Oguzhan Ozturk

Istanbul Medical University, İstanbul, Istanbul, Turkey

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Publications (19)28.93 Total impact

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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD is a complex disease and inflammation is a crucial component in the disease pathogenesis. Recent genome wide association studies in hepatology area highlighted significant relations with human leukocyte antigen (HLA) DQ region and certain liver diseases. The previous animal models also emphasized the involvement of adaptive immune system in the liver damage pathways. To investigate possible polymorphisms in the HLA region that can contribute to the immune response affecting the NAFLD, we enrolled 93 consecutive biopsy proven NAFLD patients and a control group consisted of 101 healthy people and genotyped HLA DQB1 alleles at high resolution by sequence specific primers-polymerase chain reaction. The mean NAFLD activity score (NAS) was 5.2 ± 1.2, fibrosis score was 0.9 ± 0.9, ALT was 77 ± 47.4 U/L, AST was 49.4 ± 26.3 U/L. Among 13 HLA DQB1 alleles analyzed in this study, DQB1*06:04 was observed significantly at a more frequent rate among the NAFLD patients compared to that of healthy controls (12.9 vs. 2 % χ(2) = 8.6, P = 0.003, P c = 0.039, OR: 7.3 95 % CI 1.6-33.7). In addition, the frequency of DQB1*03:02 was significantly higher in the healthy control group than the NAFLD patients (24.8 vs. 7.5 %, χ(2) = 10.4, P = 0.001, P c = 0.013, OR: 0.2, 95 % CI 0.1-0.6). NAFLD patients were grouped according to their fibrosis score and NAS. The distribution of DQB1 alleles over stratified NAFLD patients did not reveal any statistically significant relation. Taken together, immune repertoire of individuals may have an effect on NAFLD pathogenesis and therefore, in NAFLD, adaptive immunity pathways should be investigated.
    Molecular Biology Reports 08/2014; · 2.51 Impact Factor
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    ABSTRACT: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B.
    World journal of gastroenterology : WJG. 07/2014; 20(25):8179-86.
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    ABSTRACT: We sought to examine whether the presence of gallstone disease (GD) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) is associated with liver fibrosis and histological nonalcoholic steatohepatitis (NASH) score. We included 441 Turkish patients with biopsy-proven NAFLD. GD was diagnosed in the presence of sonographic evidence of gallstones, echogenic material within the gallbladder with constant shadowing and little or no visualization of the gallbladder or absence of gallbladder at ultrasonography, coupled with a history of cholecystectomy. Fifty-four patients (12.2%) had GD (GD+ subjects). Compared with the GD- subjects, GD+ patients were older, had a higher body mass index and were more likely to be female and have metabolic syndrome. However, GD+ patients did not have a higher risk of advanced fibrosis or definite NASH on histology. After adjustment for potential confounding variables, the prevalence of GD in NAFLD patients was not associated with significant fibrosis (≥2) (odds ratio [OR], 1.06; 95% confidence interval [CI], 0.53 to 2.21; p=0.68) or definite NASH (OR, 1.03; 95% CI, 0.495 to 2.12; p=0.84). The presence of GD is not independently associated with advanced fibrosis and definite NASH in adult Turkish patients with biopsy-proven NAFLD.
    Gut and Liver 05/2014; 8(3):313-7.
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    ABSTRACT: Background&Aims: Nonalcoholic fatty liver disease (NAFLD) and cholelithiasis are among the most frequent diseases of gastrointestinal diseases. Recently, it was reported that cholelithiasis is approximately two times more often (20%) than normal in patients with NAFLD. However, to date no study showed a casual relationship and gallbladder kinetics in patients with NAFLD. In this study we aimed to evaluate the gallbladder kinetics and probable relationship with NAFLD. Material and Methods: A total of 50 patients diagnosed histopathologically with NAFLD and 38 healthy controls were included in the study. After an 8 hour overnight fasting the measurements of gallbladder were performed and after standard food ingestion the measurements were repeated at 45. minutes. Results: Fasting gallbladder wall thickness (1.120.38 and 1.480.46 mm respectively, p<0.001), volume (21.7311.1 and 27.868.4 ml respectively, p=0.006) and postprandial residual volume (10.735.7 and 17.848.18 respectively, p<0.001) of patients with NAFLD was significantly higher than controls, whereas gallbladder ejection fraction (4819.15 and 36.819.3% respectively, p= 0.008) was significantly lower than controls. When all individuals divided as control, simple steatosis and nonalcoholic steatohepatitis (NASH) groups, fasting gallbladder wall thickness (1.120.38, 1.310.37, 1.520.48 mm respectively, p=0.001), fasting gallbladder volume (21.7311.1 27.3611.1 27.948.55 ml respectively, p=0.019,) postprandial residual volume ((10.735.7, 16.87.6, 18.18.5 ml respectively, p<0.001) and gallbladder ejection fraction (4819.15, 38.416.6, 36.120.2% respectively, p=0.023) were significantly different between three groups. In linear regression analysis, we found that severity of histological steatosis in patients with NAFLD was independent predictor of gallbladder ejection fraction (= -0.414, t = -2.275, P=0.028). Conclusions: Increased gallbladder fasting volume and disturbed gallbladder emptying may be related by increased gallstone formation in patient with NAFLD. Additionally increased gallbladder wall thickness in patients with NAFLD may be associated with steatosis of gallbladder wall and this association could also affect the ejection fraction. However, our data should be supported with more comprehensive studies.
    The 64th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2013.; 11/2013
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    ABSTRACT: Aim: It is known that insulin resistance has an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and that serum 25-hidroksivitamin D3 [25-(OH)D] levels are found low in the presence of insulin resistance. Metabolic syndrome (MetS) is characterized by insulin resistance. The purpose of the present study was to determine the levels of 25-(OH)D and the frequency of MetS in patients with NAFLD, and to evaluate the association of 25-(OH)D with the histology of NAFLD and metabolic parameters. Method: Sixty-three patients with NAFLD confirmed by liver biopsy (29 females and 34 males, mean age 42.70±9.82 years) and 46 healthy controls (16 females and 30 males, mean age 37.54±8.56 years) were included in the study. International Diabetes Federation criteria were used for MetS diagnosis. Insulin resistance was determined according to the Homeostasis Model of Assessment (HOMA-IR) method. The groups were compared for 25-(OH)D levels and MetS frequencies. Correlation analysis was used to evaluate relationships between 25-(OH)D and metabolic parameters and/or NAFLD histology. Results: 25-(OH)D levels were lower in the NAFLD group compared to the control group (36.06±13.07 ng/mL vs. 51.19±23.45 ng/mL, respectively, P<0.01), while MetS frequency was higher (66.7% vs. 15.2%, P<0.01). In the NAFLD group, 25-(OH)D levels were negatively correlated with non-alcoholic steatohepatitis scores and HOMA-IR (r=-0.317, P=0.011 and r=-0.437, P=0.001, respectively). Conclusion: The present study demonstrated higher frequency of MetS and lower levels of 25-(OH)D in patients with NAFDL, and a negative association of 25-(OH)D levels with non-alcoholic steatohepatitis scores and insulin resistance.
    Minerva medica 08/2013; 104(4):447-53. · 0.77 Impact Factor
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    ABSTRACT: BACKGROUND: Chronic hepatitis B treatment with oral antiviral drugs is a long course. During this course, antiviral resistance is a serious issue, particularly, if genetically low barrier drugs are in use. Host immunity is accepted to have an effect on antiviral resistance development. The earliest clinical sign of drug resistance is virologic breakthrough. In this study, we aimed to investigate the relation between HLA-DQB1 alleles and virologic breakthrough events. SUBJECTS AND METHODS: The patient records at single institution hepatology clinic were reviewed. Local institution ethics committee approval was taken. The patients' demographic data, virologic parameters, treatment statues were noted. Patients who had received lamivudine or adefovir were recruited and grouped into two according to virologic breakthrough occurrence. Patients who were not compliant to the given treatment were excluded. Blood samples were taken for DNA extraction. HLA-DQB1 alleles were determined at high level by sequence-specific primers-polymerase chain reaction. The distribution of DQB1 alleles among groups was analyzed. RESULTS: One hundred ninety-eight patients were eligible for the study. Ninety-six of them had virologic breakthrough where 102 did not have. DQB1 0503 allele was more frequent in patients without breakthrough (28.4% vs. 12.4%, P=0.006). In univariate analysis, HBeAg seropositivity (P<0.001), absence of cirrhosis (P=0.007), younger age (P=0.002) and higher pretreatment logDNA (P<0.001) were related to breakthrough events. However, in multivariate analysis only logDNA (P<0.001) and DQB1*0503 (P=0.02) allele revealed statistically significant relation with breakthrough events. CONCLUSION: Host immunity may have an effect on outcome during treatment with oral antiviral drugs. A patient with better immunologic profile may suppress the viral replication better and this may cause less resistance occurrence during treatment with genetically low barrier drugs.
    Gastroentérologie Clinique et Biologique 12/2012; · 0.80 Impact Factor
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    ABSTRACT: BACKGROUND: 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 (β=0.294, p<0.01) and serum aminotransferase levels (aspartate aminotransferase: β=0.295, p<0.01; alanine aminotransferase; β=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.
    Digestive and Liver Disease 09/2012; · 3.16 Impact Factor
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    ABSTRACT: In this study, we aimed to evaluate the endothelial functions in patients with nonalcoholic fatty liver disease (NAFLD). In this observational case-control study, a total of 51 patients with NAFLD in study group and a total of 21 with age- and sex-equivalent individuals in control group were enrolled. In both patients and control groups, levels of asymmetric dimethylarginine (ADMA), systemic endothelial function (brachial artery flow-mediated dilation) (FMD) and carotid artery intima-media thickness (C-IMT) were measured. FMD and C-IMT were evaluated by vascular ultrasound. Plasma levels of ADMA were measured by ELISA. C-IMT was significantly higher in patients with NAFLD group than control group (0.67 ± 0.09 vs. 0.52 ± 0.11 mm, P < 0.001). The average C-IMT measurements were found in groups of control, simple steatosis, and NAFLD with (borderline and definite) NASH as 0.52 ± 0.11, 0.63 ± 0.07, and 0.68 ± 0.1 mm, respectively. The differences between groups were significant (P < 0.001). Measurement of brachial artery FMD was significantly lower in patients with NAFLD group compared to control group (7.3 ± 4.8 vs. 12.5 ± 7.1 %, P < 0.001). FMD measurements in groups of control, the simple steatosis, and NAFLD with NASH as 12.5 ± 7.1, 9.64 ± 6.63, and 7.03 ± 4.57 %, respectively, and the differences were statistically significant (P < 0.001). The increase in C-IMT and decrease in FMD was independent from metabolic syndrome and it was also more evident in patients with simple steatosis and NASH compared to control group. There was no significant difference between the control and NAFLD groups in terms of plasma ADMA levels (0.61 ± 0.11 vs. 0.69 ± 0.37 μmol/L, P = 0.209). Our data suggested that NAFLD is associated with endothelial dysfunction and increased earlier in patients with atherosclerosis compared to control subjects.
    Endocrine 06/2012; · 3.53 Impact Factor
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    ABSTRACT: Currently, nonalcoholic fatty liver disease (NAFLD) itself has been accepted as an atherosclerotic risk factor and related to increased cardiovascular disease risk. In this study, we aimed to investigate the relationship of epicardial fat thickness (EFT), a parameter associated with atherosclerosis in recent years, with carotid artery intima-media thickness (C-IMT), another parameter of subclinical atherosclerosis. We investigated 57 patients with biopsy-proven NAFLD and 30 age-matched and sex-matched controls. EFT was obtained by transthoracic echocardiography and C-IMT was evaluated by an ultrasonographic measurement using a linear type B-mode probe. EFT and C-IMT were significantly higher in NAFLD patients compared with the controls (EFT: 0.58 ± 0.18 vs. 0.36 ± 0.17 cm, P<0.001 and C-IMT: 0.64 ± 0.1 vs. 0.52 ± 0.1 mm, P<0.001, respectively). We found a statistically significant correlation between EFT and BMI, C-IMT, waist circumference, homeostasis model assessment of insulin resistance, and nonalcoholic steatohepatitis scores in both groups. Stepwise regression analysis showed that C-IMT (β=0.36, t=2.86, P=0.006) and waist circumference (β=0.3, t=2.44, P=0.018), in the order they entered into the model, were independent predictors of EFT in patients with NAFLD. Our findings indicate that EFT and C-IMT were significantly higher in patients with NAFLD compared with the controls and waist circumference and C-IMT are independent predictors for EFT in patients with NAFLD.
