05=*, p≤0.01=**). This data differs from studies in nontransplant populations where preactivation of ISGs is considered predictive of NR. In this post-transplant population, ICG-001 we do not see significant preactivation of ISGs. However, we see markedly higher levels in NRs in the post-treatment stage while SVRs remain low. It seems unlikely that persistent HCV infection alone is responsible for this ISG induction, as levels are uniformly low in the pre-treatment population. Disclosures: Richard Gilroy – Advisory Committees or Review Panels: FDA GIDAC; Speaking and Teaching: Salix, Vertex, Gilead The following

people have nothing to disclose: Zoe Raglow, Chuanghong Wu, Yu Jui Yvonne Wan Introduction The role of natural killer (NK) cell alloreactivity after liver transplantation (LT) remains undefined. We have previously demonstrated that NK cells from LT recipients are more difficult to activate than Stem Cells inhibitor those from healthy controls, apart from those transplanted for hepatitis C virus (HCV). This suggests that the allograft can induce NK cell tolerance.

In this study we investigated a mechanism for this through microarray analysis and subsequent quantitative RT-PCR. Methods Blood was collected from post LT patients attending out-patient clinics, including those infected with HCV (LT HCV), and uninfected patients (LT non HCV). RNA was extracted from purified NK cells and microarray analysis was performed on the Agilent Whole Genome Oligo Microarray platform. Gene expression was compared between LT HCV, LT non HCV and healthy controls (HC). Ingenuity Pathway Analysis (IPA) software was used to analyse differences in cellular processes and canonical pathways. Candidate genes were identified and expression

of these in a further cohort of individuals was assessed using quantitative real-time RT PCR. Results Microarray analysis was performed on samples from 4 HCs, 4 LT non HCV and 4 LT HCV patients. Over 850 genes were differentially expressed, with the largest effects on cellular development, growth and differentiation and cell-to-cell signalling. JAK-STAT signalling was the most significant canonical pathway affected. Candidate genes were then selected for qRT-PCR in 13 HCs, 17 LT non HCV and 13 LT HCV patients. qRT-PCR confirmed Dichloromethane dehalogenase the microarray data for STAT4, ZNF683 and KIR2DS3. STAT4 was significantly down-regulated in both LT groups relative to HC (10.7, and 3.8 fold downregulation in LT non HCV (p=0.0004) and LT HCV (p-0.01) respectively). ZNF683 was upregulated (2-fold, p=0.06), and KIR2DS3 was downregulated (2-fold, p=0.05) in LT non HCV vs HC. Conclusions We have demonstrated that, after LT, there is altered gene expression in important differentiation and signalling pathways in recipient NK cells. Specifically, STAT4, which is highly downregulated regardless of HCV status, appears to be a key factor in this NK cell response to LT.