Perhaps one of our most promising applications of genomics to HCV-associated liver disease is our work with serial liver biopsy samples from HCV-infected liver transplant patients. Liver transplant recipients infected with HCV develop recurrent hepatitis soon after transplantation and, in some cases, progress to fibrosis within two years of the transplant. Our goals are to identify molecular processes influencing liver disease progression and to find potential gene expression markers of early fibrosis. To achieve these goals, we are working closely with clinicians in the liver transplant unit at the University of Washington, including Anne Larson, Robert Carithers, and James Perkins, to collect biopsy samples and to integrate the gene expression data obtained from these samples with clinical observations. Our initial analyses were performed on serial liver biopsy specimens obtained from 13 transplant recipients at 0, 3, 6, and 12 months after transplantation [12] . Gene expression data were compared with clinical observations and with gene expression data obtained from 55 nontransplant HCV-infected and uninfected liver samples. Our analyses revealed several specific gene expression patterns, the first of which was unique for the transplant recipients regardless of their infection status. The corresponding genes encoded stress response proteins and blood proteins involved in coagulation that were differentially expressed in response to post-transplantation graft recovery. The second pattern was specific to HCV-infected samples and included the increased expression of genes encoding components of the interferonmediated antiviral response and immune system. This pattern was absent or suppressed in the patients who developed early fibrosis, indicating that disease progression might result from an impaired liver response to infection. Finally, we identified gene expression patterns that were specific for the 12-month biopsy specimens of all four HCV-infected patients who developed early fibrosis after transplantation. The identified gene expression patterns may prove useful for diagnostic and prognostic applications in HCV-infected patients, including predicting early progression to fibrosis. We are continuing to collect and analyze biopsy samples as new patients are recruited into the study, which should enable us to obtain increasing levels of confidence in the predictive power of the markers that we identify.