Ramazan Kurt

Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease

Eur J Clin Invest 2010; 40 (10): 887–892

Serum levels of omentin, chemerin and adipsin in patients with biopsy-proven nonalcoholic fatty liver disease

Abstract Objective. The novel adipokines omentin, chemerin, and adipsin are associated with insulin resistance and the components of the metabolic syndrome. We assayed circulating levels of these molecules and examined their association with clinical, biochemical, and histological phenotypes in patients with nonalcoholic fatty liver disease (NAFLD). Material and methods. Serum levels of omentin, chemerin, and adipsin were assayed by enzyme-linked immunosorbent assay in 99 patients with biopsy-proven NAFLD and 75 control subjects. We analyzed associations between adipokines and the characteristics of patients with NAFLD using multivariable linear regression models. Results. Adipsin levels did not differ between patients and controls, whereas both omentin and chemerin levels were significantly higher in patients with biopsy-proven NAFLD than in controls (both p values <0.001). Serum omentin levels were significantly associated with C-reactive protein (r = 0.29, p < 0.01) and the degree of hepatocyte ballooning (r = 0.27, p < 0.01), whereas chemerin showed a modest association with liver fibrosis (r = 0.22, p = 0.04). After stepwise linear regression analysis adjusting for potential confounders, serum omentin levels retained their independent significance as a predictor of hepatocyte ballooning in patients with NAFLD (β = 1.42; t = 2.79, p < 0.01). Conclusions. Our results suggest that serum omentin levels are raised in patients with NAFLD regardless of potential confounders and represent an independent predictor of hepatocyte ballooning.

Microalbuminuria in nondiabetic patients with nonalcoholic fatty liver disease: association with liver fibrosis.

Recent evidence has suggested an association between microalbuminuria and ultrasound-diagnosed nonalcoholic fatty liver disease (NAFLD) in patients with diabetes and prediabetes. However, few data are available on the occurrence of microalbuminuria in nondiabetic subjects with histologically proven NAFLD. We thus evaluated the relationships between microalbuminuria and liver histology in a hospital-based sample of 87 adults with biopsy-proven NAFLD from Turkey. An albumin excretion rate less than 30 mg/d was considered within the reference range, whereas an albumin excretion rate from 30 to 300 mg/d was considered to indicate microalbuminuria. Compared with those without microalbuminuria (n = 73), NAFLD patients with microalbuminuria (n = 14) had significantly higher homeostasis model assessment of insulin resistance values (3.9 +/- 1.3 vs 5.8 +/- 3.7, P < .001). There were no differences in the prevalence of microalbuminuria in patients with definite nonalcoholic steatohepatitis, borderline nonalcoholic steatohepatitis, and simple fatty liver. In the entire study cohort, mean fibrosis scores were significantly higher in patients with microalbuminuria than in those without (1.27 +/- 0.26 vs 0. 80 +/- 0.11, P < .05). This difference persisted after adjustment for potential confounders. These results indicate the presence of a significant association between the severity of insulin resistance and microalbuminuria in patients with NAFLD. In addition, microalbuminuria may identify NAFLD patients with higher fibrosis scores.

Coronary flow reserve is impaired in patients with nonalcoholic fatty liver disease: Association with liver fibrosis

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. Coronary flow reserve (CFR) is widely used to examine the integrity of coronary microvascular circulation. We evaluated the prevalence of impaired CFR in patients with biopsy-proven NAFLD. We also investigated the independent clinical, biochemical, and liver histology predictors of CFR in the setting of NAFLD. METHODS Fifty-nine consecutive patients with NAFLD and 77 age- and gender-matched controls were evaluated. CFR recordings were performed by transthoracic Doppler harmonic echocardiography. CFR>or=2.0 was considered normal. RESULTS CFR was significantly lower in patients with NAFLD than in controls (2.11+/-0.45 vs. 2.52+/-0.62, P<0.001). An impaired CFR (i.e. <2) was found in 25 NAFLD patients (42.4%) whereas all controls had normal CFR values (P<0.001). A stepwise linear regression analysis in NAFLD patients identified liver fibrosis scores as the only independent predictor of CFR values (beta=-0.60; t=-2.44, P=0.021). CONCLUSION Our findings indicate that in patients with biopsy-proven NAFLD: (a) an abnormal CFR is found in approximately 42.4% of cases, and (b) liver fibrosis scores are an independent predictor of depressed CFR.

