A matched cross-sectional study of the association between circulating tissue factor activity, immune activation and advanced liver fibrosis in hepatitis C infection

Abstract Background Tissue factor (TF) is a protein that mediates the initiation of the coagulation cascade. TF expression is increased in patients with poorly-controlled HIV, and may be associated with increased immune activation that leads to cardiovascular morbidity. The role of TF in immune activation in liver disease in hepatitis C virus (HCV)-monoinfection and HIV/HCV-coinfection has not been explored. Methods Fifty-nine patients were stratified: A) HIV-monoinfection (N = 15), B) HCV-monoinfection with chronic hepatitis C (CHC) (N = 15), C) HIV/HCV-coinfection with CHC (N = 14), and D) HIV/HCV-seropositive with cleared-HCV (N = 15). All HIV+ patients had undetectable HIV viremia. Whole blood was collected for CD4/CD8 immune activation markers by flow cytometry and plasma was assayed for microparticle TF (MPTF) activity. Subjects underwent transient elastography (TE) to stage liver fibrosis. Undetectable versus detectable MPTF was compared across strata using Fisher's Exact test. Results MPTF activity was more frequently detected among patients with HCV-monoinfection (40%), compared to HIV-monoinfection and HIV/HCV-seropositive with cleared HCV (7%) and HIV/HCV-coinfection with CHC (14%) (p = 0.02). Mean TE-derived liver stiffness score in kPa was higher in patients with detectable MPTF (12.4 ± 8.5) than those with undetectable MPTF (6.4 ± 3.0) (p = 0.01). Mean CD4 + HLADR+ and CD4 + CD38-HLADR+ expression were higher in those with detectable MPTF (44 ± 9.8% and 38 ± 8.7%, respectively) than those with undetectable MPTF (36 ± 11% and 31 ± 10.4% respectively) (p = 0.05 and 0.04 respectively). Conclusions HCV-monoinfection and HIV/HCV-coinfection with CHC were associated with MPTF activity. MPTF activity is also associated with advanced liver fibrosis and with CD4 + HLADR+ immune activation

Contributing role of extracellular vesicles on vascular endothelium haemostatic balance in cancer.

Extracellular vesicles (EVs) generated during tumourigenesis are thought to play a major role in the hypercoagulant state observed in cancer patients. They exhibit negatively charged phospholipids and tissue factor (TF) that promote coagulation cascade activation. In addition, they contain surface proteins and cytoplasmic molecules, both originating from the producing cell that can impact target cells' expression. By targeting endothelial cells of blood vessels, these EVs could disturb the physiological anticoagulant properties of these cells and be partly responsible for the vascular endothelium activation observed in cancer patients. Indeed, vascular endothelium naturally exhibits heparin-like proteoglycan, TF pathway inhibitor and protein C anticoagulant pathway that prevent thrombosis in physiological condition. An overexpression of TF and a decreased expression of coagulation cascade inhibitors have been reported after EVs' treatment of endothelial cells. The induction of apoptosis and an increased expression of platelet adhesion molecules have also been highlighted. These events may promote thrombus formation in cancer. The aim of this paper is to provide a targeted review on the current evidence and knowledge of roles and impact of EVs on endothelial surface anticoagulant and procoagulant factors and cellular adhesion molecules expression

Novel Nonbiologic Therapies for Ulcerative Colitis

An extensive array of compounds has been studied for the treatment of ulcerative colitis (UC). The most frequently used nonbiologic drugs for the oral and intravenous treatment of ulcerative colitis include 5-aminosalicylate (5-ASA) drugs (mesalamine and derivatives), sulfasalazine, and other azo-bonded molecules of 5-ASA, steroids, calcineurin inhibitors (cyclosporine, tacrolimus, and sirolimus), thiopurines (azathioprine, 6-mercaptopurine), and methotrexate, which are already presented in other sections of this book and are thus not considered in this chapter. The therapies presented in this section should be considered as potential alternatives, mostly for mild-to-moderate ulcerative colitis (UC). They are substances mostly used without FDA indications, such as heparin, nicotine, rosiglitazone, and N-acetylcysteine as well as “natural” compounds suggested to have anti-inflammatory or reparative properties, such as aloe vera, curcumin, short-chain fatty acids, and Bowman-Birk inhibito