Drug-induced Liver Injury Caused by Phenprobamate: Strong Probability Due to Repeated Toxicity.

Drug-induced liver injury (DILI) is an important cause of morbidity and mortality. DILI can even cause acute liver failure and the need for liver transplantation. Identifying DILI may be particularly difficult because it is actually an exclusion diagnosis and individuals are usually exposed to several drugs during a lifetime. Causality assessment methods are needed for objective diagnosis. The most common methods are; updated Roussel Uclaf causality assessment method (RUCAM), Narenjo adverse drug reaction probability scale and Maria and Victorino (M&V) causality assessment scale. Phenprobamate is a widely used muscle relaxant. Herein we report a rare case of repeated DILI caused by phenprobamate and review the objective diagnostic process for hepatotoxicities. Physicians should be aware of the potential adverse effects of this drug, including hepatotoxicity. How to cite this article: Duzenli T, Tanoglu A, et al. Drug-induced Liver Injury Caused by Phenprobamate: Strong Probability Due to Repeated Toxicity. Euroasian J Hepatogastroenterol 2019;9(1) :49-51.

Evaluation of endothelial dysfunction in patients with nonalcoholic fatty liver disease: Association of selenoprotein P with carotid intima-media thickness and endothelium-dependent vasodilation.

BACKGROUND: In patients with NAFLD, there is an increased risk of cardiovascular disease (CVD). Selenoprotein P (SelP), a hepatokine, is associated with insulin resistance (IR) and serum SelP was found to be elevated in patients with NAFLD. AIM: This study aimed to determine the risk of CVD in NAFLD patients and the association of serum SelP levels with this NAFLD related CVD risk. METHODS: Ninety-three patients with NAFLD and 37 healthy controls were included in the study. Complete blood count, C-reactive protein (CRP), fasting glucose, serum lipid levels, and SelP levels were tested from fasting blood samples. Moreover, body mass index (BMI), HOMA-IR, carotid intima-media thickness (cIMT) and flow-mediated dilatation (FMD) were measured. RESULTS: In patients with NAFLD, the FMD ratio was significantly lower than in controls (P=0.027). cIMT measurements were similar in both groups (P=0.996). Serum SelP levels were significantly higher than controls (P<0.001). SelP levels were significantly correlated with BMI, fasting glucose, LDL-cholesterol and HOMA-IR (r=0.395, P<0.001; r=0.322, P=0.002; r=0.353, P<0.001; r=0.521, P<0.001, respectively). Also, SelP levels were significantly lower and correlated with FMD (r=-0.674, P<0.001). SelP, ESR and CRP were significantly higher (P<0.05) and FMD ratios were significantly lower (P<0.05) in patients with nonalcoholic steatohepatitis (NASH) when compared to patients with simple steatosis. CONCLUSION: These results suggest that in young NAFLD patients without additional comorbidities, there is an increased risk of CVD. FMD may be a better predictor for assessment of CVD risk when compared with cIMT. We assume that there could also be an important role of SelP in the pathogenesis of NASH.

Evaluation of endothelial dysfunction in patients with familial Mediterranean fever: the relationship between the levels of asymmetric dimethylarginine and endocan with carotid intima-media thickness and endothelium-dependent vasodilation.

It has been suggested that there is an ongoing subclinical inflammation in familial Mediterranean fever (FMF) patients also in attack-free periods as well. Due to this ongoing inflammation, endothelial dysfunction (ED) may develop. Previously, ED has been suggested to increase the risk of the atherosclerosis and cardiovascular disease (CVD). Endocan is recognized as a specific molecule of the endothelium and has been shown to increase in some cases associated with inflammation. However, there is not sufficient data whether those with FMF could develop ED in the early period of life. In this study, we aimed to investigate ED and its relation with endocan in young FMF patients. A total of 57 male patients diagnosed with FMF according to the Tel Hashomer criteria and a total of 33 healthy males with similar characteristics to the patient group were included in this research. Complete blood count, erythrocyte sedimentation rate (ESR), fibrinogen, serum glucose, serum LDL cholesterol (LDL-C) and triglyceride (TG), asymmetric dimethylarginine (ADMA), and endocan levels were tested from fasting blood samples. Moreover, carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD) were measured. The endocan levels of the FMF patients during an attack-free period were significantly higher than those of the control group (p < 0.001). On the other hand, FMD measurements were significantly lower among FMF patients (p < 0.001). ADMA levels were higher in the patient group; however, this difference was similar (p > 0.05). CIMT values were similar among FMF patients and healthy controls (p > 0.05). These results have suggested that ED may develop in the patients with FMF who have no additional CVD risk, even during young adulthood, and endocan may be a favorable biomarker at demonstration of ED than ADMA among FMF patients.

