Dynamic thiol-disulfide homeostasis is disturbed in hepatitis B virus-related chronic hepatitis and liver cirrhosis

Background/aim: Thiol-disulfide homeostasis is an important antioxidant defense mechanism. This study was conducted to investigate dynamic thiol-disulfide homeostasis in patients with hepatitis B virus-related chronic hepatitis and liver cirrhosis. Materials and methods: Seventy-one treatment-naive patients with chronic hepatitis B (CHB), 50 patients with hepatitis B virusassociated liver cirrhosis, and 45 healthy controls were included in the study. Serum total and native thiol concentrations and serum disulfide concentrations were measured using an automated method. Results: Mean serum total thiol concentrations in the control, CHB, and cirrhosis groups were 481.64 ± 37.87 µmol/L, 438.50 ± 71.35 µmol/L, and 358.07 ± 80.47 µmol/L, respectively (P < 0.001), and mean serum native thiol concentrations in the control, CHB, and cirrhosis groups were 452.92 ± 36.43 µmol/L, 400.16 ± 65.92 µmol/L, and 328.15 ± 74.91 µmol/L, respectively (P < 0.001). Mean serum disulfide concentrations in the control, CHB, and cirrhosis groups were 14.38 ± 3.38 µmol/L, 19.19 ± 6.16 µmol/L, and 14.98 ± 5.53 µmol/L, respectively (P < 0.001). There was a progressive decrease in both mean serum native and total thiol concentrations parallel to the liver fibrosis stage. Conclusion: : Thiol-disulfide homeostasis is disturbed in patients with hepatitis B virus-related chronic hepatitis and liver cirrhosis.

The Importance of Liver-Fatty Acid Binding Protein in Diagnosis of Liver Damage in Patients with Acute Hepatitis.

INTRODUCTION: Acute hepatitis is acute inflammation of liver elicited by a large number of causes. It sometimes spontaneously recovers, sometimes may progress to chronic hepatitis. Liver- Fatty Acid Binding Protein (L-FABP) is a small protein that is abundant in hepatocytes, and which binds most of the long-chain fatty acids present in the cytosol. AIM: The present study was aimed to investigate the levels of serum and urine L-FABP in acute hepatitis and diagnostic value of serum and urine L-FABP levels in patients with acute hepatitis. MATERIALS AND METHODS: The present study included a total of 85 patients. Total number of patients with acute hepatitis were 17 (five of acute hepatitis B, one of acute hepatitis A, two of acute hepatitis C, five of autoimmune hepatitis and four of toxic hepatitis), 19 of hepatic encephalopathy, 29 of liver cirrhosis, and 20 controls were included. Serum and urinary L-FABP levels were analyzed by the Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Serum L-FABP levels were 9110±3352.5, 9410±1355, 9715±2462 and 3672±982.5 ng/l in patients with acute hepatitis, hepatic encephalopathy and cirrhosis and control subjects, respectively. There were statistically significant positive correlations between serum levels of L-FABP and Aspartate Aminotransferases (AST), Alanine Aminotransferases (ALT), Creatinine (Cre) and Gamma Glutamyl Transferases (GGT) (p<0.001, p<0.001, p<0.001 and p<0.001, respectively). While the cut-off value of serum L-FABP for all of the patients was 5183 ng/l {p<0.001 and Area Under Curve (AUC) 0.985}, the sensitivity and specificity were 95.4% and 100%, respectively. Positive and negative predictive values for serum L-FABP were 100% and 87%, respectively. CONCLUSION: Serum and urine L-FABP may be a new diagnostic marker for liver damage in patients with acute hepatitis. However, our study showed that except of aminotransferases, L-FABP should be used for diagnosis of liver damage in patients with acute hepatitis, chronic hepatitis and also cirrhosis.

Serum ischemic modified albumin (IMA) concentration and IMA/albumin ratio in patients with hepatitis B-related chronic liver diseases.

