Risk of Non-Alcoholic Fatty Liver Disease in Xanthelasma Palpebrarum

BACKGROUND: Xanthelasma palpebrarum (XP) is a sign of hyperlipidemia and is closely linked to atherosclerosis. Since fatty liver shares similar risk factors with atherosclerosis, we hypothesized that patients with XP are also at risk of non-alcoholic fatty liver disease (NAFLD). METHODS: In this retrospective cohort study, 37 patients with XP were compared with sex- and age-matched controls undergoing general health examination. Moreover, demographic information and lipid profiles were compared. The risk of NAFLD was evaluated using the hepatic steatosis and ZJU indices. In addition, we analyzed publicly available RNA sequencing data from the GSE48452 and GSE61260 datasets in the Gene Expression Omnibus database. FINDINGS: Patients with XP had higher scores of hepatic steatosis index (37 ± 1.13 vs 32 ± 0.82, p=0.0006) and ZJU index (38.77 ± 1.0 vs 33.88 ± 0.74, p=0.0002). In addition, they had higher levels of lipid parameters, including total cholesterol, low-density lipoprotein (LDL), and fasting glucose. Among patients with fatty liver, individuals presenting with XP showed higher serum levels of total cholesterol (216 ± 10.4 vs 188.9 ± 7.6, p=0.04), fasting glucose (117.1 ± 6.4 vs 98.3 ± 2.4, p=0.002), and low-density lipoprotein (145.1 ± 8.7 vs 115.6 ± 6.4, p=0.009) than those without XP. In gene expression analysis, individuals presenting with non-alcoholic steatohepatitis showed higher Z scores of xanthelasma than those without non-alcoholic steatohepatitis. CONCLUSION: Our results suggest that individuals with XP have a higher risk of progression to NAFLD and develop a more severe dyslipidemia.