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.

Pentraxin 3 Is a Predictor for Fibrosis and Arterial Stiffness in Patients with Nonalcoholic Fatty Liver Disease.

Objective. The aim of the present study was to investigate whether pentraxin 3 (PTX3) can be a new noninvasive marker for prediction of liver fibrosis in patients with NAFLD. We also aimed to evaluate the relationship between PTX3 and atherosclerosis in patients with NAFLD. Method. Fifty-four male patients with biopsy-proven NAFLD and 20 apparently healthy male volunteers were included. PTX3 levels were determined, using an ELISA method (R&D Sysytems, Quantikine ELISA, USA). To detect the presence of subclinical atherosclerosis in NAFLD, measurements of CIMT, FMD, and cf-PWV levels were performed. Results. PTX3 levels in NAFLD patients with fibrosis were higher than both NAFLD patients without fibrosis and controls (P = 0.032 and P = 0.028, respectively), but there was no difference between controls and NAFLD patients without fibrosis in terms of PTX3 levels (P = 0.903). PTX3 levels were strongly correlated with cf-PWV (r = 0.359, P = 0.003), whereas no significant correlation was found with other atherosclerosis markers, CIMT and FMD. Conclusion. Elevated plasma PTX3 levels are associated with the presence of fibrosis in patients with NAFLD, independently of metabolic syndrome components. This study demonstrated that for the first time there is a close association between elevated PTX3 levels and increased arterial stiffness in patients with NAFLD.

Low- and high-density lipoprotein subclasses in subjects with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with increased cardiometabolic risk. Although dyslipidemia represents a key factor in this disease, its impact on serum levels of distinct lipoprotein subfractions is largely unknown. OBJECTIVE: To assess the full low-density lipoprotein (LDL) and high-density lipoprotein (HDL) profiles in patients with NAFLD. METHODS: Seven LDL and 10 HDL subfractions were assessed by gel electrophoresis (Lipoprint, Quantimetrix Corporation, USA) in men with biopsy proven NAFLD (simple steatosis [n = 17, age, 34 ± 7 years] and nonalcoholic steatohepatitis [NASH; n = 24, age, 32 ± 6 years]). Exclusion criteria included robust alcohol consumption, infection with hepatitis B or C virus, body mass index ≥ 40 kg/m(2), diabetes mellitus, and hypertension. RESULTS: Compared with simple steatosis, NASH patients had similar body mass index, homeostasis model assessment of insulin resistance index and plasma lipids, with increased levels of both aspartate aminotransferase and alanine transaminase. NASH subjects had lower levels of larger LDL1 (10 ± 4 vs 13 ± 4%, P = .010) and increased smaller LDL3 and LDL4 particles (9 ± 5 vs 5 ± 5%, P = .017 and 3 ± 3 vs 1 ± 2%, P = .012, respectively). No changes were found in the HDL subclass profile. By multiple regression analysis, we found that NASH was associated only with increased levels of LDL3 (P = .0470). CONCLUSIONS: The increased levels of small, dense LDL3 and LDL4 in NASH may help to at least partly explain the increased risk for atherosclerosis and cardiovascular diseases in these patients.

Efficacy of autologous mesenchymal stem cell transplantation in patients with liver cirrhosis.

BACKGROUND/AIMS: Because of several limitations and complications of liver transplantation, new alternative treatment modalities are required for patients with liver cirrhosis. Many study results encourage the use of autologous bone marrow-derived mesenchymal stem cells for liver diseases. In this study, we assessed the impact of autologous mesenchymal stem cell transplantation on liver tissue and liver chemistry. MATERIALS AND METHODS: Twenty-five patients with biopsy-proven liver cirrhosis were enrolled in the study. Patients received 1×106 autologous mesenchymal stem cells/kg via a peripheral vein. Biochemical parameters were checked monthly. Periodical radiological screening and liver biopsies before mesenchymal stem cell transplantation were performed after 6 months. Liver specimens were assessed by a pathologist. RESULTS: No side effect was observed and the mesenchymal stem cell transplantation procedure was well tolerated. Twelve patients completed the study. In 8 patients, improvements in Model for End-Stage Liver Disease (MELD) scores were observed. Serum albumin levels markedly increased in the third month. In patients with non-responder hepatitis C, HCV RNA levels both became negative after mesenchymal stem cell transplantation. Histopathological examinations of liver tissues before and at 6 months after transplantation revealed no change in liver tissue regeneration or fibrosis. However, in 5 patients, hepatitis activity index scores decreased. CONCLUSION: Autologous mesenchymal stem cell transplantation via peripheral vein is safe and feasible. Consecutive liver biopsy examinations suggested that mesenchymal stem cells could not reach the liver in a sufficient amount. Improvement in patients and clearance of HCV RNA may have occurred through immunomodulatory mediators secreted by transplanted mesenchymal stem cells, namely the "endocrine" effect.

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.

Is the neutrophil to lymphocyte ratio associated with liver fibrosis in patients with chronic hepatitis B?

