title: Activation of extrinsic apoptosis pathway in HCV monoinfected and HIV-HCV coinfected patients, irrespective of liver disease severity.
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.
authors.affiliation: Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Huispostnummer F.02.126, P.O. Box 8500, 3508 GA, Utrecht, The Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Feuth
authors.forename: Debbie
authors.initials: D
authors.lastname: Van Baarle
authors.forename: Andy I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: Karel J
authors.initials: KJ
authors.lastname: Van Erpecum
authors.forename: Peter D
authors.initials: PD
authors.lastname: Siersema
authors.forename: Joop E
authors.initials: JE
authors.lastname: Arends
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D016022:Case-Control Studies; D060085:Coinfection; D005260:Female; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology*; D015497:HIV-1; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology