The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.
The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.
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DOI：
10.1016/j.mam.2017.04.004
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发表时间：
2017-08
影响因子：
10.6
通讯作者：
Guo GL
中科院分区：
文献类型：
--
作者：
Chow MD;Lee YH;Guo GL
非酒精性脂肪肝在世界范围内的患病率正在上升。它开始于肝脏组织学上出现大脂肪变性，但通常临床无症状。然而，它可以发展为非酒精性脂肪性肝炎，这是一种以炎症和纤维化为特征的更严重的肝脏疾病。进一步发展会导致肝硬化，使患者易患肝细胞癌或肝功能衰竭。单纯脂肪变性发展为脂肪性肝炎的机制尚不完全清楚。然而，已经提出了多种途径。许多这些途径之间的一个共同联系是破坏胆汁酸的体内平衡。除了帮助脂质和脂溶性维生素的吸收外，胆汁酸还起到配体的作用。例如，它们与法脂类X受体结合，该受体在维持胆汁酸、葡萄糖和脂质稳态的许多途径中起关键作用。这些通路的改变可导致能量平衡的失调和炎症和纤维化的增加。长期反复的损伤可能是脂肪性肝炎发展的关键。由于这个原因，目前的药物针对这些途径的各个方面，试图减少和停止炎症和纤维化。本文将重点讨论胆汁酸在这些不同途径中的作用，以及这些途径的变化如何导致脂肪性肝炎。虽然没有批准的药物治疗肝脂肪变性或脂肪性肝炎，这篇综述也将触及众多潜在的治疗方法。
Nonalcoholic fatty liver disease is growing in prevalence worldwide. It is started by the presence of macrosteatosis on liver histology but is often clinically asymptomatic. However, it can progress into nonalcoholic steatohepatitis which is a more severe form of liver disease characterized by inflammation and fibrosis. Further progression leads to cirrhosis, which predisposes patients to hepatocellular carcinoma or liver failure. The mechanism by which simple steatosis progresses to steatohepatitis is not entirely clear. However, multiple pathways have been proposed. A common link amongst many of these pathways is disruption of the homeostasis of bile acids. Other than aiding in the absorption of lipids and lipid-soluble vitamins, bile acids act as ligands. For example, they bind to farnesoid X receptor, which is critically involved in many of the pathways responsible for maintaining bile acid, glucose, and lipid homeostasis. Alterations to these pathways can lead to deregulation in energy balance and increased inflammation and fibrosis. Repeated insults over time may be the key to development of steatohepatitis. For this reason, current drugs target aspects of these pathways to try to reduce and halt inflammation and fibrosis. This review will focus on the role of bile acids in these various pathways and how changes in these pathways may result in steatohepatitis. While there is no approved pharmaceutical treatment for either hepatic steatosis or steatohepatitis, this review will also touch upon the multitude of potential therapies.
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DOI：
10.1002/hep.28689
发表时间：
2016-09
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Ding L;Sousa KM;Jin L;Dong B;Kim BW;Ramirez R;Xiao Z;Gu Y;Yang Q;Wang J;Yu D;Pigazzi A;Schones D;Yang L;Moore D;Wang Z;Huang W
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Huang W
影响因子：
4.5
作者：
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通讯作者：
Nakamuta, Makoto
DOI：
10.1097/meg.0b013e328345c8c7
发表时间：
2011-05
影响因子：
2.1
作者：
Dasarathy S;Yang Y;McCullough AJ;Marczewski S;Bennett C;Kalhan SC
通讯作者：
Kalhan SC
影响因子：
4.8
作者：
Guo, GL;Lambert, G;Sinal, CJ
通讯作者：
Sinal, CJ
影响因子：
9.8
作者：
Buzzetti, Elena;Pinzani, Massimo;Tsochatzis, Emmanuel A.
通讯作者：
Tsochatzis, Emmanuel A.