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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
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
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
Research Progress on the Role and Mechanism of IL-37 in Liver Diseases. IL-37在肝病中的作用及机制研究进展。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-08-01 Epub Date: 2023-08-15 DOI: 10.1055/a-2153-8836
Baoyi Jiang, Yulin Zhou, Yanting Liu, Siqi He, Baojian Liao, Tieli Peng, Leyi Yao, Ling Qi
{"title":"Research Progress on the Role and Mechanism of IL-37 in Liver Diseases.","authors":"Baoyi Jiang, Yulin Zhou, Yanting Liu, Siqi He, Baojian Liao, Tieli Peng, Leyi Yao, Ling Qi","doi":"10.1055/a-2153-8836","DOIUrl":"10.1055/a-2153-8836","url":null,"abstract":"<p><p>Cytokines are important components of the immune system that can predict or influence the development of liver diseases. IL-37, a new member of the IL-1 cytokine family, exerts potent anti-inflammatory and immunosuppressive effects inside and outside cells. IL-37 expression differs before and after liver lesions, suggesting that it is associated with liver disease; however, its mechanism of action remains unclear. This article mainly reviews the biological characteristics of IL-37, which inhibits hepatitis, liver injury, and liver fibrosis by inhibiting inflammation, and inhibits the development of hepatocellular carcinoma (HCC) by regulating the immune microenvironment. Based on additional evidence, combining IL-37 with liver disease markers for diagnosis and treatment can achieve more significant effects, suggesting that IL-37 can be developed into a powerful tool for the clinical adjuvant treatment of liver diseases, especially HCC.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"336-350"},"PeriodicalIF":4.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10264190","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
Genetic Contributions to Biliary Atresia: A Developmental Cholangiopathy. 胆道闭锁的遗传因素：一种发育性胆管疾病。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-08-01 Epub Date: 2023-08-15 DOI: 10.1055/a-2153-8927
Dominick J Hellen, Saul J Karpen
{"title":"Genetic Contributions to Biliary Atresia: A Developmental Cholangiopathy.","authors":"Dominick J Hellen, Saul J Karpen","doi":"10.1055/a-2153-8927","DOIUrl":"10.1055/a-2153-8927","url":null,"abstract":"<p><p>Biliary atresia (BA) is the most prevalent serious liver disease of infancy and childhood, and the principal indication for liver transplantation in pediatrics. BA is best considered as an idiopathic panbiliary cholangiopathy characterized by obstruction of bile flow and consequent cholestasis presenting during fetal and perinatal periods. While several etiologies have been proposed, each has significant drawbacks that have limited understanding of disease progression and the development of effective treatments. Recently, modern genetic analyses have uncovered gene variants contributing to BA, thereby shifting the paradigm for explaining the BA phenotype from an acquired etiology (e.g., virus, toxin) to one that results from genetically altered cholangiocyte development and function. Herein we review recently reported genetic contributions to BA, highlighting the enhanced representation of variants in biological pathways involving ciliary function, cytoskeletal structure, and inflammation. Finally, we blend these findings as a new framework for understanding the resultant BA phenotype as a developmental cholangiopathy.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"323-335"},"PeriodicalIF":4.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10381081","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
Hepatitis Delta Infection: A Clinical Review. 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: 2023-07-20 DOI: 10.1055/a-2133-8614
Brian Pearlman
{"title":"Hepatitis Delta Infection: A Clinical Review.","authors":"Brian Pearlman","doi":"10.1055/a-2133-8614","DOIUrl":"10.1055/a-2133-8614","url":null,"abstract":"<p><p>First discovered over 40 years ago, the hepatitis delta virus (HDV) is a unique RNA virus, requiring hepatitis B virus (HBV) antigens for its assembly, replication, and transmission. HBV and HDV can be acquired at the same time (coinfection) or HDV infection can occur in persons with chronic HBV (superinfection). Screening guidelines for HDV are inconsistent. While some guidelines recommend universal screening for all people with HBV, others recommend risk-based screening. Estimates of the global HDV prevalence range from 4.5 to 14.6% among persons with HBV; thus, there may be up to 72 million individuals with HDV worldwide. HDV is the most severe form of viral hepatitis. Compared to HBV monoinfection, HDV coinfection increases the risk of cirrhosis, hepatocellular carcinoma, hepatic decompensation, mortality, and necessity for liver transplant. Despite the severity of HDV, there are few treatment options. Pegylated interferon (off-label use) has long been the only available treatment, although bulevirtide is conditionally approved in some European countries. There are many potential treatments in development, but as yet, there are few effective and safe therapies for HDV infection. In conclusion, given the severity of HDV disease and the paucity of treatments, there is a great unmet need for HDV therapies.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"293-304"},"PeriodicalIF":4.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119435","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
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