Seminars in liver disease最新文献

Integrated Patient Digital and Biomimetic Twins for Precision Medicine: A Perspective. 精准医学中整合病人数字和仿生双胞胎：一个视角。

IF 3.7 3区医学

Seminars in liver disease Pub Date : 2025-07-23 DOI: 10.1055/a-2649-1560

Mark T Miedel, Mark E Schurdak, Andrew M Stern, Alejandro Soto-Gutierrez, Eric von Strobl, Jaideep Behari, D Lansing Taylor

{"title":"Integrated Patient Digital and Biomimetic Twins for Precision Medicine: A Perspective.","authors":"Mark T Miedel, Mark E Schurdak, Andrew M Stern, Alejandro Soto-Gutierrez, Eric von Strobl, Jaideep Behari, D Lansing Taylor","doi":"10.1055/a-2649-1560","DOIUrl":"10.1055/a-2649-1560","url":null,"abstract":"A new paradigm for drug development and patient therapeutic strategies is required, especially for complex, heterogeneous diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). Heterogeneity in MASLD patients is driven by genetics, various comorbidities, gut microbiota composition, lifestyle, environment, and demographics that produce multiple patient disease presentations and outcomes. Existing drug development methods have had limited success for complex, heterogeneous diseases like MASLD where only a fraction of patients respond to specific treatments, prediction of a therapeutic response is not presently possible, and the cost of the new classes of drugs is high. However, it is now possible to generate patient digital twins (PDTs) that are computational models of patients using clinomics and other \"omics\" data collected from patients to make various predictions, including responses to therapeutics. PDTs are then integrated with patient biomimetic twins (PBTs) that are patient-derived organoids or induced pluripotent stem cells that are then differentiated into the optimal number of organ-specific cells to produce organ experimental models. The PBTs mimic key aspects of the patient's pathophysiology, enabling predictions to be tested. In conclusion, integration of PTDs and PBTs has the potential to create a powerful precision medicine platform, yet there are challenges.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565127","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

Aging and Aging-Related Senescence in Liver. 衰老及与衰老相关的肝脏衰老。

IF 4.3 3区医学

Seminars in liver disease Pub Date : 2025-07-04 DOI: 10.1055/a-2637-2549

Souradipta Ganguly, Sadatsugu Sakane, Kanani Hokutan, Vivian Zhang, Charlene Miciano, Allen Wang, David A Brenner, Tatiana Kisseleva

{"title":"Aging and Aging-Related Senescence in Liver.","authors":"Souradipta Ganguly, Sadatsugu Sakane, Kanani Hokutan, Vivian Zhang, Charlene Miciano, Allen Wang, David A Brenner, Tatiana Kisseleva","doi":"10.1055/a-2637-2549","DOIUrl":"https://doi.org/10.1055/a-2637-2549","url":null,"abstract":"Aging is characterized by the progressive deterioration of cell and tissue functions. The liver, which regulates metabolic homeostasis, detoxification, and immune responses, undergoes structural and functional changes with age. These include increasing genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing and intracellular communication, mitochondrial dysfunction, cell senescence, stem cell exhaustion, chronic inflammation, disabled macroautophagy, and dysbiosis. These alterations contribute to hepatocyte dysfunction, impaired regenerative responses, and fibrosis risk, which all exacerbate existing liver diseases. Senescence involves irreversible cell cycle arrest resulting in an inflammatory, senescence-associated secretory cell phenotype. Senescent hepatocytes, liver sinusoidal endothelial cells, hepatic stellate cells, and Kupffer cells accumulate in the aged liver, creating an inflammatory and fibrotic microenvironment that promotes tumorigenesis. As the burden of aging-related liver disease increases, therapeutic strategies targeting hepatic senescence have gained attention. We review these, along with the mechanisms and pathogenic effects of liver aging.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565126","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

MetALD: Genetic Factors and Clinical Outcomes. MetALD：遗传因素与临床结果。

IF 4.3 3区医学

Seminars in liver disease Pub Date : 2025-06-27 DOI: 10.1055/a-2630-0952

Mads Israelsen, Eric Trépo, Aleksander Krag, Stefan Stender

引用次数: 0

Portosinusoidal Vascular Disorder: When to Suspect and How to Manage? 门窦血管疾病：何时怀疑及如何治疗？

IF 4.3 3区医学

Seminars in liver disease Pub Date : 2025-06-27 DOI: 10.1055/a-2630-0848

Sarah Shalaby, Wagner Enrique Ramírez-Quesada, Asunción Ojeda, Valeria Perez-Campuzano, Anna Baiges, Fanny Turon, Carla Fuster, Alba Díaz, Virginia Hernández-Gea, Juan Carlos García-Pagán

