Betatrophin Levels Are Related to the Early Histological Findings in Nonalcoholic Fatty Liver Disease.

Betatrophin, a liver hormone, regulates glucose and lipid metabolism. We investigated the betatrophin levels in nonalcoholic fatty liver disease (NAFLD) and searched for any relationship with histological severity and metabolic parameters. Fifty males with NAFLD [Nonalcoholic Steatohepatitis (NASH) (n = 32); non-NASH (n = 18)] and 30 healthy controls were included. Plasma betatrophin was measured by ELISA method. Insulin sensitivity was assessed by HOMA-IR index. Histological features were scored by the semi quantitative classification and combined as the NAFLD activity score (NAS). Betatrophin levels in the non-NASH group were significantly higher than the controls. Betatrophin was positively correlated to the age, waist circumference, total cholesterol, triglycerides, LDL cholesterol, glucose, insulin, HOMA-IR index and gamma glutamyl transpeptidase levels, and negatively correlated to the steatosis and NAS. In the stepwise linear regression analysis, the triglyceride (ß = 0.457, p < 0.001), glucose (ß = 0.281, p = 0.02) and NAS (ß = -0.260, p = 0.03) were the independent determinants of betatrophin. Betatrophin levels are higher in the early stages of NAFLD and tend to decrease when the disease progresses. This could be an important preliminary mechanistic finding to explain the increased frequency of glucose intolerance during the course of NAFLD.

Is the choice of anesthesia during gastrointestinal endoscopic procedures a result of anxiety?

BACKGROUND AND STUDY AIMS: Esophagogastroduodenoscopy (EGD) and colonoscopy (CS) are vital endoscopic procedures in the diagnosis and follow-up of gastrointestinal tract diseases. Endoscopic procedures can be performed with or without anesthesia as per patient preferences. These procedures can cause some anxiety in almost all patients, and the degree of anxiety differs for each individual. Thus, we aimed to evaluate the trait and state anxiety levels of the patients and assess the relationship between the preference of anesthesia and anxiety levels. PATIENTS AND METHODS: To investigate this issue, 723 patients who underwent elective endoscopy (EGD and/or CS) were enrolled. The researchers collected sociodemographic data and medical history records as reported by the patients. State and trait anxiety levels of the patients were evaluated using the State and Trait Anxiety Inventory (STAI). RESULTS: The patients were divided into two groups as with anesthesia and without anesthesia. Of the respondents, 43.4% requested anesthesia during endoscopic procedure. Sociodemographic data, except sex, showed similar characteristics. The STAI trait scores of the two groups were similar; however, there was a significant difference in the STAI state scores of the groups (p = 0.018). A significant difference was observed in the anesthesia preference and the type of endoscopic procedure (EGD, CS, or both) (p < 0.001). Type of endoscopic procedure, STAI state scores, and sex were determined as the predictors of the anesthesia choice. CONCLUSION: Endoscopic procedures are known to cause anxiety among many patients. Our findings suggest that the anesthesia preferences of patients are an important factor in preventing these situational concerns. However, this study found that being a woman and undergoing a CS procedure are important factors related to anesthesia preferences. Thus, more detailed assessments on this subject are required.

High-dose dual therapy is effective as first-line treatment for Helicobacter pylori infection.

BACKGROUND/AIMS: Although many regimens, including quadruple, sequential, and concomitant treatment, are used and recommended as first-line or rescue therapies for Helicobacter pylori infection, eradication rates are still below 90% in intention-to-treat analyses. Treatment protocols with substantially high eradication rates and low antibiotic resistance are needed. In this study, we investigated the efficacy of high-dose dual therapy as first-line treatment in a Turkish population. MATERIALS AND METHODS: All patients underwent upper gastrointestinal endoscopy for the initial H. pylori status because of dyspeptic symptoms. All patients received a 14-day, high-dose dual therapy comprising rabeprazole (20 mg t.i.d.) and amoxicillin (1 g t.i.d.) for H. pylori eradication. H. pylori stool antigen tests of eradication were administered to all participants at least 4 weeks after the completion of the treatment. RESULTS: The high-dose dual therapy demonstrated a 91.3% rate of successful eradication of H. pylori infection. Per-protocol success was 94.4% among female patients (n=51) and 89.6% among male patients (n=86); in terms of gender, the differences were not significant (p=0.310). No side effects were observed during the study in any patient. Six other patients did not take adequate doses of the treatment protocol. CONCLUSION: High-dose dual therapy with rabeprazole and amoxicillin was highly effective and well tolerated as a first-line therapy for H. pylori eradication.

