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The Ploidy State as a Determinant of Hepatocyte Proliferation. 倍性状态是肝细胞增殖的决定因素。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-11-01 Epub Date: 2023-11-15 DOI: 10.1055/a-2211-2144
Sierra R Wilson, Andrew W Duncan
{"title":"The Ploidy State as a Determinant of Hepatocyte Proliferation.","authors":"Sierra R Wilson, Andrew W Duncan","doi":"10.1055/a-2211-2144","DOIUrl":"10.1055/a-2211-2144","url":null,"abstract":"<p><p>The liver's unique chromosomal variations, including polyploidy and aneuploidy, influence hepatocyte identity and function. Among the most well-studied mammalian polyploid cells, hepatocytes exhibit a dynamic interplay between diploid and polyploid states. The ploidy state is dynamic as hepatocytes move through the \"ploidy conveyor,\" undergoing ploidy reversal and re-polyploidization during proliferation. Both diploid and polyploid hepatocytes actively contribute to proliferation, with diploids demonstrating an enhanced proliferative capacity. This enhanced potential positions diploid hepatocytes as primary drivers of liver proliferation in multiple contexts, including homeostasis, regeneration and repopulation, compensatory proliferation following injury, and oncogenic proliferation. This review discusses the influence of ploidy variations on cellular activity. It presents a model for ploidy-associated hepatocyte proliferation, offering a deeper understanding of liver health and disease with the potential to uncover novel treatment approaches.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"460-471"},"PeriodicalIF":4.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10862383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134649723","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
Hedgehog Signaling: Implications in Liver Pathophysiology. Hedgehog信号传导：肝脏病理生理学的意义。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-11-01 Epub Date: 2023-10-06 DOI: 10.1055/a-2187-3382
Rajesh Kumar Dutta, JiHye Jun, Kuo Du, Anna Mae Diehl
{"title":"Hedgehog Signaling: Implications in Liver Pathophysiology.","authors":"Rajesh Kumar Dutta, JiHye Jun, Kuo Du, Anna Mae Diehl","doi":"10.1055/a-2187-3382","DOIUrl":"10.1055/a-2187-3382","url":null,"abstract":"<p><p>The purpose of this review is to summarize current knowledge about the role of the Hedgehog signaling pathway in liver homeostasis and disease. Hedgehog is a morphogenic signaling pathway that is active in development. In most healthy tissues, pathway activity is restricted to stem and/or stromal cell compartments, where it enables stem cell self-renewal and tissue homeostasis. Aberrant over-activation of Hedgehog signaling occurs in many cancers, including hepatocellular and cholangio-carcinoma. The pathway is also activated transiently in stromal cells of injured tissues and orchestrates normal wound healing responses, including inflammation, vascular remodeling, and fibrogenesis. In liver, sustained Hedgehog signaling in stromal cells plays a major role in the pathogenesis of cirrhosis. Hedgehog signaling was thought to be silenced in healthy hepatocytes. However, recent studies show that targeted disruption of the pathway in hepatocytes dysregulates lipid, cholesterol, and bile acid metabolism, and promotes hepatic lipotoxicity, insulin resistance, and senescence. Hepatocytes that lack Hedgehog activity also produce a secretome that activates Hedgehog signaling in cholangiocytes and neighboring stromal cells to induce inflammatory and fibrogenic wound healing responses that drive progressive fibrosis. In conclusion, Hedgehog signaling must be precisely controlled in adult liver cells to maintain liver health.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"418-428"},"PeriodicalIF":4.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41170492","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
The Hepatic Porphyrias: Revealing the Complexities of a Rare Disease. 肝卟啉症:揭示一种罕见疾病的复杂性。
IF 4.3 3区 医学
Seminars in liver disease Pub Date : 2023-11-01 Epub Date: 2023-11-16 DOI: 10.1055/s-0043-1776760
Oluwashanu Balogun, Kari Nejak-Bowen
{"title":"The Hepatic Porphyrias: Revealing the Complexities of a Rare Disease.","authors":"Oluwashanu Balogun, Kari Nejak-Bowen","doi":"10.1055/s-0043-1776760","DOIUrl":"10.1055/s-0043-1776760","url":null,"abstract":"<p><p>The porphyrias are a group of metabolic disorders that are caused by defects in heme biosynthesis pathway enzymes. The result is accumulation of heme precursors, which can cause neurovisceral and/or cutaneous photosensitivity. Liver is commonly either a source or target of excess porphyrins, and porphyria-associated hepatic dysfunction ranges from minor abnormalities to liver failure. In this review, the first of a three-part series, we describe the defects commonly found in each of the eight enzymes involved in heme biosynthesis. We also discuss the pathophysiology of the hepatic porphyrias in detail, covering epidemiology, histopathology, diagnosis, and complications. Cellular consequences of porphyrin accumulation are discussed, with an emphasis on oxidative stress, protein aggregation, hepatocellular cancer, and endothelial dysfunction. Finally, we review current therapies to treat and manage symptoms of hepatic porphyria.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"446-459"},"PeriodicalIF":4.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136399097","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
