Interferon alfa regulated gene expression in patients initiating interferon treatment for chronic hepatitis C. Hepatology 37:610–621

Interferon alfa (IFN-) is an approved therapeutic agent for chronic hepatitis C. To directly characterize the effects of IFN- in humans, we used microarrays to profile gene expression in peripheral blood mononuclear cells (PBMCs) from hepatitis C patients treated with IFN-. Seven patients were studied using two strategies: (1) in vivo: PBMCs were collected immediately before the first dose of IFN-, and 3 and 6 hours after the dose; (2) ex vivo: PBMCs that were collected before the first IFN- dose were incubated with IFN- for 3 and 6 hours. The microarray datasets were analyzed with significance analysis of microarrays (SAM) to identify genes regulated by IFN-. We identified 516 named genes up-regulated at least 2-fold, at a false discovery rate (FDR) of less than 1%. In vivo and ex vivo studies generated similar results. No genes were identified as regulated differently between these 2 experimental conditions. The up-regulated genes belonged to a broad range of functional pathways and included multiple genes thought to be involved in the direct antiviral effect of IFN-. Of particular interest, 88 genes directly relating to functions of immune cells were up-regulated, including genes involved in antigen processing and presentation, T-cell acti-vation, lymphocyte trafficking, and effector functions, suggesting that IFN- up-regulate