Pub Date : 2024-05-01Epub Date: 2024-05-28DOI: 10.1055/a-2334-8525
Anja M Fischer, Nazim Lechea, Harvey O Coxson
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition with a broad spectrum defined by liver biopsy. This gold standard method evaluates three features: steatosis, activity (ballooning and lobular inflammation), and fibrosis, attributing them to certain grades or stages using a semiquantitative scoring system. However, liver biopsy is subject to numerous restrictions, creating an unmet need for a reliable and reproducible method for MASLD assessment, grading, and staging. Noninvasive imaging modalities, such as magnetic resonance imaging (MRI), offer the potential to assess quantitative liver parameters. This review aims to provide an overview of the available MRI techniques for the three criteria evaluated individually by liver histology. Here, we discuss the possibility of combining multiple MRI parameters to replace liver biopsy with a holistic, multiparametric MRI protocol. In conclusion, the development and implementation of such an approach could significantly improve the diagnosis and management of MASLD, reducing the need for invasive procedures and paving the way for more personalized treatment strategies.
{"title":"This Is What Metabolic Dysfunction-Associated Steatotic Liver Disease Looks Like: Potential of a Multiparametric MRI Protocol.","authors":"Anja M Fischer, Nazim Lechea, Harvey O Coxson","doi":"10.1055/a-2334-8525","DOIUrl":"10.1055/a-2334-8525","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition with a broad spectrum defined by liver biopsy. This gold standard method evaluates three features: steatosis, activity (ballooning and lobular inflammation), and fibrosis, attributing them to certain grades or stages using a semiquantitative scoring system. However, liver biopsy is subject to numerous restrictions, creating an unmet need for a reliable and reproducible method for MASLD assessment, grading, and staging. Noninvasive imaging modalities, such as magnetic resonance imaging (MRI), offer the potential to assess quantitative liver parameters. This review aims to provide an overview of the available MRI techniques for the three criteria evaluated individually by liver histology. Here, we discuss the possibility of combining multiple MRI parameters to replace liver biopsy with a holistic, multiparametric MRI protocol. In conclusion, the development and implementation of such an approach could significantly improve the diagnosis and management of MASLD, reducing the need for invasive procedures and paving the way for more personalized treatment strategies.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162458","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}
Primary liver cancer is a solid malignancy with a high mortality rate. The success of immunotherapy has shown great promise in improving patient care and highlights a crucial need to understand the complexity of the liver tumor immune microenvironment (TIME). Recent advances in single-cell and spatial omics technologies, coupled with the development of systems biology approaches, are rapidly transforming the landscape of tumor immunology. Here we review the cellular landscape of liver TIME from single-cell and spatial perspectives. We also discuss the cellular interaction networks within the tumor cell community in regulating immune responses. We further highlight the challenges and opportunities with implications for biomarker discovery, patient stratification, and combination immunotherapies.
原发性肝癌是一种死亡率很高的实体恶性肿瘤。免疫疗法的成功为改善患者护理带来了巨大希望,同时也凸显了了解肝脏肿瘤免疫微环境(TIME)复杂性的迫切需要。单细胞和空间全息技术的最新进展,加上系统生物学方法的发展,正在迅速改变肿瘤免疫学的面貌。在此,我们从单细胞和空间的角度回顾了肝脏 TIME 的细胞景观。我们还讨论了肿瘤细胞群落内调节免疫反应的细胞相互作用网络。我们进一步强调了生物标志物发现、患者分层和联合免疫疗法所面临的挑战和机遇。
{"title":"Heterogeneity in Liver Cancer Immune Microenvironment: Emerging Single-Cell and Spatial Perspectives.","authors":"Caiyi Cherry Li, Meng Liu, Hsin-Pei Lee, Wenqi Wu, Lichun Ma","doi":"10.1055/s-0044-1787152","DOIUrl":"10.1055/s-0044-1787152","url":null,"abstract":"<p><p>Primary liver cancer is a solid malignancy with a high mortality rate. The success of immunotherapy has shown great promise in improving patient care and highlights a crucial need to understand the complexity of the liver tumor immune microenvironment (TIME). Recent advances in single-cell and spatial omics technologies, coupled with the development of systems biology approaches, are rapidly transforming the landscape of tumor immunology. Here we review the cellular landscape of liver TIME from single-cell and spatial perspectives. We also discuss the cellular interaction networks within the tumor cell community in regulating immune responses. We further highlight the challenges and opportunities with implications for biomarker discovery, patient stratification, and combination immunotherapies.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141092633","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}