The relationship between blood urea nitrogen levels and metabolic, biochemical, and histopathologic findings of nondiabetic, nonhypertensive patients with nonalcoholic fatty liver disease.

BACKGROUND/AIM: Nonalcoholic fatty liver disease (NAFLD) is known as the most common cause of chronic liver disease. It is accepted that the leading cause of death in patients with NAFLD is from coronary events. Blood urea nitrogen (BUN) was used as a prognostic indicator for cardiovascular disease. We aimed to investigate the relationship between BUN levels and metabolic, biochemical, and histopathologic findings of nondiabetic patients with NAFLD. MATERIALS AND METHODS: A total of 195 male patients with biopsy proven NAFLD and 82 healthy controls with normal liver and renal function tests and normal abdominal ultrasonography were enrolled in the study. BUN levels were reviewed retrospectively. RESULTS: The mean BUN levels of patients and controls were 13.07 (11.3-15.41) and 13.31 (10.97-15.87) mg/dL respectively. Patients were grouped as simple steatosis (n = 33, 16.9%), borderline nonalcoholic steatohepatitis (n = 64, 32.8%), and nonalcoholic steatohepatitis (n = 98, 50.3%), and the BUN levels of the histologic subgroups were 13.14 ± 2.89, 14.34 ± 3.04, and 13.71 ± 3.21 mg/dL, respectively. We could not find any differences between the patient group and control group with respect to BUN levels. CONCLUSION: Our findings showed that there was no relationship between BUN levels and metabolic, biochemical, and histopathologic findings of patients with NAFLD. Further investigations, including in patients with late stages of NAFLD, are required.

Neutrophil-to-lymphocyte ratio is not a predictor of liver histology in patients with nonalcoholic fatty liver disease.

OBJECTIVES: It has been reported that the neutrophil-to-lymphocyte ratio (NLR) can be measured relatively easily and can serve as a valuable index for much clinical pathology. The aim of this study was to investigate the association between NLR and hepatic histological findings in patients with nonalcoholic fatty liver disease (NAFLD). DESIGN AND METHODS: A total of 226 consecutive patients with biopsy-proven NAFLD [nonalcoholic steatohepatitis (NASH, n=105), borderline-NASH (n=74), and simple steatosis (n=47)] were enrolled. NASH and fibrosis were diagnosed histologically using the NAFLD Clinical Research Network criteria. RESULTS: Significant differences were found in aspartate aminotransferase (P<0.001), alanine aminotransferase (P<0.001) levels, and white blood cell (P=0.007) and neutrophil counts (P=0.042) between the three groups of patients. In addition, significantly higher BMI (P=0.024), waist circumference (P=0.011), aspartate aminotransferase (P=0.003), alanine aminotransferase (P=0.005), insulin (P=0.008), and homeostasis model assessment-insulin resistance (P=0.009) levels were found in patients with fibrosis (n=133) in comparison with those without fibrosis (n=93). There was no correlation between NLR and glucose, homeostasis model assessment-insulin resistance, lipid parameters, and the NAFLD activity score. Analysis of the NLR in relation to histological findings also showed no association between these parameters. CONCLUSION: To the best of our knowledge, this is the largest study that has investigated these relationships in this clinically relevant condition. The findings of the present study show that NLR is not associated with the severity of hepatic inflammation or fibrosis and thus cannot be recommended as a surrogate marker of liver injury in patients with NAFLD.

