{"title":"New Nomenclature for Nonalcoholic Fatty Liver Disease: Understanding Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Dysfunction- and Alcohol-Associated Liver Disease, and Their Implications in Clinical Practice.","authors":"Clémence M Canivet, Jérôme Boursier, Rohit Loomba","doi":"10.1055/s-0044-1785196","DOIUrl":"10.1055/s-0044-1785196","url":null,"abstract":"<p><p>In June 2023, under the patronage of the American Association for Study of Liver Disease, the European Association for Study of the Liver, and the Asociación Latinoamericana para el Estudio del Hígado with the involvement of 236 participants from around the world, a new nomenclature and definition for nonalcoholic fatty liver disease (NAFLD) has been proposed. Metabolic dysfunction-associated steatotic liver disease (MASLD) was defined as presence of hepatic steatosis and at least one of the cardiometabolic risk factors with alcohol intake less than 140 g/wk for women and 210 g/wk for men and no other causes of steatosis. A new entity called combined metabolic dysfunction- and alcohol-associated liver disease (MetALD) was created outside of pure MASLD for patients with metabolic dysfunction and alcohol intake greater than that allowed for MASLD (i.e., 140-350 g/wk for women and 210-420 g/wk for men). Recent studies have confirmed a 95% overlap between NAFLD and the new MASLD diagnostic criteria. Natural history, biomarkers, and thresholds of alcohol intake in MetALD group remains to be studied and validated.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"35-42"},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294465","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}
Hao Liu, Vrishketan Sethi, Xingjie Li, Yao Xiao, Abhinav Humar
{"title":"Liver Transplantation for Hepatocellular Carcinoma: A Narrative Review and A Glimpse into The Future.","authors":"Hao Liu, Vrishketan Sethi, Xingjie Li, Yao Xiao, Abhinav Humar","doi":"10.1055/a-2242-7543","DOIUrl":"10.1055/a-2242-7543","url":null,"abstract":"<p><p>Liver transplantation (LT) is a highly effective treatment for carefully selected patients with hepatocellular carcinoma (HCC). In this review, we explored the development of LT selection criteria and organ allocation policies, comparing original data to underscore their historical progression into the intricate task of quantitatively estimating pre- and post-LT survivals. We emphasized the role of biomarkers such as serum alpha-fetoprotein, Des-gamma-carboxy-prothrombin, circulating tumor cells, and circulating tumor DNA in predicting patient outcomes. Additionally, we examined the transplant-associated survival benefits and the difficulties in accurately calculating these benefits. We also reviewed recent advancements in targeted therapy and checkpoint inhibitors for advanced, inoperable HCC and projected their integration into LT for HCC. We further discussed the growing use of living donor liver transplants in the United States and compared its outcomes with those of deceased donor liver transplants. Furthermore, we examined the progress in machine perfusion techniques, which have shown potential in improving patient outcomes and enlarging the donor pool. These advancements present opportunities to enhance LT patient survivals, refine selection criteria, establish new priority metrics, develop innovative bridging and downstaging strategies, and formulate redesigned LT strategies for HCC treatments.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"79-98"},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139425457","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}
Fernando Bessone, Geraldine L Hillotte, Natalia Ahumada, Fernanda Jaureguizahar, Anabela C Medeot, Marcelo G Roma
{"title":"UDCA for Drug-Induced Liver Disease: Clinical and Pathophysiological Basis.","authors":"Fernando Bessone, Geraldine L Hillotte, Natalia Ahumada, Fernanda Jaureguizahar, Anabela C Medeot, Marcelo G Roma","doi":"10.1055/s-0044-1779520","DOIUrl":"10.1055/s-0044-1779520","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) is an adverse reaction to medications and other xenobiotics that leads to liver dysfunction. Based on differential clinical patterns of injury, DILI is classified into hepatocellular, cholestatic, and mixed types; although hepatocellular DILI is associated with inflammation, necrosis, and apoptosis, cholestatic DILI is associated with bile plugs and bile duct paucity. Ursodeoxycholic acid (UDCA) has been empirically used as a supportive drug mainly in cholestatic DILI, but both curative and prophylactic beneficial effects have been observed for hepatocellular DILI as well, according to preliminary clinical studies. This could reflect the fact that UDCA has a plethora of beneficial effects potentially useful to treat the wide range of injuries with different etiologies and pathomechanisms occurring in both types of DILI, including anticholestatic, antioxidant, anti-inflammatory, antiapoptotic, antinecrotic, mitoprotective, endoplasmic reticulum stress alleviating, and immunomodulatory properties. In this review, a revision of the literature has been performed to evaluate the efficacy of UDCA across the whole DILI spectrum, and these findings were associated with the multiple mechanisms of UDCA hepatoprotection. This should help better rationalize and systematize the use of this versatile and safe hepatoprotector in each type of DILI scenarios.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"1-22"},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913404","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}
