Agnieszka Berdowska

Serum chemerin and vaspin in non-alcoholic fatty liver disease.

Abstract Objective. Chemerin and vaspin are new adipokines which may modulate inflammatory response and insulin sensitivity in non-alcoholic fatty liver disease (NAFLD). The aims of this study were to assess: (1) circulating levels of chemerin and vaspin and their association with liver histology and markers of liver injury in NAFLD patients; and (2) the relationship between the analyzed adipokines and insulin resistance. Material and methods. A total of 41 NAFLD patients with body mass index (BMI) 30.4 ± 3.3 kg/m2 [20 with non-alcoholic steatohepatitis (NASH) and BMI 30.3 ± 3.3 kg/m2 and 21 with simple steatosis/uncertain NASH (SS/UN) and BMI 30.5 ± 3.4 kg/m2] and 10 healthy volunteers with BMI 24.0 ± 2.9 kg/m2 were included in the study. Results. Serum chemerin concentration was significantly higher in NAFLD patients compared to healthy volunteers (p = 0.009). Serum chemerin was significantly higher in patients with NASH compared to patients with SS/UN (p = 0.009). The homeostasis model assessment for insulin resistance (HOMA-IR) value was higher in patients with NASH than in patients with SS/UN (p = 0.01). Serum chemerin and HOMA-IR were positively associated with NAFLD activity score (r = 0.40, p = 0.02; and r = 0.43, p = 0.008, respectively). Serum chemerin was associated with hepatocyte ballooning degeneration (r = 0.37; p = 0.03), total cholesterol (r = 0.45; p = 0.008) and diastolic blood pressure (r = 0.41; p = 0.02). HOMA-IR was related to fibrosis stage (r = 0.51; p = 0.001) and inflammatory activity grade in portal tracts (r = 0.40; p = 0.01). Serum vaspin correlated with hepatocyte ballooning degeneration (r = 0.31; p = 0.04), alanine aminotransferase and aspartate aminotransferase (r = 0.33, p = 0.03; and r = 0.32, p = 0.04, respectively) and diastolic blood pressure (r = 0.39, p = 0.01). Conclusions. This study shows for the first time that chemerin and vaspin serum concentrations are altered in patients with NAFLD. The analyzed adipokines appear to play a pivotal role in the pathogenesis of NAFLD, not only as regulators of insulin sensitivity, but also as mediators of the inflammatory process.

The Comparison of Scoring Scales for Liver Biopsy Assessment in Morbidly Obese Patients Undergoing Bariatric Surgery

Background: Many scoring systems have been applied for the grading and staging of non-alcoholic fatty liver disease (NAFLD). There is no consensus according to semiquantitative scales for the assessment of steatosis, inflammatory grading, and fibrosis staging in NAFLD. Methods: We analysed 24 consecutive patients who underwent bariatric surgery. The grading for steatosis was estimated according to the systems proposed by Brunt and by Dixon. Brunts scale and Scheuers scale modified by Gabriel were used for inflammatory activity and fibrosis staging. Additionally, types of NAFLD disease were diagnosed according to Matteonis classification. Results: Steatosis was observed in 88% and steatohepatitis in 54% of patients. We observed portal, periportal and pericellular fibrosis. Neither bridging fibrosis nor cirrhosis were found. Extent of steatosis estimated according to Dixon and Brunts scales was positively associated with appearance of steatohepatitis. The comparison of Dixons and Brunts scales according to grade of steatosis demonstrated a statistically significant difference. Inflammatory activity grades and fibrosis stages assessed according to Scheuer and Brunt scales differ significantly. Inflammatory activity evaluated with the Brunt scale was associated with the extent of steatosis and occurrence of steatohepatitis. Conclusions: Non-advanced forms of liver fibrosis do not appear to be dependent on steatosis and inflammatory grade in NAFLD. It is necessary to find the precise estimation of extent of steatosis especially occupying less than 1/3 or 1/4 of the lobule area. Brunts scale seems to be more useful for the estimation of liver biopsy in NAFLD. It is essential to create a consensus for evaluation of steatosis and necroinflammatory grading and fibrosis staging in NAFLD.

Interactions between the histaminergic and angiotensinergic systems in the central cardiovascular regulation in rats

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Serum leptin concentration in patients after heart transplantation.

Abstract:  Leptin is primarily produced by adipocytes but its receptors are expressed in a variety of tissues including the heart. Elevated plasma leptin levels predict acute myocardial infarction and it has been shown as acute phase reactant and a risk factor for coronary heart disease. The present study was undertaken to answer the question whether there exists a relationship or not, between serum leptin levels and grades of acute cellular rejection confirmed by elective endomyocardial biopsies in stable patients after orthotopic heart transplantation. We observed higher serum leptin levels compared with reference values, regardless of histopathologic biopsy findings studied. There was a positive correlation between serum leptin concentrations and body mass index, diastolic blood pressure, total cholesterol and low‐density lipoprotein. The elevated leptin levels found in heart transplant recipients could be due to the result of steroid therapy. These results point the need for further studies to explain the leptin role in heart transplant recipients.

