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Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency. α-1抗胰蛋白酶缺乏的儿童和成人肝病。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-08-01 Epub Date: 2023-07-04 DOI: 10.1055/a-2122-7674
Mathias Ruiz, Florence Lacaille, Christina Schrader, Monica Pons, Piotr Socha, Aleksander Krag, Ekkehard Sturm, Marion Bouchecareilh, Pavel Strnad
{"title":"Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency.","authors":"Mathias Ruiz, Florence Lacaille, Christina Schrader, Monica Pons, Piotr Socha, Aleksander Krag, Ekkehard Sturm, Marion Bouchecareilh, Pavel Strnad","doi":"10.1055/a-2122-7674","DOIUrl":"10.1055/a-2122-7674","url":null,"abstract":"<p><p>Alpha-1 antitrypsin deficiency (AATD) arises due to inherited variants in <i>SERPINA1</i>, the AAT gene that impairs the production or secretion of this hepatocellular protein and leads to a gain-of-function liver proteotoxicity. Homozygous Pi*Z pathogenic variant (Pi*ZZ genotype) is the leading cause of severe AATD. It manifests in 2 to 10% of carriers as neonatal cholestasis and 20 to 35% of adults as significant liver fibrosis. Both children and adults may develop an end-stage liver disease requiring liver transplantation. Heterozygous Pi*Z pathogenic variant (Pi*MZ genotype) constitutes an established disease modifier. Our review summarizes the natural history and management of subjects with both pediatric and adult AATD-associated liver disease. Current findings from a phase 2 clinical trial indicate that RNA silencing may constitute a viable therapeutic approach for adult AATD. In conclusion, AATD is an increasingly appreciated pediatric and adult liver disorder that is becoming an attractive target for modern pharmacologic strategies.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"258-266"},"PeriodicalIF":4.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9954734","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
Angiocrine Signaling in Sinusoidal Health and Disease. 窦性健康和疾病中的血管分泌信号传导。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-08-01 Epub Date: 2023-07-13 DOI: 10.1055/a-2128-5907
Shawna A Cooper, Enis Kostallari, Vijay H Shah
{"title":"Angiocrine Signaling in Sinusoidal Health and Disease.","authors":"Shawna A Cooper, Enis Kostallari, Vijay H Shah","doi":"10.1055/a-2128-5907","DOIUrl":"10.1055/a-2128-5907","url":null,"abstract":"<p><p>Liver sinusoidal endothelial cells (LSECs) are key players in maintaining hepatic homeostasis. They also play crucial roles during liver injury by communicating with liver cell types as well as immune cells and promoting portal hypertension, fibrosis, and inflammation. Cutting-edge technology, such as single cell and spatial transcriptomics, have revealed the existence of distinct LSEC subpopulations with a clear zonation in the liver. The signals released by LSECs are commonly called \"angiocrine signaling.\" In this review, we summarize the role of angiocrine signaling in health and disease, including zonation in healthy liver, regeneration, fibrosis, portal hypertension, nonalcoholic fatty liver disease, alcohol-associated liver disease, aging, drug-induced liver injury, and ischemia/reperfusion, as well as potential therapeutic advances. In conclusion, sinusoidal endotheliopathy is recognized in liver disease and promising preclinical studies are paving the path toward LSEC-specific pharmacotherapies.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"245-257"},"PeriodicalIF":4.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9977079","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
FXR Friend-ChIPs in the Enterohepatic System. 肠肝系统中的FXR Friend ChIP。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-08-01 Epub Date: 2023-07-13 DOI: 10.1055/a-2128-5538
Vik Meadows, Zhenning Yang, Veronia Basaly, Grace L Guo
