The Role of PCSK9 in the Pathogenesis of Non-alcoholic Fatty Liver Disease and the Effect of PCSK9 Inhibitors.

Abstract

Statin treatment exhibits a beneficial effect on non-alcoholic fatty liver disease (NAFLD) and on cardiovascular disease (CVD) in patients with NAFLD. The aim of this review is to summarize the role of proprotein convertase subtilisin kexin type- 9(PCSK9) in the pathogenesis of NAFLD and discuss the effects of the new hypolipidaemic drugs PCSK9 inhibitors on NAFLD. Data indicates that high intrahepatic or circulating PCSK9 levels increase muscle and liver lipid storage, adipose energy storage and hepatic fatty acids, as well as triglycerides storage and secretion, thus contributing to the pathogenesis of NAFLD. The findings of animal and human studies, aiming to reduce PCSK9 with inhibitors (human IGG antibodies, antisense particles against PCSK9 mRNA, and small anti PCSK9 antibodies) point towards liver protection from NAFLD through inhibition of PCSK9 expression in the induction of degradation of hepatic HNF1a protein, insulin resistance (IR), and other mechanisms. The use of PCSK9 inhibitors ameliorates NAFLD, aside from beneficial effects on CVD and independently of low density lipoprotein cholesterol level reduction.