Abstract
BACKGROUND: Steatotic liver disease, characterized by hepatic steatosis, increases the risk of metabolic and cardiovascular diseases. We previously reported that the plasma activity of xanthine oxidoreductase (XOR), primarily expressed in the human liver, is also associated with these diseases. The present study examined whether hepatic steatosis is associated with increased XOR activity. METHODS: This cross-sectional study included 334 participants who underwent health examinations and were not receiving urate-lowering or insulin therapy. Values for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) obtained with vibration-controlled transient elastography were used to assess hepatic steatosis and fibrosis. Plasma XOR activity was determined with our highly sensitive assay. RESULTS: Median CAP, LSM, and plasma XOR activity values were 234.0 dB/m, 3.6 kPa, and 27.2 pmol/h/mL, respectively. CAP was correlated with plasma XOR activity (ρ = 0.540, P < 0.001) and subjects with hepatic steatosis (CAP ≥248 dB/m; n = 136) showed higher activity levels than those without (40.8 vs. 21.2 pmol/h/mL, P < 0.001). Multivariable regression analyses, adjusted for confounding factors including aspartate aminotransferase, alanine aminotransferase, adiponectin, and homeostasis model assessment of insulin resistance (IR), indicated associations of CAP and hepatic steatosis with plasma XOR activity (β = 0.163, P < 0.001; β = 0.086, P = 0.037, respectively). These associations remained consistent across subgroups stratified by alcohol consumption. Neither LSM nor hepatic fibrosis (LSM ≥7.9 kPa; n = 4) was associated with plasma XOR activity. CONCLUSIONS: These results suggest that hepatic steatosis increases plasma XOR activity independent of liver enzymes, adiponectin, and IR.