Insulin Resistance but Not Visceral Adiposity Index Is Associated with Liver Fibrosis in Nondiabetic Subjects with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, type 2 diabetes mellitus, and dyslipidemia. It is well known that the presence of visceral fat increases the risk for metabolic complications of obesity, especially NAFLD. The visceral adiposity index (VAI), a novel marker of visceral fat dysfunction, shows a strong association with insulin resistance and also cardiovascular and cerebrovascular events. However, there is conflicting data regarding the association between VAI and NAFLD. Our aim was to assess the relationship between VAI, insulin resistance, adipocytokines, and liver histology, in nondiabetic subjects with NAFLD. METHODS: A total of 215 male patients with biopsy-proven NAFLD were included. Among this group, serum levels of adiponectin, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were measured in 101 patients whose blood samples were available. RESULTS: High gamma-glutamyl transferase (GGT), high total cholesterol (TC), high triglycerides (TGs), low high-density lipoprotein cholesterol (HDL-C), and presence of metabolic syndrome were significantly associated with higher VAI, although only higher GGT and TC were independent factors on multiple linear regression analysis. On the other hand, no significant association was found between VAI and adiponectin, TNF-α, IL-6, and hsCRP levels. The multivariate analysis of variables in patients with (n=124) and without (n=91) fibrosis showed that only higher homeostasis model assessment of insulin resistance value was independently associated with liver fibrosis. CONCLUSIONS: Our findings suggest that VAI is not related to the severity of hepatic inflammation or fibrosis in nondiabetic patients with NAFLD. The lack of association between the adipocytokines and VAI also implies that the VAI may not be a significant indictor of the adipocyte functions.

The relationship of circulating fetuin-a with liver histology and biomarkers of systemic inflammation in nondiabetic subjects with nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Fetuin-A, a glycoprotein with anti-inflammatory properties, plays an important role in counter-regulating inflammatory responses. It has also been associated with insulin resistance and metabolic syndrome. We aimed to investigate circulating concentrations of fetuin-A and its possible association with hepatic and systemic inflammation in nondiabetic subjects with nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: We included 105 nondiabetic male subjects with NAFLD [nonalcoholic steatohepatitis (NASH, n = 86) and simple steatosis (SS, n = 19)]. Plasma levels of fetuin-A and markers of inflammation [high-sensitive C reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and adiponectin] were measured by enzyme-linked immunosorbent assay method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index. RESULTS: Fetuin-A was negatively correlated with age (r = -0.27, P = 0.006), however there was no association between fetuin-A and body mass index, waist circumference (WC), glucose, insulin, HOMA-IR, lipid parameters, and inflammatory markers. In addition, no significant association was observed between fetuin-A and histological findings including liver fibrosis. CONCLUSION: This study demonstrated that plasma fetuin-A levels are not correlated with the hepatic histology and systemic markers of inflammation in nondiabetic subjects with NAFLD. Our data also suggested that age is significantly associated with fetuin-A in this clinically relevant condition.

The efficacy of mesenchymal stem cell transplantation in caustic esophagus injury: an experimental study.

Introduction. Ingestion of corrosive substances may lead to stricture formation in esophagus as a late complication. Full thickness injury seems to exterminate tissue stem cells of esophagus. Mesenchymal stem cells (MSCs) can differentiate into specific cell lineages and have the capacity of homing in sites of injury. Aim and Methods. We aimed to investigate the efficacy of MSC transplantation, on prevention of esophageal damage and stricture formation after caustic esophagus injury in rats. 54 rats were allocated into four groups; 4 rats were sacrificed for MSC production. Group 1, untreated controls (n: 10). Group 2, membrane labeled MSCs-treated rats (n: 20). Group 3, biodistribution of fluorodeoxyglucose labeled MSCs via positron emission tomography (PET) imaging (n: 10). Group 4, sham operated (n: 10). Standard caustic esophageal burns were created and MSCs were transplanted 24 hours after. All rats were sacrificed at the 21st days. Results. PET scan images revealed the homing behavior of MSCs to the injury site. The histopathology damage score was not significantly different from controls. However, we demonstrated Dil labeled epithelial and muscle cells which were originating from transplanted MSCs. Conclusion. MSC transplantation after caustic esophageal injury may be a helpful treatment modality; however, probably repeated infusions are needed.

