Alanine-aminotransferase (ALT) and uric acid cut-off levels used in non-alcoholic fatty liver disease (NAFLD) diagnosis are advised to be lowered. Due to contradictory results on the utility of both these biomarkers for NAFLD screening, we aimed to determine their cut-off levels that can be applied to Montenegrin population with the fatty liver disease.
A total of 771 volunteers were enrolled. A fatty liver index (FLI) score ≥60 was used as proxy of NAFLD. The receiver operating characteristic curve analysis with the area under the curve (AUC) was used to determine the cut-off values of ALT and uric acid associated with FLI ≥60.
ALT was independent predictor of FLI in both men and women, whereas serum uric acid was its independent predictor only in women. Lower cut-off levels of ALT are associated with the increased prevalence of NAFLD [i.e., ALT was 19 IU/L (AUC=0.746, sensitivity 63%, specificity 72%, P<0.001) in women and 22 IU/L (AUC=0.804, sensitivity 61%, specificity 95%, P<0.001) in men]. The cut-off value for uric acid was 274 μmol/L (AUC=0.821, sensitivity 68%, specificity 82%, P<0.001) in women.
Lower cut-off levels of ALT in both genders, and serum uric acid in females, can be reliable predictors of the FLI.
Aleksandra Klisic, Gordana Kocic, Nebojsa Kavaric, Radmila Pavlovic, Ivan Soldatovic and Ana Ninic
Nitric oxide (NO) is oxidative stress biomarker which is regarded as one of the key determinants of energy metabolism and vascular tone. Considering the controversial reports on the association between nitric oxide products (NOx) and metabolic syndrome (MetS), the aim of the current study was to examine that potential relationship. Additionally, we aimed to evaluate a broad spectrum of other oxidative stress biomarkers [i.e., malondialdehyde (MDA), advanced oxidation protein products (AOPP), xanthine oxidoreductase (XOD), xanthine oxidase (XO) xanthine dehydrogenase (XDH)] in relation with MetS.
A total of 109 volunteers (46.8% of them with MetS) were included in this cross-sectional study. Biohemical and anthropometric parameters, as well as blood pressure, were obtained. The MetS was diagnosed according to the International Diabetes Federation criteria.
Multivariate logistic regression analysis showed that XOD (OR=1.011; 95% CI 1.002–1.019; p=0.016), XO (OR=1.014; 95% CI 1.003–1.026; p=0.016), MDA (OR=1.113; 95% CI 1.038–1.192; p=0.003) and AOPP (OR=1.022; 95% CI 1.005–1.039; p=0.012) were the independent predictors of MetS, whereas no association between NOx and MetS was found. As XOD rose for 1 U/L, XO for 1 U/L, MDA for 1 μmol/L and AOPP for 1 T/L, probability for MetS rose for 1.1%, 1.4%, 11.3% and 2.2%, respectively. Adjusted R2 for the Model was 0.531, which means that 53.1% of variation in MetS could be explained with this Model.
Unlike XOD, MDA and AOPP, NOx is not associated with MetS.
Aleksandra Klisic, Nebojsa Kavaric, Ivan Soldatovic, Bojko Bjelakovic and Jelena Kotur-Stevuljevic
Background: Since the cardiovascular (CV) risk score in the young population, children and adolescents, is underestimated, especially in developing countries such as Montenegro, where a strong interaction exists between the genetically conditioned CV risk and environmental factors, the purpose of this study was to estimate CV risk in apparently healthy adolescent girls. Moreover, we aimed to test some new, emerging CV risk factors and their interaction with the traditional ones, such as obesity. Precisely, we aimed to assess the impact of low bilirubin levels, as a routine biochemical parameter, as an additional risk factor for atherosclerotic disease in the adult phase.
Methods: Forty-five obese adolescent girls (mean age 17.8±1.22 years) and forty-five age-and sex-matched normal weight controls, all nonsmokers, were included. Anthropometric and biochemical parameters were measured. Cardiovascular Risk Score (CVRS) was calculated by adding the points for each risk factor (e.g. sex, HDL-c, non-HDLc, blood pressure and fasting glycemia).
Results: A significant positive relationship between CVRS and ALT, hsCRP and TG/HDL-c, but an opposite relationship between CVRS and total bilirubin were found (P<0.001). Multiple linear regression analysis showed that higher waist circumference (WC) and LDL-c, but lower HDL-c were independent predictors of lower bilirubin values (adjusted R2=0.603, P<0.001).
Conclusions: Obese adolescent girls are at an increased risk of cardiovascular disease late in life. In addition to the traditional risk factors, total bilirubin may have the potential to discriminate between low and higher risk for cardiovascular disturbances in healthy adolescent girls.
Aleksandra Klisic, Nebojsa Kavaric, Ludovico Abenavoli, Verica Stanisic, Vesna Spasojevic-Kalimanovska, Jelena Kotur-Stevuljevic and Ana Ninic
Studies that evaluated endocan levels in nonalcoholic fatty liver disease (NAFLD) and liver fibrosis are scarce. We aimed to explore endocan levels in relation to different stages of liver diseases, such as NAFLD, as determined with fatty liver index (FLI) and liver fibrosis, as assessed with BARD score.
A total of 147 participants with FLI≥60 were compared with 64 participants with FLI <30. An FLI score was calculated using waist circumference, body mass index, gamma-glutamyl transferase and triglycerides. Patients with FLI≥60 were further divided into those with no/mild fibrosis (BARD score 0–1 point; n=23) and advanced fibrosis (BARD score 2–4 points; n=124). BARD score was calculated as follows: diabetes mellitus (1 point) + body mass index≥28 kg/m2 (1 point) + aspartate amino transferase/alanine aminotransferase ratio≥0.8 (2 points).
Endocan was independent predictor for FLI and BARD score, both in univariate [OR=1.255 (95% CI= 1.104–1.426), P=0.001; OR=1.208 (95% CI=1.029– 1.419), P=0.021, respectively] and multivariate binary logistic regression analysis [OR=1.287 (95% CI=1.055– 1.570), P=0.013; OR=1.226 (95% CI=1.022–1.470), P=0.028, respectively]. Endocan as a single predictor showed poor discriminatory capability for steatosis/fibrosis [AUC=0.648; (95% CI=0.568–0.727), P=0.002; AUC= 0.667 (95% CI=0.555–0.778), P=0.013, respectively], whereas in a Model, endocan showed an excellent clinical accuracy [AUC=0.930; (95% CI=0.886–0.975), P<0.001, AUC=0.840 (95% CI=0.763–0.918), P<0.001, respectively].
Endocan independently correlated with both FLI and BARD score. However, when tested in models (with other biomarkers), endocan showed better discriminatory ability for liver steatosis/fibrosis, instead of its usage as a single biomarker.