Acute HCV: Gene expression changes in response to acute HCV in circulating PBMCs Gene expression profiles from PBMCs from patients with acute Genotype 1 HCV will be determined and compared to those from normal healthy controls and chronic genotype 1 HCV. Genes will be identified by statistical and fold differences between groups (p value of <0.01, fold change of at least 1.5). This comparison will define which gene expression alterations are specific to acute HCV infection. In order to associate individual genes with the progression to chronic disease, subgroup analyses will be done in which gene expression in acutely infected individuals is compared between those who went on to chronic infection and those who spontaneously eliminated the virus. After real-time PCR confirmation of these genes we will use a number of unsupervised (hierarchical clustering, principal components) and supervised (nearest neighbours, linear discriminants) analyses to develop predictive gene sets which accurately classify patients who go on to develop chronic infection. Taken together these results will identify those genes whose expression is altered in the systemic immunologic response to acute HCV and how these relate to the establishment of chronic disease. Genes which are of interest as possible therapeutic targets will be further studied using the HCV replicon model, as described earlier. By the end of the second year of the study we expect to have analyzed 40 acute genotype 1 patients, and in the third year we will analyze 20 genotype 4 patients.