Fas antigen expression on hepatocytes predicts the short- and long-term response to interferon therapy in patients with chronic hepatitis C.
BACKGROUND
Interaction between Fas antigen on hepatocytes and Fas ligand on cytotoxic T cells induces apoptosis, a major mechanism of hepatitis C virus (HCV) -induced hepatocyte injury. We investigated the usefulness of Fas expression on hepatocytes as a predictor of short-and long-term response to interferon (IFN) therapy in 72 patients with chronic hepatitis C.


METHODS
Ten million units of recombinant IFN-alpha2b were administered daily for the first 2 weeks, and three times a week for another 22 weeks. The short-term efficacy of IFN therapy was evaluated after 12-month follow-up from cessation of treatment. We also examined the long-term response to IFN at 56.6 +/- 10.8 (mean +/- s) months after termination of IFN therapy in 55 of 72 patients.


RESULTS
Univariate analysis showed that serum HCV-RNA levels, HCV genotype and Fas expression significantly correlated with the short-term efficacy of IFN therapy (P = 0.005, 0.006, and 0.04, respectively). Fas antigen expression did not correlate with serum HCV-RNA levels (P = 0.286), but significantly correlated with HCV genotype (P = 0.003). Multivariate analysis indicated that Fas expression and serum HCV-RNA levels were independent determinants of the short-term response to IFN therapy. Combined together, Fas expression and serum HCV-RNA levels accurately predicted the short-term response to IFN therapy. On the other hand, in 55 patients who were examined the long-term response to IFN, about 60% of Fas-positive patients were HCV-RNA negative, whereas 30% of Fas-negative patients were HCV-RNA negative (P = 0.04). Among Fas-positive patients, the percentage of those with serum ALT levels persistently lower than twice the normal upper limit in long-term study (81.8%; 9/11) was significantly higher than those in short-term study even among patients who failed to show elimination of HCV-RNA (36.4%; 4/11, P = 0.03).


CONCLUSIONS
Our results indicate that Fas expression on hepatocytes is a good predictor of the short-and long-term response to IFN therapy.
Abe
S
S
Third Dept. of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu.
Kotoh
K
K
Arao
S
S
Tabaru
A
A
Otsuki
M
M
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D022781:Hepatocytes / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011994:Recombinant Proteins; D018709:Statistics, Nonparametric; D013997:Time Factors; D016896:Treatment Outcome; D019014:fas Receptor / Q000032:analysis* / Q000187:drug effects
D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019014:fas Receptor