thromboplastin and Hepatitis-C

A large amount of endotoxin can be detected in the peripheral venous blood of patients with liver cirrhosis, contributing to the pathogenesis of hepatotoxicity because of its role in oxidative stress. The present study aimed to test the effect of the supplementation with red palm oil (RPO), which is a natural oil obtained from oil palm fruit (Elaeis guineensis) rich in natural fat-soluble tocopherols, tocotrienols and carotenoids, on lipid peroxidation and endotoxemia with plasma endotoxin-inactivating capacity, proinflammatory cytokines profile, and monocyte tissue factor in patients with chronic liver disease.. The study group consisted of sixty patients (34 males and 26 females; mean age 62 years, range 54-75) with Child A/B, genotype 1 HCV-related cirrhosis without a history of ethanol consumption, randomly enrolled into an 8-week oral daily treatment with either vitamin E or RPO. All patients had undergone an upper gastrointestinal endoscopy 8 months before, and 13 out of them showed esophageal varices.. Both treatments significantly decreased erythrocyte malondialdehyde and urinary isoprostane output, only RPO significantly affected macrophage-colony stimulating factor and monocyte tissue factor. Liver ultrasound imaging did not show any change.. RPO beneficially modulates oxidative stress and, not least, downregulates macrophage/monocyte inflammatory parameters. RPO can be safely advised as a valuable nutritional implementation tool in the management of chronic liver diseases.

Topics: Aged; Cells, Cultured; Dietary Supplements; Erythrocytes; Female; Hepatitis C; Humans; Inflammation Mediators; Isoprostanes; Italy; Lipid Peroxidation; Liver; Liver Cirrhosis; Macrophage Colony-Stimulating Factor; Male; Malondialdehyde; Middle Aged; Monocytes; Oxidative Stress; Palm Oil; Plant Oils; Thromboplastin; Time Factors; Treatment Outcome

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.. 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.. 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).. 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.

Topics: Adult; Biomarkers; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Coinfection; Cross-Sectional Studies; Female; Flow Cytometry; Hepatitis C; Hepatitis C, Chronic; HIV Infections; Humans; Liver; Liver Cirrhosis; Male; Middle Aged; Thromboplastin; Ultrasonography

Patients with liver disease often show substantial changes in their hemostatic system, which may aggravate further during liver transplantation. Recently, thrombin generation in patients with stable disease was shown to be indistinguishable from controls provided thrombomodulin, the natural activator of the anticoagulant protein C system, was added to the plasma. These results indicated that the hemostatic balance is preserved in patients with liver disease, despite conventional coagulation tests suggest otherwise.. Here we examined thrombin generation profiles in serial plasma samples taken from ten consecutive patients undergoing liver transplantation.. At all time points, the endogenous thrombin potential (ETP) was slightly lower compared to healthy volunteers, despite substantially prolonged PT and APTT values. However, when thrombin generation was tested in the presence of thrombomodulin, the ETP was equal to or even higher than that in healthy subjects. In fact, thrombin generation was hardly affected by thrombomodulin, while thrombin generation in healthy subjects decreased profoundly upon the addition of thrombomodulin. In patients undergoing liver transplantation, efficient thrombin generation in the presence of thrombomodulin may be explained by decreased levels of protein C, S, and antithrombin, and by elevated levels of FVIII.. Thrombin generation in patients undergoing liver transplantation is equal or even superior to thrombin generation in healthy volunteers when tested in the presence of exogenous thrombomodulin. These results support the recently advocated restrictive use of plasma during liver transplantation and warrants further study of the prophylactic use of anticoagulants to reduce thromboembolic complications after transplantation.

Topics: Adult; Blood Coagulation Tests; Case-Control Studies; Cholangitis, Sclerosing; Factor VIII; Female; Hepatitis C; Humans; Liver Cirrhosis; Liver Diseases; Liver Transplantation; Male; Middle Aged; Prothrombin Time; Thrombin; Thrombomodulin; Thromboplastin; Time Factors

Fibrinogen-like protein 2/fibroleukin (Fgl2) plays a pivotal role in the pathogenesis of both experimental and human fulminant hepatic failure. We have reported recently that the nucleocapsid (N) protein from strains of murine hepatitis virus (MHV-3, MHV-A59), which cause massive hepatocellular necrosis but not from strains (MHV-JHM, MHV-2) which do not produce serious liver disease, induces transcription of fgl2. The purpose of the present study was to characterize both viral and host factor(s) necessary for viral induced transcription of fgl2. Mutation of residues Gly-12, Pro-38, Asn-40, Gln-41, and Asn-42 within domain 1 of the N protein of MHV-A59 to their corresponding residues found in MHV-2 abrogated fgl2 transcription, whereas mutation of other N protein domains, including a protein expressed from an internal reading frame (I protein), did not affect fgl2 gene transcription. We then examined the -372 to -306 sequence within the 1.3-kb fgl2 promoter region upstream from the transcription start site that was previously identified as necessary for N protein-induced gene transcription. We demonstrated that the -331/-325 HNF4 cis-element and its cognate transcription factor, HNF4alpha, are necessary for virus-induced fgl2 gene transcription. In uninfected macrophages and macrophages infected with MHV-2, an unidentified protein occupies the HNF4 cis-element. Following stimulation with MHV-A59, it was shown by electrophoretic mobility shift assay that HNF4alpha binds the HNF4 cis-element in the fgl2 promoter. We further report the unprecedented presence of HNF4alpha in peritoneal macrophages. Collectively, the results of this study define both viral and host factors necessary for induction of fgl2 prothrombinase gene transcription in MHV infection and may provide an explanation for the hepatotrophic nature of MHV-induced fulminant hepatic failure.

Topics: Amino Acid Sequence; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; CHO Cells; Cricetinae; DNA-Binding Proteins; Female; Fibrinogen; Gene Expression Regulation; Hepatitis B; Hepatitis C; Hepatocyte Nuclear Factor 4; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Murine hepatitis virus; Nucleocapsid Proteins; Phosphoproteins; Promoter Regions, Genetic; Thromboplastin; Transcription Factors; Transcription, Genetic

Topics: ADAM Proteins; ADAMTS13 Protein; Blood Coagulation Factor Inhibitors; Congresses as Topic; Creutzfeldt-Jakob Syndrome; Genetic Therapy; Hemorrhage; Hemostasis; Hepatitis C; Humans; Metalloendopeptidases; Protein C; Thromboplastin; Virus Diseases

Topics: Drug Contamination; Factor IX; Hepatitis C; Hepatitis, Viral, Human; Hot Temperature; Humans; Thromboplastin