Association of Endothelial Dysfunction and Microalbuminuria with Fibrosis Severity in Patients with MASLD
Hicran Xıdırova
ABSTRACT
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multisystem metabolic disorder in which advanced liver fibrosis is a major determinant of long-term clinical risk. Endothelial dysfunction and microvascular injury may contribute to hepatic fibrogenesis, but the clinical relationship between microalbuminuria, endothelial biomarkers, and fibrosis severity in MASLD remains insufficiently characterized.
Objective: To evaluate the association of microalbuminuria with liver steatosis and fibrosis severity in patients with MASLD and to assess the relationship of microalbuminuria with circulating biomarkers of endothelial dysfunction and systemic inflammation.
Methods: This observational, comparative, cross-sectional study included 180 patients with MASLD and hepatic steatosis confirmed by FibroScan (iLivTouch). Participants were classified according to urinary albumin-to-creatinine ratio into a microalbuminuria group (n=84) and a group without microalbuminuria (n=96). Liver steatosis and stiffness were assessed by controlled attenuation parameter/ultrasound attenuation parameter (CAP/UAP) and liver stiffness measurement (LSM), respectively. FIB-4, Endocan, asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were evaluated. Group comparisons, correlation analyses, and multivariable linear regression were performed.
Results: Patients with microalbuminuria had higher CAP/UAP (301.8 ± 28.4 vs. 275.8 ± 30.7 dB/m; p<0.001) and LSM (13.8 ± 5.1 vs. 9.3 ± 3.2 kPa; p<0.001) than patients without microalbuminuria. Severe steatosis (S3) was more frequent (61.9% vs. 33.3%; p<0.001), as were F3–F4 fibrosis (23.8% vs. 8.3%; p=0.005) and F4-stage findings (21.4% vs. 4.2%; p<0.001). FIB-4, Endocan, ADMA, hs-CRP, and IL-6 were all significantly higher in the microalbuminuria group (all p≤0.001). In multivariable linear regression, microalbuminuria (standardized β=0.42; p<0.001) and elevated Endocan (standardized β=0.31; p=0.004) were independently associated with greater fibrosis severity. Based on the observed 2×2 distribution, the unadjusted odds of an F4-stage finding were 6.27-fold higher in patients with microalbuminuria (95% CI 2.03–19.39).
Conclusion: Microalbuminuria was strongly associated with greater hepatic steatosis, higher liver stiffness, increased fibrosis burden, endothelial dysfunction, and systemic inflammation in patients with MASLD. Microalbuminuria and Endocan were independently associated with fibrosis severity after multivariable adjustment. These findings support further prospective investigation of microalbuminuria and endothelial biomarkers as noninvasive tools for fibrosis risk stratification in MASLD.
