Longitudinal Examination of the UA/HDL-C Ratio as a Biomarker for Fatty Liver Disease: Findings from a Five-Year Follow-Up. Genetics of Atherosclerotic Disease (GEA) Study

<b>Background</b>: This longitudinal study assessed the Uric Acid/HDL-Cholesterol (UA/HDL-C) ratio as a prognostic biomarker for fatty liver disease (FLD) during a five-year follow-up of 1022 participants from the Genetics of Atherosclerotic Disease (GEA) Study. FLD is a multifactorial disease associated with cardiometabolic comorbidities, and genetic variants affecting uric acid transport (<i>ABCG2</i> rs2231142) and hepatic lipid metabolism (<i>PNPLA3</i> rs738409). Early diagnosis is essential to prevent disease progression; however, standard diagnostics are expensive and not widely accessible, highlighting the need for noninvasive tools. <b>Objectives</b>: The study aimed to validate the UA/HDL-C as a long-term predictor for FLD and its effectiveness in risk stratification, including adjustment for cardiometabolic factors and genetics. <b>Methods</b>: Non-contrast computed tomography was used to diagnose FLD and rs738409 and rs2231142 were genotyped by real-time PCR. ROC curves, Kaplan-Meier survival analysis, and logistic regression were used. <b>Results</b>: The findings show that FLD patients exhibited significantly higher UA/HDL-C than controls at both baseline and follow-up (<i>p</i> < 0.0001). Higher UA/HDL-C quartiles were associated with greater FLD prevalence, exceeding 50% in the highest quartile. The index cut-off points were 0.18 in men and 0.09 in women. ROC analysis showed significant discrimination for FLD (AUC: 0.637 overall, 0.650 in men, 0.626 in women). <b>Conclusions</b>: Logistic regression confirmed a strong independent association between UA/HDL-C and FLD over five years, even after adjustment for genetic, biochemical, and anthropometric factors, OR = 3.53, 95% CI: 2.39-4.68, <i>p</i> < 0.0001. Results suggest this ratio could be an alternative to find and follow FLD early on, especially in places with few resources.