Background: The clinical relevance of the circulating soluble form of the Fas-Receptor (sFas) was investigated in patients with hepatitis C receiving type 1 interferon (IFN) therapy.
Methods: sFas was quantified by enzyme-linked immunosorbent assay in 66 hepatitis C virus (HCV) carriers and 30 HCV-naive or previously infected controls. The levels were then monitored during enhanced treatment with type 1 IFNs in 15 chronic hepatitis C patients.
Results: The HCV carriers had high levels of sFas compared with controls (3.8+/-1.3 vs 2.7+/-0.8 ng/ml; P<0.001). sFas levels in patients with chronic HCV infection were directly related to serum alanine aminotransferase levels (r=0.440; P<0.001) and the histological grade (r=0.403; P=0.019). Among necroinflammatory reactions, only piecemeal necrosis showed a correlation with sFas levels (r=0.556; P=0.001). Pretreatment sFas levels, however, were not predictive of therapeutic outcomes. A sustained virological response to enhanced IFN therapy showed a relation to only the pretreatment HCV load. Interestingly, circulating sFas was upregulated when IFN-beta was administered at short intervals (3 MU/every 12 h). This upregulation was accompanied by parallel aminotransferase elevation, which was observed regardless of a virological response.
Conclusions: sFas elevation, in parallel with the severity of liver injury, suggests the possible upregulation of hepatic Fas expression and the Fas-mediated pathway in both HCV- and type 1 IFN-induced liver injury. The essential function of sFas to protect hepatocytes against Fas-mediated liver injury was not evident in these clinical settings.