BACKGROUND/AIM: Albumin is the most important protein synthesized by the liver. Posttranscriptional changes occur in the molecular structure of albumin due to various factors and isoforms arise. Ischemic modified albumin (IMA) is one such isoform. This study was conducted to evaluate serum IMA concentrations in patients with hepatitis B virus (HBV)-related chronic liver diseases. MATERIALS AND METHODS: This study included 74 treatment-naive chronic hepatitis B patients, 25 patients with HBV-related cirrhosis, and 49 healthy controls. Serum IMA concentration was measured spectrophotometrically using the albumin cobalt binding test. RESULTS: The mean IMA concentrations in the chronic hepatitis B group and healthy controls were 0.33 ± 0.11 ABSU and 0.27 ± 0.70 ABSU, respectively, and the difference was statistically significant (P < 0.001). Mean IMA/albumin ratios (IMAR) in the chronic hepatitis B and control groups were 0.08 ± 0.04 and 0.06 ± 0.17, respectively, and the difference was also statistically significant (P < 0.001). Higher serum IMA concentrations and IMAR were detected in patients with advanced fibrosis. CONCLUSION: Serum IMA concentration and IMAR are increased in patients with HBV-related chronic liver diseases and IMA and IMAR are associated with the degree of liver fibrosis. IMA and IMAR may have potential use as noninvasive markers of fibrosis in chronic hepatitis B patients.

Is there any potential or additive effect of anemia on hepatorenal syndrome?

BACKGROUND/AIMS: Hepatorenal syndrome (HRS) is a severe complication of advanced cirrhosis and is characterized by renal dysfunction and poor survival rates. Although anemia is a non-rare condition in advanced liver cirrhosis, there is no publication regarding the potential or additive effects of anemia on HRS and renal dysfunction in patients with cirrhosis. We investigated whether severe anemia is a precipitant factor for HRS. MATERIALS AND METHODS: In this prospective study, consecutive patients with cirrhosis with and without renal dysfunction were enrolled. A total of 29 patients with cirrhosis with HRS meeting the HRS diagnostic criteria (9 patients with type 1 HRS and 20 with type 2 HRS) and 37 patients with cirrhosis without HRS were included. The demographic features, laboratory data (particularly anemic parameters), and clinical scores of patients with and without HRS were evaluated. RESULTS: Grades of ascites, Child-Turcotte-Pugh (CTP) scores, and Model of End Stage Liver Disease (MELD) scores were significantly higher in contrast to hemoglobin levels; hematocrit concentrations were significantly lower in patients with type 1 and 2 HRS than in those with non-HRS stable cirrhosis. There was a negative correlation between the hemoglobin-hematocrit and serum creatinine levels. In the logistic regression analysis, the hemoglobin levels and CTP and MELD scores were statistically significant for an onset of HRS. CONCLUSION: Anemia may contribute to HRS and deteriorated renal function in patients with HRS because anemic hypoxia can lead to microcirculatory renal ischemia in the kidneys and anemia can also activate sympathetic activity and hyperdynamic circulation in the pathogenesis of HRS.

Effects of diclofenac sodium and octreotide on treatment of caerulein-induced acute pancreatitis in mice.

BACKGROUND: Research continues to develop novel therapeutic modalities that particularly focus on the pathogenesis of acute pancreatitis. This study aimed to assess the effects of diclofenac sodium and octreotide, alone or in combination, on pancreatic enzymes, pancreatic myeloperoxidase activity, histopathology and apoptosis of pancreas cells, using a model of experimentally induced acute pancreatitis. OBJECTIVES: We aimed to demonstrate effects of diclofenac sodium, octreotide and their combined use on pancreatic enzymes, activity of pancreatic myeloperoxidase (MPO) activity, histopathology and apoptosis of pancreas on treatment of caerulin-induced experimental acute pancreatitis. MATERIALS AND METHODS: Caerulin-induced acute pancreatitis model was created using a total of 58 male BALB-C mice of 25 gr in seven groups. Serum amylase, lipase levels and pancreatic myeloperoxidase activity were examined as well as apoptotic values in pancreatic acinar cells through TUNNEL method. Histopathology of pancreas was evaluated for presence of edema, hemorrhage, parenchymal necrosis, fat necrosis, leukocyte infiltration, and fibrosis. RESULTS: In the diclofenac sodium group, apoptotic values in the pancreatic acinar cells were found to be statistically lower than in the acute pancreatitis group in terms of parenchymal necrosis and hemorrhage scores (P = 0.007, P = 0.002, and P = 0.052, respectively). No statistically significant differences were found in serum level of amylase, lipase, pancreatic myeloperoxidase activity and the other histopathological scores (P > 0.05). CONCLUSION: Diclofenac sodium, a cost-effective agent with a favorable side-effect profile, may represent a novel therapeutic agent for the treatment of acute pancreatitis. Findings of this study suggest a better efficacy for diclofenac sodium monotherapy as compared to octreotide alone or octreotide/diclofenac combination.