Serum levels of vaspin, obestatin, and apelin-36 in patients with nonalcoholic fatty liver disease.

The novel adipokines vaspin, obestatin, and apelin-36 are associated with insulin resistance and the components of the metabolic syndrome. We assayed circulating levels of these molecules and examined their association with clinical, biochemical, and histologic phenotypes in patients with nonalcoholic fatty liver disease (NAFLD). Serum levels of vaspin, obestatin, and apelin-36 were assayed by enzyme-linked immunosorbent assay in 91 patients with biopsy-proven NAFLD and 81 controls. We analyzed associations between adipokines and the characteristics of patients with NAFLD using multivariable linear regression models. Univariable analysis showed that concentrations of vaspin and apelin-36 were significantly higher in patients with NAFLD than in controls, whereas no differences in obestatin levels were found. Serum vaspin levels showed a statistically significant association with C-reactive protein (r = 0.378, P < .001) and liver fibrosis scores (r = 0.401, P < .001), whereas apelin-36 levels showed a modest association with homeostasis model assessment of insulin resistance (r = 0.204, P < .01). After stepwise linear regression analysis, serum vaspin levels were the only independent predictor of liver fibrosis scores in patients with NAFLD (β = 0.37, t = 3.99, P < .01). Serum vaspin levels are raised in patients with NAFLD regardless of potential confounders and represent an independent predictor of liver fibrosis scores. These findings support further investigation of this novel adipokine in metabolic liver diseases.

Serum fetuin A/α2HS-glycoprotein levels in patients with non-alcoholic fatty liver disease: relation with liver fibrosis

Background Serum concentrations of fetuin A/α2HS-glycoprotein (AHSG) have been linked to human metabolic alterations and can serve as an indicator of liver cell function. We assayed serum levels of AHSG in patients with non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, and examined their association with clinical, biochemical and histological phenotypes. Methods Serum AHSG levels were determined by enzyme linked immunosorbent assay in 99 patients with biopsy-proven NAFLD and 75 age- and gender-matched controls. Results Serum AHSG levels were significantly higher in patients with NAFLD (940 ± 120 μg/mL) compared with healthy controls (800 ± 130 μg/mL, Students t test, P < 0.001). Bivariate analyses (Spearmans rank correlation) in patients with NAFLD showed a statistically significant association between AHSG levels and insulin resistance as assessed by the HOMA (homeostasis model assessment) index (r = 0.31, P < 0.01) and the liver fibrosis score index (r = 0.36, P < 0.001). The association between AHSG and fibrosis remained statistically significant even after adjustment for potential confounders, including the HOMA index ([beta] = 1.65, t = 2.38, P < 0.05). Conclusion Serum AHSG levels are significantly increased in adult patients with biopsy-proven NAFLD and are associated with insulin resistance. Importantly, our pilot data indicate that serum AHSG levels may identify NAFLD patients with higher fibrosis scores.

Circulating vaspin levels and epicardial adipose tissue thickness are associated with impaired coronary flow reserve in patients with nonalcoholic fatty liver disease

BACKGROUND Patients with nonalcoholic fatty liver disease (NAFLD) have a reduced coronary flow reserve (CFR) and an increased risk of cardiovascular disease. The fat cells that surround coronary arteries may play a central and underrecognized role in development of cardiovascular disease through the systemic secretion of adipokines. We therefore evaluated the relation of epicardial fat thickness, serum levels of epicardial fat-related adipokines (chemerin and vaspin), and CFR in patients with NAFLD. METHODS We investigated 54 patients with biopsy-proven NAFLD and 56 age- and sex-matched controls. CFR and epicardial fat thickness (EFT) were measured by transthoracic echocardiography. Serum levels of chemerin and vaspin were measured by ELISA. RESULTS EFT was significantly higher (0.64 ± 0.13 vs. 0.54 ± 0.10 cm, P<0.001) and CFR significantly lower (2.11 ± 0.45 vs. 2.52 ± 0.62, P < 0.001) in patients with NAFLD than in controls. Serum levels of vaspin and chemerin were both significantly increased in patients with NAFLD compared with controls. Stepwise regression analysis showed that EFT (β=-0.53, t=-3.7, P<0.001), serum vaspin levels (β=-0.30, t=-2.5, P=0.014), and liver fibrosis (β=-0.31, t=-2.11, P=0.041), in the order they entered into the model, were independent predictors of CFR in NAFLD patients. CONCLUSION Our data suggest the presence of a complex interplay between EFT, serum vaspin, and liver histology in promoting an impaired hyperemic stimulation of coronary blood flow in patients with NAFLD.