The relationship of serum uric acid with non-alcoholic fatty liver disease.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological entity which is characterized by the presence of fat droplets in hepatocytes without alcohol consumption, representing a spectrum of hepatic injuries, ranging from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. In recent years, experimental and observational studies suggest a role for serum uric acid (SUA) in NAFLD. However, there are few reports investigating SUA in histologically proven NAFLD. The aim of the present study was to evaluate the relationship of SUA with liver histology in non-diabetic patients with NAFLD. DESIGN AND METHODS: A total of 242 male patients with NAFLD (102 with NASH and 140 with SS) were included. Histopathological evaluation was carried out according to Kleiner's scoring scale. Hyperuricemia was diagnosed as SUA of more than 7 mg/dL. RESULTS: The prevalence of hyperuricemia was 33.4%. SUA levels in patients with NASH were significantly higher than those of SS (p=0.035). Univariate and multivariate analyses both demonstrated that hyperuricemia had a significant association with younger age [OR (95%CI), 0.930 (0.884-0.979), p=0.005], higher body mass index [OR (95%CI), 1.173 (1.059-1.301), p=0.002] and hepatocellular ballooning [OR (95%CI), 1.678 (1.041-2.702), p=0.033]. CONCLUSIONS: Hyperuricemia is a common finding in patients with NAFLD and is independently associated with early histological findings in this clinically relevant condition. Further longitudinal studies are needed to characterize the role of SUA in the natural history of NAFLD.

Efficacy of a modified sequential therapy including bismuth subcitrate as first-line therapy to eradicate Helicobacter pylori in a Turkish population.

BACKGROUND: Eradication rates of Helicobacter pylori with standard triple therapy are not satisfactory. Sequential therapy is an alternative method to overcome this problem. OBJECTIVES: The aim of this study was to assess efficacy of a modified sequential therapy with the addition of a bismuth preparation, as first-line treatment in the eradication of H. pylori infection. MATERIALS AND METHODS: One hundred and forty-two H. pylori-positive patients were included in the study. Patients were given a 14-day sequential therapy program consisting of pantoprazole, 40 mg (b.i.d. for 14 days); colloidal bismuth subcitrate, 300 mg 4 (two tablets before breakfast and dinner, for 14 days); amoxicillin, 1 g (b.i.d.for the first 7 days); tetracycline, 500 mg (q.i.d. for the second 7 days); and metronidazole, 500 mg (t.i.d. for the second 7 days). Eradication was tested by urea breath test (UBT) 6 weeks after completion of treatment. RESULTS: Of the 142 patients included, 131 completed the study. "Per-protocol" and "intention-to-treat" analyses revealed high eradication rates in this group (92.0-95% CI, 87.2-96.8%, and 81.0-95% CI, 74.5-87.4%, respectively). There was no relation to sex and age with this modified sequential therapy. Compliance was satisfactory (11 patients - four women and seven men were unavailable for follow-up), and side effects were minimal (six patients had to stop treatment - metronidazole-related facial swelling and numbness on the face and hands in two patients; tetracycline-related fever and epigastric pain and nausea and vomiting in two patients; and amoxicillin-related diarrhea and vaginal discharge in two patients). These side effects were reversible and resolved after the cessation of the related medication. CONCLUSIONS: This 14-day modified sequential treatment, including bismuth, achieves a significantly high eradication rates in patients with H. pylori infection, with five satisfactory patient compliance and minor side effects.

Soluble CD40 ligand, soluble P-selectin and von Willebrand factor levels in subjects with prediabetes: the impact of metabolic syndrome.

OBJECTIVES: The data regarding circulating levels of markers of platelet activation and endothelial function in people with prediabetes are scant. The aim of the present study was to search blood levels of soluble CD40 ligand (sCD40L), soluble P-selectin (sP-sel) and von Willebrand Factor (vWF) in subjects with prediabetes, along with the effects of the metabolic syndrome (MetS) on these markers. DESIGN AND METHODS: A total of 77 prediabetic individuals and 81 age, sex and body mass index matched healthy subjects with normal glucose tolerance (NGT) were prospectively analyzed. Anthropometric parameters, fasting plasma glucose, blood d lipid profiles and insulin resistance indexes were determined. Plasma sCD40L, sP-sel and vWF levels were measured by ELISA. RESULTS: sCD40L, sP-sel and vWF levels in the prediabetic group were similar to those in the controls. However, prediabetic subjects with the MetS had significantly higher level of sCD40L compared to those without MetS. Moreover, sCD40L level correlated significantly with waist circumference, systolic blood pressure and HDL-cholesterol level in the patient group. CONCLUSION: These data imply that MetS may contribute, at least in part, to the mechanism of platelet activation and endothelial dysfunction in people with prediabetes.