Landmark reading alterations in patients with gastro-oesophageal reflux symptoms undergoing diagnostic gastroscopy.

BACKGROUND AND STUDY AIMS: There is still a debate about the exact measurement of the oesophagogastric junction and the diaphragmatic hiatus among clinicians. The aim of this study was to investigate the differences between landmark readings of gastroscopy on intubation and extubation, and to correlate these readings with a gastro-oesophageal reflux questionnaire. PATIENTS AND METHODS: 116 cases who underwent diagnostic gastroscopy between January 2013 and June 2013 were included in this study. Landmark measurements were noted while withdrawing the endoscope and were also evaluated after the gastric air was fully emptied. We first used a frequency scale for the gastro-oesophageal reflux disease symptoms (FSSG) questionnaire in order to investigate dysmotility and acid reflux symptoms in the study population and correlated the FSSG questionnaire with intubation and extubation measurements at endoscopic examination. RESULTS: Mean age of included subjects was 49.41±17.7 (19-82) years. Males and females were equally represented. On FSSG scores, the total dysmotility score was 7.99±5.06 and the total score was 15.18±10.11. The difference between intubation and extubation measurements ranged from -3cm to +2cm (mean: -0.4). When an FSSG score of 30 was accepted as a cut-off value, we detected a significant difference between the measurements (p<0.05; t: 0.048). CONCLUSION: Accuracy of landmark measurements during gastroscopy is clearly affected from insertion or withdrawal of the endoscope. When differences in measurements between insertion and withdrawal were evident, comparable with the FSSG scores, the results became significantly different. In conclusion, according to FSSG scores, these measurements should be performed at the end of the endoscopy.

Immunohistochemical activity of Prohibitin-2 and Stomatin-Like Protein-2 in patients with ulcerative colitis.

BACKGROUND/AIMS: We aimed to semi-quantitatively investigate prohibitin-2 (Phb-2) and stomatin-like protein-2 (Slp-2) expressions in patients with ulcerative colitis (UC) and healthy controls using the immunohistochemical (IHC) method. We also aimed to evaluate the correlations between the activity of UC and the expressions of these two proteins. MATERIALS AND METHODS: Ninety-five patients with UC (82 males and 13 females) and 38 healthy controls (35 males and 3 females) were included. Clinical and endoscopic activities of UC were assessed. Conventional laboratory activation parameters and severity of inflammation measures were used for the evaluation of histological activity. IHC staining of biopsy samples for the two proteins were semi-quantitatively applied, similar to previously described methods for colon adenocarcinomas. RESULTS: IHC scores of Phb-2 were lower but Slp-2 scores were higher in the UC group than in the healthy controls (p<0.05 and p=0.003, respectively). Phb-2 scores were positively correlated with clinical and histological activities (r=0.364, p<0.05 and r=0.220, p<0.032, respectively). In the UC group, endoscopic activity scores, C-reactive protein levels, and sedimentation rates were also positively correlated with Phb-2 scores (r=0.279, p<0.05, r=0.216, p<0.05, and r=0.216, p<0.05, respectively). IHC scores of Slp-2 were not significantly correlated with the activity parameters of UC. However, there was a significant positive correlation between the expressions of Phb-2 and Slp-2 proteins (p<0.001). CONCLUSION: Phb-2 may serve as a valuable new biomarker for predicting the severity of all UC activity parameters. The therapeutic effectiveness of both Phb-2 and Slp-2 should be taken into consideration.

Mean platelet volume and red cell distribution width to platelet ratio for predicting the severity of hepatic fibrosis in patients with chronic hepatitis C.

