Maintenance of T1 response as induced during PEG-IFNalpha plus ribavirin therapy controls viral replication in genotype-1 patients with chronic hepatitis C
Trapero, M.; García-Buey, L.; Muñoz, C.; Vitón, M.; Moreno-Monteagudo, J.A.; Borque, M.J.; Quintana, N.E.; Moreno-Otero, R.
Revista Espanola de Enfermedades Digestivas Organo Oficial de la Sociedad Espanola de Patologia Digestiva 97(7): 481-490
2005
ISSN/ISBN: 1130-0108 PMID: 16262527 Document Number: 593975
Objectives: 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) alpha 2a plus ribavirin (RBV). To correlate Th1/Th2 balance with virological response.Patients and methods: in this prospective longitudinal study, a total of 28 naive genotype-1 CHC patients received Peg-IFN alpha 2a (180 mu g/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, IFN gamma, and TNF alpha by CD8 T cells was measured by intracytoplasmic detection using flow cytometry in both resting and stimulated cells with a phorbol ester. Statistics: Student's t test for independent values, chi(2) 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 us 2.58; p = 0. 1). No statistically significant differences were found in IFN gamma and TNF alpha levels at month 3. At EOT, the stimulated-IFN gamma production was significantly higher in patients with SVR (20 us. 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 TNFa (14 vs. 7; p < 0.2).Conclusions: Cytokine T1 induced-response maintenance during combination treatment, measured as IFN gamma production by CD8+ T lymphocytes, is associated with SVR and suggests the replication control and later clearance of patients infected by genotype-1 HCV.