Cytokine network in nonresponding chronic hepatitis C patients with genotype 1: role of triple therapy with interferon alpha, ribavirin, and ursodeoxycholate.
OBJECTIVE
(i) to characterize the profile of tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), IL 10, Fas-ligand and transforming growth factor beta (TGF beta), chronic hepatitis C (HCV) patients with genotype 1; (ii) to determine the influence of triple therapy (TT) with interferon alpha (IFN alpha) + ribavirin + ursodeoxycholic acid on these cytokines and (iii) to establish the relationship between the pro-inflammatory cytokines and the outcome of treatment.


METHODS
22 patients infected with HCV-genotype 1 a/b and non responsive to IFN-alpha monotherapy were enrolled in the TT. The controls were 49 HCV naïve patients with genotype 1 a/b. Cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA).


RESULTS
The baseline TNF alpha values (pg/mL) in the sustained responders (SRs) (63+/-3) were significantly lower than non-responders (NRs) (140+/-16) (p < 0.001). Baseline Fas (ng/mL) levels were also lower in SRs (4.3+/-0.2) than NRs (5.4+/-0.4) (p < 0.05).


CONCLUSIONS
Fas and TNF alpha may be used as serological markers of inflammation and effectiveness of therapy.
Neuman
M G
MG
Division of Clinical Pharmacology, E-240, Sunnybrook & Women's College Health Sciences Centre, Department of Pharmacology and Medicine, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada. manuela@sten.sunnybrook.utoronto.ca
Blendis
L M
LM
Shear
N H
NH
Malkiewicz
I M
IM
Ibrahim
A
A
Katz
G G
GG
Sapir
D
D
Halpern
Z
Z
Brill
S
S
Peretz
H
H
Magazinik
S
S
Konikoff
F M
FM
D000328:Adult; D016207:Cytokines / Q000097:blood*; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use*
D016207:Cytokines; D016898:Interferon-alpha; D012254:Ribavirin; D014580:Ursodeoxycholic Acid