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Pathogenesis and Management of Intestinal Failure-Associated Liver Disease. 肠功能衰竭相关肝病的发病机制和管理。
IF 4.3 3区 医学
Seminars in liver disease Pub Date : 2025-03-01 Epub Date: 2025-02-27 DOI: 10.1055/a-2545-7370
Sasha-Jane Abi-Aad, Mark Lovell, Racha T Khalaf, Ronald J Sokol
{"title":"Pathogenesis and Management of Intestinal Failure-Associated Liver Disease.","authors":"Sasha-Jane Abi-Aad, Mark Lovell, Racha T Khalaf, Ronald J Sokol","doi":"10.1055/a-2545-7370","DOIUrl":"10.1055/a-2545-7370","url":null,"abstract":"<p><p>Long-term parenteral nutrition (PN) has considerably improved the management of intestinal failure (IF) in children and adults, particularly those with short bowel syndrome; however, it carries a significant risk of hepatotoxicity, specifically, intestinal failure-associated liver disease (IFALD), also known as PN-associated liver disease. This review provides an update on the latest understanding of IFALD pathogenesis, emerging therapies, and ongoing challenges in the management of this complication. A number of factors are associated with the development of IFALD. PN lipid emulsions, phytosterol exposure, bacterial dysbiosis, an altered gut-liver axis, and episodes of sepsis disrupt bile acid homeostasis and promote liver inflammation in the active phase of IFALD, favoring the development of PN-associated cholestasis (PNAC) and the more chronic form of steatohepatitis with fibrosis. Based on the identification of pathophysiological pathways, potential therapies are being studied in preclinical and clinical trials, including lipid emulsion modifications; targeted therapies such as Farnesoid X receptor (FXR) and liver receptor homolog 1 (LRH-1) agonists, tumor necrosis factor inhibitors, glucagon-like peptide-2 analogs; microbiome modulation; and supplementation with choline and antioxidants. In conclusion, the pathogenesis of IFALD is complex, and PN dependence and liver injury remain challenging, particularly in patients with IF who cannot advance to enteral nutrition and be weaned off PN.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"66-80"},"PeriodicalIF":4.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12031023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524432","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
Hepatic Stellate Cells Functional Heterogeneity in Liver Cancer. 肝星状细胞在肝癌中的功能异质性。
IF 3.7 3区 医学
Seminars in liver disease Pub Date : 2025-03-01 Epub Date: 2025-03-05 DOI: 10.1055/a-2551-0724
Laura Sererols-Viñas, Gemma Garcia-Vicién, Paloma Ruiz-Blázquez, Ting-Fang Lee, Youngmin A Lee, Ester Gonzalez-Sanchez, Javier Vaquero, Anna Moles, Aveline Filliol, Silvia Affò
{"title":"Hepatic Stellate Cells Functional Heterogeneity in Liver Cancer.","authors":"Laura Sererols-Viñas, Gemma Garcia-Vicién, Paloma Ruiz-Blázquez, Ting-Fang Lee, Youngmin A Lee, Ester Gonzalez-Sanchez, Javier Vaquero, Anna Moles, Aveline Filliol, Silvia Affò","doi":"10.1055/a-2551-0724","DOIUrl":"10.1055/a-2551-0724","url":null,"abstract":"<p><p>Hepatic stellate cells (HSCs) are the liver's pericytes, and play key roles in liver homeostasis, regeneration, fibrosis, and cancer. Upon injury, HSCs activate and are the main origin of myofibroblasts and cancer-associated fibroblasts (CAFs) in liver fibrosis and cancer. Primary liver cancer has a grim prognosis, ranking as the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) being the predominant type, followed by intrahepatic cholangiocarcinoma (iCCA). Moreover, the liver hosts 35% of all metastatic lesions. The distinct spatial distribution and functional roles of HSCs across these malignancies represent a significant challenge for universal therapeutic strategies, requiring a nuanced and tailored understanding of their contributions. This review examines the heterogeneous roles of HSCs in liver cancer, focusing on their spatial localization, dynamic interactions within the tumor microenvironment (TME), and emerging therapeutic opportunities, including strategies to modulate their activity, and harness their potential as targets for antifibrotic and antitumor interventions.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"33-51"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568075","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