Pub Date : 2024-05-01Epub Date: 2024-03-18DOI: 10.1055/a-2289-2298
Takahiro Kodama, Tetsuo Takehara
This review examines the latest epidemiological and molecular pathogenic findings of metabolic-associated hepatocellular carcinoma (HCC). Its increasing prevalence is a significant concern and reflects the growing burden of obesity and metabolic diseases, including metabolic dysfunction-associated steatotic liver disease, formerly known as nonalcoholic fatty liver disease, and type 2 diabetes. Metabolic-associated HCC has unique molecular abnormality and distinctive gene expression patterns implicating aberrations in bile acid, fatty acid metabolism, oxidative stress, and proinflammatory pathways. Furthermore, a notable frequency of single nucleotide polymorphisms in genes such as patatin-like phospholipase domain-containing 3, transmembrane 6 superfamily member 2, glucokinase regulator, and membrane-bound O-acyltransferase domain-containing 7 has been observed. The tumor immune microenvironment of metabolic-associated HCC is characterized by unique phenotypes of macrophages, neutrophils, and T lymphocytes. Additionally, the pathogenesis of metabolic-associated HCC is influenced by abnormal lipid metabolism, insulin resistance, and dysbiosis. In conclusion, deciphering the intricate interactions among metabolic processes, genetic predispositions, inflammatory responses, immune regulation, and microbial ecology is imperative for the development of novel therapeutic and preventative measures against metabolic-associated HCC.
{"title":"Molecular Genealogy of Metabolic-associated Hepatocellular Carcinoma.","authors":"Takahiro Kodama, Tetsuo Takehara","doi":"10.1055/a-2289-2298","DOIUrl":"10.1055/a-2289-2298","url":null,"abstract":"<p><p>This review examines the latest epidemiological and molecular pathogenic findings of metabolic-associated hepatocellular carcinoma (HCC). Its increasing prevalence is a significant concern and reflects the growing burden of obesity and metabolic diseases, including metabolic dysfunction-associated steatotic liver disease, formerly known as nonalcoholic fatty liver disease, and type 2 diabetes. Metabolic-associated HCC has unique molecular abnormality and distinctive gene expression patterns implicating aberrations in bile acid, fatty acid metabolism, oxidative stress, and proinflammatory pathways. Furthermore, a notable frequency of single nucleotide polymorphisms in genes such as patatin-like phospholipase domain-containing 3, transmembrane 6 superfamily member 2, glucokinase regulator, and membrane-bound O-acyltransferase domain-containing 7 has been observed. The tumor immune microenvironment of metabolic-associated HCC is characterized by unique phenotypes of macrophages, neutrophils, and T lymphocytes. Additionally, the pathogenesis of metabolic-associated HCC is influenced by abnormal lipid metabolism, insulin resistance, and dysbiosis. In conclusion, deciphering the intricate interactions among metabolic processes, genetic predispositions, inflammatory responses, immune regulation, and microbial ecology is imperative for the development of novel therapeutic and preventative measures against metabolic-associated HCC.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158970","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}
Although therapy with direct-acting antiviral (DAA) agents achieves high HCV cure rates and is forgiving of missed doses, certain patient populations, such as people who inject drugs (PWID), are often denied therapy because of a perceived high risk of nonadherence. However, a relationship between adherence to DAAs for various patient populations and efficacy has not been well defined. The lack of a standardized method for evaluating adherence complicates making comparisons between studies, making it difficult to develop and implement novel measures that may improve adherent behavior. Traditional methods for assessing adherence may overestimate medication adherence, while newer, technology-based methods may assist with accurately assessing and maintaining patient adherence to therapy. Data demonstrate that special populations of patients with HCV, such as PWID, can be successfully treated, with relatively high rates of sustained virologic response (SVR) despite less-than-optimal adherence. While rates of adherence, and subsequently SVR, can be improved, antiviral therapy should not be withheld because of fear of nonadherence. This paper addresses medication adherence and forgiveness of DAA regimens, such as sofosbuvir/velpatasvir and glecaprevir/pibrentasvir, in different patient populations with HCV. Considerations in evaluating adherence in HCV therapy and available methods for assessing adherence are detailed.
