The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)
The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)
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DOI：
10.1016/j.metabol.2015.12.012
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发表时间：
2016-08-01
影响因子：
9.8
通讯作者：
Tsochatzis, Emmanuel A.
中科院分区：
文献类型：
--
作者：
Buzzetti, Elena;Pinzani, Massimo;Tsochatzis, Emmanuel A.
非酒精性脂肪性肝病（NAFLD）越来越普遍，在预防和治疗方面面临着越来越大的挑战。尽管其患病率很高，但只有一小部分受影响的患者会发生炎症，随后发生纤维化和慢性肝病，而其中大多数患者仅表现出简单的脂肪变性。在这种情况下，充分了解NAFLD和非酒精性脂肪性肝炎（NASH）发展的潜在机制是极其重要的;尽管在这一领域取得了进展，但对NAFLD发病机制的认识仍然不完整。“两次打击”假说现在已经过时，因为它不足以解释NAFLD中发生的几种分子和代谢变化。“多重打击”假说认为多重损伤共同作用于遗传易感受试者诱发NAFLD，并提供了NAFLD发病机制的更准确解释。这些影响包括胰岛素抵抗、脂肪组织分泌的激素、营养因素、肠道微生物群以及遗传和表观遗传因素。在这篇文章中，我们回顾了形成这一假设的因素。(C)2016 Elsevier Inc. All rights reserved.
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. Despite its high prevalence, only a small minority of affected patients develops inflammation and subsequently fibrosis and chronic liver disease, while most of them only exhibit simple steatosis. In this context, the full understanding of the mechanisms underlying the development of NAFLD and nonalcoholic steatohepatitis (NASH) is of extreme importance; despite advances in this field, knowledge on the pathogenesis of NAFLD is still incomplete. The 'two-hit' hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD. The "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such hits include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota and genetic and epigenetic factors. In this article, we review the factors that form this hypothesis. (C) 2016 Elsevier Inc. All rights reserved.