Cytokine/chemokine patterns connect host and viral characteristics with clinics during chronic hepatitis C

Microarray analysis was performed in peripheral whole blood (PB) samples from 36 therapy-na？ve HCV-infected patients with known liver histology. Linear regression analysis identified gene expression profiles significantly correlating (P？<？0.015) with ≥1 out of 7 variables: sustained viral response (SVR), viral non-response (NR), end of treatment viral response (ETR), viral breakthrough (VB), HCV genotype (Gt. 1 vs. Gt. 2/3), stage of hepatic fibrosis [St. 0/1 vs. St. 2/3/4] and grade of hepatic inflammation (Gr. 0/1 vs. Gr. 2/3/4). Correlation values across all seven contrasts were considered for hierarchical clustering (HCL).A total of 1,697 genes showed ≥1 significant correlation results and genes involved in cell differentiation (183), immune response (53), and apoptosis (170) were leading fractions. HCL grouped the genes into six major clusters. Functional annotation analysis using DAVID (http://david.abcc.ncifcrf.gov webcite) revealed that expression profiles that best linked these variables were highly enriched in cytokine/chemokine activity (Fisher-exact P？<？0.0001) and specific biological module-centric algorithms finally led our focus on four out of fifty-three immune response genes: SMAD family member 3 (SMAD3), interleukin 1 receptor accessory protein (IL1RAP), tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), and chemokine ‘C-C motif’ receptor 5 (CCR5). Of those, TNFRSF1A and CCR5 showed significant correlation with two out of seven variables based on microarray and/or quantitative real-time polymerase chain reaction (qRT-PCR) data.We identified molecular targets of the innate and adaptive immune system and validated their transcriptional specificity in vivo suggesting significant involvement in two unique outcomes during HCV treatment.Hepatitis C virus (HCV) is estimated to persistently infect about 170 million people worldwide [1]. Histological grade of hepatic inflammation and stage of hepatic fibrosis as well as HCV genotype (Gt.) are