UA is the final oxidation product of purine catabolism, and hyperuricemia is considered a metabolic disease; many studies have also reported a relationship between hyperuricemia and NAFLD. Li et al. examined the relationship between UA levels and NAFLD in a cross-sectional study among 8925 company employees (6008 men) and showed that hyperuricemia, as well as male gender, age, BMI, WC, GGT level, TG level, HDL-c level, low-density lipoprotein-cholesterol level, and fasting plasma glucose (FPG), was an independent risk factor for NAFLD (OR 1.291; 95% CI 1.067–1.567; P < 0.001) in multiple regression analysis (Table 1). Sirota et al. conducted a cross-sectional analysis of 10 732 non-diabetic adults who participated in the National Health and Nutrition Examination Survey 1988–1994 in the United States. They defined sex-specific UA quartiles (≤ 5.2, 5.3–6.0, 6.1–6.9, and > 6.9 mg/dL for men and ≤ 3.7, 3.8–4.5, 4.6–5.3, and > 5.3 mg/dL for women) and revealed that the OR for the highest quartile was 1.43 (95% CI 1.16–1.76, P < 0.001) compared with the lowest quartile after adjusting for demographic data, hypertension, WC, TG level, HDL-c level, HOMA-IR, estimated glomerular filtration rate (eGFR), and AST level (Table 1). In addition, Hwang et al. studied 9019 Korean individuals who visited a health checkup center and had UA levels within the normal range. These patients were categorized into four groups according to UA quartiles for both sexes, and the relationship between the UA level and the presence of NAFLD was examined. After adjusting for age, smoking status, regular exercise, BMI, BP, FPG, TC level, TG level, HDL-c level, AST level, ALT level, and GGT level, the adjusted ORs (95% CIs) for the presence of NAFLD in the subjects with the highest UA level was 1.46 (1.17–1.82) for men and 2.13 (1.42–3.18) for women as compared with the subjects with the lowest UA level (Table 1). These authors suggested that increased UA concentrations, even those within the normal range, were independently associated with the presence of NAFLD.
Another study, which was hospital-based, enrolled 54 325 Taiwanese subjects who underwent a health-screening program, and these individuals were classified into eight groups according to their UA level and gout status (≤ 4.9, 5.0–6.9, 7.0–8.9, and ≥ 9.0 mg/dL, with and without gout) to examine the association between gout and NAFLD. The prevalence of NAFLD was significantly higher in subjects with gout (23.1%, n = 445) than in those without gout (10.9%, n = 5724, P < 0.001). Gout remained associated with an increased risk for NAFLD (OR 1.42; 95% CI 1.25–1.60; P < 0.001) after adjusting for age, gender, presence of metabolic syndrome, and low eGFR. The results showed an independent association between gout and the risk of NAFLD and a dose–response relationship between UA levels and the presence of NAFLD in subjects with and without gout, with UA ≤ 4.9 mg/dL in the absence of gout as a reference: OR (95% CI) 2.16 (1.94–2.41)–5.99 (5.19–6.90) without gout and 2.61 (1.39–4.91)–6.31 (5.12–7.77) with gout (Table 1).