NASH is an Inflammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications.
NASH is an Inflammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications.
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纳什（Nash）是一种炎症障碍：致病性，预后和治疗意义。
DOI：
10.5009/gnl.2012.6.2.149
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发表时间：
2012-04
期刊：
影响因子：
3.4
通讯作者：
Chitturi S
中科院分区：
文献类型：
--
作者：
Farrell GC;van Rooyen D;Gan L;Chitturi S
虽然非酒精性脂肪性肝病（NAFLD）在现代社会中非常普遍（15%至45%），但只有10%至25%的病例发生肝纤维化，导致肝硬化，终末期肝病或肝细胞癌。除了既存的纤维化，NAFLD中纤维化进展的最强预测因子是脂肪性肝炎或非酒精性脂肪性肝炎（NASH）。除脂肪变性外的关键特征是肝细胞变性（气球样变、马洛里透明样变）和混合炎性细胞浸润。虽然对脂肪变性与代谢因素（营养过剩、胰岛素抵抗、高血糖症、代谢综合征、低脂联素血症）的关系了解很多，但对炎症募集的了解较少，尽管其对肝损伤和纤维化的持续存在具有重要意义。在这篇综述中，我们提出的证据表明肝脏炎症在NAFLD中具有预后意义。然后我们考虑NASH中肝脏炎症的起源和成分。由毒性脂质分子（脂毒性）损伤的肝细胞在涉及Toll样受体（TLR）、枯否细胞（KC）、淋巴细胞和中性粒细胞以及可能的炎性小体的先天免疫的募集中起核心作用。NASH中的关键促炎信号通路是核因子-κ B（NF-κB）和c-Jun N-末端激酶（JNK）。下游效应物包括粘附分子、趋化因子、细胞因子和导致细胞凋亡的细胞死亡途径的激活。NF-κB和JNK的上游激活剂更有争议，可能取决于所使用的实验模型。TLR是强有力的竞争者。NASH中的炎症仍然可能起源于肝脏外部和引发KC/TLR反应的肠道微生物群、发炎的脂肪组织和循环炎性细胞。我们简要回顾这些机制的考虑和项目的影响NASH的有效治疗。
While non-alcoholic fatty liver disease (NAFLD) is highly prevalent (15% to 45%) in modern societies, only 10% to 25% of cases develop hepatic fibrosis leading to cirrhosis, end-stage liver disease or hepatocellular carcinoma. Apart from pre-existing fibrosis, the strongest predictor of fibrotic progression in NAFLD is steatohepatitis or non-alcoholic steatohepatitis (NASH). The critical features other than steatosis are hepatocellular degeneration (ballooning, Mallory hyaline) and mixed inflammatory cell infiltration. While much is understood about the relationship of steatosis to metabolic factors (over-nutrition, insulin resistance, hyperglycemia, metabolic syndrome, hypoadiponectinemia), less is known about inflammatory recruitment, despite its importance for the perpetuation of liver injury and fibrogenesis. In this review, we present evidence that liver inflammation has prognostic significance in NAFLD. We then consider the origins and components of liver inflammation in NASH. Hepatocytes injured by toxic lipid molecules (lipotoxicity) play a central role in the recruitment of innate immunity involving Toll-like receptors (TLRs), Kupffer cells (KCs), lymphocytes and neutrophils and possibly inflammasome. The key pro-inflammatory signaling pathways in NASH are nuclear factor-kappa B (NF-κB) and c-Jun N-terminal kinase (JNK). The downstream effectors include adhesion molecules, chemokines, cytokines and the activation of cell death pathways leading to apoptosis. The upstream activators of NF-κB and JNK are more contentious and may depend on the experimental model used. TLRs are strong contenders. It remains possible that inflammation in NASH originates outside the liver and in the gut microbiota that prime KC/TLR responses, inflamed adipose tissue and circulating inflammatory cells. We briefly review these mechanistic considerations and project their implications for the effective treatment of NASH.
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影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
DOI：
10.1016/j.bbrc.2006.02.032
发表时间：
2006-04-21
影响因子：
3.1
作者：
Arsov, T;Larter, CZ;Farrell, GC
通讯作者：
Farrell, GC
影响因子：
29.4
作者：
Bugianesi, E;Leone, N;Rizzetto, M
通讯作者：
Rizzetto, M
影响因子：
13.5
作者：
Brunt, Elizabeth M.;Kleiner, David E.;Wilson, Laura A.;Unalp, Aynur;Behling, Cynthia E.;Lavine, Joel F.;Neuschwander-Tetri, Brent A.
通讯作者：
Neuschwander-Tetri, Brent A.
DOI：
10.1111/j.1440-1746.2011.06774.x
发表时间：
2011-10-01
影响因子：
4.1
作者：
Adams, Leon A.;George, Jacob;Jeffrey, Gary P.
通讯作者：
Jeffrey, Gary P.