Mohamed El-Kassas, Abeer Awad, Mohamed Elbadry, Juan Pablo Arab
{"title":"Tailored Model of Care for Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Mohamed El-Kassas, Abeer Awad, Mohamed Elbadry, Juan Pablo Arab","doi":"10.1055/a-2253-9181","DOIUrl":"10.1055/a-2253-9181","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is increasing globally, creating a growing public health concern. However, this disease is often not diagnosed, and accurate data on its epidemiology are limited in many geographical regions, making it challenging to provide proper care and implement effective national plans. To combat the increasing disease burden, screening and diagnosis must reach a significant number of high-risk subjects. Addressing MASLD as a health care challenge requires a multidisciplinary approach involving prevention, diagnosis, treatment, and care, with collaboration between multiple stakeholders in the health care system. This approach must be guided by national and global strategies, to be combined with efficient models of care developed through a bottom-up process. This review article highlights the pillars of the MASLD model of care (MoC), including screening, risk stratification, and establishing a clinical care pathway for management, in addition to discussing the impact of nomenclature change on the proposed MoC.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"54-68"},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139565004","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}
Hao Liu, Vrishketan Sethi, Xingjie Li, Yao Xiao, Abhinav Humar
{"title":"Corrigendum: Liver Transplantation for Hepatocellular Carcinoma: A Narrative Review and A Glimpse into The Future.","authors":"Hao Liu, Vrishketan Sethi, Xingjie Li, Yao Xiao, Abhinav Humar","doi":"10.1055/s-0044-1787737","DOIUrl":"10.1055/s-0044-1787737","url":null,"abstract":"","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"44 1","pages":"e1-e3"},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262894","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":"Gestational and Developmental Contributors of Pediatric MASLD.","authors":"Marialena Mouzaki, Jessica G Woo, Senad Divanovic","doi":"10.1055/s-0044-1782210","DOIUrl":"10.1055/s-0044-1782210","url":null,"abstract":"<p><p>Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) is common and can be seen as early as <i>in utero</i>. A growing body of literature suggests that gestational and early life exposures modify the risk of MASLD development in children. These include maternal risk factors, such as poor cardiometabolic health (e.g., obesity, gestational diabetes, rapid weight gain during pregnancy, and MASLD), as well as periconceptional dietary exposures, degree of physical activity, intestinal microbiome, and smoking. Paternal factors, such as diet and obesity, also appear to play a role. Beyond gestation, early life dietary exposures, as well as the rate of infant weight gain, may further modify the risk of future MASLD development. The mechanisms linking parental health and environmental exposures to pediatric MASLD are complex and not entirely understood. In conclusion, investigating gestational and developmental contributors to MASLD is critical and may identify future interventional targets for disease prevention.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"43-53"},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997392","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}
Katrine Tholstrup Bech, Katrine Prier Lindvig, Maja Thiele, Laurent Castera
{"title":"Algorithms for Early Detection of Silent Liver Fibrosis in the Primary Care Setting.","authors":"Katrine Tholstrup Bech, Katrine Prier Lindvig, Maja Thiele, Laurent Castera","doi":"10.1055/s-0043-1778127","DOIUrl":"10.1055/s-0043-1778127","url":null,"abstract":"<p><p>More than one-third of the adult world population has steatotic liver disease (SLD), with a few percent of individuals developing cirrhosis after decades of silent liver fibrosis accumulation. Lack of systematic early detection causes most patients to be diagnosed late, after decompensation, when treatment has limited effect and survival is poor. Unfortunately, no isolated screening test in primary care can sufficiently predict advanced fibrosis from SLD. Recent efforts, therefore, combine several parameters into screening algorithms, to increase diagnostic accuracy. Besides patient selection, for example, by specific characteristics, algorithms include nonpatented or patented blood tests and liver stiffness measurements using elastography-based techniques. Algorithms can be composed as a set of sequential tests, as recommended by most guidelines on primary care pathways. Future use of algorithms that are easy to interpret, cheap, and semiautomatic will improve the management of patients with SLD, to the benefit of global health care systems.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"23-34"},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542906","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}
