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Hepatic Innervations and Nonalcoholic Fatty Liver Disease. 肝脏支配与非酒精性脂肪肝
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-05-01 Epub Date: 2023-05-08 DOI: 10.1055/s-0043-57237
Monika Adori, Sadam Bhat, Roberto Gramignoli, Ismael Valladolid-Acebes, Tore Bengtsson, Mathias Uhlèn, Csaba Adori
{"title":"Hepatic Innervations and Nonalcoholic Fatty Liver Disease.","authors":"Monika Adori, Sadam Bhat, Roberto Gramignoli, Ismael Valladolid-Acebes, Tore Bengtsson, Mathias Uhlèn, Csaba Adori","doi":"10.1055/s-0043-57237","DOIUrl":"10.1055/s-0043-57237","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. Increased sympathetic (noradrenergic) nerve tone has a complex role in the etiopathomechanism of NAFLD, affecting the development/progression of steatosis, inflammation, fibrosis, and liver hemodynamical alterations. Also, lipid sensing by vagal afferent fibers is an important player in the development of hepatic steatosis. Moreover, disorganization and progressive degeneration of liver sympathetic nerves were recently described in human and experimental NAFLD. These structural alterations likely come along with impaired liver sympathetic nerve functionality and lack of adequate hepatic noradrenergic signaling. Here, we first overview the anatomy and physiology of liver nerves. Then, we discuss the nerve impairments in NAFLD and their pathophysiological consequences in hepatic metabolism, inflammation, fibrosis, and hemodynamics. We conclude that further studies considering the spatial-temporal dynamics of structural and functional changes in the hepatic nervous system may lead to more targeted pharmacotherapeutic advances in NAFLD.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 2","pages":"149-162"},"PeriodicalIF":4.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/17/a6/10-1055-s-0043-57237.PMC10348844.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9858598","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
To TIPS or Not to TIPS in High Risk of Variceal Rebleeding and Acute-on-Chronic Liver Failure. 静脉曲张再出血和急性慢性肝功能衰竭高风险人群的 TIPS 选择与否。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-05-01 Epub Date: 2023-06-07 DOI: 10.1055/a-2107-0576
Wenyi Gu, Markus Kimmann, Wim Laleman, Michael Praktiknjo, Jonel Trebicka
{"title":"To TIPS or Not to TIPS in High Risk of Variceal Rebleeding and Acute-on-Chronic Liver Failure.","authors":"Wenyi Gu, Markus Kimmann, Wim Laleman, Michael Praktiknjo, Jonel Trebicka","doi":"10.1055/a-2107-0576","DOIUrl":"10.1055/a-2107-0576","url":null,"abstract":"<p><p>Variceal bleeding is a consequence of severe portal hypertension in patients with liver cirrhosis. Although the rate of bleeding has decreased over time, variceal bleeding in the presence of acute-on-chronic liver failure (ACLF) carries a high risk of treatment failure and short-term mortality. Treatment and/or removal of precipitating events (mainly bacterial infection and alcoholic hepatitis) and decrease of portal pressure may improve outcome of patients with acute decompensation or ACLF. Transjugular intrahepatic portosystemic shunts (TIPSs), especially in the preemptive situation, have been found to efficiently control bleeding, prevent rebleeding, and reduce short-term mortality. Therefore, TIPS placement should be considered <i>as an option</i> in the management of ACLF patients with variceal bleeding.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 2","pages":"189-205"},"PeriodicalIF":4.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9867981","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
Genetic and Epigenetic Basis of Drug-Induced Liver Injury. 药物性肝损伤的遗传学和表观遗传学基础
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-05-01 Epub Date: 2023-05-24 DOI: 10.1055/a-2097-0531
Snigdha Singh, P V S N Kiran Kumar, J Pradeep Kumar, Sojit Tomo, Dharamveer Yadav, Praveen Sharma, Mahadev Rao, Mithu Banerjee
{"title":"Genetic and Epigenetic Basis of Drug-Induced Liver Injury.","authors":"Snigdha Singh, P V S N Kiran Kumar, J Pradeep Kumar, Sojit Tomo, Dharamveer Yadav, Praveen Sharma, Mahadev Rao, Mithu Banerjee","doi":"10.1055/a-2097-0531","DOIUrl":"10.1055/a-2097-0531","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) is a rare but severe adverse drug reaction seen in pharmacotherapy and a major cause of postmarketing drug withdrawals. Advances in genome-wide studies indicate that genetic and epigenetic diversity can lead to inter-individual differences in drug response and toxicity. It is necessary to identify how the genetic variations, in the presence of environmental factors, can contribute to development and progression of DILI. Studies on microRNA, histone modification, DNA methylation, and single nucleotide polymorphisms related to DILI were retrieved from databases and were analyzed for the current research and updated to develop this narrative review. We have compiled some of the major genetic, epigenetic, and pharmacogenetic factors leading to DILI. Many validated genetic risk factors of DILI, such as variants of drug-metabolizing enzymes, HLA alleles, and some transporters were identified. In conclusion, these studies provide useful information in risk alleles identification and on implementation of personalized medicine.