Pathogenesis of NAFLD and NASH
Pathogenesis of NAFLD and NASH
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DOI：
10.1007/978-3-319-20538-0_4
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
J. Maher
中科院分区：
文献类型：
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作者：
J. Maher
NAFLD和NASH是复杂的疾病，涉及脂质代谢、细胞完整性、免疫稳态和组织修复的紊乱。虽然它们是影响肝脏的异常，但NAFLD和NASH是由肝脏内外发生的病理生理过程引起的。为了全面了解脂肪肝疾病的演变，必须将肝脏视为一个综合代谢网络的组成部分，该网络接收来自脂肪组织、肠道、胰腺和大脑的信号。人们还必须考虑到疾病过程受到遗传背景、环境因素和个人行为的影响，所有这些因素共同调节或失调肝脏的内稳态。本章总结了导致NAFLD和NASH的病理生理过程。它首先讨论了与肥胖有关的异常，这些异常使肝脏积累脂肪。此后，焦点转移到肝脏内外的过程，使肝脂肪变性持续并加重。本章的后半部分讨论NASH肝损伤的发病机制。本文首先对NASH的细胞死亡机制进行了总结，随后讨论了肝脏炎症、纤维化和癌症。由于NAFLD和NASH密切相关，而且该疾病并不总是以“简单”脂肪变性开始，然后发展为脂肪性肝炎，因此两者之间的机制区别有时是模糊的。目前，促使一些人发展为肝脂肪变性而另一些人发展为完全的NASH的因素仍不完全清楚。
NAFLD and NASH are complex conditions that involve derangements of lipid metabolism, cellular integrity, immune homeostasis, and tissue repair. Although they are abnormalities affecting the liver, NAFLD and NASH result from pathophysiologic processes that occur within and outside the liver. To develop a comprehensive understanding of the evolution of fatty liver disease, one must view the liver as a component of an integrated metabolic network that takes signals from the adipose tissue, intestine, pancreas, and brain. One must also consider that the disease process is influenced by genetic background, environmental factors, and personal behavior, all of which come together to regulate, or dysregulate, liver homeostasis. This chapter summarizes the pathophysiologic processes that lead to NAFLD and NASH. It begins with a discussion of abnormalities related to obesity that prime the liver to accumulate fat. Thereafter, the focus shifts to processes inside and outside the liver that perpetuate and accentuate hepatic steatosis. The second half of the chapter addresses the pathogenesis of liver injury in NASH. Here the discussion begins with a summary of cell death mechanisms in NASH and follows with sections devoted to hepatic inflammation, fibrosis, and cancer. Because NAFLD and NASH are so closely related, and because the disease does not always begin with “simple” steatosis and then evolve to steatohepatitis, the mechanistic distinction between the two entities is sometimes blurred. For the moment, the factors that prompt some individuals to develop hepatic steatosis while others develop full-blown NASH remain incompletely understood.