A promising therapy for fatty liver disease: PCSK9 inhibitors

作者：Lizhu Han, Liuyun Wu, Qinan Yin, Lian Li, Xingyue Zheng, Shan Du, Xuefei Huang, Lan Bai, Yi Wang, Yuan Bian · 发表于：Phytomedicine · 年份：2024 · DOI：10.1016/j.phymed.2024.155505 · 被引用次数：31 · 研究领域：Lipoproteins and Cardiovascular Health、Liver Disease Diagnosis and Treatment、Drug-Induced Hepatotoxicity and Protection

BACKGROUND: Fatty liver disease (FLD) poses a significant global health concern worldwide, with its classification into nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) contingent upon the presence or absence of chronic and excessive alcohol consumption. The absence of specific therapeutic interventions tailored to FLD at various stages of the disease renders its treatment exceptionally arduous. Despite the fact that FLD and hyperlipidemia are intimately associated, there is still debate over how lipid-lowering medications affect FLD. Proprotein Convertase Subtilisin/ Kexin type 9 (PCSK9) is a serine protease predominantly synthesized in the liver, which has a crucial impact on cholesterol homeostasis. Research has confirmed that PCSK9 inhibitors have prominent lipid-lowering properties and substantial clinical effectiveness, thereby justifying the need for additional exploration of their potential role in FLD. PURPOSE: Through a comprehensive literature search, this review is to identify the relationship and related mechanisms between PCSK9, lipid metabolism and FLD. Additionally, it will assess the pharmacological mechanism and applicability of PCSK9 inhibitors (including naturally occurring PCSK9 inhibitors, such as conventional herbal medicines) for the treatment of FLD and serve as a guide for updating the treatment protocol for such conditions. METHODS: A comprehensive literature search was conducted using several electronic databases, i...