{"title":"Adherence in HCV Treatment: What We Know.","authors":"Steven L. Flamm, A. Mangia","doi":"10.1055/a-2313-0111","DOIUrl":"https://doi.org/10.1055/a-2313-0111","url":null,"abstract":"Although therapy with direct-acting antiviral (DAA) agents achieves high HCV cure rates and is forgiving of missed doses, certain patient populations, such as people who inject drugs (PWID), are often denied therapy because of a perceived high risk of nonadherence. However, a relationship between adherence to DAAs for various patient populations and efficacy has not been well defined. The lack of a standardized method for evaluating adherence complicates making comparisons between studies, making it difficult to develop and implement novel measures that may improve adherent behavior. Traditional methods for assessing adherence may overestimate medication adherence, while newer, technology-based methods may assist with accurately assessing and maintaining patient adherence to therapy. Data demonstrate that special populations of patients with HCV, such as PWID, can be successfully treated, with relatively high rates of sustained virologic response (SVR) despite less-than-optimal adherence. While rates of adherence, and subsequently SVR, can be improved, antiviral therapy should not be withheld because of fear of nonadherence. This paper addresses medication adherence and forgiveness of DAA regimens, such as sofosbuvir/velpatasvir and glecaprevir/pibrentasvir, in different patient populations with HCV. Considerations in evaluating adherence in HCV therapy and available methods for assessing adherence are detailed.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140664035","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}
Antonio Saviano, Natascha Roehlen, Thomas F. Baumert
In the last decade tight junction proteins exposed at the surface of liver or cancer cells have been uncovered as mediators of liver disease biology: Claudin-1 and Occludin are host factors for hepatitis C virus entry and Claudin-1 has been identified as a driver for liver fibrosis and hepatocellular carcinoma (HCC). Moreover, Claudins have emerged as therapeutic targets for liver disease and HCC. CLDN1 expression is upregulated in liver fibrosis and HCC. Monoclonal antibodies (mAbs) targeting Claudin-1 have completed preclinical proof-of-concept studies for treatment of liver fibrosis and HCC and are currently in clinical development for advanced liver fibrosis. Claudin-6 overexpression is associated with an HCC aggressive phenotype and treatment resistance. Claudin-6 mAbs or chimeric antigen receptor-T cells therapies are currently being clinically investigated for Claudin-6 overexpressing tumors. In conclusion, targeting Claudin proteins offers a novel clinical opportunity for the treatment of patients with advanced liver fibrosis and HCC.
{"title":"Tight Junction Proteins as Therapeutic Targets to Treat Liver Fibrosis and Hepatocellular Carcinoma.","authors":"Antonio Saviano, Natascha Roehlen, Thomas F. Baumert","doi":"10.1055/s-0044-1785646","DOIUrl":"https://doi.org/10.1055/s-0044-1785646","url":null,"abstract":"In the last decade tight junction proteins exposed at the surface of liver or cancer cells have been uncovered as mediators of liver disease biology: Claudin-1 and Occludin are host factors for hepatitis C virus entry and Claudin-1 has been identified as a driver for liver fibrosis and hepatocellular carcinoma (HCC). Moreover, Claudins have emerged as therapeutic targets for liver disease and HCC. CLDN1 expression is upregulated in liver fibrosis and HCC. Monoclonal antibodies (mAbs) targeting Claudin-1 have completed preclinical proof-of-concept studies for treatment of liver fibrosis and HCC and are currently in clinical development for advanced liver fibrosis. Claudin-6 overexpression is associated with an HCC aggressive phenotype and treatment resistance. Claudin-6 mAbs or chimeric antigen receptor-T cells therapies are currently being clinically investigated for Claudin-6 overexpressing tumors. In conclusion, targeting Claudin proteins offers a novel clinical opportunity for the treatment of patients with advanced liver fibrosis and HCC.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140674212","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}
Manuel Romero-Gómez, Juan Pablo Arab, Claudia P. Oliveira, María Hernández, Marco Arrese, Helena Cortez-Pinto, Ramón Bataller
Excessive alcohol consumption represents an important burden for health systems worldwide and is a major cause of liver- and cancer-related deaths. Alcohol consumption is mostly assessed by self-report that often underestimates the amount of drinking. While alcohol use disorders identification test - version C is the most widely used test for alcohol use screening, in patients with liver disease the use of alcohol biomarker could help an objective assessment. The amount of alcohol that leads to significant liver disease depends on gender, genetic background, and coexistence of comorbidities (i.e., metabolic syndrome factors). All patients with alcohol-associated liver disease are recommended to follow complete abstinence and they should be treated within multidisciplinary teams. Abstinence slows down and even reverses the progression of liver fibrosis and can help recompensate patients with complicated cirrhosis. Whether there is a safe amount of alcohol in the general population is a matter of intense debate. Large epidemiological studies showed that the safe amount of alcohol to avoid overall health-related risks is lower than expected even in the general population. Even one drink per day can increase cancer-related death. In patients with any kind of chronic liver disease, especially in those with metabolic-associated steatotic liver disease, no alcohol intake is recommended. This review article discusses the current evidence supporting the deleterious effects of small-to-moderate amounts of alcohol in the general population and in patients with underlying chronic liver disease.