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 2","pages":"163-175"},"PeriodicalIF":4.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9859070","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
HNF4α in Hepatocyte Health and Disease. 肝细胞健康与疾病中的 HNF4α
IF 4.3 3区 医学
Seminars in liver disease Pub Date : 2023-05-01 Epub Date: 2023-05-22 DOI: 10.1055/a-2097-0660
Manasi Kotulkar, Dakota R Robarts, Udayan Apte
{"title":"HNF4α in Hepatocyte Health and Disease.","authors":"Manasi Kotulkar, Dakota R Robarts, Udayan Apte","doi":"10.1055/a-2097-0660","DOIUrl":"10.1055/a-2097-0660","url":null,"abstract":"<p><p>Hepatocyte nuclear factor 4 α (HNF4α) is a highly conserved member of the nuclear receptor superfamily expressed at high levels in the liver, kidney, pancreas, and gut. In the liver, HNF4α is exclusively expressed in hepatocytes, where it is indispensable for embryonic and postnatal liver development and for normal liver function in adults. It is considered a master regulator of hepatic differentiation because it regulates a significant number of genes involved in hepatocyte-specific functions. Loss of HNF4α expression and function is associated with the progression of chronic liver disease. Further, HNF4α is a target of chemical-induced liver injury. In this review, we discuss the role of HNF4α in liver pathophysiology and highlight its potential use as a therapeutic target for liver diseases.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 2","pages":"234-244"},"PeriodicalIF":4.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10947958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9868772","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
Screening for At-Risk Nonalcoholic Fatty Liver Disease in the Primary Care Setting. 初级保健环境中高危非酒精性脂肪性肝病的筛查
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-05-01 Epub Date: 2023-04-27 DOI: 10.1055/a-2082-5203
Esteban Urias, Vincent L Chen
{"title":"Screening for At-Risk Nonalcoholic Fatty Liver Disease in the Primary Care Setting.","authors":"Esteban Urias, Vincent L Chen","doi":"10.1055/a-2082-5203","DOIUrl":"10.1055/a-2082-5203","url":null,"abstract":"<p><p>While nonalcoholic fatty liver disease is a leading cause of end-stage liver disease, most patients with nonalcoholic fatty liver disease do not develop cirrhosis and its complications. Therefore, risk stratification using inexpensive, noninvasive screening modalities is critical to avoid overdiagnosis and overtreatment of a large proportion of the population. In this review, we discuss the data supporting screening and current professional society recommendations on this topic. Screening for at-risk nonalcoholic fatty liver disease is recommended in patients with risk factors including diabetes, the metabolic syndrome, hepatic steatosis, and elevated aminotransferases. Screening typically consists of noninvasive testing using serum biomarkers followed by elastography using specialized imaging modalities. This sequential screening approach accurately identifies both high- and low-risk patients and is cost-effective when applied to at-risk populations. In conclusion, screening for advanced nonalcoholic fatty liver disease in the primary care setting is a crucial part of identifying high-risk patients who may benefit from aggressive intervention while avoiding overtreatment of patients at low risk of liver-related complications.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 2","pages":"133-141"},"PeriodicalIF":4.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10668862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012362","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
Current Challenges and Future Direction in Surveillance for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease. 非酒精性脂肪肝患者肝细胞癌监测的当前挑战和未来方向
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-02-01 DOI: 10.1055/a-1957-8540
George Cholankeril, Hashem El-Serag