AIM: To determine the association between the neutrophil to lymphocyte (N/L) ratio and the degree of liver fibrosis in patients with chronic hepatitis B (CHB) infection. METHODS: Between December 2011 and February 2013, 129 consecutive CHB patients who were admitted to the study hospitals for histological evaluation of chronic hepatitis B-related liver fibrosis were included in this retrospective study. The patients were divided into two groups based on the fibrosis score: individuals with a fibrosis score of F0 or F1 were included in the "no/minimal liver fibrosis" group, whereas patients with a fibrosis score of F2, F3, or F4 were included in the "advanced liver fibrosis" group. The Statistical Package for Social Sciences 18.0 for Windows was used to analyze the data. A P value of < 0.05 was accepted as statistically significant. RESULTS: Three experienced and blinded pathologists evaluated the fibrotic status and inflammatory activity of 129 liver biopsy samples from the CHB patients. Following histopathological examination, the "no/minimal fibrosis" group included 79 individuals, while the "advanced fibrosis" group included 50 individuals. Mean (N/L) ratio levels were notably lower in patients with advanced fibrosis when compared with patients with no/minimal fibrosis. The mean value of the aspartate aminotransferase-platelet ratio index was markedly higher in cases with advanced fibrosis compared to those with no/minimal fibrosis. CONCLUSION: Reduced levels of the peripheral blood N/L ratio were found to give high sensitivity, specificity and predictive values in CHB patients with significant fibrosis. The prominent finding of our research suggests that the N/L ratio can be used as a novel noninvasive marker of fibrosis in patients with CHB.

The degree of mucosal damage to the small intestine and serum immunoglobulin G4 levels correlate with celiac disease.

BACKGROUND: Celiac disease (CD) is an immune-mediated and chronic inflammatory enteropathy, triggered by the ingestion of gluten in genetically susceptible individuals. Immunoglobulin G4 (IgG4)-related diseases are a recently defined emerging clinical condition, characterized by increased serum IgG4 concentrations. The aim of this study was to investigate whether IgG4 levels correlate with the titers of intestinal antibodies and the degree of mucosal damage in CD patients. MATERIALS AND METHODS: A total of 41 CD patients and 28 healthy controls were included in the study. All patients underwent a duodenal biopsy and were then diagnosed with the modified Marsh classification. Blood samples were obtained for IgG4 measurements. Serums were kept at -80 °C until the analysis was carried out and plasma IgG4 levels were determined using an enzyme-linked immune sorbent assay method with a diagnostic cutoff value of 135 mg/dl. RESULTS: The mean age of the CD and the control group was 26.8 ± 8.3 and 26.9 ± 6.2 years, respectively. The mean IgG4 levels were significantly higher in CD patients (283.21 ± 39.02 mg/dl) compared with the healthy control group (68.97 ± 15.89 mg/dl, P<0.0001). In the CD group, 27/41 patients and in the control group, 4/28 patients had high IgG4 levels (>135 mg/dl, P < 0.0001). A close correlation was found between the grade of mucosal damage, IgG4 levels, and antigliadin-IgA; the higher the grade Marsh score, the higher the measured IgG4 (P < 0.05). CONCLUSION: In our study, IgG4 levels of CD patients were higher than normal ranges whereas the results of the control group were within physiologic limits. We also showed for the first time that there was a correlation between IgG4 levels, autoantibody, and severity of mucosal damage. To the best of our knowledge, this is the first study to evaluate IgG4 levels and mucosal damage in CD patients.

Pulse Wave Velocity, Intima Media Thickness, and Flow-mediated Dilatation in Patients with Normotensive Normoglycemic Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have increased risk for atherosclerosis. The cause of increased cardiovascular risk is not fully understood. Chronic inflammatory process may predispose to atherosclerosis. We aimed primarily to investigate subclinical atherosclerosis in patients with IBD, by measuring carotid femoral pulse wave velocity (PWV), carotid intima media thickness, and flow-mediated dilatation compared with matched normal controls. METHODS: Patients with IBD were recruited among individuals proven to have Crohn's disease (CD) and ulcerative colitis (UC). To exclude any interference of confounding factors for endothelial dysfunction or atherosclerosis, we studied a specifically selected group with no additional cardiovascular risk. PWV, carotid intima media thickness, and flow-mediated dilatation levels were measured in all patients and controls. RESULTS: The carotid femoral PWV levels were 8.13 ± 1.61 m/sec in the patients with UC, 8.16 ± 1.74 m/sec in the patients with CD, and 6.85 ± 0.95 m/sec in the healthy subjects. The levels of carotid femoral PWV were significantly higher in patients with CD and UC than control group (P < 0.001). Flow-mediated dilatation levels were significantly decreased in patients with UC and CD (9.6% ± 5.1% versus 108% ± 4.4%) when compared with control subjects (15.1% ± 9.7%) (P = 0.004). No significant difference in carotid intima media thickness was detected between UC, CD, and control groups (P = 0.152). CONCLUSIONS: This study suggests that patients with IBD without traditional cardiovascular risk factors have increased risk of endothelial dysfunction and atherosclerosis.