Seminars in liver disease最新文献

Rethinking Pathogenesis of Primary Sclerosing Cholangitis. 原发性硬化性胆管炎发病机制的再思考。

IF 4 3区医学

Seminars in liver disease Pub Date : 2026-10-19 DOI: 10.1055/a-2983-6480

Münevver Demir, Jakob Weglage, Michael Sigal

{"title":"Rethinking Pathogenesis of Primary Sclerosing Cholangitis.","authors":"Münevver Demir, Jakob Weglage, Michael Sigal","doi":"10.1055/a-2983-6480","DOIUrl":"https://doi.org/10.1055/a-2983-6480","url":null,"abstract":"Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive fibroinflammatory injury of intrahepatic and extrahepatic bile ducts that may lead to cirrhosis, hepatobiliary malignancy, and death, with liver transplantation representing the only effective intervention in end-stage disease. Rather than a single dominant pathomechanism, the data support a model in which four axes - bile acid metabolism, the intestinal microbiome and gut barrier, biliary epithelial dysfunction, and Th17-skewed immune dysregulation - are reciprocally coupled and converge on a shared periductal fibrogenic output dominated by TGF-beta signaling. This review summarizes key mechanistic advances from genetic, epigenomic, single-cell, spatial transcriptomic, and microbiome studies. These investigations implicate antigen presentation pathways, Th17-skewed immune responses, cholangiocyte senescence and profibrotic signaling, and disrupted gut-liver communication as central drivers of chronic biliary injury. Emerging spatial and multi-omics approaches further reveal complex cellular crosstalk among cholangiocytes, immune cells, macrophages, and mesenchymal populations within portal inflammatory niches. We discuss evolving biomarkers and recent clinical trial data targeting bile acid metabolism, fibrosis, the microbiome, and immune pathways. In conclusion, research data suggests viewing PSC as a network disease, which provides a unifying framework for disease pathogenesis and may enable biomarker-guided patient stratification and mechanism-based therapy development targeting distinct pathogenic pathways.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Microbiome Targeted Therapies for Primary Sclerosing Cholangitis. 微生物组靶向治疗原发性硬化性胆管炎。

IF 4 3区医学

Seminars in liver disease Pub Date : 2026-10-16 DOI: 10.1055/a-2983-7443

Matthew Carson, Vik Meadows, Kari Nejak-Bowen

引用次数: 0

Expert Practical Recommendations for Portal Hypertension in Cirrhosis. 肝硬化门静脉高压的专家实用建议。

IF 4 3区医学

Seminars in liver disease Pub Date : 2026-09-24 DOI: 10.1055/a-2956-4625

Daniel Segna, Asunción Ojeda, Sonia Torres, Juan Carlos García-Pagán

{"title":"Expert Practical Recommendations for Portal Hypertension in Cirrhosis.","authors":"Daniel Segna, Asunción Ojeda, Sonia Torres, Juan Carlos García-Pagán","doi":"10.1055/a-2956-4625","DOIUrl":"10.1055/a-2956-4625","url":null,"abstract":"The purpose of these expert practical recommendations is to provide an updated, clinically oriented overview of the screening, diagnosis, treatment, and surveillance of portal hypertension (PH) in cirrhosis. Building on recent advances in the understanding and management of PH, this review summarizes evidence-based strategies for the identification and management of clinically significant PH in patients with advanced chronic liver disease, in-line with the recent Baveno VIII consensus recommendations. It presents practical clinical pathways for risk stratification, the prevention of first and further decompensation, and the longitudinal follow-up focusing on promising non-invasive techniques, also in terms of diagnosing resolution of clinically significant PH. In addition, the review offers a comprehensive overview of the contemporary management of acute variceal bleeding, including initial resuscitation, pharmacological and endoscopic therapy, and the appropriate use of transjugular intrahepatic portosystemic shunts and other invasive strategies. In conclusion, these expert recommendations offer an updated and practical decision tool for the management of PH in cirrhosis by combining the latest evidence with expert consensus to optimize patient care and improve clinical outcomes.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Context-Dependent Roles of Liver Macrophages in MASH. 肝巨噬细胞在MASH中的环境依赖性作用。