{"title":"Current Challenges and Future Direction in Surveillance for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease.","authors":"George Cholankeril,&nbsp;Hashem El-Serag","doi":"10.1055/a-1957-8540","DOIUrl":"https://doi.org/10.1055/a-1957-8540","url":null,"abstract":"<p><p>The burden for hepatocellular carcinoma (HCC) attributed to nonalcoholic fatty liver disease (NAFLD) continues to grow in parallel with rising global trends in obesity. The risk of HCC is elevated among patients with NAFLD-related cirrhosis to a level that justifies surveillance based on cost-effectiveness argument. The quality of current evidence for HCC surveillance in all patients with chronic liver disease is poor, and even lower in those with NAFLD. For a lack of more precise risk-stratification tools, current approaches to defining a target population in noncirrhotic NAFLD are limited to noninvasive tests for liver fibrosis, as a proxy for liver-related morbidity and mortality. Beyond etiology and severity of liver disease, traditional and metabolic risk factors, such as diabetes mellitus, older age, male gender and tobacco smoking, are not enough for HCC risk stratification for surveillance efficacy and effectiveness in NAFLD. There is an association between molecular and genetic factors and HCC risk in NAFLD, and risk models integrating both clinical and genetic factors will be key to personalizing HCC risk. In this review, we discuss concerns regarding defining a target population, surveillance test accuracy, surveillance underuse, and other cost-effective considerations for HCC surveillance in individuals with NAFLD.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 1","pages":"89-99"},"PeriodicalIF":4.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9161175","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: 2
The Changing Epidemiology of Alcohol-Associated Liver Disease: Gender, Race, and Risk Factors. 酒精相关肝病的流行病学变化:性别、种族和危险因素
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-02-01 DOI: 10.1055/a-2000-6680
Ahmad Anouti, Jessica Leigh Mellinger
{"title":"The Changing Epidemiology of Alcohol-Associated Liver Disease: Gender, Race, and Risk Factors.","authors":"Ahmad Anouti,&nbsp;Jessica Leigh Mellinger","doi":"10.1055/a-2000-6680","DOIUrl":"https://doi.org/10.1055/a-2000-6680","url":null,"abstract":"<p><p>Cases of alcohol-associated liver disease (ALD) are increasing at a steady rate in the United States with more patients presenting with alcohol-associated hepatitis and alcohol-associated cirrhosis. While alcohol use has increased across many demographic groups, women are suffering from a greater increase in alcohol use disorder (AUD), and are at a greater risk of ALD due to pathophysiological differences which include absorption of alcohol, first pass metabolism, and hormonal differences. Differences across race have also been found with Native Americans and Hispanics suffering from some of the largest increases in ALD rates. Younger adults are heavily impacted by rising rates of both AUD and ALD. Comorbidities such as obesity and NASH have been shown to augment the deleterious effects of AUD and ALD, resulting in more advanced liver disease. Finally, COVID-19 and policies related to the pandemic have resulted in increased AUD across many cohorts, which have resulted in marked increases in ALD. In conclusion, ALD rates are rising, with young people and women particularly impacted.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 1","pages":"50-59"},"PeriodicalIF":4.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9531584","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: 1
Physiomimetic In Vitro Human Models for Viral Infection in the Liver. 体外模拟人肝脏病毒感染模型的建立。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-02-01 DOI: 10.1055/a-1981-5944
Dennis Gregory McDuffie, David Murat Barr, Madeline Grace Helm, Thomas F Baumert, Ashutosh Agarwal, Emmanuel Thomas
{"title":"Physiomimetic In Vitro Human Models for Viral Infection in the Liver.","authors":"Dennis Gregory McDuffie,&nbsp;David Murat Barr,&nbsp;Madeline Grace Helm,&nbsp;Thomas F Baumert,&nbsp;Ashutosh Agarwal,&nbsp;Emmanuel Thomas","doi":"10.1055/a-1981-5944","DOIUrl":"https://doi.org/10.1055/a-1981-5944","url":null,"abstract":"<p><p>Viral hepatitis is a leading cause of liver morbidity and mortality globally. The mechanisms underlying acute infection and clearance, versus the development of chronic infection, are poorly understood. In vitro models of viral hepatitis circumvent the high costs and ethical considerations of animal models, which also translate poorly to studying the human-specific hepatitis viruses. However, significant challenges are associated with modeling long-term infection in vitro. Differentiated hepatocytes are best able to sustain chronic viral hepatitis infection, but standard two-dimensional models are limited because they