Circulating soluble Fas levels in patients with hepatitis C virus infection and interferon therapy.
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.
Kakiuchi
Yoshimi
Y
Department of Gastroenterology, Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan.
Yuki
Nobukazu
N
Iyoda
Kenya
K
Sugiyasu
Yasunori
Y
Kaneko
Akira
A
Kato
Michio
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006526:Hepatitis C / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D019014:fas Receptor / Q000097:blood*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019014:fas Receptor; D016899:Interferon-beta