Biliary Tract Cancer: Molecular Biology of Precursor Lesions. 癌症胆道：前驱病变的分子生物学。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-11-01 Epub Date: 2023-11-09 DOI: 10.1055/a-2207-9834
Fátima Manzano-Núñez, Lara Prates Tiago Aguilar, Christine Sempoux, Frédéric P Lemaigre
{"title":"Biliary Tract Cancer: Molecular Biology of Precursor Lesions.","authors":"Fátima Manzano-Núñez, Lara Prates Tiago Aguilar, Christine Sempoux, Frédéric P Lemaigre","doi":"10.1055/a-2207-9834","DOIUrl":"10.1055/a-2207-9834","url":null,"abstract":"<p><p>Biliary tract cancer is a devastating malignancy of the bile ducts and gallbladder with a dismal prognosis. The study of precancerous lesions has received considerable attention and led to a histopathological classification which, in some respects, remains an evolving field. Consequently, increasing efforts have been devoted to characterizing the molecular pathogenesis of the precursor lesions, with the aim of better understanding the mechanisms of tumor progression, and with the ultimate goal of meeting the challenges of early diagnosis and treatment. This review delves into the molecular mechanisms that initiate and promote the development of precursor lesions of intra- and extrahepatic cholangiocarcinoma and of gallbladder carcinoma. It addresses the genomic, epigenomic, and transcriptomic landscape of these precursors and provides an overview of animal and organoid models used to study them. In conclusion, this review summarizes the known molecular features of precancerous lesions in biliary tract cancer and highlights our fragmentary knowledge of the molecular pathogenesis of tumor initiation.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"472-484"},"PeriodicalIF":4.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72015321","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
Mechanisms of Lipid Droplet Accumulation in Steatotic Liver Diseases. 脂滴在脂肪性肝病中积聚的机制。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-11-01 Epub Date: 2023-10-05 DOI: 10.1055/a-2186-3557
Joseph L Dempsey, George N Ioannou, Rotonya M Carr
{"title":"Mechanisms of Lipid Droplet Accumulation in Steatotic Liver Diseases.","authors":"Joseph L Dempsey, George N Ioannou, Rotonya M Carr","doi":"10.1055/a-2186-3557","DOIUrl":"10.1055/a-2186-3557","url":null,"abstract":"<p><p>The steatotic diseases of metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and chronic hepatitis C (HCV) account for the majority of liver disease prevalence, morbidity, and mortality worldwide. While these diseases have distinct pathogenic and clinical features, dysregulated lipid droplet (LD) organelle biology represents a convergence of pathogenesis in all three. With increasing understanding of hepatocyte LD biology, we now understand the roles of LD proteins involved in these diseases but also how genetics modulate LD biology to either exacerbate or protect against the phenotypes associated with steatotic liver diseases. Here, we review the history of the LD organelle and its biogenesis and catabolism. We also review how this organelle is critical not only for the steatotic phenotype of liver diseases but also for their advanced phenotypes. Finally, we summarize the latest attempts and challenges of leveraging LD biology for therapeutic gain in steatotic diseases. In conclusion, the study of dysregulated LD biology may lead to novel therapeutics for the prevention of disease progression in the highly prevalent steatotic liver diseases of MASLD, ALD, and HCV.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"367-382"},"PeriodicalIF":4.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41150633","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
Unraveling the Complexities of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma. 揭示肝细胞癌中免疫检查点抑制剂的复杂性。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-11-01 Epub Date: 2023-11-06 DOI: 10.1055/s-0043-1776127
Xinpu Han, Qianhui Sun, Manman Xu, Guanghui Zhu, Ruike Gao, Baoyi Ni, Jie Li
{"title":"Unraveling the Complexities of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma.","authors":"Xinpu Han, Qianhui Sun, Manman Xu, Guanghui Zhu, Ruike Gao, Baoyi Ni, Jie Li","doi":"10.1055/s-0043-1776127","DOIUrl":"10.1055/s-0043-1776127","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have emerged as effective therapeutics for multiple cancers. Nevertheless, as immunotherapeutic approaches are being extensively utilized, substantial hurdles have arisen for clinicians. These include countering ICIs resistance and ensuring precise efficacy assessments of these drugs, especially in the context of hepatocellular carcinoma (HCC). This review attempts to offer a holistic overview of the latest insights into the ICIs resistance mechanisms in HCC, the molecular underpinnings, and immune response. The intent is to inspire the development of efficacious combination strategies. This review also examines the unconventional response patterns, namely pseudoprogression (PsP) and hyperprogression (HPD). The prompt and rigorous evaluation of these treatment efficacies has emerged as a crucial imperative. Multiple clinical, radiological, and biomarker tests have been advanced to meticulously assess tumor response. Despite progress, precise mechanisms of action and predictive biomarkers remain elusive. This necessitates further investigation through prospective cohort studies in the impending future.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"383-401"},"PeriodicalIF":4.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71485746","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
