combination and patients may require intensive care unit (ICU) treatment. Therefore, it seems necessary to identify prognostic clinical parameters and risk factors at the time of ICU admission. Aim of the study: To estimate the frequency of mortality and cirrhosis morbidity among patients with end stage liver disease (ESLD) admitted to the ICU and to evaluate the relation between demographic, clinical and laboratory data (potential risk factors) of those patients and mortality.Methods:120 patients with ESLD were enrolled [102 males (85%) and 18 females (15%)].History,clinical examination,full investigations and classification of patients according to Child-Turcotte-Pugh (CTP) and Model for end stage liver disease(MELD)score were done. Results: Regarding clinical presentation, hepatic encephalopathy (HE) was found in 87.5%, jaundice (60%), hematemesis (41.7%), hepatorenal syndrome (HRS)( 35.8%) and spontaneous bacterial peritonitis (SBP)(20.8%). Mortality rate was 57.5%; the main causes of death were HRS (40.8%), HE (21.7), aspiration pneumonia (10%), septic shock (2.5%) and irreversible shock in only 1.7%. There was a significant relation between mortality and old age, CTP and MELD scores and a longer stay at the ICU. Increased white blood cell count, increased hemoglobin and decreased prothrombin concentration and raised creatinine were independent risk factors of mortality in ESLD patients in the ICU. Mortality rates were higher(86.2%) with 5-6 risk factors and (21.7%) with 1-2 risk factor(s).Conclusions: Mortality rate in ESLD patients admitted to ICU was 57.5% and the most common cause of death was HRS. CTP, MELD score, HE, HRS and jaundice were significant predictors of mortality in ESLD patients. Mortality increased with increased number of risk factors. Creatinine level, white blood cell count, hemoglobin and prothrombin concentration were independent risk factors of mortality in ESLD patients

combination and patients may require intensive care unit (ICU) treatment. Therefore, it seems necessary to identify prognostic clinical parameters and risk factors at the time of ICU admission. Aim of the study: To estimate the frequency of mortality and cirrhosis morbidity among patients with end stage liver disease (ESLD) admitted to the ICU and to evaluate the relation between demographic, clinical and laboratory data (potential risk factors) of those patients and mortality.Methods:120 patients with ESLD were enrolled [102 males (85%) and 18 females (15%)].History,clinical examination,full investigations and classification of patients according to Child-Turcotte-Pugh (CTP) and Model for end stage liver disease(MELD)score were done. Results: Regarding clinical presentation, hepatic encephalopathy (HE) was found in 87.5%, jaundice (60%), hematemesis (41.7%), hepatorenal syndrome (HRS)( 35.8%) and spontaneous bacterial peritonitis (SBP)(20.8%). Mortality rate was 57.5%; the main causes of death were HRS (40.8%), HE (21.7), aspiration pneumonia (10%), septic shock (2.5%) and irreversible shock in only 1.7%. There was a significant relation between mortality and old age, CTP and MELD scores and a longer stay at the ICU. Increased white blood cell count, increased hemoglobin and decreased prothrombin concentration and raised creatinine were independent risk factors of mortality in ESLD patients in the ICU. Mortality rates were higher(86.2%) with 5-6 risk factors and (21.7%) with 1-2 risk factor(s).Conclusions: Mortality rate in ESLD patients admitted to ICU was 57.5% and the most common cause of death was HRS. CTP, MELD score, HE, HRS and jaundice were significant predictors of mortality in ESLD patients. Mortality increased with increased number of risk factors. Creatinine level, white blood cell count, hemoglobin and prothrombin concentration were independent risk factors of mortality in ESLD patients

Background : Articular involvement is a frequent extrahepatic manifestation of hepatitis C virus (HCV) infection. The distinction between HCV associated arthropathy and oncomitant rheumatoid arthritis (RA) may be very difficult, especially with recent onset RA before articular damage and erosions develop. This study aims to determine whether anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are a highly specific test for RA, could differentiate between chronic HCV-associated arthropathy and RA with concomitant HCV. Methods: Three patients' groups were included. Group I: patients with chronic HCV infection without arthropathy, Group II: patients with chronic HCV infection with arthropathy and to compare the prevalence of anti-CCP antibodies in HCV patients with that in patients with RA and concomitant HCV we enrolled 22 (Group III) consecutive RA patients fulfilling the American College of Rheumatology (ACR) revised criteria for Rheumatoid arthritis and the new EULAR / ACR criteria with concomitant HCV. Twenty two healthy controls (Group IV) were also included. For each group anti-CCP antibodies and rheumatoid factor were measured. Results: Anti-CCP antibodies were positive in 4.5% , 4.5%, 100% and 0% of groups I to IV respectively. However, RF was positive in 13.6% , 45.5%, 100% and 0% of Group I to IV respectively. Anti-CCP antibodies showed higher specificity compared with RF (97% vs. 80%) in the diagnosis of RA, but the two tests had similar sensitivity (100%). Conclusions: Measurement of anti-CCP antibodies is more specific than RF to discriminate HCV-associated arthropathy from RA with concomitant HCV. Moreover it may contribute in establishing the diagnosis of RA in patients with concurrent chronic HCV infection

