Elevated serum uric acid levels are associated with non-alcoholic
fatty liver disease independently of metabolic syndrome features
in the United States: Liver ultrasound data from the National
Health and Nutrition Examination Survey
Jeffrey C. Sirota
, Kim McFann
, Giovanni Targher
, Richard J. Johnson
, Diana I. Jalal
Division of Renal Diseases & Hypertension, University of Colorado Denver, Aurora, CO, USA
Section of Endocrinology and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona,
ARTICLE INFO ABSTRACT
Received 19 March 2012
Accepted 24 August 2012
Objective. Experimental and observational studies suggest a role for uric acid in non-
alcoholic fatty liver disease (NAFLD). We examined the association between serum uric acid
levels and NAFLD in a large population-based study from the United States.
Materials/Methods. A cross-sectional analysis of 10,732 nondiabetic adults who participated
in the National Health and Nutrition Examination Survey 1988–1994. Sex specific uric acid
quartiles were defined: ≤5.2, 5.3–6.0, 6.1–6.9, and >6.9mg/dL for men and ≤3.7, 3.8–4.5, 4.6–5.3,
and >5.3mg/dL for women. NAFLD presence and severity were defined by ultrasonographic
detection of steatosis in the absence of other liver diseases. We modeled the probability that
more severe NAFLD would be associated with the highest quartiles of uric acid.
Results. Compared to the 1st quartile, the odds ratio for NAFLD was 1.79 (95% C.I. 1.49–2.15,
p<0.001) and 3.14 (95% C.I. 2.63–3.75, p<0.001) for the 3rd and 4th quartiles, respectively. After
adjusting for demographics, hypertension, waist circumference, triglycerides, high-density
lipoprotein-cholesterol, homeostasis model assessment-estimated insulin resistance,
estimated glomerular filtration rate, and aspartate aminotransferase, uric acid (4th quartile)
was significantly associated with NAFLD (odds ratio 1.43; 95% C.I. 1.16–1.76, p<0.001). Positive
parameter estimates suggest increasing uric acid is associated with greater severity of NAFLD.
Conclusions. Elevated uric acid level is independently associated with ultrasound-
diagnosed NAFLD in a nationally representative sample of United States nondiabetic
adults. Increasing uric acid is associated with increasing severity of NAFLD on
ultrasonography. These findings warrant further studies on the role of uric acid in NAFLD.
Published by Elsevier Inc.
METABOLISM CLINICAL AND EXPERIMENTAL 62 (2013) 392– 399
Abbreviations: NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; NHANES, National Health and Nutrition
Examination Survey; HDL-C, high density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; HOMA-IR, homeostasis
model assessment of insulin resistance; AST, aspartate aminotransferase; ALT, alanine aminotransferase; MDRD, Modification of Diet in
Renal Disease; OR, odds ratio; C.I., confidence interval.
⁎ Corresponding author. University of Colorado Denver Health Sciences Center, 12700 E. 19th Avenue, Box C-281, Aurora, CO 80045, USA.
Tel.: +1 303 724 4867; fax: +1 303 724 4868.
E-mail address: firstname.lastname@example.org (D.I. Jalal).
0026-0495/$ – see front matter. Published by Elsevier Inc.
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