Type 1 IFN-alpha Receptor Expression in Peripheral Blood Lymphocytes Independently Predicts Sustained Virological Response in Chronic Hepatitis C Genotype 1b with High Viral Load
Abstract
Ishii Koji, Kanayama Kaori, Shinohara Mie, Kogame Michio, Shinohara Masao and Sumino Yasukiyo
Background: We have been investigating serial changes in Type I Interferon (IFN) receptor alpha-2 (IFNAR-2) expression in peripheral blood leukocyte subsets in Chronic Hepatitis C (CHC) patients during IFN-based therapy. The aim of this study was to clarify whether changes in IFNAR-2 expression by peripheral blood leukocyte subsets are predictive factors for Sustained Virological Response (SVR).
Methods: One hundred and thirty-six patients with CHC and receiving Pegylated (PEG)-IFN alpha-2a or -2b in combination with ribavirin (RBV) for a median 48 (16-96) weeks were studied. A negative result for serum HCV-RNA on RT-PCR at week 24 after the End Of Therapy (EOT) was defined as SVR. IFNAR-2 expression by peripheral blood leukocyte subsets was quantified using flow cytometry by measuring the mean fluorescence intensity before and up to 28 days after therapy initiation. Of the 136 patients, 124 consented to genetic investigation for interleukin (IL)-28B genetic variants at rs8099917. We then used logistic regression analysis to retrospectively investigate the influence of serum viral load, as measured before the start of therapy, and age, sex, body weight, body mass index, IFN regimen, IFN dose/kg, RBV dose/kg and history of prior IFN-based therapy on SVR.
Results: Overall SVR rate was 53% (77/146). Of the 97 patients with IL-28 genotype TT, 67 (69%) showed SVR. In contrast, of the 27 patients with IL-28 genotype TG, 5 (19%) showed SVR. IL-28B genotype at rs8099917 and patient age were factors having an independent influence on SVR on multivariate regression analysis. When we added serial changes in IFNAR-2 expression by leukocyte subsets before and up to 28 days after EOT to the logistic regression model, IFNAR-2 expression by lymphocytes at day 28 was identified as an independent additive factor.
Conclusion: This study provided the first evidence that IFNAR-2 expression by peripheral blood lymphocytes is an additive but independent factor predicting SVR to PEG-IFN and RBV in patients with CHC genotype 1b and high viral load.
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