An Association of Elevated Blood Vitamin A Level and Severity of Metabolic Dysfunction–Associated Steatotic Liver Disease in Humans

Abstract

Background

In recent years, improvements in living standards and shifts in dietary patterns have led to metabolic dysfunction–associated steatotic liver disease (MASLD) becoming the most common cause of chronic liver disease worldwide. MASLD is closely associated with obesity, insulin resistance, and metabolic syndrome, although its precise pathogenesis remains incompletely understood. The disease encompasses a spectrum of conditions ranging from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH) . Global estimates indicate that the prevalence of MASLD is 25% and continues to rise, with even higher rates observed in Asia. NASH represents a critical stage in the progression of MASLD, and approximately 20% of patients with NASH eventually progress to metabolic dysfunction–associated steatotic liver disease (MASLD)-related cirrhosis or even hepatocellular carcinoma.

Objectives

This study aimed to investigate the association between serum levels of vitamin A, retinol-binding protein 4 (RBP4), and the severity of metabolic dysfunction–associated steatotic liver disease (MASLD) in humans.

Methods

A total of 231 patients with MASLD were recruited and stratified into mild (n = 38), moderate (n = 68), and severe (n = 65) groups on the basis of diagnosis of transient elastography. A control group with 60 healthy individuals was also enrolled. Serum levels of vitamin A, RBP4, alanine transaminase (ALT), aspartate aminotransferase (AST), γ–glutamyl transferase (γ-GT), total bilirubin, bile acids, carcinoembryonic antigen (CEA), lipid profiles, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 were measured and compared among groups.

Results

No significant differences were observed in age, sex, or smoking status among the groups (P > 0.05). However, the prevalence of dyslipidemia was significantly higher in patients with MASLD than in healthy individuals (P < 0.001). The serum levels of ALT, AST, and γ-GT increased significantly with MASLD severity (P < 0.001). Among inflammatory markers, interleukin-6 level was significantly elevated in patients with MASLD (P < 0.001). The serum levels of CRP, PCT, total bilirubin, bile acids, CEA, and AFP were not significantly different among the groups. Serum vitamin A and RBP4 levels were significantly higher in patients with MASLD than in controls and showed a strong positive correlation with disease severity (P < 0.001).

Conclusions

Serum levels of vitamin A and RBP4 in patients with MASLD are significantly elevated and correlated with disease severity, showing an association between blood vitamin A level and MASLD severity. Further well-designed studies are needed to evaluate whether these changes can serve as potential biomarkers for assessing MASLD severity.