title: 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.
authors.affiliation: Ruth M. Rothstein CORE Center, 2020 W. Harrison St, Chicago, IL, 60612, USA. aimee_hodowanec@rush.edu.|Rush University Medical Center, Section of Infectious Diseases, Chicago, IL, USA. aimee_hodowanec@rush.edu.
authors.forename: Aimee C
authors.initials: AC
authors.lastname: Hodowanec
authors.affiliation: University of North Carolina at Chapel Hill, Division of Hematology and Oncology, Chapel Hill, NC, USA. rlee@wakehealth.edu.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Lee
authors.affiliation: Rush University Medical Center, Department of Immunology and Microbiology, Chicago, IL, USA. kirsten_brady@rush.edu.
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Brady
authors.affiliation: Center for Clinical and Translational Sciences, University of Illinois at Chicago, Chicago, IL, USA. weihua.gao2@gmail.com.
authors.forename: Weihua
authors.initials: W
authors.lastname: Gao
authors.affiliation: Ruth M. Rothstein CORE Center, 2020 W. Harrison St, Chicago, IL, 60612, USA. slk1220@aol.com.
authors.forename: Stacey
authors.initials: S
authors.lastname: Kincaid
authors.affiliation: Rush University Medical Center, Department of Immunology and Microbiology, Chicago, IL, USA. jill_plants@rush.edu.
authors.forename: Jill
authors.initials: J
authors.lastname: Plants
authors.affiliation: Ruth M. Rothstein CORE Center, 2020 W. Harrison St, Chicago, IL, 60612, USA. mbahk@cookcountyhhs.org.
authors.forename: Mieoak
authors.initials: M
authors.lastname: Bahk
authors.affiliation: University of North Carolina at Chapel Hill, Division of Hematology and Oncology, Chapel Hill, NC, USA. nigel_mackman@med.unc.edu.
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
authors.affiliation: Rush University Medical Center, Department of Immunology and Microbiology, Chicago, IL, USA. alan_landay@rush.edu.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.affiliation: Ruth M. Rothstein CORE Center, 2020 W. Harrison St, Chicago, IL, 60612, USA. gregory_huhn@rush.edu.|Rush University Medical Center, Section of Infectious Diseases, Chicago, IL, USA. gregory_huhn@rush.edu.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Huhn
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D060085:Coinfection / Q000175:diagnosis; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis* / Q000276:immunology; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis* / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013925:Thromboplastin / Q000032:analysis*; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D013925:Thromboplastin