IF 4 3区医学

Seminars in liver disease Pub Date : 2026-09-15 DOI: 10.1055/a-2954-5433

Paul Horn, Frank Tacke

{"title":"Context-Dependent Roles of Liver Macrophages in MASH.","authors":"Paul Horn, Frank Tacke","doi":"10.1055/a-2954-5433","DOIUrl":"https://doi.org/10.1055/a-2954-5433","url":null,"abstract":"Metabolic dysfunction-associated steatohepatitis is a consequence of pathological hepatocellular lipid accumulation where lipotoxic stress triggers chronic inflammation. Liver macrophages are important regulators in the transition from simple steatosis to steatohepatitis and progression toward fibrosis, cirrhosis, and hepatocellular carcinoma. In this process, the hepatic macrophage pool undergoes a significant transformation with loss of embryonic Kupffer cells (KCs) and infiltration of diverse subsets of monocyte-derived macrophages, including monocytic KCs and lipid-associated macrophages (LAMs). Emerging evidence supports macrophage infiltration and the emergence of LAMs as primary adaptive responses aimed at restoring tissue homeostasis by mitigating lipotoxic stress, clearing cell death signals, and promoting the resolution of steatohepatitis and fibrosis regression. Chronic exposure of LAMs to lipotoxic and inflammatory conditions, however, induces inflammatory and fibrogenic programs that drive steatohepatitis and fibrosis progression. In conclusion, these context-dependent roles of liver macrophage subsets have important therapeutic implications, supporting approaches to shift macrophages toward tissue-restoring responses.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Toward Precision Medicine in MASLD: Evolution of Disease Subtyping. 面向MASLD的精准医学：疾病亚型的进化。

IF 4 3区医学

Seminars in liver disease Pub Date : 2026-06-01 Epub Date: 2026-07-29 DOI: 10.1055/a-2926-5401

Ting Feng, Jiaming Li, Xiaoyi Ma, Junzhao Ye

{"title":"Toward Precision Medicine in MASLD: Evolution of Disease Subtyping.","authors":"Ting Feng, Jiaming Li, Xiaoyi Ma, Junzhao Ye","doi":"10.1055/a-2926-5401","DOIUrl":"10.1055/a-2926-5401","url":null,"abstract":"Traditional classifications of metabolic dysfunction-associated steatotic liver disease (MASLD) based on histology or biochemical traits are insufficient to capture its complexity, and clinical strategies rely on generalized treatment approaches that may not target to patient heterogeneity. As MASLD is a highly prevalent and heterogeneous condition with diverse clinical trajectories and outcomes ranged from liver-related complications to multiple extrahepatic complications, emerging approaches integrating clinical features, genotypes, multi-omics (microbiota, metabolomics, proteomics, and related post-translational modifications), machine learning-based clustering, and molecular profiling have enabled more refined disease subtyping. This review underscores novel subtyping frameworks of MASLD beyond traditional methods, focusing on their clinical relevance and translational potential. We further identify gaps in standardization across studies, the limitations of existing models, and highlight the need for integrative, longitudinal approaches to improve precision medicine. In conclusion, clustering subtypes might facilitate risk stratification and guide personalized therapeutic strategies to prioritize these expensive treatments to the right phenotype of MASLD.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"196-213"},"PeriodicalIF":4.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Advances in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis. 原发性胆道性胆管炎和原发性硬化性胆管炎的研究进展。

IF 4 3区医学

Seminars in liver disease Pub Date : 2026-06-01 Epub Date: 2026-09-15 DOI: 10.1055/a-2952-2261

Sunny Sandhu, Aparna Goel

引用次数: 0

Molecular Mechanisms of Progressive Familial Intrahepatic Cholestasis. 进行性家族性肝内胆汁淤积症的分子机制。

IF 4 3区医学

Seminars in liver disease Pub Date : 2026-06-01 Epub Date: 2026-08-07 DOI: 10.1055/a-2933-3012

Richa Gupta, Rodrigo M Florentino, Amala Alenchery, Lara E Berklite, James E Squires

引用次数: 0

MASH-Associated T Cell Activation and Neuroinflammation: Evidence for a Hepatosystemic Immune Axis. 肝系统T细胞许可在masld相关神经炎症中的作用。

IF 4 3区医学

Seminars in liver disease Pub Date : 2026-06-01 Epub Date: 2026-07-06 DOI: 10.1055/a-2908-1230

Britton S Cartee, Fabiola Diniz, Ravi P Rai, Pabitra B Pal, Rahul Srivastava, Daniel Rossmiller, Reben Raeman, Smita S Iyer