Serum Levels of Hepcidin in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease

BACKGROUND Research suggests the presence of mild-to-moderate iron overload in patients with nonalcoholic fatty liver disease (NAFLD). The role played by hepcidin, the master regulatory hormone of systemic iron metabolism, in the pathogenesis of NAFLD remains controversial. The aims of this study were to: (1) Evaluate serum hepcidin levels in patients with biopsy-proven NAFLD and age- and sex-matched controls and (2) identify the potential associations of hepcidin with the clinical and biochemical characteristics of the study participants. METHODS Serum levels of hepcidin were measured by enzyme-linked immunosorbent assay and compared in 88 patients with NAFLD (56 males and 32 females; mean age, 44 ± 11 years) and 88 controls (51 males and 37 females; mean age, 43 ± 12 years). Moreover, concentrations of hepcidin were assessed in relation to the general characteristics of the study participants and the results of liver biopsy. RESULTS Serum levels of hepcidin were significantly higher in patients with NAFLD (63.5 ± 19.5 ng/mL, P<0.001) compared with controls (32.7 ± 8.3 ng/mL). Multivariable regression analyses in patients with NAFLD showed that hepcidin levels were positively associated with total cholesterol (β=6.9, t=3.3, P<0.01) and triglycerides (β=1.4, t=2.4, P<0.05), but not with iron parameters, histological staging, and pathological characteristics of NAFLD. CONCLUSIONS Although subject to future confirmation, our data suggest that hepcidin levels are elevated in NAFLD and could be associated with lipid parameters in this setting.

Preliminary evidence of a reduced serum level of fibroblast growth factor 19 in patients with biopsy-proven nonalcoholic fatty liver disease.

OBJECTIVES We sought to determine whether serum concentrations of fibroblast growth factor 19 (FGF19) - an ileum-derived enterokine which plays a role in the control of glucose and lipid homeostasis - are altered in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). DESIGN AND METHODS Serum levels of FGF19 were measured using enzyme-linked immunosorbent assay in 91 patients with biopsy-proven NAFLD and 74 controls. RESULTS FGF19 levels were significantly lower in patients with biopsy-proven NAFLD (median: 130pg/mL) than in controls (median: 210pg/mL, P<0.001). Serum FGF19 levels were significantly but modestly associated with hepatocyte ballooning scores in univariate analysis (r=-0.25, P<0.05) but not after adjustment for potential confounders (β=-0.18; t=1.78, P=0.08). CONCLUSIONS This pilot study suggests that serum FGF19 levels are decreased in patients with NAFLD but are not independently associated with liver histology findings.

Serum osteocalcin levels in patients with nonalcoholic fatty liver disease: Association with ballooning degeneration

Abstract Our aim was to examine the relation of serum osteocalcin (OCN) levels with the clinical, biochemical, and histological characteristics of patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). We carried out a case-control study including 99 patients with biopsy-proven NAFLD and 75 age- and sex-matched controls. Concentrations of OCN were measured in aprotinin-treated serum samples using a solid-phase enzyme amplified sensitivity immunoassay. Serum OCN levels were significantly lower in patients with NAFLD than in healthy controls. In patients with NAFLD, serum OCN levels were inversely associated with ALT (r =−0.36, p < 0.001), AST (r =−0.39, p < 0.001), HOMA-IR (r =−0.30, p < 0.01) and the degree of hepatocyte ballooning (r =−0.20, p < 0.05). Serum OCN was the only independent predictor of the degree of hepatocyte ballooning in NAFLD patients (β =−0.24; t = −2.146, p < 0.05). Compared with controls, NAFLD patients have a decrease in serum OCN concentrations, which is significantly associated with serum transaminases and the extent of hepatocyte ballooning.