Cellular immune responses during high-dose interferon-α induction therapy for hepatitis C virus infection

Abstract

Background. The effect that high-dose interferon (IFN)-α induction therapy for hepatitis C virus (HCV) infection has on cellular immune responses is currently unknown. Methods. Thirty-one treatment-naive patients with chronic HCV infection received amantadine and ribavirin, combined with 6 weeks of high-dose IFN-α-2b induction therapy followed by weekly pegylated IFN-α-2b, for 24 or 48 weeks. Using IFN-γ and interleukin (IL)-2 enzyme-linked immunospot (ELISpot) assays, we analyzed the pattern of cytokine secretion by structural and nonstructural HCV- and cytomegalovirus (CMV)-specific T cells before, during, and after therapy. Results. HCV-specific T cell responses, which were predominantly IFN-γ secreting and which correlated with alanine transaminase levels (r2 = 0.45; P = .001), were found before treatment in 10 of 15 patients with a sustained virological response (SVR) and in 11 of 16 in the non-SVR group. There was a striking loss of IFN-γ and IL-2 HCV-specific T cells during therapy, predominantly in the SVR group. This response recovered after cessation of therapy, regardless of outcome. Suppression of CMV-specific T cell responses, in addition to total lymphocyte counts, was also observed. Conclusions. High-dose IFN-α induction therapy leads to a profound decline in IL-2-and IFN-γ-secreting HCV- and CMV-specific T cells. These data indicate that restoration of T cell responses is unlikely to be causally linked to an early response or SVR to therapy. © 2009 by the Infectious Diseases Society of America.