Preface (Introduction). 前言(介绍)。
IF 4.3 3区 医学
Seminars in liver disease Pub Date : 2025-02-19 DOI: 10.1055/a-2541-3502
Ashwani K Singal
{"title":"Preface (Introduction).","authors":"Ashwani K Singal","doi":"10.1055/a-2541-3502","DOIUrl":"https://doi.org/10.1055/a-2541-3502","url":null,"abstract":"<p><p>Not applicable.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459456","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
Managing Multiorgan Failure in Acute on Chronic Liver Failure. 处理急性慢性肝功能衰竭 (ACLF) 的多器官功能衰竭。
IF 4.3 3区 医学
Seminars in liver disease Pub Date : 2024-11-01 Epub Date: 2024-10-23 DOI: 10.1055/a-2448-0664
Enrico Pompili, Giulia Iannone, Daniele Carrello, Giacomo Zaccherini, Maurizio Baldassarre, Paolo Caraceni
{"title":"Managing Multiorgan Failure in Acute on Chronic Liver Failure.","authors":"Enrico Pompili, Giulia Iannone, Daniele Carrello, Giacomo Zaccherini, Maurizio Baldassarre, Paolo Caraceni","doi":"10.1055/a-2448-0664","DOIUrl":"10.1055/a-2448-0664","url":null,"abstract":"<p><p>Acute-on-chronic liver failure (ACLF) is defined as a clinical syndrome that develops in patients with chronic liver disease characterized by the presence of organ failure and high short-term mortality, although there is still no worldwide consensus on diagnostic criteria. Management of ACLF is mainly based on treatment of \"precipitating factors\" (the most common are infections, alcohol-associated hepatitis, hepatitis B flare, and bleeding) and support of organ failure, which often requires admission to the intensive care unit. Liver transplantation should be considered in patients with ACLF grades 2 to 3 as a potentially life-saving treatment. When a transplant is not indicated, palliative care should be considered after 3 to 7 days of full organ support in patients with at least four organ failures or a CLIF-C ACLF score of >70. This review summarizes the current knowledge on the management of organ failure in patients with ACLF, focusing on recent advances.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"492-509"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507454","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
Role of Complement in Liver Diseases. 补体在肝脏疾病中的作用。
IF 4.3 3区 医学
Seminars in liver disease Pub Date : 2024-11-01 Epub Date: 2024-11-28 DOI: 10.1055/s-0044-1795143
Luan G Prado, Laura E Nagy
{"title":"Role of Complement in Liver Diseases.","authors":"Luan G Prado, Laura E Nagy","doi":"10.1055/s-0044-1795143","DOIUrl":"10.1055/s-0044-1795143","url":null,"abstract":"<p><p>This review aims to summarize recent research using animal models, cell models, and human data regarding the role of complement in liver disease. Complement is part of the innate immune system and was initially characterized for its role in control of pathogens. However, evidence now indicates that complement also plays an important role in the response to cellular injury that is independent of pathogens. The liver is the main organ responsible for producing circulating complement. In response to liver injury, complement is activated and likely plays a dual role, both contributing to and protecting from injury. In uncontrolled complement activation, cell injury and liver inflammation occur, contributing to progression of liver disease. Complement activation is implicated in the pathogenesis of multiple liver diseases, including alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease, fibrosis and cirrhosis, hepatocellular carcinoma, and autoimmune hepatitis. However, the mechanisms by which complement is overactivated in liver diseases are still being unraveled.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"510-522"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751603","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
Therapeutic Potential of Nutraceuticals against Drug-Induced Liver Injury. 营养保健品对药物引起的肝损伤的治疗潜力。
IF 4.3 3区 医学
