Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans.
Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans.
复制标题
非酒精性脂肪肝（NAFLD）从人类发病机制到治疗概念。
DOI：
10.1016/j.molmet.2020.101122
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发表时间：
2021-08
影响因子：
8.1
通讯作者：
Roden M
中科院分区：
文献类型：
--
作者：
Pafili K;Roden M
非酒精性脂肪性肝病（NAFLD）包括在没有其他肝病原因的情况下具有增加的脂质积聚（脂肪变性）的肝脏改变，没有或具有炎症（非酒精性脂肪性肝炎，NASH）和/或纤维化。NAFLD正在发展成为一个新兴的健康挑战，主要是由于世界范围内的肥胖和糖尿病流行。本文综述了NAFLD发病机制的相关知识，重点关注人类和高热量营养的研究，包括饱和脂肪和果糖的影响，以及脂肪组织功能障碍，导致肝脏脂毒性，线粒体功能异常和氧化应激，并强调肠道生态失调。这些机制的背景下，目前针对代谢途径的治疗和相关的临床试验的结果进行了讨论。最近的研究提供的证据表明，某些条件，例如，严重的胰岛素抵抗糖尿病（SIRD）亚组（簇）和基因变异数量的增加，似乎容易导致NAFLD的过度风险及其加速进展。最近的临床试验在阻止或预防NAFLD进展方面经常不成功，可能部分原因是在NAFLD的后期阶段纳入了非酒精性脂肪肝队列。在此文献综述的基础上，本研究建议筛查具有最高遗传或获得性疾病进展风险的个体，例如SIRD亚组，并制定针对最早期病理生理学改变（即脂肪细胞功能障碍和胰岛素抵抗）的治疗概念。
Nonalcoholic fatty liver disease (NAFLD) comprises hepatic alterations with increased lipid accumulation (steatosis) without or with inflammation (nonalcoholic steatohepatitis, NASH) and/or fibrosis in the absence of other causes of liver disease. NAFLD is developing as a burgeoning health challenge, mainly due to the worldwide obesity and diabetes epidemics. This review summarizes the knowledge on the pathogenesis underlying NAFLD by focusing on studies in humans and on hypercaloric nutrition, including effects of saturated fat and fructose, as well as adipose tissue dysfunction, leading to hepatic lipotoxicity, abnormal mitochondrial function, and oxidative stress, and highlights intestinal dysbiosis. These mechanisms are discussed in the context of current treatments targeting metabolic pathways and the results of related clinical trials. Recent studies have provided evidence that certain conditions, for example, the severe insulin-resistant diabetes (SIRD) subgroup (cluster) and the presence of an increasing number of gene variants, seem to predispose for excessive risk of NAFLD and its accelerated progression. Recent clinical trials have been frequently unsuccessful in halting or preventing NAFLD progression, perhaps partly due to including unselected cohorts in later stages of NAFLD. On the basis of this literature review, this study proposed screening in individuals with the highest genetic or acquired risk of disease progression, for example, the SIRD subgroup, and developing treatment concepts targeting the earliest pathophysiolgical alterations, namely, adipocyte dysfunction and insulin resistance.
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