Hepatic Steatosis and Low‐Density Lipoprotein Cholesterol Response After Statin Initiation: A Prospective Cohort Analysis

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with dyslipidemia, which is a major risk factor for cardiovascular diseases and the leading cause of mortality in MASLD. This study aimed to compare the low-density lipoprotein cholesterol (LDL-C) response to statins in patients with and without hepatic steatosis. METHODS: We identified subjects from a population screening program for MASLD who were subsequently started on statins. Statin response was defined as the absolute decrease between prestatin LDL-C level and LDL-C levels from months 0 to 3 and from months 3 to 12, modelled using multivariable linear mixed models. RESULTS: Among 922 subjects who underwent proton-magnetic resonance spectroscopy screening, 286 received statin during follow-up, among whom 132 (46%) had hepatic steatosis (liver fat fraction ≥ 5%) at baseline. The mean defined daily dose of statins was 0.50 ± 0.32 units. The analysis on LDL-C average change per month over 12 months revealed no significant association between hepatic steatosis and statin response. Hepatic steatosis showed a nonsignificant association with poorer statin response over months 0-3 (difference of 0.097 mmol/L per month vs. no hepatic steatosis, p = 0.231) and months 3-12 (-0.037 mmol/L per month, p = 0.141), which remained after adjusting for diabetes, BMI, defined daily dose of statin, use of other lipid-lowering drugs, age, and sex. CONCLUSIONS: The association between hepatic steatosis and poorer LDL-C response to statins, if any, is not clinically significant. Patients with hepatic steatosis are recommended to receive a standard statin dose according to clinical indications.