PDGF-dependent hepatic stellate cell (HSC) recruitment is an essential step in liver fibrosis and the sinusoidal vascular changes that accompany this process. However, the mechanisms that regulate PDGF signaling remain incompletely defined. Here, we found that in two rat models of liver fibrosis, the axonal guidance molecule neuropilin-1 (NRP-1) was upregulated in activated HSCs, which exhibit the highly motile myofibroblast phenotype. Additionally, NRP-1 colocalized with PDGF-receptor β (PDGFRβ) in HSCs both in the injury models and in human and rat HSC cell lines. In human HSCs, siRNA-mediated knockdown of NRP-1 attenuated PDGF-induced chemotaxis, while NRP-1 overexpression increased cell motility and TGF-β–dependent collagen production. Similarly, mouse HSCs genetically modified to lack NRP-1 displayed reduced motility in response to PDGF treatment. Immunoprecipitation and biochemical binding studies revealed that NRP-1 increased PDGF binding affinity for PDGFRβ-expressing cells and promoted downstream signaling. An NRP-1 neutralizing Ab ameliorated recruitment of HSCs, blocked liver fibrosis in a rat model of liver injury, and also attenuated VEGF responses in cultured liver endothelial cells. In addition, NRP-1 overexpression was observed in human specimens of liver cirrhosis caused by both hepatitis C and steatohepatitis. These studies reveal a role for NRP-1 as a modulator of multiple growth factor targets that regulate liver fibrosis and the vascular changes that accompany it and may have broad implications for liver cirrhosis and myofibroblast biology in a variety of other organ systems and disease conditions.

Purpose: To evaluate the role of pre-treatment vitamin D serum level and interleukin28B (IL28B) (rs 12979860) polymorphism in chronic hepatitis C (CHC) genotype 4a patients treated with pegylated interferon α2-A and ribavirin (peg IFN+RBV) as predictors of response. Methods: A retrospective study of clinical and pathological data and stored blood samples of 150 naïve chronic hepatitis C (CHC) genotype 4a patients, treated with pegylated interferon and ribavirin for 48 weeks. Follow-up to detect sustained virological response (SVR) was carried out. Based on SVR, two groups were studied; group 1 consisted of 75 responder patients to pegylated IFN + RBV therapy while group 2 comprised of 75 non-responder patients to standard hepatitis C virus (HCV) therapy. Vitamin D serum levels were assessed using Enzyme Linked Immunoassay (ELISA), quantitative reverse transcriptase- polymerase chain reaction (qRT-PCR for HCV RNA ), and IL28B gene polymorphism by Restriction Fragment Length Polymorphism Polymerase Cchain Reaction (RFLP-PCR). Results: Pretreatment vitamin D level was significantly higher in group 1 than in group 2 (p 0.001). The sensitivity and specificity of vitamin D level for prediction of SVR at a cutoff value of 29.75 ng/ml were 100 and 96 %, respectively, with area under the curve (AUC) of 0.995 (p 0.001). A significant difference was detected between baseline vitamin D level for early versus advanced fibrosis stage (p = 0.01) in group 1. Conclusion: Pretreatment vitamin D serum level (at a cutoff value of 29.75 ng/ml), IL28B gene polymorphism and quantitative HCV RNA are independent trait predictors of SVR

Background/Objectives: Circulating endothelial cells (CECs) are indicative of vascular injury and correlate with severity of vascular diseases. A pilot study showed that the ratio of CEC to platelet count (CEC/PC) was effective in predicting cirrhosis. Therefore, we evaluated CEC/PC in a larger cohort of patients, correlated it with cirrhosis, and compared its operating characteristics with previously described biomarker for cirrhosis, the AST/platelet ratio index (APRI). Methods: Fifty-three patients with cirrhosis, 20 matched healthy controls, and 9 patients with noncirrhotic liver disease were recruited. Peripheral blood sample was collected and analyzed to enumerate nucleated CEC CD146+, CD105+, CD45- using a commercial assay. Results: Median CEC counts were significantly higher in patients with cirrhosis (62 cells/4 mL, interquartile range [IQR]: 43.5–121) as compared with controls (31 cells/4 mL, IQR: 22.2–40). The CEC/PC was also significantly elevated in cirrhotics (0.69, IQR: 0.39–1.48) compared with controls (0.12, IQR: 0.09–0.20) and noncirrhotics (0.21, IQR: 0.08–0.43). Receiver operator characteristic (ROC) analysis revealed that CEC cutoff value of ≥37 cells/4 mL showed sensitivity of 81% and specificity of 75% for differentiating cirrhosis from controls (area under the curve [AUC]: 0.80; 95% confidence interval [CI] 0.67–0.91). The CEC/PC ratio cutoff value of ≥0.23 showed sensitivity of 91% and specificity of 82% (AUC: 0.92; 95% CI 0.83–0.99). The APRI cutoff value of ≥0.4 showed sensitivity of 94% and specificity of 85% for differentiating cirrhosis from control patients (AUC: 0.96; 95% CI 0.90–1.0). A product of CEC and APRI, termed CAPRI (CEC-APRI), effectively distinguished patients with cirrhosis from controls; with cutoff value of ≥12.7, showing higher sensitivity of 98% and specificity of 85% (AUC: 0.98; 95% CI 0.96–1.0). Conclusion: The CEC/PC ratio is significantly elevated in patients with cirrhosis and demonstrates comparable operating characteristics to previously described APRI. Furthermore, CAPRI, compiled as product of CEC to APRI showed outstanding ability to distinguish patients with cirrhosis from controls, although larger studies are necessary for validation