Despite Evidence Demonstrating Safety, Statins Underused in MASLD Patients

Quang Le, PharmD, PhD
Credit: Western University of Health Sciences

A new study leveraging real-world data from US patients has brought forth 2 conclusions for healthcare providers: statin use was not associated with elevated liver enzymes in patients with nonalcoholic fatty liver disease (NAFLD) and, given this backdrop, statins are underused in this patient population.

A cross-sectional analysis of survey data from patients in the US NHANES database, the examination of data, which was representative of 22.6 million US adults, suggested less than 30% were receiving statin therapy despite use associated with significantly lower levels of alanine transaminase (ALT), total cholesterol, and LDL-C.

“Our study uniquely provided evidence from the real-world setting to better understand the effects of statin outside of rigorously controlled environments of clinical trials,” wrote investigators. “The clinical implications focused on resolving the concern of statin-induced hepatotoxicity in patients with NAFLD among PCPs and re-stressing the lipid-lowering benefits of statins among those with an additional diagnosis of dyslipidemia.”

Few advances in pharmacotherapy have had a measurable impact on mortality, particularly ASCVD-related mortality, as statin therapy. However, despite the demonstrated safety profile, decreased cost, and increased accessibility, the healthcare providers have failed to achieve optimal prescription of the agent for many of the same reasons that plague uptake of other therapies, but also as a result of concerns surrounding the potential for liver injury.

Given the prevalence of dyslipidemia among patients with nonalcoholic fatty liver disease, which was recently redefined as metabolic dysfunction-associated steatotic liver disease (MASLD), a team led by Quang Le, PharmD, PhD, Western University of Health Sciences College of Pharmacy, sought to provide an overview of real-world safety and efficacy of statin use in patients with NAFLD. With this in mind, investigators designed a cross-sectional study of survey data obtained from the US NHANES database from 2009 through 2018.^1,2

For the purpose of analysis, NAFLD was defined as having a Fatty Liver Index (FLI) greater than 60 and a United States Fatty Liver Index (USFLI) greater than 30. In total, investigators identified 2,533 participants with NAFLD for inclusion in the study. This figure is representative of 22.76 million adults in the US.

Of note, patients with significant alcohol consumption, positive Hepatitis B, positive Hepatitis C, missing hepatitis serology, or missing components needed to calculate FLI or USFLI were excluded from the study.¹

The primary outcomes of interest for the study were the mean differences in serum liver enzymes including AST, ALT, ALP, and GGT between statin and non-statin use in patients with NAFLD. Investigators noted multivariate regression analyses adjusted for baseline clinical and demographic characteristics were used to compare liver enzymes and lipid profile among statin users and non-users.¹

Upon analysis, results indicated just 27% of these patients received statin therapy during the study period. A total of 1127 of the 2533 individuals included in the study had a diagnosis of dyslipidemia. Among this subgroup, 50% received statin therapy.¹

In an adjusted analysis, results suggested the mean differences of liver enzymes for AST, ALT, ALP, and GGT between statin and non-statin users were -0.86 (P=.539), -3.49 (P=.042), -0.25 (P=.913), and 0.57 (P=.901), respectively. Among the subgroup of patients with dyslipidemia and NAFLD, total cholesterol (mean difference, -28.9; P < .001) and LDL levels were significantly lower in statin users compared to non-statin users(mean difference, -27.7; P < .001).¹

Investigators called attention to limitations within their study ton consider when interpreting results. These limitations included lack of confirmed diagnosis of NAFLD, lack of follow-up information, self-reporting and recall bias associated with survey data, and lack of information on specific statins, among others.¹

“Our study results highlighted the safety of statin use regarding serum liver enzymes in patients with NAFLD and underlined the lipid-lowering effects of statin on total cholesterol and LDL in patients with NAFLD and dyslipidemia,” investigators added.¹

References:

1. ^{Ho A, Kiener T, Nguyen Q-N, Le QA. Effect of statin use on liver enzymes and lipid profile in patients with non-alcoholic fatty liver disease (NAFLD). Journal of Clinical Lipidology. Published online March 12, 2024. doi:10.1016/j.jacl.2024.03.003}
2. ^{Brooks A. From NAFLD TO MASLD: 2023 brings new liver disease nomenclature. HCP Live. December 13, 2023. Accessed March 19, 2024. https://www.hcplive.com/view/from-nafld-to-masld-2023-new-liver-disease-nomenclature.}