Effect of Non-Statin Lipid-Lowering Therapy on Hepatic Outcomes in Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Systematic Review.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are significant health concerns affecting a large segment of the population and are known to be associated with adverse cardiovascular outcomes. As a result, various lipid-lowering medications are commonly employed in clinical practice to address the elevated cardiovascular risk in these patients. This systematic review summarizes the current evidence on emerging non-statin lipid-lowering therapies-ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, eicosapentaenoic acid (EPA), and bempedoic acid-and their effects on hepatic outcomes in patients with MASLD or MASH. A total of 18 studies involving 933 participants were deemed eligible for inclusion, along with 1 ongoing study included for descriptive analysis. Ezetimibe had the most extensive supporting evidence: 4 of 5 non-randomized studies reported improvements in hepatic enzyme levels, whereas 5 of 8 randomized controlled trials found no significant changes. Imaging results were mixed, with some studies demonstrating reduced hepatic fat content by magnetic resonance imaging or ultrasound, while others found no effect. Histological improvements were observed in non-randomized studies, but randomized trials showed no significant histopathological changes. Only 3 studies on PCSK9 inhibitors were included, of which 2 reported imaging-based improvements in hepatic steatosis. Two studies assessed EPA, but yielded conflicting results, and only 1 ongoing study has examined bempedoic acid. Although preclinical data suggest potential hepatic benefits of these therapies in MASLD, current clinical evidence remains limited and inconsistent, highlighting the need for larger, high-quality trials to establish definitive conclusions.