{"title":"非酒精性脂肪肝——个性化治疗和药物开发的机会","authors":"Aurino M. Kemas, Sonia Youhanna, V. Lauschke","doi":"10.1080/23808993.2022.2053285","DOIUrl":null,"url":null,"abstract":"ABSTRACT Introduction Non-alcoholic fatty liver disease (NAFLD) constitutes a highly prevalent liver disorder whose rise in prevalence is closely connected to the growing rates of obesity, dyslipidemia, and type 2 diabetes. Importantly, kinetics and likelihood of NAFLD onset and its progression to non-alcoholic steatohepatitis (NASH) and fibrosis differs considerably between individuals. In recent years, the understanding of NAFLD pathogenesis has increased substantially and a multitude of factors, genetic predispositions, molecular signatures or NAFLD-related liver injury and comorbidities have been identified. Areas Covered This article summarizes inter-individual differences in NAFLD, including genetic variations, epigenetic and metabolic alterations and differences in the microbiome. We also discuss how these features might be leveraged for treatment personalization. Expert opinion The complexity and heterogeneity of NAFLD provides considerable challenges for drug developers and has resulted in numerous costly project failures. We expect that increased knowledge and appreciation of patient-specific factors will facilitate better patient stratification and identification of those individuals that benefit most from a given therapeutic strategy. Furthermore, we anticipate that pathophysiologically relevant in vivo and ex vivo disease models as well as large-scale chemogenomic projects hold promise to drastically improve NAFLD drug development to complement lifestyle and surgical interventions with pharmacological approaches.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.0000,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Non-alcoholic fatty liver disease - opportunities for personalized treatment and drug development\",\"authors\":\"Aurino M. Kemas, Sonia Youhanna, V. Lauschke\",\"doi\":\"10.1080/23808993.2022.2053285\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"ABSTRACT Introduction Non-alcoholic fatty liver disease (NAFLD) constitutes a highly prevalent liver disorder whose rise in prevalence is closely connected to the growing rates of obesity, dyslipidemia, and type 2 diabetes. Importantly, kinetics and likelihood of NAFLD onset and its progression to non-alcoholic steatohepatitis (NASH) and fibrosis differs considerably between individuals. In recent years, the understanding of NAFLD pathogenesis has increased substantially and a multitude of factors, genetic predispositions, molecular signatures or NAFLD-related liver injury and comorbidities have been identified. Areas Covered This article summarizes inter-individual differences in NAFLD, including genetic variations, epigenetic and metabolic alterations and differences in the microbiome. We also discuss how these features might be leveraged for treatment personalization. Expert opinion The complexity and heterogeneity of NAFLD provides considerable challenges for drug developers and has resulted in numerous costly project failures. We expect that increased knowledge and appreciation of patient-specific factors will facilitate better patient stratification and identification of those individuals that benefit most from a given therapeutic strategy. Furthermore, we anticipate that pathophysiologically relevant in vivo and ex vivo disease models as well as large-scale chemogenomic projects hold promise to drastically improve NAFLD drug development to complement lifestyle and surgical interventions with pharmacological approaches.\",\"PeriodicalId\":12124,\"journal\":{\"name\":\"Expert Review of Precision Medicine and Drug Development\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.0000,\"publicationDate\":\"2022-01-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Review of Precision Medicine and Drug Development\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/23808993.2022.2053285\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Review of Precision Medicine and Drug Development","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/23808993.2022.2053285","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Non-alcoholic fatty liver disease - opportunities for personalized treatment and drug development
ABSTRACT Introduction Non-alcoholic fatty liver disease (NAFLD) constitutes a highly prevalent liver disorder whose rise in prevalence is closely connected to the growing rates of obesity, dyslipidemia, and type 2 diabetes. Importantly, kinetics and likelihood of NAFLD onset and its progression to non-alcoholic steatohepatitis (NASH) and fibrosis differs considerably between individuals. In recent years, the understanding of NAFLD pathogenesis has increased substantially and a multitude of factors, genetic predispositions, molecular signatures or NAFLD-related liver injury and comorbidities have been identified. Areas Covered This article summarizes inter-individual differences in NAFLD, including genetic variations, epigenetic and metabolic alterations and differences in the microbiome. We also discuss how these features might be leveraged for treatment personalization. Expert opinion The complexity and heterogeneity of NAFLD provides considerable challenges for drug developers and has resulted in numerous costly project failures. We expect that increased knowledge and appreciation of patient-specific factors will facilitate better patient stratification and identification of those individuals that benefit most from a given therapeutic strategy. Furthermore, we anticipate that pathophysiologically relevant in vivo and ex vivo disease models as well as large-scale chemogenomic projects hold promise to drastically improve NAFLD drug development to complement lifestyle and surgical interventions with pharmacological approaches.
期刊介绍:
Expert Review of Precision Medicine and Drug Development publishes primarily review articles covering the development and clinical application of medicine to be used in a personalized therapy setting; in addition, the journal also publishes original research and commentary-style articles. In an era where medicine is recognizing that a one-size-fits-all approach is not always appropriate, it has become necessary to identify patients responsive to treatments and treat patient populations using a tailored approach. Areas covered include: Development and application of drugs targeted to specific genotypes and populations, as well as advanced diagnostic technologies and significant biomarkers that aid in this. Clinical trials and case studies within personalized therapy and drug development. Screening, prediction and prevention of disease, prediction of adverse events, treatment monitoring, effects of metabolomics and microbiomics on treatment. Secondary population research, genome-wide association studies, disease–gene association studies, personal genome technologies. Ethical and cost–benefit issues, the impact to healthcare and business infrastructure, and regulatory issues.