapeutic options available to hepatologists managing cholestasis have been limited. Apart from bile acid--binding resins and the choleretic ursodeoxycholic acid, the medical management of cholestasis in children has been predominately focused on managing the complications of cholestasis, namely pruritus, malnutrition, fat-soluble vitamin deficiencies, and portal hypertension. As such, invasive surgical procedures such as biliary diversion and liver transplantation may become the only options for progressive and unremitting cases of cholestasis. Particularly in the pediatric population, where debilitating pruritus is a common indication for a liver transplant, effective anti-cholestatic medications have the potential to prolong native liver survival without the need for biliary diversion. Ileal bile acid transporter (IBAT) inhibitors are a relatively new class of drugs which that target the ileal re-uptake of bile acids, thus interrupting the enterohepatic circulation and reducing the total bile acid pool size and exposure of the liver. Oral, minimally absorbed IBAT inhibitors have been demonstrated to reduce serum bile acid levels and pruritus with a minimal side effect profile in clinical trials in Alagille Ssyndrome and progressive familial intrahepatic cholestasis, leading to FDA and EMA approval. The indications for IBAT inhibitors will likely expand in the coming years as clinical trials in other adult and pediatric cholestatic conditions are ongoing. This review will summarize the published clinical and pre-clinical data on IBAT inhibitors and offer providers guidance on their practical use.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"985-995"},"PeriodicalIF":15.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755919","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}

引用次数: 0

Immunobiology of primary sclerosing cholangitis. 原发性硬化性胆管炎的免疫生物学。

IF 15.8 1区医学

Hepatology Pub Date : 2025-10-01 Epub Date: 2024-09-02 DOI: 10.1097/HEP.0000000000001080

Martin Cornillet, Daniel Geanon, Annika Bergquist, Niklas K Björkström

引用次数: 0

Drug-induced cholestatic liver diseases. 药物诱发的胆汁淤积性肝病。

IF 15.8 1区医学

Hepatology Pub Date : 2025-10-01 Epub Date: 2024-08-08 DOI: 10.1097/HEP.0000000000001052

Einar S Bjornsson, Harshad C Devarbhavi

{"title":"Drug-induced cholestatic liver diseases.","authors":"Einar S Bjornsson, Harshad C Devarbhavi","doi":"10.1097/HEP.0000000000001052","DOIUrl":"10.1097/HEP.0000000000001052","url":null,"abstract":"Cholestatic DILI is an important and frequently challenging differential diagnosis in patients presenting with elevated liver tests with predominant elevation in alkaline phosphatase. A number of competing etiologies need to be ruled out, such as hepatobiliary malignancy, choledocholithiasis, cholestatic forms of viral hepatitis, cholestasis of sepsis, primary and secondary cholangitis, and right-sided cardiac failure to name a few. Important advances have occurred in the understanding and knowledge of the clinical phenotypes, new etiological agents, risk factors, pathophysiology, and genetic determinants of drug-induced cholestasis since the last review on drug-induced cholestasis was published in Hepatology in 2011. Secondary sclerosing cholangitis (SSC) due to drugs has been well documented for several different drugs. Checkpoint inhibitors are one of the types of drugs shown to lead to secondary sclerosing cholangitis. Several new herbal and dietary supplements have recently been shown to lead to cholestatic liver injury. A number of genetic risk factors for cholestasis due to drugs have been identified in the last decade, and the pathogenesis behind cholestatic injury is better defined. In this review, the focus is on diagnostic approach and description of new clinical phenotypes such as secondary sclerosing cholangitis and vanishing bile duct syndrome. Furthermore, the review provides an overview of the risk factors, genetic determinants, and the pathophysiology of hepatobiliary transporters leading to cholestasis. Management, areas of uncertainty, and future direction are also presented.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"996-1015"},"PeriodicalIF":15.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909736","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}

引用次数: 0

Erratum: P53 up-regulated modulator of apoptosis induction mediates acetaminophen-induced necrosis and liver injury in mice. 更正：P53上调凋亡诱导调节剂介导对乙酰氨基酚诱导的小鼠坏死和肝损伤。

IF 13.5 1区医学

Hepatology Pub Date : 2025-09-29 DOI: 10.1097/hep.0000000000001529

Dongshi Chen,Hong-Min Ni,Lei Wang,Xiaowen Ma,Jian Yu,Wen-Xing Ding,Lin Zhang

引用次数: 0

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