Abstract
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-β 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.
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Kakiuchi, Y., Yuki, N., Iyoda, K. et al. Circulating soluble Fas levels in patients with hepatitis C virus infection and interferon therapy. J Gastroenterol 39, 1189–1195 (2004). https://doi.org/10.1007/s00535-004-1470-2
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DOI: https://doi.org/10.1007/s00535-004-1470-2