OBJECTIVE: We designed this study to investigate the relationship between the severity of fibrosis and mean platelet volume (MPV), red cell distribution width, and red cell distribution width to platelet ratio (RPR) in patients with chronic hepatitis C (CHC). DESIGN: Overall, 98 biopsy-proven naïve CHC cases were enrolled in the study. Complete blood count variables, including white blood cell, hemoglobin, platelet count, MPV, red cell distribution width, platelet distribution width as well as aspartate transaminase, alanine transaminase, total bilirubin, albumin, and other routine biochemical parameters, were tested. Liver biopsy samples were assessed according to the Ishak scoring system. Data analyses were carried out using SPSS-15 software. Statistical significance was set at a P-value of less than 0.05. RESULTS: Of the 98 cases, 80 (81.6%) were men and 18 (18.4%) were women. Fibrosis scores of 69 cases (70.4%) (group 1) were less than 3, whereas 29 cases had fibrosis scores at least 3 (29.6%) (group 2). Significant differences in MPV and RPR were observed between these two groups (MPV: 8.19±1.002 vs. 8.63±0.67 fl, P<0.05; RPR: 0.0526±0.02 vs. 0.0726±0.02, P=0.001). The areas under the curve of the RPR and MPV for predicting significant fibrosis were 0.705 and 0.670, which was superior to the aspartate transaminase-to-alanine transaminase ratio and aspartate transaminase-to-platelet ratio index scores of the study group. Cut-off values were calculated for diagnostic performance, and the cut-off values for MPV and RPR were 8.5 and 0.07 fl, respectively. CONCLUSION: MPV and RPR values were significantly higher in patients with CHC, associated with severity, and can be used to predict advanced histological liver damage. The use of MPV and RPR may reduce the need for liver biopsy. Further studies are required to determine the relationship between these parameters and the severity of fibrosis in hepatitis C patients.

Nonalcoholic fatty liver disease-related cardiovascular risk: Is there an association with blood hemoglobin levels?

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries. There is emerging evidence on the relationship between NAFLD and increased cardiovascular risk. NAFLD is strongly associated with metabolic syndrome, but several other entities play a role in the pathogenesis of NAFLD more than metabolic syndrome. Currently, studies suggest that elevated hemoglobin levels are associated not only with the existence of nonalcoholic steatohepatitis but also with the severity of hepatic fibrosis. In this review, we aimed to discuss the potential role of high hemoglobin levels in the pathogenesis of NAFLD and NAFLD-associated cardiovascular risk.

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.

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.

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.

Trimetazidine significantly reduces cerulein-induced pancreatic apoptosis.

OBJECTIVE: Acute pancreatitis continues to be associated with significant rates of mortality and morbidity, and therapeutic options are still very limited. We aimed to investigate the efficacy of trimetazidine on cerulein-induced pancreatic apoptosis and histopathological and biochemistrical consequences of acute pancreatitis. METHODS: Thirty-two Wistar albino rats were randomized into four groups (group 1: control group; group 2: acute pancreatitis group; group 3: acute pancreatitis and trimetazidine treatment group; group 4: placebo group). Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 µg/kg) four times at one-hour intervals. Trimetazidine was prepared in suspension form. In group 3, after gas anesthesia, trimetazidine was administrated to rats via a catheter. Serum interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, amylase, lipase and leukocyte levels, pancreatic apoptotic status and pancreatic Schoenberg scores were determined for all groups. Results are given as the mean ± SD. A value of P<0.05 was accepted as statistically significant. SPSS for Windows v15.0 was used for statistical analyses. RESULTS: In the acute pancreatitis group IL-1ß, amylase, lipase and leukocyte levels were elevated and pancreatic histopathological evaluation revealed a diagnosis of acute pancreatitis IL-1ß amylase and lipase levels and pancreatic inflammation were decreased significantly in the trimetazidine group (P<0.01). White blood cell counts and TNF-α concentrations for the trimetazidine group and the acute pancreatitis group were not significantly different. Trimetazidine significantly reduced apoptosis in pancreatic tissues and Schoenberg scores were also significantly reduced (P<0.05). CONCLUSION: In this study, we showed that trimetazidine treatment significantly decreases the levels of IL-1ß, amylase and lipase reduces pancreatic apoptosis and ameliorates the histopathological findings of cerulein-induced acute pancreatitis. Trimetazidine could be a new therapeutic option in the early treatment of acute pancreatitis.

Clinical usefulness of mean platelet volume and red blood cell distribution width to platelet ratio for predicting the severity of hepatic fibrosis in chronic hepatitis B virus patients.

