非酒精性脂肪肝——个性化治疗和药物开发的机会

IF 1 Q4 PHARMACOLOGY & PHARMACY
Aurino M. Kemas, Sonia Youhanna, V. Lauschke
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引用次数: 0

摘要

非酒精性脂肪性肝病(NAFLD)是一种高度流行的肝脏疾病,其患病率的上升与肥胖、血脂异常和2型糖尿病的发病率增长密切相关。重要的是,NAFLD发病的动力学和可能性及其进展为非酒精性脂肪性肝炎(NASH)和纤维化在个体之间有很大差异。近年来,对NAFLD发病机制的认识有了很大的提高,许多因素、遗传易感性、分子特征或NAFLD相关的肝损伤和合并症已经被确定。本文综述了NAFLD的个体间差异,包括遗传变异、表观遗传和代谢改变以及微生物组的差异。我们还讨论了如何利用这些特性来实现治疗个性化。NAFLD的复杂性和异质性给药物开发人员带来了相当大的挑战,并导致了许多代价高昂的项目失败。我们期望增加对患者特定因素的了解和欣赏,将有助于更好地对患者进行分层,并确定那些从给定治疗策略中获益最多的个体。此外,我们预计病理生理学相关的体内和体外疾病模型以及大规模的化学基因组学项目有望大大改善NAFLD药物开发,以补充生活方式和手术干预与药理学方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.
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来源期刊
CiteScore
2.30
自引率
0.00%
发文量
9
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.
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