The relationship of circulating MOTS-c level with liver fibrosis and metabolic components in patients with metabolic dysfunction-associated fatty liver disease.

OBJECTIVE: Mitochondrial open reading frame of the 12s ribosomal RNA type-c (MOTS-c) is a novel identified mitochondrial signal transmission peptide that plays an important role in glucose, amino acid and lipid metabolism. In this study, we aimed to investigate the relationship of circulating MOTS-c level with noninvasive scores of fibrosis and the components of metabolic syndrome (MetS) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). PATIENTS AND METHODS: This was a single-center cross-sectional study, and the participants were divided into two groups based on their liver ultrasound results: the fatty liver group and the healthy control group. The MOTS-c level was measured by the ELISA method. Non-alcoholic fatty liver disease fibrosis score (NFS) and fibrosis 4 (FIB-4) were used to determine the level of liver fibrosis. Statistical analyses were performed using Statistical Package for Social Science 15.0 package program. RESULTS: One hundred fifty patients (male, n=57) with MAFLD [median age 41.0 (14) years] and 84 healthy controls (male, n=34) [median age 36.0 (22) years] were included in this study. Patients with MAFLD had significantly lower MOTS-c levels than the healthy controls (p=0.009). The MOTS-c level was significantly lower in subjects with MetS (n=48) compared to those without MetS (n=186) (p=0.01). In the total population (n=234), MOTS-c levels negatively correlated with the presence of MAFLD, NFS, FIB-4, and components of MetS. CONCLUSIONS: Individuals diagnosed with MetS and MAFLD tend to have lower levels of MOTS-c. Additionally, these lower levels are inversely correlated with both the components of MetS and noninvasive fibrosis scores. MAFLD negatively correlated to the MetS components and noninvasive scores of fibrosis.

Microvesicular steatosis: a missed item in the management of nonalcoholic fatty liver disease?

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease and cirrhosis. In NAFLD, histological course of steatosis is usually macrovesicular (MacroS), but it may be accompanied by varying degrees of microvesicular steatosis (MicroS). Thus, in this study, we aimed to evaluate the prevalence and significance of MicroS in subjects with NAFLD. METHODS: A retrospective analysis of clinical and laboratory data of patients with histologically proven NAFLD was performed. The liver biopsy specimens which stained with hematoxylin eosin, reticulin, and Masson's Trichrome stains were evaluated by single expert liver pathologist. Scoring and semiquantitative assessment of steatosis and NAFLD severity was done according to Kleiner scale known as NAFLD activity score (NAS). Grading for steatosis, steatosis type, zonal distribution of steatosis and other histological findings were also determined. RESULTS: The prevalence of MicroS among the study population (n= 191) was 30.4%. There was no difference regarding the demographic and biochemical parameters between patients with or without MicroS. On the other hand, the prevalence of ballooning injury and megamitochondria were higher in patients with MicroS (p= 0.019 and p= 0.036, respectively). There was a significant association of MicroS with ballooning injury (OR 2.65, 95% CI= 1.26-5.55 ; p= 0.005) and the presence of megamitochondria (OR 3.72, 95% CI= 1.00-13.72 ; p= 0.037). CONCLUSION: MicroS is common in patients with NAFLD and is associated with early histological findings in this clinically relevant condition. Further longitudinal studies are needed to characterize the role of MicroS in the natural history of NAFLD.

Plasma pentraxin-3 is associated with endothelial dysfunction in non-alcoholic fatty liver disease.

OBJECTIVE: Pentraxin-3 (PTX-3) is an acute-phase protein belonging to the PTX family. It has been reported that PTX-3 is significantly associated with obesity, metabolic syndrome, and cardiovascular diseases (CVD). Non-alcoholic fatty liver disease (NAFLD) is strongly associated with atherosclerosis and CVD. In this study, we aimed to investigate the relationship of PTX-3 with circulating markers of endothelial dysfunction and atherosclerosis in patients with NAFLD. PATIENTS AND METHODS: Seventy patients with biopsy-proven NAFLD and seventy healthy controls were enrolled in the study. Plasma asymmetric dimethylarginine (ADMA), adiponectin, and PTX-3 levels were determined using enzyme-linked immunosorbent assay (ELISA). High-sensitivity C-reactive protein (hsCRP) serum levels were measured with the immunoturbidimetric assay. Insulin resistance was estimated using the HOMA-IR index. RESULTS: PTX-3 and hsCRP levels were higher and adiponectin levels were lower in the NAFLD group compared to the healthy controls (p < 0.001 for all). In correlation analysis, a significant association was observed between PTX-3 and ADMA levels (r = 0.423, p < 0.001). CONCLUSIONS: Our study demonstrated for the first time that increased circulating PTX-3 is strongly associated with endothelial dysfunction in subjects with NAFLD. However, large prospective studies are needed to establish the independent predictive value of PTX-3 for CVD endpoints in this clinically relevant condition.