Chitotriosidase activity predicts endothelial dysfunction in type-2 diabetes mellitus.

The enzyme chitotriosidase (ChT) is secreted by activated macrophages and play active role in human immune response. ChT activity is increased in atherosclerosis in association to the extent of the disease. We investigated the relevance of ChT to endothelial functions and insulin resistance in patients with T2DM. Forty newly diagnosed and untreated patients with T2DM (male 17; age 47.0 ± 6.2 years) and 50 healthy volunteers (male 21; age 50.2 ± 8.8 years) were enrolled. Plasma asymmetric dimethyl arginine (ADMA) levels were determined by ELISA. ChT activity was measured by the fluorescence method. Insulin resistance was calculated by the HOMA-IR formula. The patients had higher systolic blood pressures, HOMA-IR, ADMA levels, and ChT activities (P < 0.001 for all) and lower HDL cholesterol levels (P = 0.03) than the control group. The ChT activities of the total group were significantly correlated to the age (r = 0.031, p = 0.003), ADMA (r = 0.22, p = 0.04), and plasma glucose levels (r = 0.27, p = 0.01). ChT was the independent determinant of the plasma ADMA levels (r = 0.26, p = 0.02). The results of this study show that serum ChT activity is increased in patients with newly diagnosed, untreated, and uncomplicated patients with T2DM. The results also imply that increased ChT activity may be a predictor of endothelial dysfunction.

Plasma apelin and ADMA Levels in patients with essential hypertension.

Both apelin and asymetric dymethyl arginine (ADMA) regulate blood pressures. Low apelin and high ADMA levels have been reported in several cardiometabolic disorders. However, there is no data about ADMA and apelin levels in essential hypertension and any relationship between them. We investigated a group of newly diagnosed and untreated 30 young hypertensive men and 30 healthy controls. Apelin levels were significantly lower and the ADMA levels were significantly higher in the patients (p = 0.04 for both). Both ADMA and apelin were related to the systolic blood pressures (SBP) (beta = -0.393, p = 0.003; beta = 0.285, p = 0.03, respectively). Future studies are necessary in order to clearly define the role of ADMA and apelin in the pathogenesis of essential hypertension.

Relationship between hemoglobin and CD40 ligand in prediabetes.

PURPOSE: Hemoglobin (Hb) regulates the endothelial function by modulating the bio-availability of NO at the tissue level. A significant direct relationship is present between the Hb levels and endothelial functions in patients with Type 2 diabetes. Testing whether this association also exists in subjects with prediabetes is important because prediabetes is associated with an increased risk of cardiovascular disease and mortality. Therefore, we investigated the association of Hb both with the classical cardiac risk factors and the markers for endothelial dysfunction and inflammation, in subjects with impaired glucose tolerance (IGT). METHODS: We enrolled 69 normotensive, and cardiovascular events free subjects with IGT (M=40, age=45.50+/-6.8 yr). Plasma insulin, hsCRP, soluble CD40L, vonWillebrand factor, p-selectin levels were measured. The parameters given according to the higher and lower median Hb values of the subjects were compared. RESULTS: Subjects with the higher Hb levels exhibited lower HDL-C (46.68+/-10.8 mg/dl vs 51.5+/-8.9 mg/dl; P=0.04) and higher systolic (122.57+/-6.2 mmHg vs 116.17+/-7.4 mmHg; p < 0.001) and diastolic (79.14+/-3.73 mmHg vs 75.58+/-6.1 mmHg; P=0.005) blood pressures and sCD40L (7.9+/-3.8 ng/ml vs 6.07+/-2.1 ng/ml; P=0.02) levels. Hb levels were correlated to the HDL cholesterol, sCD40L, systolic and diastolic blood pressures and waist circumference (r=-0.28, P=0.02; r=0.29, P=0.02; r=0.53, P < 0.001; r=0.41, P=0.001; r=0.42, P < 0.001 respectively). According to the multiple logistic regression analysis, Hb was the determinant of sCD40L levels (beta=0.437, P < 0.001). CONCLUSION: These results indicate that there may be a link with higher Hb values and cardiovascular risk factors in patients with IGT. Further investigation is warranted to understand the clinical implications of these findings in subjects with prediabetes.