    European journal of gastroenterology & hepatology 04/2012; 24(6):613-8. · 1.66 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease in many countries, and its prevalence is increasing. NAFLD is often considered to be a hepatic component of metabolic syndrome, and studies have established that insulin resistance plays a major role in the pathogenesis of NAFLD. Treatments for NAFLD primarily target insulin resistance. Interestingly, the most common environmental cause of insulin resistance is diet. This article examines the correlations between NAFLD and diet and provides some diet recommendations based on the most current data available.
    Metabolic syndrome and related disorders 03/2012; 10(3):161-6.
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    ABSTRACT: In this study, we aimed to investigate the relationship between the histological fibrosis stage of nonalcoholic fatty liver disease (NAFLD) and serum connective tissue growth factor (CTGF) to determine the usefulness of this relationship in clinical practice. Serum samples were collected from 51 patients with biopsy-proven NAFLD and 28 healthy controls, and serum levels of CTGF were assayed by ELISA. Levels of CTGF were significantly higher in patients with NAFLD compared with controls (P=0.001). The serum CTGF levels were significantly increased, that correlated with histological fibrosis stage, in patients with NAFLD [in patients with no fibrosis (stage 0) 308.2 ± 142.9, with mild fibrosis (stage 1-2) 519.9 ± 375.2 and with advanced fibrosis (stage 3-4) 1353.2 ± 610 ng/l, P < 0.001]. Also serum level of CTGF was found as an independent predictor of histological fibrosis stage in patients with NAFLD (β = 0.662, t=5.6, P <0.001). The area under the ROC curve was estimated 0.931 to separate patients with severe fibrosis from patients with other fibrotic stages. Serum levels of CTGF may be a clinical utility for distinguishing NAFLD patients with and without advanced fibrosis.
    Disease markers 01/2012; 33(2):77-83. · 2.14 Impact Factor
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    ABSTRACT: In this study, we aimed to investigate the relationship between the histological features of nonalcoholic fatty liver disease (NAFLD) and serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-5 (IGFBP-5) to determine the usefulness of this relationship in clinical practice. Serum samples were collected from 92 patients with biopsy-proven NAFLD and 51 healthy controls and serum levels of IGF-1 and IGFBP-5 were assayed by enzyme-linked immunosorbent assay. Serum IGFBP-5 levels were correlated with liver steatosis, fibrosis, and nonalcoholic steatohepatitis scores. IGF-1 levels were significantly decreased in patients with moderate-to-severe fibrosis compared with patients with no or mild fibrosis. Serum IGFBP-5 levels may be useful to differentiate both advanced fibrosis and definite nonalcoholic steatohepatitis from other NAFLD groups. Also, serum IGF-1 levels may be useful to differentiate advanced fibrosis in patients with NAFLD.
    European journal of gastroenterology & hepatology 12/2011; 24(3):255-61. · 1.66 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is one of the most common causes of chronic liver disease, worldwide. Lipoprotein-associated phospholipase A2 (Lp-PLA2) was recently characterized as a novel inflammatory biomarker that is correlated with several components constituting the metabolic syndrome. In this study, we determined the serum levels of Lp-PLA2 in patients with definite nonalcoholic steatohepatitis (NASH, n=25), borderline NASH (n=22), simple fatty liver (n=10), and healthy controls without evidence of liver disease (n=38). The levels of Lp-PLA2 were measured by enzyme-linked immunosorbent assay and compared in the four study groups. Moreover, concentrations of Lp-PLA2 were assessed in relation to the general characteristics of the study participants and the results of liver biopsy. Concentrations of Lp-PLA2 were significantly higher in patients with definite NASH (161.8±0.9 μg/L, P<0.001), borderline NASH (135.4±47.7 μg/L, P=0.001), and simple fatty liver (132.4±46.2 μg/L, P=0.042) compared with healthy controls (86.2±40.7 μg/L). Furthermore, the serum Lp-PLA2 level was strongly associated to histological steatosis scores in patients with NAFLD (β=0.32, t=2.50, P=0.016). Although subject to future confirmation, our data suggest that Lp-PLA2 levels are elevated in NAFLD.