fail to mimic the architecture and cellular microenvironment of the liver, and cannot maintain a differentiated hepatocyte phenotype over extended periods. Alternatively, physiomimetic models facilitate important interactions between hepatocytes and their microenvironment by incorporating liver-specific environmental factors such as three-dimensional ECM interactions and co-culture with non-parenchymal cells. These physiologically relevant interactions help maintain a functional hepatocyte phenotype that is critical for sustaining viral hepatitis infection. In this review, we provide an overview of distinct, novel, and innovative in vitro liver models and discuss their functionality and relevance in modeling viral hepatitis. These platforms may provide novel insight into mechanisms that regulate viral clearance versus progression to chronic infections that can drive subsequent liver disease.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 1","pages":"31-49"},"PeriodicalIF":4.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/20/10-1055-a-1981-5944.PMC10005888.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163001","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: 1
Beyond Varices: Complications of Cirrhotic Portal Hypertension in Pediatrics. 静脉曲张之外:儿科肝硬化门静脉高压的并发症。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-02-01 DOI: 10.1055/s-0042-1759613
Anna M Banc-Husu, Henry Shiau, Peace Dike, Benjamin L Shneider
{"title":"Beyond Varices: Complications of Cirrhotic Portal Hypertension in Pediatrics.","authors":"Anna M Banc-Husu,&nbsp;Henry Shiau,&nbsp;Peace Dike,&nbsp;Benjamin L Shneider","doi":"10.1055/s-0042-1759613","DOIUrl":"https://doi.org/10.1055/s-0042-1759613","url":null,"abstract":"<p><p>Complications of cirrhotic portal hypertension (PHTN) in children are broad and include clinical manifestations ranging from variceal hemorrhage, hepatic encephalopathy (HE), ascites, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS) to less common conditions such as hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy. The approaches to the diagnosis and management of these complications have become standard of practice in adults with cirrhosis with many guidance statements available. However, there is limited literature on the diagnosis and management of these complications of PHTN in children with much of the current guidance available focused on variceal hemorrhage. The aim of this review is to summarize the current literature in adults who experience these complications of cirrhotic PHTN beyond variceal hemorrhage and present the available literature in children, with a focus on diagnosis, management, and liver transplant decision making in children with cirrhosis who develop ascites, SBP, HRS, HE, and cardiopulmonary complications.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 1","pages":"100-116"},"PeriodicalIF":4.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9255313","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
Growth Hormone Signaling in Liver Diseases: Therapeutic Potentials and Controversies. 肝脏疾病中的生长激素信号:治疗潜力和争议。
IF 4.2 3区 医学
Seminars in liver disease Pub Date : 2023-02-01 DOI: 10.1055/a-2015-1359
Madisyn Oxley, Heather Francis, Keisaku Sato
{"title":"Growth Hormone Signaling in Liver Diseases: Therapeutic Potentials and Controversies.","authors":"Madisyn Oxley,&nbsp;Heather Francis,&nbsp;Keisaku Sato","doi":"10.1055/a-2015-1359","DOIUrl":"https://doi.org/10.1055/a-2015-1359","url":null,"abstract":"<p><p>Growth hormone (GH) and downstream insulin-like growth factor 1 (IGF1) signaling mediate growth and metabolism. GH deficiency causes short stature or dwarfism, and excess GH causes acromegaly. Although the association of GH/IGF1 signaling with liver diseases has been suggested previously, current studies are controversial and the functional roles of GH/IGF1 signaling are still undefined. GH supplementation therapy showed promising therapeutic effects in some patients, such as non-alcoholic fatty liver disease, but inhibition of GH signaling may be beneficial for other liver diseases, such as hepatocellular carcinoma. The functional roles of GH/IGF1 signaling and the effects of agonists/antagonists targeting this signaling may differ depending on the liver injury or animal models. This review summarizes current controversial studies of GH/IGF1 signaling in liver diseases and discusses therapeutic potentials of GH therapy.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"43 1","pages":"24-30"},"PeriodicalIF":4.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516027","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: 2
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