Anna Tutusaus, Albert Morales, Pablo García de Frutos, Montserrat Marí
{"title":"GAS6/TAM Axis as Therapeutic Target in Liver Diseases.","authors":"Anna Tutusaus, Albert Morales, Pablo García de Frutos, Montserrat Marí","doi":"10.1055/a-2275-0408","DOIUrl":"10.1055/a-2275-0408","url":null,"abstract":"<p><p>TAM (TYRO3, AXL, and MERTK) protein tyrosine kinase membrane receptors and their vitamin K-dependent ligands GAS6 and protein S (PROS) are well-known players in tumor biology and autoimmune diseases. In contrast, TAM regulation of fibrogenesis and the inflammation mechanisms underlying metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and, ultimately, liver cancer has recently been revealed. GAS6 and PROS binding to phosphatidylserine exposed in outer membranes of apoptotic cells links TAMs, particularly MERTK, with hepatocellular damage. In addition, AXL and MERTK regulate the development of liver fibrosis and inflammation in chronic liver diseases. Acute hepatic injury is also mediated by the TAM system, as recent data regarding acetaminophen toxicity and acute-on-chronic liver failure have uncovered. Soluble TAM-related proteins, mainly released from activated macrophages and hepatic stellate cells after hepatic deterioration, are proposed as early serum markers for disease progression. In conclusion, the TAM system is becoming an interesting pharmacological target in liver pathology and a focus of future biomedical research in this field.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":" ","pages":"99-114"},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11027478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139940678","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}
Cathrin L.C. Gudd, Roosey Sheth, Mark R. Thursz, Evangelos Triantafyllou, Lucia A. Possamai
{"title":"Immune Checkpoint Inhibitor-Induced Liver Injury","authors":"Cathrin L.C. Gudd, Roosey Sheth, Mark R. Thursz, Evangelos Triantafyllou, Lucia A. Possamai","doi":"10.1055/s-0043-1776761","DOIUrl":"https://doi.org/10.1055/s-0043-1776761","url":null,"abstract":"<p>In recent years cancer treatment has been revolutionized by the development and wide application of checkpoint inhibitor (CPI) drugs, which are a form of immunotherapy. CPI treatment is associated with immune-related adverse events, off-target tissue destructive inflammatory complications, which may affect a range of organs, with liver inflammation (hepatitis) being one of the more commonly noted events. This is a novel form of drug-induced liver injury and a rapidly evolving field, as our understanding of both the basic immunopathology of CPI hepatitis (CPI-H) and optimal clinical management, races to catch up with the increasing application of this form of immunotherapy in clinical practice. In this review, we summarize current evidence and understanding of CPI-H, from fundamental immunology to practical patient management.</p> ","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"33 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138687912","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}
MohammadMahdi Saeidinejad, Ahmed Elshabrawi, Supachaya Sriphoosanaphan, Fausto Andreola, Gautam Mehta, Banwari Agarwal, Rajiv Jalan
{"title":"Novel Therapeutic Approaches in Treatment of Acute-on-Chronic Liver Failure","authors":"MohammadMahdi Saeidinejad, Ahmed Elshabrawi, Supachaya Sriphoosanaphan, Fausto Andreola, Gautam Mehta, Banwari Agarwal, Rajiv Jalan","doi":"10.1055/s-0043-1776773","DOIUrl":"https://doi.org/10.1055/s-0043-1776773","url":null,"abstract":"<p>Acute-on-chronic liver failure (ACLF), a clinical syndrome that can develop at any stage in the progression of cirrhotic liver disease, is characterized by an acute decompensation in liver function with associated multiorgan failure and high short-term mortality. Current evidence points to ACLF being reversible, particularly in those at the lower end of the severity spectrum. However, there are no specific treatments for ACLF, and overall outcomes remain poor. Expedited liver transplantation as a treatment option is limited by organ shortage and a lack of priority allocation for this indication. Other options are therefore urgently needed, and our improved understanding of the condition has led to significant efforts to develop novel therapies. In conclusion, this review aims to summarize the current understanding of the pathophysiological processes involved in the onset, progression, and recovery of ACLF and discuss novel therapies under development.</p> ","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":"49 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138688351","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}