{"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}
{"title":"Targeting Fibroblast Growth Factor Receptor Pathway: Precision Medicine for Biliary Cancer and Beyond.","authors":"Pedro Luiz Serrano Uson Junior, 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}
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}
{"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}
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}
{"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}
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}
{"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}
{"title":"Current Challenges and Future Direction in Surveillance for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease.","authors":"George Cholankeril, 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}
{"title":"The Changing Epidemiology of Alcohol-Associated Liver Disease: Gender, Race, and Risk Factors.","authors":"Ahmad Anouti, 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}