The Association of Cardiovascular Disease (CVD) with Progression of Advanced Fibrosis Risk in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Objective: Advanced fibrosis is the best predictor of future severe liver outcomes in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Our study aims to determine the association between cardiovascular disease (CVD) with time to a high-risk Fibrosis-4 Index (FIB-4) in patients with low-risk MASLD. Methods: This retrospective cohort study was conducted at a primary care clinic between 2012 and 2021. The cohort included patients with MASLD and a FIB-4 score at low risk for advanced fibrosis (<1.3). Patients were followed for the outcome of having a high-risk FIB-4 (≥2.67) or until the end of the study period. The primary predictor variable was CVD, a composite of ICD-9/10 codes for coronary artery, cerebrovascular, and peripheral arterial disease. Covariates included demographic and comorbidity variables. Unadjusted and adjusted Cox regression models were developed for the outcome of time to a high-risk FIB-4 score. Results: The cohort included 859 patients with a mean age of 49.6 years (± 13.7) and mean body mass index of 34.1 (± 8.3) kg/m2. The included patients were 70% female and 41% non-white. Of the cohort, 32%, 36%, and 74% had CVD, type 2 diabetes mellitus, and hypertension, respectively. During a mean follow-up of 3.8 (± 2.7) years, 9.3% (80) of the sample had a subsequent high-risk FIB-4 score. The multivariable Cox regression model demonstrated a significant association between CVD (HR 2.13; 95%CI 1.33–3.40) and chronic kidney disease (HR 2.05; 95%CI 1.23–3.42) with the time to transition to a high-risk FIB-4 score. Conclusion: Our study showed that CVD is associated with an increased risk of progression of FIB-4 scores at low to high risk for advanced fibrosis in MASLD patients. Future research investigating how control of cardiometabolic comorbidities impact fibrosis progression in MASLD is warranted.