{"title":"MASH-Associated T Cell Activation and Neuroinflammation: Evidence for a Hepatosystemic Immune Axis.","authors":"Britton S Cartee, Fabiola Diniz, Ravi P Rai, Pabitra B Pal, Rahul Srivastava, Daniel Rossmiller, Reben Raeman, Smita S Iyer","doi":"10.1055/a-2908-1230","DOIUrl":"10.1055/a-2908-1230","url":null,"abstract":"\"The liver is the origin of the veins and the source of the blood.\"-De Usu Partium Galen.Galen's hepatocentric physiology foreshadowed the liver-brain axis, a network linking vagal signaling, cytokines, metabolites, and migratory immune cells. Central to the immune arm of this axis, the liver generates 25 to 50% of thoracic duct lymph, positioning hepatic lymphatic output as a significant, though not yet fully characterized, source of T cells and cytokines in systemic circulation, a contribution that increases with hepatic inflammation in chronic metabolic diseases. We propose that T lymphocytes are the key cellular effectors through which inflammation originating in the liver, propagating systemically, a process we term hepatosystemic inflammation, reaches the central nervous system (CNS). In metabolic dysfunction-associated steatotic liver disease, hepatosystemic inflammation generates peripheral \"push signals\" that may license T cells for CNS access, while neuroinflammatory \"pull signals\" at CNS barrier interfaces may establish permissive entry points. In conclusion, we propose that T cell licensing by hepatosystemic signals represents the immune arm of the liver-brain axis and a mechanistic bridge between metabolic liver disease and neuroimmune dysfunction and associated cognitive decline, and identifies candidate therapeutic targets along this cascade.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"135-155"},"PeriodicalIF":4.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic Dysfunction-Associated Steatotic Liver Disease Reprograms the Hepatic Metastatic Niche. 代谢功能障碍相关的脂肪变性肝病重编程肝转移生态位

IF 4 3区医学

Seminars in liver disease Pub Date : 2026-06-01 Epub Date: 2026-08-04 DOI: 10.1055/a-2921-0092

Mustafa Karabicici, Ekihiro Seki

{"title":"Metabolic Dysfunction-Associated Steatotic Liver Disease Reprograms the Hepatic Metastatic Niche.","authors":"Mustafa Karabicici, Ekihiro Seki","doi":"10.1055/a-2921-0092","DOIUrl":"10.1055/a-2921-0092","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a driver of metastatic progression in the liver. In addition to its association with hepatocellular carcinoma, the steatotic liver supports metastatic colonization from extrahepatic malignancies by altering hepatic metabolism, stromal organization, vascular architecture, and immune surveillance. Clinical and experimental studies show higher rates of liver metastasis and postoperative recurrence for colorectal, pancreatic, and breast cancers in MASLD. The underlying mechanisms are multifactorial. Hepatocyte lipid overload reshapes lipid metabolism and availability, generating lipotoxic stress signals that support the metabolic adaptation of tumor cells. The steatotic liver also promotes extracellular matrix remodeling, hepatic stellate cell activation, sinusoidal capillarization, and the accumulation of immunosuppressive macrophages and exhausted T cells. Tumor- and liver-derived extracellular vesicles further amplify these changes by transporting lipids, cytokines, and microRNAs that establish a permissive premetastatic niche. Although the contribution of hepatic zonation to metastatic outgrowth is poorly characterized, altered zonation likely enhances metastatic fitness by creating spatial gradients in oxygen tension, lipid metabolism, and immune activity. In conclusion, MASLD can reshape the hepatic metastatic microenvironment, which may lead to metabolic- and immune-targeted therapies to treat liver metastasis in patients with MASLD.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"156-170"},"PeriodicalIF":4.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Neutrophils in Liver Diseases: Functions and Challenging Therapies. 中性粒细胞在肝脏疾病中的作用和挑战性治疗。

IF 4 3区医学

Seminars in liver disease Pub Date : 2026-06-01 Epub Date: 2026-04-07 DOI: 10.1055/a-2847-3228

Rui Ma, Haoran Meng, Xiutong Chen, Haiyuan Shen, Li Zuo, Hua Wang

{"title":"Neutrophils in Liver Diseases: Functions and Challenging Therapies.","authors":"Rui Ma, Haoran Meng, Xiutong Chen, Haiyuan Shen, Li Zuo, Hua Wang","doi":"10.1055/a-2847-3228","DOIUrl":"10.1055/a-2847-3228","url":null,"abstract":"This review explores the pivotal and multifaceted roles of neutrophils in the context of liver pathophysiology. Although traditionally recognized as primary effectors of antibacterial immunity, recent evidence reveals that these abundant leukocytes function as complex regulators in the development and progression of various hepatic conditions. Neutrophils act as double-edged swords: they serve as critical instigators of inflammatory cascades and fibrogenesis, yet simultaneously provide essential contributions to immune defense and the orchestration of tissue repair. This paper synthesizes current research regarding neutrophil behavior within diverse hepatic microenvironments and evaluates their specific contributions to disease resolution versus exacerbation. Furthermore, we deliberate on the emerging potential of targeting neutrophil-specific pathways as a novel therapeutic strategy for liver diseases. Understanding these intricate balances is essential for transitioning from broad anti-inflammatory approaches to precise, neutrophil-modulated interventions. In conclusion, given their status as a dynamic research hotspot, a deeper mechanical understanding of neutrophil functions is imperative for the development of targeted clinical treatments for liver disorders.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"89-102"},"PeriodicalIF":4.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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