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

Aimee C Hodowanec,Mieoak Bahk,Nigel Mackman,Stacey Kincaid,Weihua Gao,Rebecca D Lee,Jill Plants,Kirsten E Brady,Gregory D Huhn,Alan L Landay

doi:10.1186/s12879-015-0920-1

Abstract

BackgroundTissue 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.MethodsFifty-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.ResultsMPTF 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).ConclusionsHCV-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.

Highlights

Tissue factor (TF) is a protein that mediates the initiation of the coagulation cascade
We examine the relationship between circulating microparticle TF (MPTF) activity and immune activation markers and their association with the development of advanced liver fibrosis among hepatitis C virus (HCV) monoinfected patients and patients co-infected with well-controlled HIV
Patients with suppressed HIV viremia are the focus of this study because data on TF, immune activation, and liver fibrosis are limited in this contemporary HIV population

Summary

Introduction

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. In HIV infected patients, increased TF expression has been found to be associated with increased HIV viral load, hepatitis B or C coinfection, markers of lipopolysaccharide (LPS) exposure, and importantly, markers of immune activation [7,14]. We examine the relationship between circulating MPTF activity and immune activation markers and their association with the development of advanced liver fibrosis among HCV monoinfected patients and patients co-infected with well-controlled HIV. Patients with suppressed HIV viremia are the focus of this study because data on TF, immune activation, and liver fibrosis are limited in this contemporary HIV population

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