Seminars in liver disease Pub Date : 2024-11-01 Epub Date: 2024-10-11 DOI: 10.1055/s-0044-1791559
Namya Sethi, Manoj Khokhar, Mitali Mathur, Yashi Batra, Amal Mohandas, Sojit Tomo, Mahadev Rao, Mithu Banerjee
{"title":"Therapeutic Potential of Nutraceuticals against Drug-Induced Liver Injury.","authors":"Namya Sethi, Manoj Khokhar, Mitali Mathur, Yashi Batra, Amal Mohandas, Sojit Tomo, Mahadev Rao, Mithu Banerjee","doi":"10.1055/s-0044-1791559","DOIUrl":"10.1055/s-0044-1791559","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) continues to be a major concern in clinical practice, thus necessitating a need for novel therapeutic approaches to alleviate its impact on hepatic function. This review investigates the therapeutic potential of nutraceuticals against DILI, focusing on examining the underlying molecular mechanisms and cellular pathways. In preclinical and clinical studies, nutraceuticals, such as silymarin, curcumin, and N-acetylcysteine, have demonstrated remarkable efficacy in attenuating liver injury induced by diverse pharmaceutical agents. The molecular mechanisms underlying these hepatoprotective effects involve modulation of oxidative stress, inflammation, and apoptotic pathways. Furthermore, this review examines cellular routes affected by these nutritional components focusing on their influence on hepatocytes, Kupffer cells, and stellate cells. Key evidence highlights that autophagy modulation as well as unfolded protein response are essential cellular processes through which nutraceuticals exert their cytoprotective functions. In conclusion, nutraceuticals are emerging as promising therapeutic agents for mitigating DILI, by targeting different molecular pathways along with cell processes involved in it concurrently.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"430-456"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406786","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
Role of the Gut Microbiome in Metabolic Dysfunction-Associated Steatotic Liver Disease. 肠道微生物组在代谢功能障碍相关性脂肪肝中的作用
IF 4.3 3区 医学
Seminars in liver disease Pub Date : 2024-11-01 Epub Date: 2024-10-10 DOI: 10.1055/a-2438-4383
Salim Maher, Jayashi Rajapakse, Emad El-Omar, Amany Zekry
{"title":"Role of the Gut Microbiome in Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Salim Maher, Jayashi Rajapakse, Emad El-Omar, Amany Zekry","doi":"10.1055/a-2438-4383","DOIUrl":"10.1055/a-2438-4383","url":null,"abstract":"<p><p>The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-previously described as nonalcoholic fatty liver disease-continues to rise globally. Despite this, therapeutic measures for MASLD remain limited. Recently, there has been a growing interest in the gut microbiome's role in the pathogenesis of MASLD. Understanding this relationship may allow for the administration of therapeutics that target the gut microbiome and/or its metabolic function to alleviate MASLD development or progression. This review will discuss the interplay between the gut microbiome's structure and function in relation to the development of MASLD, assess the diagnostic yield of gut microbiome-based signatures as a noninvasive tool to identify MASLD severity, and examine current and emerging therapies targeting the gut microbiome-liver axis.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"457-473"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401201","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
Inflammation in Steatotic Liver Diseases: Pathogenesis and Therapeutic Targets. 脂肪肝中的炎症：发病机制与治疗靶点》。
IF 4.3 3区 医学
Seminars in liver disease Pub Date : 2024-08-01 Epub Date: 2024-06-05 DOI: 10.1055/a-2338-9261
Shengying Qian, Xiaolin Wang, Yingfen Chen, Qiuhong Zai, Yong He