{"title":"Portosinusoidal Vascular Disorder: When to Suspect and How to Manage?","authors":"Sarah Shalaby, Wagner Enrique Ramírez-Quesada, Asunción Ojeda, Valeria Perez-Campuzano, Anna Baiges, Fanny Turon, Carla Fuster, Alba Díaz, Virginia Hernández-Gea, Juan Carlos García-Pagán","doi":"10.1055/a-2630-0848","DOIUrl":"https://doi.org/10.1055/a-2630-0848","url":null,"abstract":"Portosinusoidal vascular disorders (PSVD) represent a group of rare conditions characterized by abnormalities in the liver's vascular architecture, often manifesting with clinical features of portal hypertension (PH), in the absence of cirrhosis. The pathophysiology of PSVD remains unclear, but it is frequently linked to underlying immunological disorders, medications, hematological disorders, and thrombophilia. Laboratory tests typically show preserved liver function with or without slight alteration on the transaminase profile. A key diagnostic feature is the presence of clear signs of PH alongside normal or only slightly elevated liver stiffness and hepatic venous pressure gradient. Liver biopsy remains essential for confirming the diagnosis and excluding other causes of PH and cirrhosis. However, histological examination may reveal subtle or mild changes, making expert pathological analysis and high-quality specimens crucial for an accurate diagnosis. In some cases, characteristic histological findings may be identified in patients without overt PH, which could represent an early stage of the disease. The long-term prognosis for patients with PSVD is mainly influenced by severity of the underlying condition and development of PH. However, treatments that modify the disease's natural history are still lacking, and management primarily focuses on controlling complications related to PH. Further research into the pathogenesis and potential therapeutic strategies for PSVD is needed to improve patient outcomes.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512487","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

Extracellular Vesicles and Micro-RNAs in Liver Disease. 肝脏疾病中的细胞外囊泡和微rna。

IF 4.3 3区医学

Seminars in liver disease Pub Date : 2025-06-01 Epub Date: 2024-12-03 DOI: 10.1055/a-2494-2233

Alexander M Washington, Enis Kostallari

引用次数: 0

Environmental Pollutants, Occupational Exposures, and Liver Disease. 环境污染物、职业暴露与肝脏疾病。

IF 4.3 3区医学

Seminars in liver disease Pub Date : 2025-06-01 Epub Date: 2025-03-21 DOI: 10.1055/a-2540-2861

Juliane I Beier, Jianzhu Luo, Charis-Marie Vanderpuye, Paxton Brizendine, Pooja Muddasani, Oluwanifemiesther Bolatimi, Shannon A Heinig, Frederick A Ekuban, Hamda Siddiqui, Abigail Ekuban, Tyler C Gripshover, Banrida Wahlang, Walter H Watson, Matthew C Cave

{"title":"Environmental Pollutants, Occupational Exposures, and Liver Disease.","authors":"Juliane I Beier, Jianzhu Luo, Charis-Marie Vanderpuye, Paxton Brizendine, Pooja Muddasani, Oluwanifemiesther Bolatimi, Shannon A Heinig, Frederick A Ekuban, Hamda Siddiqui, Abigail Ekuban, Tyler C Gripshover, Banrida Wahlang, Walter H Watson, Matthew C Cave","doi":"10.1055/a-2540-2861","DOIUrl":"10.1055/a-2540-2861","url":null,"abstract":"Environmental pollutants significantly impact liver disease development, progression, and outcomes. This review examines the complex relationship between environmental exposures and liver pathology, from malignant conditions like hepatocellular carcinoma to steatotic and cholestatic liver diseases. Key environmental factors include air pollutants, volatile organic compounds, persistent organic pollutants, heavy metals, and per- and polyfluoroalkyl substances. These compounds can act through multiple mechanisms, including endocrine disruption, metabolic perturbation, oxidative stress, and direct hepatotoxicity. The impact of these exposures is often modified by factors such as sex, diet, and genetic predisposition. Recent research has revealed that even low-level exposures to certain chemicals can significantly affect liver health, particularly when combined with other risk factors. The emergence of exposomics as a research tool promises to enhance our understanding of how environmental factors influence liver disease. Importantly, exposure effects can vary by demographic and socioeconomic factors, highlighting environmental justice concerns. Implementation of this knowledge in clinical practice requires new diagnostic approaches, healthcare system adaptations, and increased awareness among medical professionals. In conclusion, this review provides a comprehensive examination of current evidence linking environmental exposures to liver disease and discusses implications for clinical practice and public health policy.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"148-166"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674659","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): Metabolic Liver Disease: A New Era in Hepatology. 前言（引言）：代谢性肝病：肝病学的新时代。

