Association of non-invasive liver-related scores with cardiovascular disease and a four-domain cardiovascular–renal–hepatic–metabolic phenotype in patients with type 2 diabetes mellitus and MASLD

Abstract

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a systemic disorder associated with cardiovascular, renal, and metabolic comorbidities. We evaluated cardiovascular disease (CVD), four-domain cardiovascular–renal–hepatic–metabolic (CRHM) involvement, and their associations with non-invasive liver-related scores in patients with type 2 diabetes mellitus (T2DM) and MASLD. We retrospectively analyzed 216 patients with T2DM and MASLD. A study-specific four-domain CRHM phenotype was defined as the coexistence of T2DM, MASLD, chronic kidney disease (CKD), and atherosclerotic CVD. FIB-4, AST-to-ALT ratio (AAR), APRI, Hellenic Score II, Fibrotic NASH Index (FNI), and CORE model were evaluated. CVD was present in 75/216 participants (34.7%). Among 206 participants with sufficient classification data, 35 (17.0%) had the four-domain CRHM phenotype. Patients with CVD had higher Hellenic Score II, creatinine, glycated hemoglobin, FNI, and CORE scores, and lower HDL. FNI showed modest discrimination for CVD (AUROC 0.65; 95%CI 0.56–0.74), while FNI combined with Hellenic Score II showed higher discrimination (AUROC 0.80; 95%CI 0.72–0.87). Participants with CRHM phenotype had higher APRI and FIB-4 and lower platelet counts. FIB-4 was independently associated with CRHM (OR 5.4; 95%CI 1.6–18.6) and showed moderate discriminative ability (AUROC 0.69; 95%CI 0.56–0.83). FIB-4 combined with CORE showed greater discriminative ability (AUROC 0.81; 95%CI 0.70–0.92). In patients with T2DM and MASLD, liver-related scores showed distinct associations with cardiovascular and multidomain disease burden. FNI was associated with CVD, whereas FIB-4 was associated with a study-specific four-domain CRHM phenotype. These findings are exploratory and require external validation.