Statins May Prevent Fibrosis Risk Progression in MASLD, Study Finds

Statins may play an important role in preventing advanced fibrosis risk progression in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), according to findings from a recent study.¹

The retrospective assessment of electronic health record data revealed statin prescriptions, specifically those of moderate and high intensity, demonstrated a protective association with fibrosis risk progression in primary care patients with MASLD.¹

“In addition to providing needed cardiovascular risk reduction to patients with MASLD, statins have also shown potential benefits for chronic liver disease, demonstrating an association with a lower hazard of incident cirrhosis, hepatocellular carcinoma and liver-related mortality in studies of retrospective data,” Andrew Schreiner, MD, an associate professor of medicine at the Medical University of South Carolina, and colleagues wrote.¹ “Whether statins can play a role in treating patients with MASLD at low risk for advanced fibrosis and preventing fibrosis progression is not known.”

MASLD is the most common form of chronic liver disease, affecting more than 30% of the global population. It is associated with a greater risk of heart failure and cardiovascular disease, underscoring the importance of addressing cardiovascular risk in patients with MASLD. Statins are often prescribed to reduce low-density lipoprotein cholesterol levels and reduce subsequent risk of stroke or heart attack, and although their association with reducing cardiovascular event risk in MASLD is well understood, their impact on the risk of liver fibrosis is not.^2,3

To determine the association between statins and progression to advanced fibrosis in patients with MASLD, investigators conducted a retrospective cohort study of electronic health record data from an internal medicine primary care clinic at an academic medical center in the southeastern United States from July 2012 through December 2021. Patients with a diagnosis of MASLD by International Classification of Diseases (ICD)-9/10 code or radiographic imaging results with hepatic steatosis were identified.¹

Patients with a competing chronic liver disease diagnosis, cirrhosis, complication of cirrhosis, hepatocellular carcinoma, or history of liver transplant at baseline were excluded. Remaining patients with an MASLD diagnosis or hepatic steatosis finding on imaging were evaluated for available laboratory inputs to calculate a FIB-4 score within 1 year before or after the first MASLD diagnosis or image.¹

The first FIB-4 score calculated at the time of MASLD ascertainment served as the index FIB-4 and subsequent scores were calculated for the remainder of the study period, with FIB-4s separated by ≥ 6 months. Once calculated, FIB-4 scores were categorized by advanced fibrosis risk: low, defined as FIB-4 <1.3; indeterminate, defined as FIB-4 ≤1.3 and <2.67; and high, defined as FIB-4 ≥2.67. Investigators further excluded patients with a high-risk FIB-4 at baseline, patients without 2 FIB-4s during the study period, and patients without 12 months of prescription data preceding the index FIB-4.¹

Time to a high-risk advanced fibrosis risk assessment was the primary outcome of interest, determined by a FIB-4 ≥2.67 during follow-up. Patients were followed from the date of the index FIB-4 until the occurrence of a high-risk FIB-4 or the end of the study period.¹

Prescription of a statin medication was the primary exposure of interest, identified through review of electronic health record data for transmitted and printed prescriptions for any statin medication during follow-up and the year preceding the index FIB-4. Statin prescriptions were categorized by intensity based on definitions from the American College of Cardiology and the American Heart Association.¹

In total, 1238 patients with MASLD and an index FIB-4 score <2.67 were included in the study. Among the cohort, the mean age was 53.7 years, 64% of patients were female, and 40% were non-white. Patients were followed for a mean duration of 3.3 (±2.5) years, during which 47% received a prescription for a statin and 18% progressed to a high risk for advanced fibrosis.¹

By the end of follow-up, 6.6% of patients received a diagnosis for a severe liver disease outcome comprising cirrhosis, a complication of cirrhosis, or hepatocellular carcinoma. Investigators noted a significantly lower proportion of patients with a statin prescription had a severe liver disease outcome compared with patients without a statin script (4.8% vs 8.3%; P = .01).¹

In an adjusted Cox model with statin prescription serving as the primary exposure, statins were associated with a lower risk of progressing to a FIB-4 ≥2.67 (Hazard ratio [HR], 0.60; 95% CI, 0.45-0.80). Further analysis with statin prescription intensity as the exposure revealed moderate (HR, 0.60; 95% CI, 0.42-0.84) and high intensity (HR, 0.61; 95% CI, 0.42-0.88) statins were associated with a lower risk of progressing to a high-risk FIB-4 compared with patients not receiving a statin prescription. Of note, no significant association was observed with the prescription of low-intensity statins.¹

Investigators acknowledged multiple limitations to these findings, including the use of FIB-4 advanced fibrosis risk as a surrogate for advanced fibrosis from histology; the potential for low sensitivity with ICD-9/10 codes for chronic liver disease and comorbidity identification; the threat from immortal time bias because healthier patients are likely to have longer follow-up times and greater opportunity to receive statin therapies; and the potentially insufficient follow-up time for fully addressing the research question.¹

“Generalized use of statin therapies in the primary care management of MASLD is going to be an important consideration in future iterations of MASLD care guidelines,” investigators concluded.¹

References

1. ^{Schreiner AD, Zhang J, Petz CA, et al. Statin prescriptions and progression of advanced fibrosis risk in primary care patients with MASLD. BMJ Open Gastroenterology. doi:10.1136/bmjgast-2024-001404}
2. ^{Christensen, T. Fatty liver disease may increase heart failure risk. American Heart Association. November 16, 2022. Accessed July 23, 2024. https://www.heart.org/en/news/2022/11/16/fatty-liver-disease-may-increase-heart-failure-risk}
3. ^{Cleveland Clinic. Statins. Treatments & Procedures. March 12, 2024. Accessed July 23, 2024. https://my.clevelandclinic.org/health/treatments/22282-statins}