Sustained virological response to peginterferon plus ribavirin in chronic hepatitis C genotype 1 patients is associated with a persistent Th1 immune response

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Abstract
Summary Background An impairment of cellular immune response may contribute to the persistency of hepatitis C virus infection. Aim To analyse the Th1/Th2 cytokine profile in peripheral blood CD4+ and CD8+ T cells from patients with chronic hepatitis C (CHC) during treatment with pegylated interferon‐α2a plus ribavirin and to correlate the Th1/Th2 balance with virological response (SVR). Methods Prospective longitudinal study: 44 naïve genotype 1 CHC patients received PEG‐IFNα2a plus ribavirin for 48 weeks: 26 (59.1%) achieved a SVR, 13 relapsed (29.5%) and 5 (11.4%) were non‐responders. Sixteen healthy controls were analysed. The production of IL‐4, IFNγ and TNFα by CD4+ and CD8+ T cells was measured using flow cytometry, both in resting and phorbol‐ester‐stimulated cells. Results First three months of treatment: the synthesis of TNFα by phorbol‐ester‐stimulated‐CD4+ T cells was higher in patients with SVR (P < 0.01). At the end of treatment, SVR was associated with higher intracellular expression of IFNγ by stimulated‐CD4+ and CD8+ T cells (P < 0.05). At the end of follow‐up, a higher intracellular expression of IFNγ by CD4+ T cells was associated with a SVR. Conclusions A Th1‐type immune response was associated with achievement of a SVR, as indicated by the persistent elevation of intracellular IFNγ and TNFα.