Gut Microbiome-Centered Therapies for Alcohol-Associated Liver Disease. 以肠道微生物组为中心的酒精相关性肝病治疗。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-08-01 DOI: 10.1055/a-2145-7331
Tannaz Ranjbarian, Bernd Schnabl
{"title":"Gut Microbiome-Centered Therapies for Alcohol-Associated Liver Disease.","authors":"Tannaz Ranjbarian, Bernd Schnabl","doi":"10.1055/a-2145-7331","DOIUrl":"10.1055/a-2145-7331","url":null,"abstract":"<p><p>Globally, liver disease caused by alcohol is becoming more prevalent each year. Misuse of alcohol causes a spectrum of liver diseases, such as liver steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The cornerstone of treatment is abstinence from alcohol. In spite of this, available treatment for alcohol-associated liver disease (ALD) shows limited effectiveness currently. There are numerous ways in which alcohol disrupts the gut-liver axis, including dysbiosis of the gut microbiome, disruption of mucus and epithelial cell barriers, impaired production of antimicrobial molecules, and dysfunction of the immune system, causing translocation of viable microbes and microbial products to the liver and systemic circulation. Microbial exposure results in not only inflammation and progression of liver disease but also infections in late-stage ALD. This led scientists to focus their therapeutic strategies and targets for ALD on the gut microbiome. Throughout this review, we address the role of gut microbiome-centered therapeutic approaches for ALD focusing predominantly on randomized controlled trials. We will summarize the latest clinical trials using probiotics, antibiotics, and fecal microbial transplants in modulating the gut-liver axis and for improvement of ALD.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"311-322"},"PeriodicalIF":4.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10172577","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
Erratum to: Hepatitis Delta Infection: A Clinical Review. 勘误表：德尔塔型肝炎感染：临床综述。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-08-01 Epub Date: 2023-10-10 DOI: 10.1055/s-0043-1776037
Brian Pearlman
{"title":"Erratum to: Hepatitis Delta Infection: A Clinical Review.","authors":"Brian Pearlman","doi":"10.1055/s-0043-1776037","DOIUrl":"10.1055/s-0043-1776037","url":null,"abstract":"","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"e1"},"PeriodicalIF":4.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41212162","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
Erratum to: Genetic Contributions to Biliary Atresia: A Developmental Cholangiopathy. 勘误表：胆道闭锁的遗传贡献：一种发育性胆管病。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-08-01 Epub Date: 2023-10-12 DOI: 10.1055/s-0043-1776036
Dominick J Hellen, Saul J Karpen
{"title":"Erratum to: Genetic Contributions to Biliary Atresia: A Developmental Cholangiopathy.","authors":"Dominick J Hellen,&nbsp;Saul J Karpen","doi":"10.1055/s-0043-1776036","DOIUrl":"10.1055/s-0043-1776036","url":null,"abstract":"","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"e2"},"PeriodicalIF":4.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41212161","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
COVID-19 and Liver Disease: An Evolving Landscape. 新冠肺炎与肝脏疾病：一个演变的景观。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-08-01 Epub Date: 2023-08-21 DOI: 10.1055/a-2157-3318
Kai Zhu, Olivia Tsai, Daljeet Chahal, Trana Hussaini, Eric M Yoshida
{"title":"COVID-19 and Liver Disease: An Evolving Landscape.","authors":"Kai Zhu, Olivia Tsai, Daljeet Chahal, Trana Hussaini, Eric M Yoshida","doi":"10.1055/a-2157-3318","DOIUrl":"10.1055/a-2157-3318","url":null,"abstract":"<p><p>The COVID-19 pandemic has resulted in significant worldwide morbidity and mortality. In this review, we examine the intricate relationships between COVID-19 and liver diseases. While respiratory manifestations of COVID-19 are well known, its impact and consequences in patients with liver diseases remain an area of ongoing investigation. COVID-19 can induce liver injury through various mechanisms and is associated with higher mortality in individuals with preexisting chronic liver disease. Mortality increases with the severity of chronic liver disease and the level of care required. The outcomes in patients with autoimmune hepatitis remain unclear, whereas liver transplant recipients are more likely to experience symptomatic COVID-19 but have comparable outcomes to the general population. Despite suboptimal immunological response, COVID-19 vaccinations are safe and effective in liver disease, although cases of autoimmune hepatitis-like syndrome have been reported. In conclusion, COVID-19 has significant implications in liver diseases; early recognition and treatments are important for improving patient outcomes.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"351-366"},"PeriodicalIF":4.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10041548","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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