Characterization of soluble FAS, FAS ligand and tumour necrosis factor-alpha in patients with chronic HCV infection

Background: There are limited reports on the role of the cell surface receptor Fas and its ligand molecule in mediating apoptosis during infection with the hepatitis C virus (HCV). Objectives: The aims of this study were (1) to assess the susceptibility of the Fas antigen expressed on peripheral blood mononuclear cells to Fas ligand-induced-death in patients with chronic HCV infection and (2) to investigate the correlation between the plasma levels of soluble Fas (sFas), soluble Fas ligand (sFasL), tumour necrosis factor-alpha (TNF-alpha), alanine amino transferase (ALT), and HCV viral load. Study design: The Susceptibility of peripheral blood mononuclear cells from 17 subjects with chronic HCV infection to Fas ligand induced cell death was assessed using a water soluble tetrazolium assay. The plasma levels of associated markers such as sFas, sFasL, and TNF-alpha were quantified using immunoassays. ALT values were obtained from hospital records. Viral loads were quantified using a commercially available quantitative assay-the Amplicor Monitor (version 2.0). Controls for comparison included a group of healthy individuals and individuals infected with the human immunodeficiency virus 1. Results: The percentage of cell death induced in hepatitis C virus infected individuals was lower than that seen in the healthy control group. Patients infected with HCV had higher average values of sFas and TNF-alpha as compared to both control groups. Plasma levels of sFas in patients with chronic HCV infection showed significant positive correlations to ALT and TNF-alpha levels. TNF-alpha levels also showed a significant positive correlation with ALT levels. Conclusions: PBMC in HCV infection exhibit decreased susceptibility to Fas ligand induced cell death. This may signify a means by which HCV escapes immune surveillance. This phenomenon merits further investigation. The strong correlations observed between plasma sFas, ALT and TNF-alpha suggest a potential role for these markers as an alternative to an invasive liver biopsy. (c) 2005 Elsevier B.V. All rights reserved.