Alpha fetoprotein levels and its relationship with histopathological findings in patients with non-alcoholic fatty liver disease.

BACKGROUND: Non alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver disorders ranging from simple steatosis (SS) to cirrhosis. In addition, increasing evidence indicates that hepatocellular carcinoma (HCC) may represent a late complication of NAFLD. Alpha-fetoprotein (AFP) serum levels can rise in adults with HCC. AIM: In the present study, we aimed to investigate circulating AFP concentrations in subjects with histologically proven NAFLD. In addition, the relationship of AFP with liver histology was also searched. PATIENTS AND METHODS: One hundred and three male NAFLD patients and 57 healthy male controls were enrolled in the study. In addition, patients with NAFLD grouped as nonalcoholic steatohepatitis (NASH) (n = 72) and SS (n = 31). AFP serum levels were measured in duplicate by the chemiluminescence's method. RESULTS: Age and gender were similar in subjects with NAFLD and controls. AFP serum levels were not different between two groups. In subgroup analysis, AFP levels were also found to be similar in patients with NASH and SS. Moreover, no significant relationship was found between AFP and histopathological findings in patients with NAFLD. CONCLUSIONS: The results of this preliminary study suggest that AFP is not involved in the pathogenesis of NAFLD.

Ewing's sarcoma of the fibula presenting with venous thrombosis

Malignancies account for about 20% of incidentally diagnosed venous thromboembolism. Surgery- or chemotherapy-induced risk of thrombosis is also high in patients with cancer. We report on a young male with skeletal Ewing's sarcoma who presented with deep vein thrombosis in the affected limb, which is quite a rare clinical condition. Venous thrombosis of the lower extremities in young patients should prompt the clinician to search for underlying local malignancies (AU)

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Low plasma apelin levels in newly diagnosed type 2 diabetes mellitus.

OBJECTIVE: To investigate blood apelin concentrations in patients with newly diagnosed and untreated type 2 diabetes mellitus (T2DM) who had no additional disorder and to investigate the association of apelin with adiponectin, body mass indexes (BMI) and insulin sensitivity. METHODS: Forty patients with T2DM and 40 healthy controls were enrolled. Apelin levels were measured along with BMI, lipids, glucose, insulin and adiponectin levels, and HOMA-IR indexes. Age, sex and BMI were similar in the two groups. RESULTS: Plasma apelin and adiponectin levels were significantly lower in the diabetic group compared to controls (p<0.001, for both). Insulin levels and HOMA indexes were significantly higher in patients with T2DM (p<0.001 and p=0.001, respectively). Apelin levels were negatively correlated with age (r=-0.315, p=0.006), fasting blood glucose (r=-0.556, p<0.001) and HOMA indexes (r=-0.411, p=0.001), and positively correlated with plasma adiponectin levels (r=0.593, p<0.001). Plasma adiponectin was negatively correlated to plasma insulin (r=-0.379, p=0.001), fasting glucose (r=-0.604, p<0.001), HOMA-IR (r=-0.559, p<0.001) and BMI (=-0.229, p=0.04). CONCLUSIONS: Plasma apelin is reduced in newly diagnosed and untreated patients with T2DM having no confounders. Regulation of circulating apelin and adiponectin seems to be in the same manner in patients with T2DM. Dysregulation of apelin might be involved in the mechanism of establishment of overt diabetes mellitus as well as associated atherosclerotic complications.

Plasma apelin is lower in patients with elevated LDL-cholesterol.

Hypercholesterolemia is a major risk factor for atherosclerosis. Dysregulation of adipokines contribute to atherosclerotic diseases. Apelin has recently been shown to be secreted by the adipose tissue in association with hyperinsulinemia and inflammation. We searched plasma apelin levels in patients with elevated low density lipoprotein (LDL)-cholesterol having no additional disorder. Thirty-three patients with hypercholesterolemia and 50 age-, sex-, and body mass index-matched healthy controls were evaluated for their apelin, adiponectin and high sensitivity C-reactive protein (hsCRP) levels, and homeostasis model assessment (HOMA) indexes. Plasma apelin-12 and adiponectin were determined by ELISA and RIA, respectively. Plasma apelin levels were lower in patients with elevated LDL-cholesterol compared to healthy controls (p<0.001). Plasma adiponectin concentration was also lower in the dyslipidemic patients (p<0.001). hsCRP levels were similar in the two groups. Fasting plasma glucose was normal in both groups. HOMA indexes in the dyslipidemic group were higher than the controls (p=0.005). A mild to moderate negative correlation with HOMA and positive correlation with high density lipoprotein cholesterol of apelin was found in the dyslipidemic group. Plasma apelin is decreased in non-obese, non-diabetic and normotensive patients with elevated LDL-cholesterol. Low apelin levels in hypercholesterolemia seem associated with insulin resistance, which needs to be investigated in larger populations as well as in other atherosclerotic conditions.