Serum omentin and vaspin levels in cirrhotic patients with and without portal vein thrombosis

AIM To investigate serum omentin and vaspin levels in cirrhotic patients; and to assess the relationship of these levels with hemostatic parameters, metabolic abnormalities, cirrhosis severity and etiology. METHODS Fifty-one cirrhotic patients (17 with portal vein thrombosis) were analyzed. Serum omentin and vaspin levels were measured with commercially available direct enzyme-linked immunosorbent assays (ELISAs). To assess platelet activity, the following tests were performed using a MULTIPLATE®PLATELET FUNCTION ANALYZER: (1) an ADP-induced platelet activation test; (2) a cyclooxygenase dependent aggregation test (ASPI test); (3) a von Willebrand factor and glycoprotein Ib-dependent aggregation (using ristocetin) test (RISTO test); and (4) a test for thrombin receptor-activating peptide-6 induced activation of the thrombin receptor, which is sensitive to IIb/IIIa receptor antagonists. RESULTS Omentin, but not vaspin, serum concentrations were significantly decreased in patients with portal vein thrombosis (PVT) (P = 0.01). Prothrombin levels were significantly increased in patients with PVT (P = 0.01). The thrombin receptor activating peptide (TRAP) test results were significantly lower in the PVT group (P = 0.03). No significant differences in adipokines serum levels were found regarding the etiology or severity of liver cirrhosis assessed according to the Child-Pugh or Model of End-Stage Liver Disease (MELD) scores. There was a significant increase in the TRAP (P = 0.03), ASPI (P = 0.001) and RISTO high-test (P = 0.02) results in patients with lower MELD scores. Serum omentin and vaspin levels were significantly down-regulated in patients without insulin resistance (P = 0.03, P = 0.02, respectively). A positive relationship between omentin and vaspin levels were found both when all of the patients were analyzed (r = 0.41, P = 0.01) and among those with PVT (r = 0.94, P < 0.001). CONCLUSION Serum omentin levels are increased in patients without PVT. Cirrhosis origin and grade do not affect omentin and vaspin levels. The analyzed adipokines do not influence platelet activity.

Hepatic chemerin mRNA in morbidly obese patients with nonalcoholic fatty liver disease

The aim of this study was to investigate hepatic chemerin mRNA, serum chemerin concentration, and immunohistochemical staining for chemerin and and chemokine receptor-like 1 (CMKLR1) in hepatic tissue in 56 morbidly obese women with nonalcoholic fatty liver disease (NAFLD) and to search for a relationship with metabolic and histopathological features. Chemerin mRNA was assessed by quantitative real-time PCR, chemerin, and CMKLR1 immunohistochemical expression with specific antibodies, while serum chemerin concentration was assessed with commercially available enzyme-linked immunosorbent assays. Serum chemerin concentration reached 874.1 ±234.6 ng/ml. There was no difference in serum chemerin levels between patients with BMI < 40 kg/m2 and ≥ 40 kg/m2. Serum chemerin concentration tended to be higher in patients with hepatocyte ballooning, greater extent of steatosis, and definite nonalcoholic steatohepatitis (NASH). Liver chemerin mRNA was observed in all included patients and was markedly, but insignificantly, higher in those with BMI ≥ 40 kg/m2, hepatocyte ballooning, greater extent of steatosis, and definite NASH. Hepatic chemerin mRNA might be a predictor of hepatic steatosis, hepatocyte ballooning, and NAFLD activity score (NAS) but seemed not to be a primary driver regulating liver necroinflammatory activity and fibrosis. The lack of association between serum chemerin and hepatic chemerin mRNA may suggest that adipose tissue but not the liver is the main source of chemerin in morbidly obese women.

Vaspin mRNA levels in the liver of morbidly obese women with nonalcoholic fatty liver disease

The aim of this study was to evaluate hepatic vaspin mRNA in morbidly obese women with nonalcoholic fatty liver disease (NAFLD) and to look for its relationships with metabolic and histopathological features. The study included 56 severely obese women who underwent intraoperative wedge liver biopsy during bariatric surgery. Hepatic vaspin mRNA was assessed by quantitative real-time PCR. Vaspin mRNA found in all included patients was markedly higher in patients with body mass index (BMI) ≥ 40 kg/m2 (4.59 ±3.09 vs. 0.44 ±0.33; p = 0.05). An evident but statistically insignificant difference in vaspin mRNA levels was observed between patients with and without hepatocyte ballooning (4.77 ±4.23 vs. 0.45 ±0.29, respectively), with and without steatosis (4.80 ±4.20 vs. 0.41 ±0.29, respectively), without and with fibrosis (0.25 ±0.80 vs. 6.23 ±7.2, respectively), and those without and with lobular inflammation (0.27 ±1.0 vs. 5.55 ±10.1, respectively). There was marked difference in vaspin mRNA between patients with simple steatosis/borderline nonalcoholic steatohepatitis (NASH) compared to those with definite NASH (0.24 ±0.96 vs. 10.5 ±10.4). Adiposity is an undoubted confounding factor influencing vaspin levels. Hepatic vaspin mRNA seems to be markedly elevated in morbidly obese patients with more advanced NAFLD and when hallmarks of NASH were observed. Pointing to non-linear mRNA levels within the NAFLD spectrum and an evident increase in patients with fibrosis and definite NASH, the detrimental action of vaspin cannot be excluded.