PCSK9 rs11591147 R46L loss-of-function variant protects against liver damage in individuals with non-alcoholic fatty liver

Background and Aims: The proprotein convertase subtilisin/kexin type 9(PCSK9) plays a key role in cholesterol homeostasis, and its inhibition represents an effective therapy to lower LDL-C levels. In this study, we examined the impact of PCSK9 rs11591147 loss-of-function(LOF) variant on liver damage in a multicenter collection of patients at risk of nonalcoholic steatohepatitis(NASH), in clinical samples and experimental models.