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The serum uric acid/creatinine ratio is associated with nonalcoholic fatty liver disease in the general population


Serum uric acid-to-creatinine ratio (sUA/CrR) may be associated with metabolic syndrome components, but limited evidence exists on a relationship between sUA/Cr and NAFLD. Here, we investigated the association between sUA/CrR and NAFLD.

We performed a cross-sectional analysis in 3359 subjects who participated in the NHANES 2017–2018 survey and consumed less than 30 and 20 g alcohol (men and women, respectively), with no positive tests of viral hepatitis. Liver steatosis was defined by controlled attenuation parameter and fibrosis by stiffness measurements obtained via transient elastography. We modeled the relationship between NAFLD and relevant demographic, anthropometric, and biochemical variables.

sUA/CrR was significantly higher in participants with NAFLD than those without NAFLD. LASSO logit regression showed that only logarithmized age (p = 1.2e-3), waist circumference (WC) (p = 1.8e-5), triglycerides (p = 5e-6), and sUA/CrR (p = 3e-5) were retained in the model. Multivariate logistic analysis demonstrated a significant association between sUA/CrR and NAFLD; the OR for NAFLD of one log(sUA/CrR) increase was 2.61 (95% CI: 1.86–3.68, p < 3e-8) after adjusting for relevant covariables, including aminotransaminase levels and the effect of sUA/CrR remained significant for highest WC quintiles. The model’s predictive power with vs. without sUA/CrR was slightly but significantly better (Auroc: 0.859 ± 0.006 vs. 0.855 ± 0.007, p < 1.1e-2). Mediation analysis showed that SUA/CrR modestly mediates the effect of WC and insulin resistance but not glycohemoglobin on NAFLD.

In conclusion, elevated sUA/CrR was significantly associated with NAFLD in the general population. Therefore, kidney function should be closely monitored in NAFLD patients.

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  1. Al-Daghri NM, Al-Attas OS, Wani K, Sabico S, Alokail MS (2017) Serum uric acid to creatinine ratio and risk of metabolic syndrome in Saudi type 2 diabetic patients. Sci Rep 7:12104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Brunt EM, Wong VW, Nobili V, Day CP, Sookoian S, Maher JJ, Bugianesi E, Sirlin CB, Neuschwander-Tetri BA, Rinella ME (2015) Nonalcoholic fatty liver disease. Nat Rev Dis Primers 1:15080.

    Article  PubMed  Google Scholar 

  3. Cassinotto, C, J Boursier, L de, V, J Lebigot, B Lapuyade, P Cales, JB Hiriart, S Michalak, BL Bail, V Cartier, A Mouries, F Oberti, I Fouchard-Hubert, J Vergniol, C Aube 2016 Liver stiffness in nonalcoholic fatty liver disease: a comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy. Hepatology 63:1817-1827.

  4. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ (2012) The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 142:1592–1609.

    Article  PubMed  Google Scholar 

  5. Darmawan G, Hamijoyo L, Hasan I (2017) Association between serum uric acid and Non-alcoholic fatty liver disease: a meta-analysis. Acta Med Indones 49:136–147

    PubMed  Google Scholar 

  6. Elliott JA, Reynolds JV (2021) Visceral Obesity, Metabolic Syndrome, and Esophageal Adenocarcinoma. Front Oncol 11:627270.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gutierrez-Cuevas J, Santos A, Armendariz-Borunda J (2021) Pathophysiological molecular mechanisms of obesity: a link between MAFLD and NASH with cardiovascular diseases. Int J Mol Sci 22.

  8. Huang F, Liu A, Fang H, Geng X (2017) Serum uric acid levels in non-alcoholic steatosis patients: a meta-analysis. Asia Pac J Clin Nutr 26:334–342.

    Article  CAS  PubMed  Google Scholar 

  9. Karlas, T, D Petroff, M Sasso, JG Fan, YQ Mi, L de, V, M Kumar, M Lupsor-Platon, KH Han, AC Cardoso, G Ferraioli, WK Chan, VW Wong, RP Myers, K Chayama, M Friedrich-Rust, M Beaugrand, F Shen, JB Hiriart, SK Sarin, R Badea, KS Jung, P Marcellin, C Filice, S Mahadeva, GL Wong, P Crotty, K Masaki, J Bojunga, P Bedossa, V Keim, J Wiegand 2017 Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol 66:1022-1030.

  10. Kawamoto R, Ninomiya D, Akase T, Kikuchi A, Kasai Y, Kusunoki T, Ohtsuka N, Kumagi T (2019) Serum uric acid to creatinine ratio independently predicts incident metabolic syndrome among community-dwelling persons. Metab Syndr Relat Disord 17:81–89.

    Article  CAS  PubMed  Google Scholar 

  11. Kawamoto R, Ninomiya D, Kikuchi A, Akase T, Kasai Y, Ohtsuka N, Kumagi T (2019) Serum uric acid to creatinine ratio is a useful predictor of renal dysfunction among diabetic persons. Diabetes Metab Syndr 13:1851–1856.

    Article  PubMed  Google Scholar 

  12. Liu S, Song J, Peng J, Tang Z, Zhang J, Zhang L (2020) Association of serum uric acid/creatinine ratio and metabolic syndrome in euthyroid population. Wei Sheng Yan Jiu 49:374–380.

    Article  CAS  PubMed  Google Scholar 

  13. Lolekha P, Wongwan P, Kulkantrakorn K (2015) Association between serum uric acid and motor subtypes of Parkinson’s disease. J Clin Neurosci 22:1264–1267.