OBJECTIVE: Hepatitis B virus infection is still one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. Liver biopsy is the gold-standard method to assess the severity of liver fibrosis, but the invasive nature of this method limits its usage. Currently, noninvasive parameters are utilized to estimate liver histology. In the present study, we aimed to investigate the relationship between the severity of fibrosis and red blood cell distribution width (RDW), platelet distribution width (PDW), mean platelet volume (MPV), and MPV and red blood cell distribution width to platelet ratio (RPR) in patients with chronic hepatitis B (CHB). DESIGN: A total of 229 biopsy-proven naïve CHB cases were included in the study. The complete blood count variables including white blood cell, hemoglobin, hematocrit value, platelet count, RDW, MPV and PDW, as well as aspartate aminotransferase, alanine aminotransferase, total bilirubin, albumin, and other routine biochemical parameters were tested. Liver biopsy samples were examined using the Ishak scoring system. Data analyses were carried out using SPSS 15 software. Statistical significance was set at a P-value of less than 0.05. RESULTS: Of the 229 cases, 210 (91.7%) were men and 19 (8.3%) were women. The mean age of the patients was 30.9 years, and 85 cases (37.1%) had HBeAg positivity. Fibrosis scores of 41 cases (17.9%) were greater than or equal to 3, whereas 188 cases (82.1%) had fibrosis scores less than 3. There was a significant difference between these two groups for MPV (group 1=7.98±1.20, group 2=8.77±1.44, P<0.05). There was also a significant difference between these two groups for RDW (P<0.05). The RDW value in group 1 patients was 11.83±0.89, whereas this value was 12.57±1.32 in group 2. Moreover, the RPR was significantly higher in group 2 than in group 1 (P<0.001). There was no significant difference between the groups for PDW. We have compared the receiver operating characteristic curves for the diagnostic performance of aspartate aminotransferase, alanine aminotransferase, platelet count, RDW, MPV, and RPR in identifying fibrosis in CHB and area under the curve values for these variables were 0.666, 0.463, 0.657, 0.672, 0.677, and 0.758, respectively. CONCLUSION: MPV and RDW values are significantly higher in hepatitis B virus-infected patients, associated with severity, and can be defined as independent predicting factors in hepatic fibrosis. Further studies are required to determine the associations between MPV and the severity of fibrosis in hepatitis B patients.

Association of reflux symptom index scores with gastroesophageal flap valve status.

OBJECTIVE: Gastroesophageal reflux disease is a chronic symptom of mucosal damage caused by gastric acid reflux. Impaired gastroesophageal flap valve (GEFV) is one of the common etiologic factors of gastroesophageal reflux. The aim of this study was to investigate the association between GEFV, RSI, and GER in patients who underwent gastroesophageal endoscopy. METHODS: Two hundred and fifty seven consecutive patients with reflux symptoms (151 men and 106 women, mean age was 50.22 years) who underwent routine upper gastrointestinal endoscopy were enrolled to our study. GEFV was graded as I through IV according to the Hill's classification. Symptoms of laryngopharyngeal and upper gastrointestinal disease and endoscopic severity of esophageal injury were correlated with GEFV status. The GEFV was classified into two groups: normal GEFV group (grade I) and the abnormal GEFV group (grades II-III and IV). The reflux symptom index (RSI) was used as a diagnostic tool for LPR. RESULTS: Age, male gender, and body mass index were significantly related to an abnormal GEFV. The rate of abnormal grades of GEFV (Grade II+III+IV) was 31%. Age of normal and abnormal grades of GEFV (49.0/50.8 vs 52.9) and values of BMI (26.2/26.7 vs 26.5) were similar. RSI scores were correlated with gastroesophageal flap valve grades but RSI scores were not correlated with Los Angeles gastroesophageal reflux (GER) Classification. Moreover, gastroesophageal reflux grade of Los Angeles Classification was positively correlated with gastroesophageal flap valve grades. CONCLUSION: Endoscopic grading of GEFV is a simple and useful technique which may provide an accurate diagnosis of laryngopharyngeal and gastroesophageal reflux. Also, reflux symptom index (RSI) is a simple, economic and noninvasive diagnostic tool for gastroesophageal reflux. However, in this research, we did not find any correlation between reflux symptom index and degree of esophageal mucosal injury which was classified according to LA classification.

Effectiveness of interleukin-1 receptor antagonist (Anakinra) on cerulein-induced experimental acute pancreatitis in rats.

