Maintenance of T1 response as induced during PEG-IFNalpha plus ribavirin therapy controls viral replication in genotype-1 patients with chronic hepatitis C La respuesta inmune T1 inducida durante el tratamiento con PEG-IFNα mαs ribavirina controla la replicaciσn viral en pacientes con hepatitis crónica C

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) α2a plus ribavirin (RBV). To correlate Th1/Th2 balance with virological response. Patients and methods: in this prospective longitudinal study, a total of 28 naïve genotype-1 CHC patients received Peg-IFNα2a (180 µg/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, IIFNγ, and TTNFα 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, χ2 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 IIFNγ and TTNFα levels at month 3. At EOT, the stimulated-IIFNγ 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 TTNFα (14 vs. 7; p < 0.2). Conclusions: Cytokine T1 induced-response maintenance during combination treatment, measured as IIFNgamma production by CD8+ T lymphocytes, is associated with SVR and suggests the replication control and later clearance of patients infected by genotype-1 HCV.Objetivos: analizar el perfil de citocinas T1/T2 producidas por los linfocitos T CD8+ de sangre periférica en pacientes con hepatitis crónica C (HCC) y genotipo 1 durante el tratamiento con interferón pegilado (Peg-IFN) α2a y ribavirina (RBV) y compararlos con controles sanos. Correlacionar el balance T1/T2 con la respuesta virológica al tratamiento combinado. Pacientes y métodos: en este estudio prospectivo longitudinal se incluyeron 28 pacientes naïve con HCC genotipo 1 tratados con Peg-IFNα2a (180 µg/semana) más RBV (1-1,2 g/día) durante 48 semanas. Los 28 pacientes (edad media 45 ±