Person: EREN, FATİH
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EREN
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FATİH
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Publication Metadata only Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease(WILEY-BLACKWELL, 2010) ÇELİKEL, ÇİĞDEM; Yilmaz, Yusuf; Eren, Fatih; Yonal, Oya; Kurt, Ramazan; Aktas, Bilge; Celikel, Cigdem Ataizi; Ozdogan, Osman; Imeryuz, Nese; Kalayci, Cem; Avsar, ErolP>Background The fibroblast growth factor 21 (FGF21) hormonal pathway is a metabolic signalling cascade and has been recently identified as the master hormonal regulator of glucose, lipids and overall energy balance. In this observational, case-control study, we assayed serum levels of FGF21 in patients with nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, and examined their association with clinical, biochemical and histological phenotypes. Materials and methods Serum levels of FGF21 were assayed by ELISA in 82 patients with biopsy-proven NAFLD and 77 controls. We analysed associations between FGF21 and the characteristics of patients with NAFLD by multiple linear regression analysis. Results Levels of FGF21 were significantly higher in patients with NAFLD (median 200 pg mL-1; interquartile range: 87-410 pg mL-1) than in healthy controls (median 93 pg mL-1; interquartile range: 70-180 pg mL-1, Mann-Whitney U-test, P < 0 center dot 001). There was a stepwise increase in serum FGF21 levels according to the liver steatosis score (median level in subjects with score 1: 170 pg mL-1; score 2: 220 pg mL-1; score 3: 280 pg mL-1, P for trend < 0 center dot 01). After stepwise linear regression analysis, serum FGF21 levels were the only independent predictor of hepatic steatosis scores in patients with NAFLD (beta = 0 center dot 26; t = 2 center dot 659, P < 0 center dot 01). Conclusions Serum FGF21 levels are increased in patients with NAFLD regardless of potential confounders and represent an independent predictor of liver steatosis. These findings support further investigation of this molecule in metabolic liver diseases.Publication Metadata only Identification of a support vector machine-based biomarker panel with high sensitivity and specificity for nonalcoholic steatohepatitis(ELSEVIER SCIENCE BV, 2012) EREN, FATİH; Yilmaz, Yusuf; Eren, FatihBackground: Although liver biopsy remains the best diagnostic standard for nonalcoholic steatohepatitis (NASH), non-invasive tests are eagerly awaited. In this study, we sought to develop a support vector machine (SVM) algorithm to discriminate with high accuracy between subjects with NASH and controls using a blood-based biomarker panel. Methods: A total of 17 biomarkers were measured by commercially available enzyme-linked immunosorbent assays in 136 serum samples from patients with biopsy-proven NASH (n = 60) and subjects with normal ALT and no evidence of fatty liver on ultrasound (n = 76). The database was randomly divided (1:1 fashion) into a discovery set for classification training and in a validation set of the chosen biomarkers in blinded samples. Multivariate analysis was performed by means of SVM. Results: After the identification of a group of three most discriminative biomarkers (osteoprotegerin, fibroblast growth factor 21, and M30) in the discovery set, the application of SVM to the validation test resulted in a 92.5% sensitivity and 84.1% specificity for distinguishing subjects with NASH from controls. Conclusions: A targeted biomarker profiling combined with a SVM-based pattern identification approach may allow the identification of patients with NASH with clinically relevant accuracy and validity. (C) 2012 Elsevier B.V. All rights reserved.Publication Metadata only Serum osteopontin levels as a predictor of portal inflammation in patients with nonalcoholic fatty liver disease(ELSEVIER SCIENCE INC, 2013) EREN, FATİH; Yilmaz, Yusuf; Ozturk, Oguzhan; Alandab, Yesim Ozen; Senates, Ebubekir; Colak, Yasar; Doganay, Hamdi Levent; Coskunpinar, Ender; Oltulu, Yasemin Musteri; Eren, Fatih; Atug, Ozlen; Tuncer, Ilyas; Imeryuz, NeseBackground: Osteopontin is a secreted phosphorylated glycoprotein that is expressed by a variety of cell types and that mediates numerous and diverse biological functions. Osteopontin knockout mice are protected from obesity-induced hepatic steatosis. In the present study, we sought to investigate whether serum osteopontin concentrations are associated with liver histology in patients with nonalcoholic fatty liver disease. Methods: Serum levels of osteopontin were measured by enzyme-linked immunosorbent assay in 179 Well-characterized patients with nonalcoholic fatty liver referred for liver histology and 123 control subjects. Results: Serum osteopontin levels were markedly higher in patients with nonalcoholic fatty liver disease than in controls (p < 0.001). Multivariable analysis showed that osteopontin levels were strongly and independently associated with both portal inflammation (beta = 0.294, p < 0.01) and serum aminotransferase levels (aspartate aminotransferase: beta = 0.295, p < 0.01; alanine aminotransferase; beta = 0.285, p < 0.01). Conclusion: In summary, these data demonstrate that serum levels of osteopontin are elevated in nonalcoholic fatty liver disease and are a significant independent predictor of portal inflammation in this clinical entity. (C) 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.Publication Metadata only Serum levels of omentin, chemerin and adipsin in patients with biopsy-proven nonalcoholic fatty liver disease(TAYLOR & FRANCIS LTD, 2011) EREN, FATİH; Yilmaz, Yusuf; Yonal, Oya; Kurt, Ramazan; Alahdab, Yesim Ozen; Eren, Fatih; Ozdogan, Osman; Celikel, Cigdem Ataizi; Imeryuz, Nese; Kalayci, Cem; Avsar, ErolObjective. 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 (beta = 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.Publication Metadata only Hepatic expression and serum levels of syndecan 1 (CD 138) in patients with nonalcoholic fatty liver disease(INFORMA HEALTHCARE, 2012) ÇELİKEL, ÇİĞDEM; Yilmaz, Yusuf; Eren, Fatih; Colak, Yasar; Senates, Ebubekir; Celikel, Cigdem Ataizi; Imeryuz, NeseBackground and aims. Syndecan-1 (CD 138) is a transmembrane heparan sulfate proteoglycan expressed in the liver which may exert metabolic effects by mediating the hepatic clearance of triglyceride-rich lipoproteins. In the present study, we assayed serum levels and the hepatic expression of syndecan-1 and examined their association with clinical, biochemical, and histologic phenotypes in patients with histology-proven nonalcoholic fatty liver disease (NAFLD). Methods. A total of 59 patients with biopsy-proven NAFLD and 54 matched controls were enrolled. The analysis of syndecan-1 expression in liver biopsies was performed by immunohistochemistry on formalin-fixed, paraffin-embedded samples. Serum syndecan-1 levels were measured by ELISA. Results. NAFLD patients had significantly higher serum syndecan-1 levels [median: 61 ng/mL (interquartile range: 36-97 ng/mL)] than controls [median: 37 ng/mL (interquartile range: 25-59 ng/mL, Mann Whitney U test, p < 0.001]. However, we did not find any significant association between serum syndecan-1 and the mean syndecan-1 immunohistochemical score (n = 59, r = 0.064, p = 0.63). Interestingly, the syndecan-1 immunohistochemical score was an independent predictor of HDL cholesterol in NAFLD patients (beta = 0.27; t = 1.99, p < 0.05). Conclusions. Our data suggest that serum syndecan-1 levels are raised in patients with NAFLD. Moreover, the syndecan-1 immunohistochemical score in the liver is independently associated with HDL cholesterol in this group of patients. These pilot results support further investigation of this molecule in metabolic liver diseases.Publication Metadata only Preliminary evidence of a reduced serum level of fibroblast growth factor 19 in patients with biopsy-proven nonalcoholic fatty liver disease(PERGAMON-ELSEVIER SCIENCE LTD, 2012) EREN, FATİH; Eren, Fatih; Kurt, Ramazan; Ermis, Fatih; Atug, Ozlen; Imeryuz, Nese; Yilmaz, YusufObjectives: 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: 130 pg/mL) than in controls (median: 210 pg/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 (beta = -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. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.Publication Metadata only Serum osteocalcin levels in patients with nonalcoholic fatty liver disease: Association with ballooning degeneration(INFORMA HEALTHCARE, 2011) EREN, FATİH; Yilmaz, Yusuf; Kurt, Ramazan; Eren, Fatih; Imeryuz, NeseOur 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 (beta = -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.Publication Metadata only Circulating vaspin levels and epicardial adipose tissue thickness are associated with impaired coronary flow reserve in patients with nonalcoholic fatty liver disease(ELSEVIER IRELAND LTD, 2011) EREN, FATİH; Yilmaz, Yusuf; Kurt, Ramazan; Gurdal, Ahmet; Alahdab, Yesim Ozen; Yonal, Oya; Senates, Ebubekir; Polat, Nihat; Eren, Fatih; Imeryuz, Nese; Oflaz, HuseyinBackground: 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 (beta = -0.53, t = -3.7, P < 0.001), serum vaspin levels (beta = -0.30, t = -2.5, P = 0.014), and liver fibrosis (beta = -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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.Publication Metadata only Serum levels of osteoprotegerin in the spectrum of nonalcoholic fatty liver disease(TAYLOR & FRANCIS LTD, 2010) ÇELİKEL, ÇİĞDEM; Yilmaz, Yusuf; Yonal, Oya; Kurt, Ramazan; Oral, Arzu Y.; Eren, Fatih; Ozdogan, Osman; Ari, Ferda; Celikel, Cigdem A.; Korkmaz, Seniz; Ulukaya, Engin; Imeryuz, Nese; Kalayci, Cem; Avsar, ErolObjective. Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily with pleiotropic effects on inflammation, endocrine function and the immune system. Reduced OPG levels are related to insulin resistance. We tested the hypothesis that serum levels of OPG may be associated with nonalcoholic fatty liver disease (NAFLD). Material and methods. Four groups of patients were enrolled in the present study: subjects with definite nonalcoholic steatohepatitis (NASH, n = 56), borderline NASH (n = 26), simple fatty liver (n = 17) and healthy controls without evidence of liver disease (n = 58). Serum levels of OPG were measured by ELISA. Results. Concentrations of OPG were significantly lower in patients with definite NASH (median: 45 pg/mL, p < 0.001) and borderline NASH (57 pg/mL, p < 0.001) than in controls (92 pg/mL). The area under the ROC curve for distinguishing between steatohepatitis (definite NASH plus borderline NASH) and healthy controls using OPG was 0.82. The use of a cut-off level < 74 pg/mL for serum OPG levels yielded sensitivity and specificity values of 75.6% and 75.9%, respectively. Conclusions. Serum osteoprotegerin concentrations are reduced in patients with the more severe forms of NAFLD and may serve as a noninvasive biomarker to identify patients with NASH.Publication Metadata only Serum galectin-3 levels in patients with nonalcoholic fatty liver disease(PERGAMON-ELSEVIER SCIENCE LTD, 2011) EREN, FATİH; Yilmaz, Yusuf; Eren, Fatih; Kurt, Ramazan; Yonal, Oya; Polat, Zulfikar; Senates, Ebubekir; Bacha, Mohammad; Imeryuz, NeseObjectives: Galectin-3 might serve as a biomarker of human metabolic alterations. We measured serum levels of galectin-3 in patients with nonalcoholic fatty liver disease (NAFLD) and examined their association with clinical and histological phenotypes. Design and methods: Serum levels of galectin-3 were assayed in 71 patients with biopsy-proven NAFLD and 39 controls. Results: Serum galectin-3 levels did not differ in patients with NAFLD (median 4.1 ng/mL; interquartile range: 1.5-5.5 ng/mL) compared with healthy controls (median 3.1 ng/mL; interquartile range: 0.8-7.5 ng/mL, P = 0.93). Among patients with NAFLD, however, serum galectin-3 levels correlated significantly with BMI (r = 0.267, P<0.05). This association persisted after adjustment for potential confounders (beta = 0.30; t = 2.11, P<0.05). Conclusions: Although galectin-3 was modestly associated with BMI, our results do not support the hypothesis that levels of this molecule are altered in patients with NAFLD. (C) 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.