AIM: Acute pancreatitis (AP) is defined as an inflammatory disease of the pancreas. The purpose of this study was to examine the effectiveness of Anakinra on cerulein-induced experimental pancreatitis rat model by using the results of biochemical and histopathological findings. MATERIALS AND METHODS: Cerulein was administered to induce AP in rats. Group 1 was the sham group. Subcutancerulein was injected to the rats in group 2 for experimental pancreatitis group. In groups 3 and 4, 100 and 50 mg/kg intraperitoneal Anakinra were injected after the induction of experimental pancreatitis by subcutaneous cerulein in rats, respectively. Lastly, in group 5, rats were injected with intraperitoneal saline and subcutan cerulean for placebo group. The following parameters were evaluated: histopathological score of pancreatitis, apoptotic index, amylase, lipase, TNF-α levels, IL-1ß and the leukocyte count. RESULTS: When the results of serum amylase, lipase, TNF-α and IL-1ß levels, the leukocyte count, histopathologic scores and apoptotic indices of control group compared to the results of other groups, the differences exhibited statistical significance (all p < 0.05). On the other hand, when the results of fourth group compared with the results of third group, the data demonstrated statistical insignificance (p > 0.05). However, no any significant differences were found between the results of fourth and fifth groups (p > 0.05). CONCLUSION: In the light of these results, cerulein is an appropriate agent for experimental AP rat model and Anakinra has a favorable therapeutic effect on acute experimental pancreatitis model. Moreover, Anakinra significantly decreases cerulein-related pancreatic tissue injury and pancreatic apoptosis.

Esomeprazole: a safe alternative to lansoprazole allergy?

Proton pump inhibitors (PPIs) are widely prescribed drugs in daily practice. Allergic reactions, even small number of anaphylactic reactions to PPIs have been reported. Omeprazole, lansoprazole, pantoprazole, rapeprazol and esomeprazole are classified in the same group. Despite the similarity of biochemical structures among these drugs, presence of cross-reactivity between PPIs is controversial.1,2 In this letter, we present 3 lansoprazole allergy cases, who were prescribed and took esomeprazole safely after allergic reactions to lansoprazole.

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.

Can serum fetuin-A be regarded as an inflammatory marker among patients with familial Mediterranean fever?

BACKGROUND/AIM: Familial Mediterranean fever (FMF), the most frequent periodic fever syndrome, is an autosomal recessive inherited disease that predominantly affects eastern Mediterranean populations. Fetuin-A is a well known negative acute-phase protein. Studies of this glycoprotein as a marker of inflammation in FMF are limited. We have investigated the relationship between serum levels of fetuin-A and inflammatory markers in patients with FMF before, during, and after FMF attacks. METHODS: Sixty-seven patients with FMF were enrolled in this study. Serum fetuin-A, seruloplasmin, fibrinogen, C reactive protein (CRP), white blood cell count (WBC), calcium, and erythrocyte sedimentation rate (ESR) were measured three times: during the attack-free period, 12 h after FMF attacks, and 7 days after FMF attacks. Plasma fetuin-A concentration was measured by use of an enzyme-linked immunoassay (ELISA) kit. Correlations and differentiation between the serum fetuin-A and other inflammatory markers in patients with FMF were investigated by use of the paired-samples T test and the Pearson correlation test (p < 0.01). RESULTS: Serum fetuin-A levels of all FMF patients in the attack period were significantly lower than in the attack-free period (p < 0.001). In contrast, serum seruloplasmin (p < 0.05), fibrinogen (p < 0.001), CRP (p < 0.05), WBC (p < 0.05), and ESR (p < 0.05) were all significantly higher than in the attack-free period. Plasma fetuin-A is significantly and inversely highly correlated with the other inflammatory markers. CONCLUSION: Fetuin-A might be a novel indicator of disease activity in patients with FMF and could be used as an adjunctive marker for differentiation of FMF attacks. The negative correlation between serum fetuin-A and other inflammatory markers may also be indicative of inflammation-dependent downregulation of fetuin-A expression in FMF patients.

Association of plasma visfatin with hepatic and systemic inflammation in nonalcoholic fatty liver disease.

