Department of Gastroenterology and Hepatology, Chongqing University Central Hospital (Chongqing Emergency Medical Center), Chongqing, China.
Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8515-8522. doi: 10.26355/eurrev_201910_19165.
Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide and also become an emerging risk factor for liver-related complications, such as cirrhosis and hepatocellular carcinoma (HCC). The liver-related burden of NASH is likely to increase and nonalcoholic steatohepatitis (NASH) is probably to be the leading indication for liver transplantation by 2020, as a consequence of increased disease prevalence and of the lack of an effective treatment. The first step in the NAFLD development is represented by fat accumulation in the liver, a condition that is commonly associated with features of the metabolic syndrome. Notably, it has been acknowledged that the step from nonalcoholic fatty liver (NAFL) to NASH is key step in the NASH formation, and the mechanisms behind this transition have been extensively studied. Emerging evidence indicates that innate immunity is a driving force in NAFLD progression because it directly regulates all key pathogenic features of the disease processes, including metabolic dysregulation, inflammation, and fibrosis. In this review, we summarize the currently available signaling pathways of NASH formation, including oxidative stress, NOD-like receptors (NLRs), mitochondria-associated pathways, Toll-like receptors (TLRs), nuclear receptors, and other signal pathways, for the aim of a better understanding of this disease.
非酒精性脂肪性肝病（NAFLD）已成为全球最常见的慢性肝病，也是与肝脏相关并发症（如肝硬化和肝细胞癌（HCC））相关的新兴风险因素。由于疾病流行率增加和缺乏有效治疗方法，NASH 的肝脏相关负担可能会增加，而非酒精性脂肪性肝炎（NASH）可能成为 2020 年肝移植的主要适应证。NAFLD 发展的第一步是肝脏脂肪堆积，这种情况通常与代谢综合征的特征有关。值得注意的是，人们已经认识到，从非酒精性脂肪肝（NAFL）到 NASH 的转变是 NASH 形成的关键步骤，并且已经广泛研究了这一转变背后的机制。新出现的证据表明，先天免疫是 NAFLD 进展的驱动力，因为它直接调节疾病过程的所有关键致病特征，包括代谢失调、炎症和纤维化。在这篇综述中，我们总结了目前 NASH 形成的信号通路，包括氧化应激、NOD 样受体（NLRs）、线粒体相关途径、Toll 样受体（TLRs）、核受体和其他信号通路，以期更好地了解这种疾病。