IF 4.3 3区医学

Seminars in liver disease Pub Date : 2025-06-01 Epub Date: 2025-02-19 DOI: 10.1055/a-2541-3502

Ashwani K Singal

引用次数: 0

Mitochondria and Alcohol-Associated Liver Disease: Pathogenic Role and Target for Therapy. 线粒体和 ALD：致病作用和治疗目标。

IF 4.3 3区医学

Seminars in liver disease Pub Date : 2025-06-01 Epub Date: 2024-09-24 DOI: 10.1055/a-2421-5658

Sandra Torres, Josiah Hardesty, Monica Barrios, Carmen Garcia-Ruiz, Jose C Fernandez-Checa, Ashwani K Singal

{"title":"Mitochondria and Alcohol-Associated Liver Disease: Pathogenic Role and Target for Therapy.","authors":"Sandra Torres, Josiah Hardesty, Monica Barrios, Carmen Garcia-Ruiz, Jose C Fernandez-Checa, Ashwani K Singal","doi":"10.1055/a-2421-5658","DOIUrl":"10.1055/a-2421-5658","url":null,"abstract":"Alcohol-associated liver disease (ALD) is one of the leading causes of chronic liver disease and a major cause of liver-related death. ALD is a multifactorial disease triggered by the oxidative metabolism of alcohol which leads to the activation of multiple factors that promote the progression from steatosis to more advanced stages like alcohol-associated steatohepatitis (AH) that culminate in alcohol-associated cirrhosis and hepatocellular carcinoma. Poor understanding of the complex heterogeneous pathology of ALD has limited drug development for this disease. Alterations in mitochondrial performance are considered a crucial event in paving the progression of ALD due to the crucial role of mitochondria in energy production, intermediate metabolism, calcium homeostasis, and cell fate decisions. Therefore, understanding the role of mitochondria in eliciting steatosis and progression toward AH may open the door to new opportunities for treatment. In this review, we will cover the physiological function of mitochondria, its contribution to ALD in experimental models and human disease, and explore whether targeting mitochondria may represent a game changer in the treatment of ALD.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"180-194"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353362","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

Current Concepts in Fluid Resuscitation and Vasopressor Use in Cirrhosis. 肝硬化患者液体复苏和血管加压药物应用的现状。

IF 4.3 3区医学

Seminars in liver disease Pub Date : 2025-06-01 Epub Date: 2025-01-14 DOI: 10.1055/a-2515-2783

Madhumita Premkumar, Kamal Kajal, Pankaj Gupta, K Rajender Reddy

{"title":"Current Concepts in Fluid Resuscitation and Vasopressor Use in Cirrhosis.","authors":"Madhumita Premkumar, Kamal Kajal, Pankaj Gupta, K Rajender Reddy","doi":"10.1055/a-2515-2783","DOIUrl":"10.1055/a-2515-2783","url":null,"abstract":"Critically ill patients with cirrhosis and liver failure do not uncommonly have hypotension due to multifactorial reasons, which include a hyperdynamic state with increased cardiac index (CI), low systemic vascular resistance (SVR) due to portal hypertension, following the use of beta-blocker or diuretic therapy, and severe sepsis. These changes are mediated by microvascular alterations in the liver, systemic inflammation, activation of renin-angiotensin-aldosterone system, and vasodilatation due to endothelial dysfunction. Haemodynamic assessment includes measuring inferior vena cava indices, cardiac output (CO), and SVR using point-of-care ultrasound (POCUS), arterial waveform analysis, pulmonary artery pressures, and lactate clearance to guide fluid resuscitation. Fluid responsiveness reflects the ability of fluid bolus to increase the CO and is assessed effectively by POCUS, passive leg raises manoeuvre, and dynamic tests such as pulse pressure and stroke volume variation in spontaneously breathing and mechanically ventilated patients. Albumin has pleiotropic benefits through anti-inflammatory properties besides its standard action on oncotic pressure and volume expansion in patients with cirrhosis but has the potential for precipitating pulmonary oedema. In conclusion, fluid therapy in critically ill patients with liver disease is a complex and dynamic process that requires individualized management protocols to optimize patient outcomes.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"252-268"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984055","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

Wilson Disease: Novel Diagnostic and Therapeutic Approaches. 威尔逊病：新的诊断和治疗方法。

IF 4.3 3区医学

Seminars in liver disease Pub Date : 2025-06-01 Epub Date: 2024-11-04 DOI: 10.1055/a-2460-8999

Zoe Mariño, Michael L Schilsky

引用次数: 0