Neutrophil gelatinase-associated lipocalin in prediction of mortality in patients with hepatorenal syndrome: a prospective observational study.

BACKGROUND & AIMS: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis which is characterized by renal dysfunction and associated with poor survival. Neutrophil gelatinase-associated lipocalin (NGAL) is a troponin-like biomarker for human acute kidney injury. We aimed to investigate levels of plasma and urine NGAL in HRS and predictive ability of these markers for all-cause mortality, in HRS, stable cirrhosis and control subjects. METHODS: A total of 64 patients with cirrhosis (8 patients with type 1 HRS, 22 with type 2 HRS, and 34 without HRS) and 23 control subjects were included in the study. Blood and urine samples were measured with Human NGAL sandwich ELISA. Patients were followed up prospectively. RESULTS: Patients with type 1 and type 2 HRS had significantly higher plasma and urine NGAL levels compared with stable cirrhosis and control subjects. Cox regression analysis showed that plasma NGAL and MELD-Na scores were independent predictors of mortality. ROC-curve analysis showed that the plot of the plasma NGAL, urine NGAL, MELD-Na and Child-Turcot-Pugh score could predict all-cause mortality in cirrhotic patients' area under the curve (AUC 0.819, 0.686, 0.807 and 0.795 respectively). CONCLUSIONS: NGAL could predict mortality in patients with HRS independent of other commonly used risk factors.

Blood neutrophil-to-lymphocyte ratio independently predicts survival in patients with liver cirrhosis.

OBJECTIVES: Neutrophil-to-lymphocyte ratio (NLR) is a novel inflammation index that has been shown to independently predict poor clinical outcomes. We aimed to evaluate the role of NLR in the prediction of long-term mortality in patients with stable liver cirrhosis. MATERIALS AND METHODS: This is a retrospective observational cohort study in which 145 stable cirrhotic patients without infection, hepatocellular carcinoma, and ongoing steroid therapy were enrolled between January 2009 and December 2011. The primary end point was survival during follow-up. NLR along with Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD) scores, and Charlson comorbidity index were assessed for the prediction of mortality. RESULTS: There were 86 men and 59 women, mean age 58.9±13.4 years. The etiologies of liver cirrhosis included viral hepatitis (n=73), cryptogenic (50), alcoholic (12), and other (10). The mean follow-up duration was 27.8±6.8 months, during which 40 patients died. The mean NLRs were 2.08±0.99 and 4.39±3.0 in surviving and nonsurviving patients, respectively (P<0.001). Kaplan-Meier survival analysis was carried out according to the median NLR above and below 2.72. Patients with NLR of at least 2.72 had a significantly lower survival (log rank, P<0.001). NLR was found to be an independent predictor of mortality in all Cox Regression models (odds ratio 1.2; 95% confidence interval 1.2-1.3; P<0.001). Receiver operating characteristic analysis showed that cut-off values of 4.22, 3.07, and 2.96 for NLR predicted 12, 24, and 36-month mortality, respectively (AUC: 0.806, P=0.0029; 0.841, P<0.0001 and 0.783, P<0.0001, respectively). CONCLUSION: NLR is a predictor of mortality independent of CTP and MELD scores in patients with liver cirrhosis. NLR could predict mortality in the subgroup of patients with low MELD scores as well.

Obesity is an independent determinant of ischemia-modified albumin.

OBJECTIVE: We have measured ischemia-modified albumin (IMA), total antioxidant status (TAS), total oxidant status (TOS) and high-sensitivity C-reactive protein (hsCRP) levels in obese and normal-weight subjects to investigate if IMA can be used as a biomarker of oxidative stress and inflammation and if IMA was an independent determinant of obesity or not. METHODS: The study was performed on 92 obese subjects (20 male, 72 female) aged 38 ± 11 years and 78 normal-weight controls (19 male, 59 female) aged 37 ± 11 years. Serum lipids, IMA, TAS, TOS, and hsCRP levels of the subjects were measured. RESULTS: IMA (p < 0.05), TOS (p < 0.001), and hsCRP (p < 0.001) levels of the obese subjects were significantly higher, whereas TAS levels were significantly lower (p < 0.05) than those of the controls after adjustment for age and gender. In the linear regression analysis, waist circumference (r² = 0.139, p < 0.01), BMI (r² = 0.136, p < 0.01) and insulin (r² = 0.120, p < 0.05) were shown to be significant independent determinants of IMA levels. CONCLUSIONS: We have found that oxidative stress and inflammation were increased and antioxidative defense was decreased, which resulted in increased levels of IMA, a biomarker of ischemia, in obese subjects. Also, obesity and insulin were found to be independent determinants of IMA. Thus, obese subjects are under high risk of ischemia, and IMA may be used as a biomarker of oxidative stress and ischemia. Further larger investigations are needed to confirm this opinion.

