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个体化治疗非酒精性脂肪性肝病:关注性别、基因与药物。

Personalized therapy when tackling nonalcoholic fatty liver disease: a focus on sex, genes, and drugs.

机构信息

a Centre for Functional Genomic and Biochips, Institute of Biochemistry, Faculty of Medicine , University of Ljubljana , Ljubljana , Slovenia.

出版信息

Expert Opin Drug Metab Toxicol. 2018 Aug;14(8):831-841. doi: 10.1080/17425255.2018.1492552. Epub 2018 Jul 3.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease in the world. It describes a term for a group of hepatic diseases including steatosis, fibrosis, and cirrhosis that can finally lead to hepatocellular carcinoma. There are many factors influencing NAFLD initiation and progression, such as obesity, dyslipidemia, insulin resistance, genetic factors, and hormonal changes. However, there is also lean-NAFLD which is not associated with obesity. NAFLD is considered to be a sexually dimorphic disease. In most cases, men have a higher prevalence for the disease compared to premenopausal women. Areas covered: In this review, we first summarize the NAFLD disease epidemiology, pathology, and diagnosis. We describe NAFLD progression with the focus on sexual and genetic differences for disease development and pharmacological treatment. Personalized treatment for multifactorial NAFLD is discussed in consideration of different factors, including genetics, gender and sex. Expert opinion: The livers of female and male NAFLD patients have different metabolic capacities which influence the metabolism of all drugs applied to such patients. This aspect is not yet sufficiently taken into account. The liver computational models might quicken the pace toward assessing personalized disease progression and treatment options.

摘要

非酒精性脂肪性肝病 (NAFLD) 是世界上最常见的肝脏疾病。它描述了一组包括脂肪变性、纤维化和肝硬化的肝脏疾病,这些疾病最终可能导致肝细胞癌。有许多因素影响 NAFLD 的发生和进展,如肥胖、血脂异常、胰岛素抵抗、遗传因素和激素变化。然而,也有非肥胖型 NAFLD,它与肥胖无关。NAFLD 被认为是一种性别二态性疾病。在大多数情况下,男性患该病的患病率高于绝经前女性。

涵盖领域

在这篇综述中,我们首先总结了 NAFLD 的疾病流行病学、病理学和诊断。我们描述了 NAFLD 的进展,重点关注疾病发展和药物治疗的性别和遗传差异。我们还讨论了针对多因素 NAFLD 的个体化治疗,考虑了遗传、性别等不同因素。

专家意见

男性和女性 NAFLD 患者的肝脏代谢能力不同,这会影响所有应用于此类患者的药物的代谢。这一方面尚未得到充分考虑。肝脏计算模型可能会加快评估个体化疾病进展和治疗选择的速度。

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