    Article  CAS  PubMed  Google Scholar 

  14. Moriyama K (2019) The association between the serum uric acid to creatinine ratio and metabolic syndrome, liver function, and alcohol intake in healthy Japanese subjects. Metab Syndr Relat Disord 17:380–387.

    Article  CAS  PubMed  Google Scholar 

  15. Newsome PN, Sasso M, Deeks JJ, Paredes A, Boursier J, Chan WK, Yilmaz Y, Czernichow S, Zheng MH, Wong VW, Allison M, Tsochatzis E, Anstee QM, Sheridan DA, Eddowes PJ, Guha IN, Cobbold JF, Paradis V, Bedossa P, Miette V, Fournier-Poizat C, Sandrin L, Harrison SA (2020) FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol 5:362–373.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Paschos P, Athyros VG, Tsimperidis A, Katsoula A, Grammatikos N, Giouleme O (2018) Can serum uric acid lowering therapy contribute to the prevention or treatment of nonalcoholic fatty liver disease? Curr Vasc Pharmacol 16:269–275.

    Article  CAS  PubMed  Google Scholar 

  17. Seo YB, Han AL (2021) Association of the serum uric acid-to-creatinine ratio with nonalcoholic fatty liver disease diagnosed by computed tomography. Metab Syndr Relat Disord 19:70–75.

    Article  CAS  PubMed  Google Scholar 

  18. Sirota JC, McFann K, Targher G, Johnson RJ, Chonchol M, Jalal DI (2013) 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. Metabolism 62:392–399.

    Article  CAS  PubMed  Google Scholar 

  19. Sookoian S, Castano GO, Scian R, Fernandez GT, Dopazo H, Rohr C, Gaj G, San MJ, Sevic I, Flichman D, Pirola CJ (2016) Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level. Am J Clin Nutr 103:422–434.

    Article  CAS  PubMed  Google Scholar 

  20. Sookoian S, Pirola CJ (2008) Non-alcoholic fatty liver disease is strongly associated with carotid atherosclerosis: a systematic review. J Hepatol 49:600–607.

    Article  PubMed  Google Scholar 

  21. Sookoian S, Pirola CJ (2012) DNA methylation and hepatic insulin resistance and steatosis. Curr Opin Clin Nutr Metab Care 15:350–356.

    Article  CAS  PubMed  Google Scholar 

  22. Sookoian S, Pirola CJ (2017) Systematic review with meta-analysis: risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients. Aliment Pharmacol Ther 46:85–95.

    Article  CAS  PubMed  Google Scholar 

  23. Sookoian S, Pirola CJ (2019) Review article: shared disease mechanisms between non-alcoholic fatty liver disease and metabolic syndrome - translating knowledge from systems biology to the bedside. Aliment Pharmacol Ther 49:516–527.

    Article  PubMed  Google Scholar 

  24. Sookoian S, Rosselli MS, Gemma C, Burgueno AL, Fernandez GT, Castano GO, Pirola CJ (2010) Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: impact of liver methylation of the peroxisome proliferator-activated receptor gamma coactivator 1alpha promoter. Hepatology 52:1992–2000.

    Article  CAS  PubMed  Google Scholar 

  25. Toledo-Ibelles P, Gutierrez-Vidal R, Calixto-Tlacomulco S, Delgado-Coello B, Mas-Oliva J (2021) Hepatic accumulation of hypoxanthine: a link between hyperuricemia and nonalcoholic fatty liver disease. Arch Med Res 52:692–702.

    Article  CAS  PubMed  Google Scholar 

  26. Wang Z, Cui T, Ci X, Zhao F, Sun Y, Li Y, Liu R, Wu W, Yi X, Liu C (2019) The effect of polymorphism of uric acid transporters on uric acid transport. J Nephrol 32:177–187.

    Article  PubMed  Google Scholar 

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This study was partially supported by grants PICT 2018–889 and PICT 2019–0528 (SS), PICT 2016–0135 and PICT2018-0620 (CJP) (Agencia Nacional de Promoción Científica y Tecnológica, FONCyT), CONICET Proyectos Unidades Ejecutoras 2017, PUE 0055 (SS, CJP).

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Authors and Affiliations



SS and CJP designed research (project conception, development of overall research plan, and study oversight); CJP conducted data collection; CJP and SS analyzed data or performed statistical analysis; SS and CJP wrote the paper and had primary responsibility for the final content. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding authors

Correspondence to Silvia Sookoian or Carlos J. Pirola.

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The authors declare no competing interests.

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Key Points

• Increased serum uric acid (UA) is a hallmark of the MetSyn, but its association with NAFLD has been less explored. The normalization of serum UA by serum creatinine (sUA/CrR) may help to correct for renal dysfunction.

• sUA/CrR was independently associated with NAFLD in a large representative sample of the US general population surveyed by NHANES 2017–2018.

• sUA/CrR seems not to influence liver fibrosis.

• Adding sUA/CrR to traditional risk factors increases the model's predictive power of having NAFLD.

• Only a minor portion of the impact on liver fat infiltration and disease progression of central adiposity and insulin resistance is mediated by sUA/CrR.

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Sookoian, S., Pirola, C.J. The serum uric acid/creatinine ratio is associated with nonalcoholic fatty liver disease in the general population. J Physiol Biochem (2022).

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  • Biomarkers
  • Renal function
  • Metabolic syndrome
  • Diabetes
  • Central obesity
  • Insulin resistance