Plasma ω-3 fatty acid levels negatively and ω-6 fatty acid levels positively associated with other cardiovascular risk factors including homocysteine in severe obese subjects.

Obesity and homocysteine (tHcy) are important risk factors for cardiovascular diseases (CVD). Plasma omega-3 fatty acids (ω-3 FAs) and omega-6 fatty acids (ω-6 FAs) are essential fatty acids with diverse biological effects in human health and disease. We have investigated the relation of plasma ω-3 FAs and ω-6 FAs levels with other cardiovascular risk factors including tHcy in severe obese subjects. This study was performed on 96 severe obese and 65 normal weight subjects. Plasma fatty acid composition was measured by GC/MS and serum tHcy level was measured by HPLC methods. There were no differences between groups in terms of concentrations of serum tHcy, plasma ω-3 FAs, ω-6 FAs and ω-3/ω-6 ratio, whereas serum vitamin B-12 (p<0.01) and folic acid (p<0.05) levels were lower than those of the normal weight subjects. Homocysteine positively correlated with ω-6 FAs and negatively correlated with ω-3 FAs in severe obese and normal weight subjects. Serum vitamin B-12 positively correlated with ω-3 FAs (p<0.01) and ω-3/ω-6 ratio (p<0.01) and negatively correlated with ω-6 FAs (p<0.05) in severe obese subjects. Serum folic acid positively correlated with ω-3 FAs (p<0.01) in severe obese subjects. Our results suggest an association between the plasma ω-3 FAs and ω-6 FAs and serum tHcy concentrations in severe obese and normal weight subjects. Low levels vitamin B-12 and folic acid may have been responsible for the elevated tHcy levels in severe obese subjects, increasing the risk for future development of cardiovascular diseases.

Liver abscess after implantation of dental prosthesis.

Pyogenic liver abscesses are rare but a life-threatening important condition. Dental procedures constitute only rare cases of pyogenic liver abscesses, with only a few cases in the literature. We report a patient with liver abscess following a dental procedure. A 74 years old diabetic male patient was admitted to our hospital with complaints of fatigue, 40 °C fever, rigors and right upper quadrant pain, 3-4 d after a dental procedure. Physical examination revealed fever and tenderness in the right upper quadrant. Laboratory examination revealed leucocytosis, elevated erythrocyte sedimentation rate and C-reactive protein and moderately elevated transaminases. An abscess was detected in radiological examination in the medial part of the left lobe of liver, neighboring the gall bladder. He was successfully treated with percutaneous abscess drainage and antibiotherapy.

Comparison of a newly developed automated and quantitative hepatitis C virus (HCV) core antigen test with the HCV RNA assay for clinical usefulness in confirming anti-HCV results.

Hepatitis C virus (HCV) is a global health care problem. Diagnosis of HCV infection is mainly based on the detection of anti-HCV antibodies as a screening test with serum samples. Recombinant immunoblot assays are used as supplemental tests and for the final detection and quantification of HCV RNA in confirmatory tests. In this study, we aimed to compare the HCV core antigen test with the HCV RNA assay for confirming anti-HCV results to determine whether the HCV core antigen test may be used as an alternative confirmatory test to the HCV RNA test and to assess the diagnostic values of the total HCV core antigen test by determining the diagnostic specificity and sensitivity rates compared with the HCV RNA test. Sera from a total of 212 treatment-naive patients were analyzed for anti-HCV and HCV core antigen both with the Abbott Architect test and with the molecular HCV RNA assay consisting of a reverse transcription-PCR method as a confirmatory test. The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 96.3%, 100%, 100%, and 89.7%, respectively. The levels of HCV core antigen showed a good correlation with those from the HCV RNA quantification (r = 0.907). In conclusion, the Architect HCV antigen assay is highly specific, sensitive, reliable, easy to perform, reproducible, cost-effective, and applicable as a screening, supplemental, and preconfirmatory test for anti-HCV assays used in laboratory procedures for the diagnosis of hepatitis C virus infection.