{"title":"Inflammation in Steatotic Liver Diseases: Pathogenesis and Therapeutic Targets.","authors":"Shengying Qian, Xiaolin Wang, Yingfen Chen, Qiuhong Zai, Yong He","doi":"10.1055/a-2338-9261","DOIUrl":"10.1055/a-2338-9261","url":null,"abstract":"<p><p>Alcohol-related liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), two main types of steatotic liver disease (SLDs), are characterized by a wide spectrum of several different liver disorders, including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Multiple immune cell-mediated inflammatory responses not only orchestrate the killing and removal of infected/damaged cells but also exacerbate the development of SLDs when excessive or persistent inflammation occurs. In recent years, single-cell and spatial transcriptome analyses have revealed the heterogeneity of liver-infiltrated immune cells in ALD and MASLD, revealing a new immunopathological picture of SLDs. In this review, we will emphasize the roles of several key immune cells in the pathogenesis of ALD and MASLD and discuss inflammation-based approaches for effective SLD intervention. In conclusion, the study of immunological mechanisms, especially highly specific immune cell population functions, may provide novel therapeutic opportunities for this life-threatening disease.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"319-332"},"PeriodicalIF":4.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262893","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
Hepatic Extracellular Matrix and Its Role in the Regulation of Liver Phenotype. 细胞外基质与肝纤维化前的伤口愈合
IF 4.3 3区 医学
Seminars in liver disease Pub Date : 2024-08-01 Epub Date: 2024-08-27 DOI: 10.1055/a-2404-7973
Gavin E Arteel
{"title":"Hepatic Extracellular Matrix and Its Role in the Regulation of Liver Phenotype.","authors":"Gavin E Arteel","doi":"10.1055/a-2404-7973","DOIUrl":"10.1055/a-2404-7973","url":null,"abstract":"<p><p>The hepatic extracellular matrix (ECM) is most accurately depicted as a dynamic compartment that comprises a diverse range of players that work bidirectionally with hepatic cells to regulate overall homeostasis. Although the classic meaning of the ECM referred to only proteins directly involved in generating the ECM structure, such as collagens, proteoglycans, and glycoproteins, the definition of the ECM is now broader and includes all components associated with this compartment. The ECM is critical in mediating phenotype at the cellular, organ, and even organismal levels. The purpose of this review is to summarize the prevailing mechanisms by which ECM mediates hepatic phenotype and discuss the potential or established role of this compartment in the response to hepatic injury in the context of steatotic liver disease.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"343-355"},"PeriodicalIF":4.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081462","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
Necrotic Liver Lesion Resolution: Another Mode of Liver Regeneration. 坏死肝脏病变的解决：肝脏再生的另一种模式。
IF 4.3 3区 医学
Seminars in liver disease Pub Date : 2024-08-01 Epub Date: 2024-07-02 DOI: 10.1055/a-2358-9505
Cheng Chen, Dechun Feng, Yang Wang, Tiantian Yao, Bryan Mackowiak, Bin Gao
{"title":"Necrotic Liver Lesion Resolution: Another Mode of Liver Regeneration.","authors":"Cheng Chen, Dechun Feng, Yang Wang, Tiantian Yao, Bryan Mackowiak, Bin Gao","doi":"10.1055/a-2358-9505","DOIUrl":"10.1055/a-2358-9505","url":null,"abstract":"<p><p>The liver has the great ability to regenerate after partial resection or injury, and the mechanisms underlying liver regeneration have been extensively investigated. Interestingly, acute liver injuries triggered by various etiologies are associated with the formation of necrotic lesions, and such necrotic lesions are also rapidly resolved. However, how necrotic liver lesions are repaired has not been carefully investigated until recently. In this review, we briefly summarize the spatiotemporal process of necrotic liver lesion resolution in several liver injury models including immune-mediated liver injury and drug-induced liver injury. The roles of liver nonparenchymal cells and infiltrating immune cells in controlling necrotic liver lesion resolution are discussed, which may help identify potential therapies for acute liver injury and failure.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"333-342"},"PeriodicalIF":4.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493256","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
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