Serum Uric Acid and Non-Alcoholic Fatty Liver Disease in Non-Diabetic Chinese Men

Abstract

Increased serum uric acid (SUA) levels may be involved in the development of non-alcoholic fatty liver disease (NAFLD) in men presenting with metabolic syndrome (MetS) and/or insulin resistance. We aimed to determine the independent relationship between SUA and NAFLD in non-diabetic Chinese male population, and to explore the determinants of SUA levels among indexes of adiposity, lipid, and genotypes pertaining to triglycerides metabolism, inflammation, oxidative stress, and SUA concentrations. A total of 1440 men, classified depending on the presence of ultrasonographically detected NAFLD, underwent a complete healthy checkup program. Genotypes were extracted from our previously established genome-wide association study database. After adjusting for age, smoking, drinking, body mass index, homeostasis model assessment of insulin resistance, C-reactive protein, creatinine, alanine aminotransferase (ALT) and components of metabolic syndrome, the odds ratio for NAFLD, comparing the highest with the lowest SUA quartile, was 2.81 (95% confidence interval 1.66–4.76). A stepwise multivariate linear regression analysis (R2 = 0.238, P<0.001) retained age, waist circumference, serum creatinine, triglycerides, the Q141K variant in ABCG2 (rs2231142) and NAFLD as significant predictors of SUA levels (all P<0.001). Besides, ALT and Met196Arg variant in TNFRSF1B (rs1061622) additionally associated with SUA among individuls with NAFLD. Our data suggest that in Chinese men, elevated SUA is significantly associated with NAFLD, independent of insulin resistance and other metabolic disorders, such as central obesity or hypertriglyceridemia. Meanwhile, among subjects with NAFLD, index of liver damage, such as elevated ALT combined with genetic susceptibility to inflammation associated with increased SUA levels.

Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

“…There is a graded, positive association between SUA levels and NAFLD severity and elevated SUA levels predict NAFLD risk independently of coexisting MetS features in different ethnicities. [99][100][101][102][103][104][105][106][107][108] Accordingly, a large study found that increased SUA levels were associated with cirrhosis and elevated serum liver enzymes, independent of potential confounders, in 5,518 participants during a mean follow-up of 12.9 years. 96 Further studies are needed to ascertain whether reducing SUA levels would prevent NAFLD/NASH development and progression.…”

Correlative Study of Hyaluronic Acid and YKL-40 with Conventional Markers for Cirrhosis of Liver

“…In Indian population, Paul et al, in their study found that hyperuricemia reflects oxidative stress and is associated with disease progression which can serve as surrogate marker for CLD with varied etiology [5]. Xie et al, documented crucial role of hyperuricemia is an important independent risk factor for NAFLD in Chinese population [4]. Shih et al, observed significant association between serum uric acid levels and NAFLD among US population; independent of multiple metabolic risk factors [15].…”

“…In cirrhotic liver, the Extra Cellular Matrix (ECM) produced by myofibroblasts which are trans-differentiated from activated Hepatic Stellate Cells (HSCs) differs qualitatively and quantitatively compared to normal liver. An increase in fibril and non fibril forming collagens along with glycoproteins, proteoglycans and glycosaminoglycans reflects ECM turnover and serve as direct biomarkers for severity of cirrhosis [3].Inflammatory factors [Tumor Necrosis Factor α (TNF-α) and interleukins] induced oxidative and apoptotic stress are important features for liver fibrosis/cirrhosis progression which results in uric acid production, an end product of purine metabolism [4]. Hyperuricemia, increased degradation of nuclear material cause endothelial dysfunction, insulin resistance, oxidative stress and systemic inflammation (metabolic syndrome) which are risk factors for hepatic damage [5].…”

Relación de la hiperuricemia con las lipoproteínas de baja densidad, las pruebas de funcionamiento hepático y los marcadores de inflamación sistémica en pacientes con obesidad mórbida

“…Convencionalmente se ha asociado la hiperuricemia con el desarrollo de gota, tofos y nefrolitiasis. Sin embargo, existe evidencia emergente que la asocia con el desarrollo de obesidad, diabetes mellitus tipo 2 (DM2), síndrome metabólico (SMet), enfermedad cardiovascular [3][4][5][6][7][8] y, aunque aún controversial, con la generación de enfermedad del hígado graso no alcohólica (EHGNA) 9,10 . Por esta razón, diversos grupos de investigación han postulado que los valores elevados de AU pueden contribuir directamente con la activación de la inflamación sistémica como trastorno desencadenador de enfermedades cardiovasculares y metabólicas [11][12][13][14] .…”