BACKGROUND: Visfatin is a proinflammatory and insulin-mimetic adipokine contributing to whole body glucose and lipid metabolism. Studies to date are conflicting regarding the relationship between visfatin and non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the relationship of circulating visfatin with NAFLD. MATERIAL AND METHODS: The study included 114 NAFLD patients and 60 healthy non-diabetic controls. Plasma visfatin, adiponectin, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels were measured by ELISA. High sensitive C-reactive protein (hsCRP) levels were measured by immunoturbidimetric fixed rate method. Insulin sensitivity determined by homeostasis model assessment (HOMA-IR) index. RESULTS: TNF-α, IL-6 and hsCRP levels were higher and, Adiponectin levels were lower in NAFLD group when compared to healthy controls (p < 0.001, for all). However, no difference was found regarding to visfatin levels between two groups. Different histologic subgroups of NAFLD had a significantly higher TNF-α, IL-6 and hsCRP, and lower adiponectin levels than those with controls (p < 0.001, for all). On the other hand, no statistically significant difference was found regarding to visfatin levels among different histologic groups. Visfatin was found to be negatively correlated with TNF-α (r = -0.236, p = 0.011) in NAFLD group. However, no association was found between visfatin and histological findings. CONCLUSION: Our findings show that plasma visfatin levels are not altered in the early stages of NAFLD. However, it is inversely associated with TNF-α. These findings suggest a role for visfatin in protection against liver injury in this widespread disease.

Plasma fetuin-A is associated with endothelial dysfunction and subclinical atherosclerosis in subjects with nonalcoholic fatty liver disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome (MetS) is closely associated with an increased risk of cardiovascular disease. Fetuin-A is associated with MetS and NAFLD. We investigated the relationship of circulating fetuin-A level with markers of endothelial dysfunction and presence of carotid atherosclerosis in subjects with NAFLD. METHODS: The consecutive 115 patients with NAFLD and age-matched 74 healthy subjects were enrolled. Plasma levels of fetuin-A and markers of endothelial dysfunction [asymmetric dimethyl arginine (ADMA) and adiponectin] were measured by ELISA method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index. Carotid artery intima-media thickness (cIMT) was assessed by high-resolution ultrasonography. RESULTS: Fetuin-A and ADMA were higher and, adiponectin was lower in NAFLD group than the control group (P = 0·004, P < 0·001 and P < 0·001, respectively). In addition, NAFLD group had greater cIMT measurements than the controls (P < 0·001). However, no difference was found for fetuin-A, ADMA, adiponectin and cIMT between two groups when the findings were adjusted according to the glucose, lipids and HOMA-IR index. In correlation analysis, fetuin-A was found to be positively correlated with triglyceride (r = 0·23, P = 0·001), HOMA-IR (r = 0·29, P < 0·001), ADMA (r = 0·24, P = 0·001), cIMT (r = 0·3, P = 0·003) and, negatively correlated with HDL-C (r = -0·17, P = 0·02) and adiponectin (r = -0·19, P = 0·01) levels. Multiple linear regression analysis showed that fetuin-A was independently associated with ADMA and cIMT levels. CONCLUSION: This study demonstrated for the first time that circulating fetuin-A in NAFLD is independently associated with endothelial dysfunction and subclinical atherosclerosis.

Low efficacy of clarithromycin including sequential regimens for Helicobacter pylori infection.

BACKGROUND: Sequential treatment for Helicobacter pylori (H. pylori) appears to achieve a better eradication rate than triple therapy. However, most of the data have been reported from the Italy, and studies from different population are needed before it is recommended in clinical practice. The present study aimed to assess and compare the efficacy of two separate clarithromycin including sequential regimens in Turkey which is well known with high clarithromycin and metronidazole resistance to H. pylori. METHODS: Consecutive H. pylori -positive patients with non-ulcer dyspepsia were randomly allocated to one of the two sequential regimens; the first group was given lansoprazole 30 mg b.i.d. plus amoxicillin 1 g b.i.d. for the first week, followed by lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg t.i.d. for the second week (LA-CM). The second arm was given the same regimen but tetracycline500 g q.i.d. instead of metronidazole (LA-CT). H. pylori was detected with urea breath test (UBT) and histology before enrollment. UBT was repeated at 6th weeks after treatment. RESULTS: A total of 200 patients were enrolled in groups and 179 of them completed their protocols. The cumulative per protocol ("PP") and intention-to-treat ("ITT") eradication rates were 74.3% and 66.5% in all patients, respectively. Both "PP" (78.2% vs 70.1%) and "ITT" (72% vs 61%) eradication rates were better in LA-CT group than LA-CM group, but the differences were not statistically significant (p > .05). Both regimens were well tolerated, and the incidence of adverse effects was comparable. CONCLUSION: Two weeks clarithromycin including sequential regimens with metronidazole or tetracycline were not achieved acceptable eradication rates in Turkey.