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Activation of extrinsic apoptosis pathway in HCV monoinfected and HIV–HCV coinfected patients, irrespective of liver disease severity

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Abstract

Chronic hepatitis C virus (HCV) infection is associated with increased levels of peripheral T cell apoptosis. We aimed to study whether T cell apoptosis markers indicate pathways that may contribute to clinical progression in HCV monoinfected and HIV–HCV coinfected patients. Activation of the extrinsic apoptosis pathways was measured by levels of death receptor Fas, initiator caspase 8 and effector caspases 3 and 7 activity and Annexin V binding on peripheral CD4 and CD8 T cells of HCV monoinfected and HIV/HCV coinfected patients, as well as healthy controls and HIV-infected, hepatitis B virus-infected and primary biliary cirrhosis disease controls. Association with liver fibrosis was assessed by biopsy or by transient elastography. HCV monoinfected and HIV–HCV coinfected patients displayed enhanced peripheral CD4 and CD8 T cell apoptosis. Caspase 8 activity was highest in HIV–HCV coinfection, without enhanced downstream activity of caspases 3 and 7. Level of peripheral T cell apoptosis was independent of liver fibrosis or other disease parameters in all disease groups. The extrinsic apoptosis pathway is upregulated in HCV monoinfection and HIV–HCV coinfection, but this is independent of liver disease severity.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Huispostnummer F.02.126, P.O. Box 8500, 3508 GA, Utrecht, The Netherlands

    Thijs Feuth, Andy I. M. Hoepelman & Joop E. Arends

  2. Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands

    Karel J. Van Erpecum & Peter D. Siersema

  3. Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands

    Debbie Van Baarle

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  1. Thijs Feuth
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  2. Debbie Van Baarle
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  3. Andy I. M. Hoepelman
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  4. Karel J. Van Erpecum
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  5. Peter D. Siersema
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  6. Joop E. Arends
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Correspondence to Joop E. Arends.

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Feuth, T., Van Baarle, D., Hoepelman, A.I.M. et al. Activation of extrinsic apoptosis pathway in HCV monoinfected and HIV–HCV coinfected patients, irrespective of liver disease severity. Apoptosis 19, 1128–1135 (2014). https://doi.org/10.1007/s10495-014-0992-1

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  • DOI: https://doi.org/10.1007/s10495-014-0992-1

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