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

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  • Hodowanec, Aimee C.
    • Other Affiliation: Ruth M. Rothstein CORE Center, 2020 W. Harrison St, Chicago, IL 60612, USA; Rush University Medical Center, Section of Infectious Diseases, Chicago, IL, USA
  • Lee, Rebecca D.
    • Affiliation: School of Medicine, Division of Hematology/Oncology
  • Brady, Kirsten E.
    • Other Affiliation: Rush University Medical Center, Department of Immunology and Microbiology, Chicago, IL, USA
  • Gao, Weihua
    • Other Affiliation: Center for Clinical and Translational Sciences, University of Illinois at Chicago, Chicago, IL, USA
  • Kincaid, Stacey
    • Other Affiliation: Ruth M. Rothstein CORE Center, 2020 W. Harrison St, Chicago, IL 60612, USA
  • Plants, Jill
    • Other Affiliation: Rush University Medical Center, Department of Immunology and Microbiology, Chicago, IL, USA
  • Bahk, Mieoak
    • Other Affiliation: Ruth M. Rothstein CORE Center, 2020 W. Harrison St, Chicago, IL 60612, USA
  • Mackman, Nigel
    • Affiliation: School of Medicine, Division of Hematology/Oncology
  • Landay, Alan L.
    • Other Affiliation: Rush University Medical Center, Department of Immunology and Microbiology, Chicago, IL, USA
  • Huhn, Gregory D.
    • Other Affiliation: Ruth M. Rothstein CORE Center, 2020 W. Harrison St, Chicago, IL 60612, USA; Rush University Medical Center, Section of Infectious Diseases, Chicago, IL, USA
Abstract
  • 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.
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  • Article
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  • Hodowanec et al.; licensee Biomed Central.
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  • English
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  • BMC Infectious Diseases. 2015 Apr 17;15(1):190
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  • BioMed Central

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