Higher serum uric acid to HDL-cholesterol ratio is associated with onset of non-alcoholic fatty liver disease in a non-obese Chinese population with normal blood lipid levels
Authors: Zhu Wentao , Liang An , Shi Pei , Yuan Songsong , Zhu Ying , Fu Jiwei , Zheng Ting , Wen Zhilong , Wu Xiaoping 
Published: April 2022

Abstract
Background
Recent studies have demonstrated the presence of associations between metabolic syndrome and the onset of nonalcoholic fatty liver disease (NAFLD). Metabolic syndrome, in turn, has been found to be linked to high serum uric acid to HDL-cholesterol ratios (UHR). However, the relationship between UHR values and the occurrence of NAFLD in non-obese individuals remains unknown. The present study aimed to examine the possible correlation between UHR values and NAFLD onset among a non-obese Chinese population without dyslipidemia, as well as comparing the predictive value of UHR versus other NAFLD onset predictors.

Methods
A total of 9837 non-obese patients, with normal blood lipid levels, were included in a 5-year retrospective cohort study, and the onset of NAFLD in these patients was diagnosed by liver ultrasound.

Results
Out of the 9837 patients, 855 were diagnosed with NAFLD during the 5-year follow-up period, for an overall total prevalence of 8.7% at the end of the study period. Across quintiles 1, 2, 3, 4 and 5 of UHR (respectively, ratios of ≤ 120.88, 120.89–154.01, 154.02–189.91, 189.92–240.46, and ≥ 240.47), the prevalence of NAFLD among the patients increased from 2.4%, 5%, 7.9%, 10.3%, and 17.8%, respectively. After adjustments for age, gender, liver and kidney functional markers, as well as metabolic indicators, multivariate Cox proportional hazard regression analysis demonstrated that the hazard ratio (HR) was the highest in quintile 5, at 1.76 (1.12–2.75), and the lowest in quintile 1. The area under the curve (AUC) for UHR (0.690) was higher than that for serum uric acid (UA, 0.666) and HDL-C (0.636), suggesting the predictive ability of UHR for NAFLD onset was better than either alone. This finding was further supported by the presence of an independent association between UHR and NAFLD, even within the normal range of UA and HDL-C; the HR (95% confidence interval, CI) for NAFLD was 1.002 (1.000–1.004). Compared with other significant predictors, AUC for UHR (0.67) was similar to that of low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C, 0.68), non-high-density lipoprotein cholesterol (NHDL-C)/HDL-C (0.68) and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ratios (0.7), and was higher than that of LDL-C (0.63), remnant cholesterol (RC,0.59), and albumin (ALB)/alkaline phosphatase (ALP) ratio (0.61). The sensitivity of UHR (71%) was the highest among all indicators. In the subgroup with ALT < 40U/L, the AUC for UHR was 0.70, which was the highest among all predictors; among ALT > 40U/L, UHR was able to predict the occurrence of NAFLD (AUC = 0.61, p = 0.007), which was not the case for RC (P = 0.441), ALB/ALP (P = 0.419), and ALT/AST (P = 0.159).

Conclusions
UHR serve as an inexpensive and reliable predictor of NAFLD onset in non-obese Chinese people with normal blood lipid levels, allowing for identification of individuals at high risk for NAFLD.