The plasma levels of soluble P-selectin in subjects with prediabetes.

Prediabetes has been associated with an increased risk of cardiovascular disease and mortality. Soluble P-selectin (sP-selectin) is an index of platelet activation and also a risk factor for future vascular events. sP-selectin levels were investigated in prediabetic subjects who had no confounding factors such as hypertension, obesity or dyslipidaemia. sP-selectin, hsCRP levels and HOMA-IR indexes were measured in 40 prediabetic subjects (n = 24 for IFG and n = 16 for IGT) and age-, sex- and BMI-matched 40 healthy controls. sP-selectin levels in prediabetic subjects were not significantly different compared with those in controls (p = 0.12). Prediabetic group had similar hsCRP (p = 0.29), higher HOMA-IR indexes (p < 0.001) and lower HDL cholesterol levels (p = 0.001) when compared with healthy controls. The power of the study was 0.93 for sP-selectin, 0.7 for hsCRP and 1.0 for HOMA. Our data suggest that sP-selectin may not contribute to the prothrombotic state as well as the accelerated atherogenesis associated with prediabetes.

Gianotti-Crosti syndrome associated with HBV infection in an adult.

BACKGROUND: Gianotti-Crosti Syndrome (GCS) is a characteristic cutaneous eruption following a viral infection. Incidence peaks in early childhood and the syndrome rarely occurs in adulthood. Hepatitis associated with GCS is usually anicteric and acute form. AIM: To report an adult with GCS associated with HBV infection and presenting icteric progress. METHODS: The clinical features of the GCS case associated with HBV infection were evaluated. RESULT: The cutaneous lesions disappeared completely on the 61st day and clearance for HBsAg was also observed. CONCLUSION: GCS may be seen in adults and may be associated with icteric HBV infection.

Soluble CD40 ligand levels in patients with hypertension.

CD40 ligand interaction with its receptor (CD40) not only mediates lymphocyte communication, but also associates with chronic inflammation and atherothrombosis. High soluble CD40L (sCD40L) levels were reported in dyslipidemia, diabetes mellitus, and coronary disease. So far, there are no data about sCD40L levels in hypertension. We investigated sCD40L and high sensitive C reactive protein (hsCRP) levels in 30 nonobese young hypertensive men and 30 matched controls. sCD40L and hsCRP levels were not different, and there were no correlations between blood pressure and sCD40L or hsCRP levels. These results might indicate lack of any inflammatory state in new onset hypertension.

Changes in immunological recovery in patients who received post-transplant G-CSF or GM-CSF after autologous peripheral blood stem cell transplantation (PBSCT).

In this prospective study, the effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on immunological reconstitution after autologous peripheral blood stem cell transplantation (PBSCT) were investigated for 6 months. Thirty-five patients received G-CSF 5 microg/kg per day and 26 patients received GM-CSF SC 5 microg/kg per day from day 1 to leukocyte engraftment (>1000 per mm3). Peripheral blood samples were obtained on 14, 28, 100, and 180 days after transplantation for immunological evaluation. CD3+, CD4+, CD8+, CD19+, and CD56+ cells were analysed by flow cytometry. Immunoglobulin levels (IgG, IgA, and IgM) and complement levels (C3c and C4) were measured by nephelometry. Both G-CSF and GM-CSF groups were comparable with respect to age, sex, the period from diagnosis to transplantation, total nucleated cells infused, the number of CD34+ cells, conditioning regimens (TBI and non-TBI), and post-transplant infection. CD3+ and CD8+ cells on day 14 following autologous PBSCT + G-CSF were significantly higher than following autologous PBSCT + GM-CSF (p = 0.008 and p = 0.021, respectively). The number of CD4 cells and the CD4/CD8 ratio were not different at several time points between the two groups. CD19+, CD56+ cells and immunoglobulin levels showed a faster recovery pattern in the autologous PBSCT + G-CSF group. The effect of G-CSF on immune reconstitution after autologous PBSCT is more prominent than that of GM-CSF. The possible role of haematopoietic growth factor on immune recovery and its clinical importance should be investigated in further studies.