{"title":"Is There a Safe Alcohol Consumption Limit for the General Population and in Patients with Liver Disease?","authors":"Manuel Romero-Gómez, Juan Pablo Arab, Claudia P. Oliveira, María Hernández, Marco Arrese, Helena Cortez-Pinto, Ramón Bataller","doi":"10.1055/s-0044-1785228","DOIUrl":"https://doi.org/10.1055/s-0044-1785228","url":null,"abstract":"<p>Excessive alcohol consumption represents an important burden for health systems worldwide and is a major cause of liver- and cancer-related deaths. Alcohol consumption is mostly assessed by self-report that often underestimates the amount of drinking. While alcohol use disorders identification test - version C is the most widely used test for alcohol use screening, in patients with liver disease the use of alcohol biomarker could help an objective assessment. The amount of alcohol that leads to significant liver disease depends on gender, genetic background, and coexistence of comorbidities (i.e., metabolic syndrome factors). All patients with alcohol-associated liver disease are recommended to follow complete abstinence and they should be treated within multidisciplinary teams. Abstinence slows down and even reverses the progression of liver fibrosis and can help recompensate patients with complicated cirrhosis. Whether there is a safe amount of alcohol in the general population is a matter of intense debate. Large epidemiological studies showed that the safe amount of alcohol to avoid overall health-related risks is lower than expected even in the general population. Even one drink per day can increase cancer-related death. In patients with any kind of chronic liver disease, especially in those with metabolic-associated steatotic liver disease, no alcohol intake is recommended. This review article discusses the current evidence supporting the deleterious effects of small-to-moderate amounts of alcohol in the general population and in patients with underlying chronic liver disease.</p> ","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140576443","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}
The application of spatial transcriptomic technologies has significantly expanded our biological understanding. Hepatic intricate cellular heterogeneity and the pivotal role of zonation in maintaining hepatic function underscore how these technologies can unravel the complex spatial and cellular dynamics within both healthy and diseased livers. The article provides a comprehensive overview of the technical innovations and bioinformatics strategies that underpin spatial transcriptome analysis. Further, through recent discoveries in liver biology and pathology, enabled by these advanced methodologies, the review illustrates novel cell types, cell-cell interactions, and cellular reprograms in healthy and injured livers, as well as tumor microenvironment associated with patient prognosis and response to immune checkpoint inhibitors. With emphasizing the challenges and future directions, it points to the immense promise these technologies hold for identifying new therapeutic targets and advancing personalized medicine in hepatology, despite the hurdles in widespread adoption and standardization.
{"title":"Emerging role of spatial transcriptomics in liver research.","authors":"Naoto Fujiwara, Genki Kimura, Hayato Nakagawa","doi":"10.1055/a-2299-7880","DOIUrl":"https://doi.org/10.1055/a-2299-7880","url":null,"abstract":"The application of spatial transcriptomic technologies has significantly expanded our biological understanding. Hepatic intricate cellular heterogeneity and the pivotal role of zonation in maintaining hepatic function underscore how these technologies can unravel the complex spatial and cellular dynamics within both healthy and diseased livers. The article provides a comprehensive overview of the technical innovations and bioinformatics strategies that underpin spatial transcriptome analysis. Further, through recent discoveries in liver biology and pathology, enabled by these advanced methodologies, the review illustrates novel cell types, cell-cell interactions, and cellular reprograms in healthy and injured livers, as well as tumor microenvironment associated with patient prognosis and response to immune checkpoint inhibitors. With emphasizing the challenges and future directions, it points to the immense promise these technologies hold for identifying new therapeutic targets and advancing personalized medicine in hepatology, despite the hurdles in widespread adoption and standardization.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140741408","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}
Pub Date : 2024-02-01Epub Date: 2024-03-26DOI: 10.1055/s-0044-1785196
Clémence M Canivet, Jérôme Boursier, Rohit Loomba
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.