{"title":"FXR Friend-ChIPs in the Enterohepatic System.","authors":"Vik Meadows, Zhenning Yang, Veronia Basaly, Grace L Guo","doi":"10.1055/a-2128-5538","DOIUrl":"10.1055/a-2128-5538","url":null,"abstract":"<p><p>Chronic liver diseases encompass a wide spectrum of hepatic maladies that often result in cholestasis or altered bile acid secretion and regulation. Incidence and cost of care for many chronic liver diseases are rising in the United States with few Food and Drug Administration-approved drugs available for patient treatment. Farnesoid X receptor (FXR) is the master regulator of bile acid homeostasis with an important role in lipid and glucose metabolism and inflammation. FXR has served as an attractive target for management of cholestasis and fibrosis; however, global FXR agonism results in adverse effects in liver disease patients, severely affecting quality of life. In this review, we highlight seminal studies and recent updates on the FXR proteome and identify gaps in knowledge that are essential for tissue-specific FXR modulation. In conclusion, one of the greatest unmet needs in the field is understanding the underlying mechanism of intestinal versus hepatic FXR function.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"267-278"},"PeriodicalIF":4.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9977080","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
Alcohol-Related Liver Disease: Is There a Safe Alcohol Consumption Limit for Liver Disease? 酒精相关肝病：肝病是否有安全的饮酒限制？
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-08-01 Epub Date: 2023-08-28 DOI: 10.1055/s-0043-1772836
Katrina Pekarska, Richard Parker
{"title":"Alcohol-Related Liver Disease: Is There a Safe Alcohol Consumption Limit for Liver Disease?","authors":"Katrina Pekarska, Richard Parker","doi":"10.1055/s-0043-1772836","DOIUrl":"10.1055/s-0043-1772836","url":null,"abstract":"<p><p>This review is to evaluate how much alcohol is safe in the context of alcohol-related liver disease (ALD). In patients without an established diagnosis of ALD consuming alcohol at quantities below 12 to 20 g daily with alcohol-free days is associated with a very low risk of developing disease. This risk is mediated by the presence of cofactors such as sex, medical comorbidity, obesity, and genetic factors. A threshold effect below which liver disease will not occur is not seen, instead a dose-response relationship where risk ranges from low to high. Once ALD is present, natural history studies confirm that continued alcohol consumption is clearly associated with an increased risk of ill health and premature death. In conclusion, low-level alcohol consumption in the absence of liver disease is associated with a very small risk of developing ALD, but once ALD is present patients should be supported to achieve complete abstinence from alcohol.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"305-310"},"PeriodicalIF":4.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10113224","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 Role of Endoplasmic Reticulum Stress Response in Liver Regeneration. 内质网应激反应在肝脏再生中的作用。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-08-01 Epub Date: 2023-07-14 DOI: 10.1055/a-2129-8977
Kshitij Deshmukh, Udayan Apte
{"title":"The Role of Endoplasmic Reticulum Stress Response in Liver Regeneration.","authors":"Kshitij Deshmukh, Udayan Apte","doi":"10.1055/a-2129-8977","DOIUrl":"10.1055/a-2129-8977","url":null,"abstract":"<p><p>Exposure to hepatotoxic chemicals is involved in liver disease-related morbidity and mortality worldwide. The liver responds to damage by triggering compensatory hepatic regeneration. Physical agent or chemical-induced liver damage disrupts hepatocyte proteostasis, including endoplasmic reticulum (ER) homeostasis. Post-liver injury ER experiences a homeostatic imbalance, followed by active ER stress response signaling. Activated ER stress response causes selective upregulation of stress response genes and downregulation of many hepatocyte genes. Acetaminophen overdose, carbon tetrachloride, acute and chronic alcohol exposure, and physical injury activate the ER stress response, but details about the cellular consequences of the ER stress response on liver regeneration remain unclear. The current data indicate that inhibiting the ER stress response after partial hepatectomy-induced liver damage promotes liver regeneration, whereas inhibiting the ER stress response after chemical-induced hepatotoxicity impairs liver regeneration. This review summarizes key findings and emphasizes the knowledge gaps in the role of ER stress in injury and regeneration.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"279-292"},"PeriodicalIF":4.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10942737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10027345","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
