Maintenance of T1 response as induced during PEG-IFNalpha plus ribavirin therapy controls viral replication in genotype-1 patients with chronic hepatitis C.
OBJECTIVE
To analyze the T1/T2 cytokine profile in CD8 T cells from peripheral blood mononuclear cells from patients with genotype-1 CHC during treatment with pegylated interferon (Peg-IFN) alpha2a plus ribavirin (RBV). To correlate Th1/Th2 balance with virological response.


METHODS
In this prospective longitudinal study, a total of 28 naïve genotype-1 CHC patients received Peg-IFNalpha2a (180 microg/week) plus RBV (1-1.2 g/day) for 48 weeks. All patients (mean age 45 +/- 8 years) completed treatment and follow-up: 12 (43%) achieved a sustained virological response (SVR), 13 relapsed after end of treatment (47%), and only 3 (10%) were non-responders. Sixteen healthy controls were also analyzed (mean age 39 +/- 17 years). The production of IL-4, IFNgamma, and TNFalpha by CD8 T cells was measured by intracytoplasmic detection using flow cytometry in both resting and stimulated cells with a phorbol ester.


METHODS
Student's t test for independent values, chi2 test, and ANOVA test were used; relapsers and non-responders were joined to achieve a higher statistical power.


RESULTS
At third month during treatment, phorbol ester-stimulated-IL-4 levels tend to be lower in patients who presented with SVR versus those who did not (0.97 vs 2.58; p = 0.1). No statistically significant differences were found in IFNgamma and TNFalpha levels at month 3. At EOT, the stimulated-IFNgamma production was significantly higher in patients with SVR (20 vs. 8; p < 0.05). Conversely, IL-4 production was higher in NR patients although these data did not reach statistical significance (p < 0.1). No significant differences were found in TNFalpha (14 vs. 7; p < 0.2).


CONCLUSIONS
Cytokine T1 induced-response maintenance during combination treatment, measured as IFNgamma production by CD8+ T lymphocytes, is associated with SVR and suggests the replication control and later clearance of patients infected by genotype-1 HCV.
Trapero
M
M
Unit of Hepatology, Hospital Universitario de La Princesa, Universidad Autónoma, Madrid, Spain.
García-Buey
L
L
Muñoz
C
C
Vitón
M
M
Moreno-Monteagudo
J A
JA
Borque
M J
MJ
Quintana
N E
NE
Moreno-Otero
R
R
D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D016207:Cytokines / Q000276:immunology; D003627:Data Interpretation, Statistical; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a