Effect of Statins and PCSK9 Inhibition on Metabolic Dysfunction–Associated Steatotic Liver Disease

Abstract

Dyslipidemia is common in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and, along with other metabolic comorbidities, accounts for an increased cardiovascular risk. Effective treatment of dyslipidemia not only reduces such risk but may have a beneficial effect on MASLD as well. Here we reviewed published data on the efficacy and safety of available hypolipidemic treatments for MASLD. Statins are the mainstay of hypolipidemic therapy for MASLD. In patients with compensated cirrhosis, statins are safe and can improve the risks of decompensation and hepatocellular carcinoma as well as mortality. However, in those with decompensated cirrhosis, statins should not be used unless there are strong indications that outweigh the risk of adverse events. Studies on proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors acting as the second-line therapy in MASLD remain scarce. Preliminary clinical data support their protective roles in MASLD; however, preclinical data raise concerns regarding safety, in particular with complete PCSK9 inhibition due to hepatocyte lipid accumulation. While more evidence is required to elucidate the role of PCSK9 inhibitors, statins should be used for the treatment of hyperlipidemia in patients with MASLD according to their cardiovascular risk stratification.