Unit of Cellular and Molecular Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy.
Int J Mol Sci. 2020 Dec 17;21(24):9646. doi: 10.3390/ijms21249646.
Nonalcoholic fatty liver disease (NAFLD) is a continuum of liver abnormalities often starting as simple steatosis and to potentially progress into nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. Because of its increasing prevalence, NAFLD is becoming a major public health concern, in parallel with a worldwide increase in the recurrence rate of diabetes and metabolic syndrome. It has been estimated that NASH cirrhosis may surpass viral hepatitis C and become the leading indication for liver transplantation in the next decades. The broadening of the knowledge about NASH pathogenesis and progression is of pivotal importance for the discovery of new targeted and more effective therapies; aim of this review is to offer a comprehensive and updated overview on NAFLD and NASH pathogenesis, the most recommended treatments, drugs under development and new drug targets. The most relevant in vitro and in vivo models of NAFLD and NASH will be also reviewed, as well as the main molecular pathways involved in NAFLD and NASH development.
非酒精性脂肪性肝病（NAFLD）是一种肝脏异常的连续谱，通常从单纯性脂肪变性开始，并可能进展为非酒精性脂肪性肝炎（NASH）、纤维化、肝硬化和肝细胞癌。由于其患病率的增加，NAFLD 正成为一个主要的公共卫生关注点，同时全球范围内糖尿病和代谢综合征的复发率也在上升。据估计，NASH 肝硬化可能超过丙型肝炎病毒，并在未来几十年成为肝移植的主要适应证。对 NASH 发病机制和进展的认识不断拓宽，对于发现新的靶向和更有效的治疗方法至关重要；本文旨在对 NAFLD 和 NASH 的发病机制、最推荐的治疗方法、正在开发的药物和新的药物靶点进行全面和最新的综述。还将回顾 NAFLD 和 NASH 最相关的体外和体内模型，以及参与 NAFLD 和 NASH 发展的主要分子途径。
