# 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

**Authors:** Rosalinda Posadas-Sánchez, Gilberto Vargas-Alarcón, Giovanny Fuentevilla-Álvarez, Guillermo C. Cardoso-Saldaña

PMC · DOI: 10.3390/diagnostics16050655 · Diagnostics · 2026-02-24

## TL;DR

A study found that the UA/HDL-C ratio can predict fatty liver disease over five years, offering a low-cost alternative for early diagnosis.

## Contribution

The study validates the UA/HDL-C ratio as a long-term, non-invasive biomarker for fatty liver disease.

## Key findings

- FLD patients had significantly higher UA/HDL-C levels than controls at baseline and follow-up.
- Higher UA/HDL-C quartiles correlated with increased FLD prevalence, with over 50% in the highest quartile.
- Logistic regression confirmed a strong independent association between UA/HDL-C and FLD after adjusting for multiple factors.

## Abstract

Background: 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 (ABCG2 rs2231142) and hepatic lipid metabolism (PNPLA3 rs738409). Early diagnosis is essential to prevent disease progression; however, standard diagnostics are expensive and not widely accessible, highlighting the need for noninvasive tools. Objectives: 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. Methods: 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. Results: The findings show that FLD patients exhibited significantly higher UA/HDL-C than controls at both baseline and follow-up (p < 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). Conclusions: 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, p < 0.0001. Results suggest this ratio could be an alternative to find and follow FLD early on, especially in places with few resources.

## Linked entities

- **Genes:** ABCG2 (ATP binding cassette subfamily G member 2 (JR blood group)) [NCBI Gene 9429], PNPLA3 (patatin like domain 3, 1-acylglycerol-3-phosphate O-acyltransferase) [NCBI Gene 80339]
- **Diseases:** fatty liver disease (MONDO:0004790)

## Full-text entities

- **Genes:** ABCG2 (ATP binding cassette subfamily G member 2 (JR blood group)) [NCBI Gene 9429] {aka ABC15, ABCP, BCRP, BMDP, CD338, CDw338}, PNPLA3 (patatin like domain 3, 1-acylglycerol-3-phosphate O-acyltransferase) [NCBI Gene 80339] {aka ADPN, C22orf20, iPLA(2)epsilon}
- **Diseases:** Atherosclerotic Disease (MESH:D050197), FLD (MESH:D005234)
- **Chemicals:** lipid (MESH:D008055), Uric Acid (MESH:D014527)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs738409, rs2231142

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12984970/full.md

## References

49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12984970/full.md

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Source: https://tomesphere.com/paper/PMC12984970