    Metabolic syndrome and related disorders 11/2011; 10(2):103-9.
  • Journal of gastrointestinal and liver diseases: JGLD 09/2011; 20(2):215-6. · 1.86 Impact Factor
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    ABSTRACT: Sirtuins are members of the silent information regulator 2 (Sir2) family, a group of Class III histone/protein deacetylases. There are 7 different sirtuins in mammals (SIRT1-7), of which SIRT1 is the best known and most studied. SIRT1 is responsible for the regulation of protein activation by means of deacetylating a variety of proteins that play important roles in the pathophysiology of metabolic diseases. Recently, it has been shown that SIRT1 plays key roles in the regulation of lipid and glucose homeostasis, control of insulin secretion and sensitivity, antiinflammatory effects, control of oxidative stress and the improvements in endothelial function that result due to increased mitochondrial biogenesis and β-oxidation capacity. Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease, and it has been accepted as the hepatic component of metabolic syndrome. Recent studies have shown that SIRT expression in the liver is significantly decreased in an NAFLD model of rats fed a high-fat diet, and moderate SIRT1 overexpression protects mice from developing NAFLD. In addition to resveratrol, a natural SIRT1 activator, small-molecule pharmacologic SIRT1 activators have positive effects on metabolic diseases. These effects are particularly promising in the case of diabetes mellitus, for which phase studies are currently being performed. With this information, we hypothesized that the pharmacologic activation of SIRT1, which has been implicated in the pathogenesis of NAFLD, will be a potential therapeutic target for treating NAFLD. In this paper, we review the metabolic effects of SIRT1 and its association with the pathophysiology of NAFLD.
    Medical science monitor: international medical journal of experimental and clinical research 05/2011; 17(5):HY5-9. · 1.22 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Metabolic syndrome and related disorders 03/2011; 9(4):287-90.
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    ABSTRACT: Elevated progranulin levels are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. Progranulin has not been previously investigated as a biomarker of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether serum progranulin levels are altered in patients with biopsy-proven NAFLD and if they are associated with their clinical, biochemical, and histological characteristics. We measured serum progranulin levels in 95 patients with biopsy-proven NAFLD and 80 age- and sex-matched controls. The potential associations between progranulin and the characteristics of NAFLD patients were examined by multiple linear regression analysis. Serum progranulin levels were significantly higher in NAFLD patients (34 ± 13 ng/mL) than in controls (28 ± 7 ng/mL, P < 0.001). In NAFLD patients, serum progranulin levels were associated with lipid levels and the degree of hepatic fibrosis. After adjustment for potential confounders, serum progranulin remained an independent predictor of the degree of hepatic fibrosis in NAFLD patients (β = 0.392; t = 2.226, P < 0.01). Compared with controls, NAFLD patients have higher serum progranulin concentrations, which are closely associated with lipid values and the extent of hepatic fibrosis.
    Disease markers 01/2011; 31(4):205-10. · 2.14 Impact Factor
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    ABSTRACT: Fibrinogen-like protein 2 (fgl2), has recently been identified as a new member of the fibrinogen-like family of proteins. In this study we assayed plasma levels of fgl2 in patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) and examined their association with clinical, biochemical and histological phenotypes. Levels of plasma fgl2 were measured by enzyme linked immunosorbent assay and compared between the study groups. Moreover, concentrations of fgl2 were assessed in relation to the general characteristics of the study participants and the results of the liver biopsy. Levels of fgl2 were significantly higher in patients with definite non-alcoholic steatohepatitis (NASH) (788±190pg/mL, p<0.001) and borderline NASH (710 ± 140pg/mL, p<0.001) compared with controls (515±174pg/mL). No significant differences were found in patients with simple steatosis (649 ± 162pg/mL) as compared with controls. There were no associations between the plasma fgl2 levels with the fibrosis stage and steatosis grade. Although subject to future confirmation, our data suggest that fgl2 levels are elevated in the more severe forms of NAFLD.
    Hepato-gastroenterology 01/2011; 58(112):2087-90. · 0.77 Impact Factor
  • Ilyas Tuncer, Levent Doganay, Oguzhan Ozturk
    Gastrointestinal endoscopy 11/2009; 71(4):873-5. · 6.71 Impact Factor