PBMCs were examined for immune markers including FoxP3, PD-1, CTLA-4, CD28 and CD127 in multi-parameter flow cytometry. Demographic, clinical and immune parameters in patients with IL28B CC and non-CC genotype were compared, using Maraviroc molecular weight non-parametric statistics. Result: Our aHCV cohort (12 CC, 9 non-CC) were mostly males in their 30–40′s, predominantly white (76%) with HCV genotype 1 infection (86%) with similar peak ALT activity (1010 CC vs 978 Non-CC U/L) and HCV RNA titers (log 6.9 CC vs 5.8 Non-CC). CC patients displayed greater viral clearance (+/- therapy) than non-CC patients (75% vs 22%, p=0.03). As for immune parameters, CC and Non-CC patients were similar in %CD3,

%CD4, %CD8 or %FoxP3+ Tregs. However, CD8 (but not CD4) T cells from non-CC patients displayed greater expression of positive costimulatory receptors CD28 (54% CC vs 72% non-CC, p=0.047) and CD127 (43% CC vs 74% non-CC, p=0.002) without significant differences in PD-1 or CTLA-4 expression. Of interest, ALT activity correlated positively with CD28 (R=0.67, Adriamycin p=0.049) and CD127 (R=0.70, p=0.04) in CD8 T cells, but only in Non-CC patients. Similarly, HCV RNA titers correlated positively with CD28 (R=0.74, p=0.04) and CD127 (R=0.71, p=0.046) only in Non-CC patients.

Significant positive associations were also observed for CD28 and CD127 in CD4 T cells and ALT (CD28: R=0.84, p=0.005; CD127: R=0.88, p=0.002) or HCV RNA (CD28: R=0.91; p=0.002, CD127: R=0.76, p=0.03), but only in Non-CC patients. Conclusion: We conclude that IL28B genotype contributes to differential regulation of immune costimula-tion during acute hepatitis C. Functional relevance of these findings is currently under investigation. Disclosures: David E. Kaplan – Grant/Research Support: Merck, Bayer Frederick Nunes – Grant/Research Support: Merck, BMS, Merck, check details BMS, Merck, BMS, Merck, BMS Kyong-Mi

Chang – Stock Shareholder: BMS (spouse employment) The following people have nothing to disclose: Keisuke Ojiro, Masahiro Kikuchi, Jang-June Park, Chalermrat Bunchorntavakul, Lisa M. Jones, Mary E. Valiga, Rajender Reddy [Background] Previously, our group reported that the existence of HCV in T lymphocytes could affect the development of CD4+ helper T cells and their proliferation, in addition to the induction of immunoglobulin hyper-mutation. [Aim] The aim of this study is to analyze the relationship between the persistent infection of HCV and the mechanism of Th 1 7 cell induction. [Methods] The prevalence and characteristics of autoimmune-related diseases in chronic hepatitis C (CH-C) patients were analyzed (n=250). In addition to the previously reported lymphotropic SB-HCV strain, we found a novel, genotype 1 b lymphotropic HCV (Ly-HCV) by deep sequencing analysis (Genome Analyzer IIxTM). IL1β, IL6, TGF-β1, IL17A, IL21 and IL23 quantification were carried out using ELISA. The mRNA expressions of TGF-β1 and IL6 in PBMCs were quantified.