Endoscopic Advances in Hepatology. 肝脏内窥镜进展。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-05-01 Epub Date: 2023-05-16 DOI: 10.1055/s-0043-1769009
Emma Vanderschueren, Jonel Trebicka, Wim Laleman
{"title":"Endoscopic Advances in Hepatology.","authors":"Emma Vanderschueren, Jonel Trebicka, Wim Laleman","doi":"10.1055/s-0043-1769009","DOIUrl":"10.1055/s-0043-1769009","url":null,"abstract":"<p><p>Endoscopy is and remains an indispensable tool in diagnosing and managing liver disease and its complications. Due to the progress in advanced endoscopy, endoscopy has become an alternative route for many surgical, percutaneous, and angiographic interventions, not only as a backup tool when conventional interventions fail but increasingly as a first-line choice. The term endo-hepatology refers to the integration of advanced endoscopy in the practice of hepatology. Endoscopy is key in the diagnosis and management of esophageal and gastric varices, portal hypertensive gastropathy, and gastric antral vascular ectasia. Endoscopic ultrasound (EUS) can be used for the evaluation of the liver parenchyma, liver lesions, and surrounding tissues and vessels, including targeted biopsy and complemented with new software functions. Moreover, EUS can guide portal pressure gradient measurement, and assess and help manage complications of portal hypertension. It is crucial that each present-day hepatologist is aware of the (rapidly increasing) full spectrum of diagnostic and therapeutic tools that exist within this field. In this comprehensive review, we would like to discuss the current endo-hepatology spectrum, as well as future directions for endoscopy in hepatology.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 2","pages":"176-188"},"PeriodicalIF":4.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10244778","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
Mast Cell and Innate Immune Cell Communication in Cholestatic Liver Disease. 胆汁淤积性肝病中的肥大细胞和先天性免疫细胞通讯
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-05-01 Epub Date: 2023-06-02 DOI: 10.1055/a-2104-9034
Jessica K Bernard, Corinn Marakovits, Leah G Smith, Heather Francis
{"title":"Mast Cell and Innate Immune Cell Communication in Cholestatic Liver Disease.","authors":"Jessica K Bernard, Corinn Marakovits, Leah G Smith, Heather Francis","doi":"10.1055/a-2104-9034","DOIUrl":"10.1055/a-2104-9034","url":null,"abstract":"<p><p>Mast cells (MCs) contribute to the pathogenesis of cholestatic liver diseases (primary sclerosing cholangitis [PSC] and primary biliary cholangitis [PBC]). PSC and PBC are immune-mediated, chronic inflammatory diseases, characterized by bile duct inflammation and stricturing, advancing to hepatobiliary cirrhosis. MCs are tissue resident immune cells that may promote hepatic injury, inflammation, and fibrosis formation by either direct or indirect interactions with other innate immune cells (neutrophils, macrophages/Kupffer cells, dendritic cells, natural killer, and innate lymphoid cells). The activation of these innate immune cells, usually through the degranulation of MCs, promotes antigen uptake and presentation to adaptive immune cells, exacerbating liver injury. In conclusion, dysregulation of MC-innate immune cell communications during liver injury and inflammation can lead to chronic liver injury and cancer.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 2","pages":"226-233"},"PeriodicalIF":4.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9859087","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
How to Identify Advanced Nonalcoholic Fatty Liver Disease in the Primary Care Setting. 如何在基层医疗机构识别晚期非酒精性脂肪肝？
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-05-01 Epub Date: 2023-07-06 DOI: 10.1055/s-0043-1770984
Pegah Golabi, Dipam Shah, Zobair M Younossi