2023 年 6 月,在美国肝病研究协会(American Association for Study of Liver Disease)、欧洲肝病研究协会(European Association for Study of the Liver)和拉丁美洲肝病研究协会(Asociación Latinoamericana para el Estudio del Hígado)的赞助下,在来自世界各地的 236 名参与者的参与下,提出了非酒精性脂肪肝(NAFLD)的新命名和定义。代谢功能障碍相关性脂肪性肝病(MASLD)的定义是:存在肝脂肪变性和至少一种心脏代谢风险因素,女性酒精摄入量低于 140 克/周,男性酒精摄入量低于 210 克/周,且无其他脂肪变性原因。在纯粹的代谢紊乱性肝病(MASLD)之外,针对代谢紊乱且酒精摄入量大于代谢紊乱性肝病允许摄入量(即女性为 140-350 克/周,男性为 210-420 克/周)的患者设立了一个新的实体,称为代谢紊乱和酒精相关性肝病(MetALD)。最近的研究证实,非酒精性脂肪肝与新的 MASLD 诊断标准有 95% 的重叠。MetALD组的自然史、生物标志物和酒精摄入阈值仍有待研究和验证。
{"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":null,"pages":null},"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}
Pub Date : 2024-02-01Epub Date: 2024-01-11DOI: 10.1055/a-2242-7543
Hao Liu, Vrishketan Sethi, Xingjie Li, Yao Xiao, Abhinav Humar
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.
肝移植(LT)是一种针对经过严格筛选的肝细胞癌(HCC)患者的高效治疗方法。在这篇综述中,我们探讨了肝移植选择标准和器官分配政策的发展,比较了原始数据,以强调其在定量估计肝移植前后存活率这一复杂任务中的历史进程。我们强调了血清甲胎蛋白、DCP、循环肿瘤细胞和循环肿瘤 DNA 等生物标志物在预测患者预后方面的作用。此外,我们还探讨了移植相关的生存益处以及准确计算这些益处的困难。我们还回顾了针对无法手术的晚期 HCC 的靶向治疗和检查点抑制剂的最新进展,并预测了它们与 HCC 肝移植的整合。我们进一步讨论了在美国越来越多地使用活体肝移植的情况,并将其结果与死亡供体肝移植的结果进行了比较。此外,我们还研究了机器灌注技术的进展,这些技术在改善患者预后和扩大供体库方面显示出了潜力。这些进步为提高LT患者存活率、完善选择标准、建立新的优先指标、开发创新的桥接和降期策略以及为HCC治疗制定重新设计的LT策略提供了机会。
{"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":null,"pages":null},"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}
Pub Date : 2024-02-01Epub Date: 2024-02-20DOI: 10.1055/s-0044-1779520
Fernando Bessone, Geraldine L Hillotte, Natalia Ahumada, Fernanda Jaureguizahar, Anabela C Medeot, Marcelo G Roma
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.
药物性肝损伤(DILI)是指药物和其他异种生物导致肝功能异常的不良反应。根据不同的临床损伤模式,DILI 可分为肝细胞型、胆汁淤积型和混合型;虽然肝细胞型 DILI 与炎症、坏死和细胞凋亡有关,但胆汁淤积型 DILI 与胆汁栓塞和胆管狭窄有关。熊去氧胆酸(UDCA)主要作为一种支持性药物用于胆汁淤积性 DILI,但根据初步临床研究,它对肝细胞性 DILI 也有治疗和预防作用。这可能反映出 UDCA 具有多种有益作用,可用于治疗这两种类型的 DILI 中出现的不同病因和病理机制的各种损伤,包括抗胆碱能、抗氧化、抗炎、抗细胞凋亡、抗坏死、有丝分裂保护、减轻内质网应激和免疫调节特性。在这篇综述中,我们对文献进行了修订,以评估 UDCA 在整个 DILI 方面的疗效,这些发现与 UDCA 的多种保肝机制有关。这将有助于在各种类型的 DILI 中更合理、更系统地使用这种多功能、安全的保肝药物。
{"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":null,"pages":null},"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}