{"title":"How to Identify Advanced Nonalcoholic Fatty Liver Disease in the Primary Care Setting.","authors":"Pegah Golabi, Dipam Shah, Zobair M Younossi","doi":"10.1055/s-0043-1770984","DOIUrl":"10.1055/s-0043-1770984","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) affects 30 to 40% of the population globally and is increasingly considered the most common liver disease. Patients with type 2 diabetes, obesity, and cardiovascular diseases are at especially increased risk for NAFLD. Although most patients with NAFLD do not have progressive liver disease, some patients progress to cirrhosis, liver cancer, and liver mortality. Given the sheer number of patients with NAFLD, the burden of disease is enormous. Despite this large and increasing burden, identification of NAFLD patients at risk for progressive liver disease in the primary care and diabetology practice settings remains highly suboptimal. In this review, our aim is to summarize a stepwise approach to risk stratify patients with NAFLD which should help practitioners in their management of patients with NAFLD.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 2","pages":"142-148"},"PeriodicalIF":4.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9869032","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
Targeting Fibroblast Growth Factor Receptor Pathway: Precision Medicine for Biliary Cancer and Beyond. 靶向成纤维细胞生长因子受体途径:胆道癌及其他肿瘤的精准医学。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-05-01 DOI: 10.1055/a-2049-3149
Pedro Luiz Serrano Uson Junior, Mitesh J Borad
{"title":"Targeting Fibroblast Growth Factor Receptor Pathway: Precision Medicine for Biliary Cancer and Beyond.","authors":"Pedro Luiz Serrano Uson Junior,&nbsp;Mitesh J Borad","doi":"10.1055/a-2049-3149","DOIUrl":"https://doi.org/10.1055/a-2049-3149","url":null,"abstract":"<p><p>Fibroblast growth factor receptor 2 (FGFR2) inhibitors are now being included in the treatment guidelines of multiple countries for patients with advanced cholangiocarcinoma (CCA). Activation of the FGF-FGFR pathway is related to proliferation and tumor progression. Targeting the FGF-FGFR pathway is effective and can yield durable responses in patients with CCA harboring FGFR2 fusions or rearrangements. In this review article, we address molecules and clinical trials evaluating FGFR inhibitors in advanced CCA. We will further discuss identified mechanisms of resistance and the strategies to overcome it. The incorporation of next-generation sequencing in advanced CCA and circulating tumor DNA on disease progression will unveil mechanisms of resistance and improve the development of future clinical trials and more selective drugs and combinations.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 2","pages":"218-225"},"PeriodicalIF":4.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9858095","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
Critical Care Management of Acute-on-Chronic Liver Failure: Certainties and Unknowns. 急性慢性肝衰竭的重症监护管理：确定与未知。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-05-01 Epub Date: 2023-06-27 DOI: 10.1055/s-0043-1769907
Enric Reverter, David Toapanta, Octavi Bassegoda, Juliana Zapatero, Javier Fernandez
{"title":"Critical Care Management of Acute-on-Chronic Liver Failure: Certainties and Unknowns.","authors":"Enric Reverter, David Toapanta, Octavi Bassegoda, Juliana Zapatero, Javier Fernandez","doi":"10.1055/s-0043-1769907","DOIUrl":"10.1055/s-0043-1769907","url":null,"abstract":"<p><p>Intensive care unit (ICU) admission is frequently required in patients with decompensated cirrhosis for organ support. This entity, known as acute-on-chronic liver failure (ACLF), is associated with high short-term mortality. ICU management of ACLF is complex, as these patients are prone to develop new organ failures and infectious or bleeding complications. Poor nutritional status, lack of effective liver support systems, and shortage of liver donors are also factors that contribute to increase their mortality. ICU therapy parallels that applied in the general ICU population in some complications but has differential characteristics in others. This review describes the current knowledge on critical care management of patients with ACLF including organ support, prognostic assessment, early liver transplantation, and futility rules. Certainties and knowledge gaps in this area are also discussed.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 2","pages":"206-217"},"PeriodicalIF":4.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9869309","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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