In an initial series of experiments, groups of mice transplanted with hepatocytes from different donors were inoculated with a single source of HCV and gene expression profiling was performed to characterize the host response to infection [17] . Although all HCV-infected animals showed evidence of an interferon response, the level of this response, both in the intensity and number of up-regulated interferon-induced genes, varied between animals depending upon the origin of the donor hepatocytes. These results indicate that host genetic factors contribute to the variation in the host response to HCV, including the activation of innate antiviral signaling pathways. Mice with weak interferon responses also tended to have high levels of intrahepatic HCV RNA, indicating that an ineffective interferon response may allow increased levels of viral replication. These animals also accumulated higher numbers of differentially expressed genes than did mice with strong interferon responses. Interestingly, we have also observed impaired interferon responses and the accumulation of increased numbers of differentially expressed genes in the intrahepatic gene expression profiles of transplant patients who develop fibrosis within one year of transplantation.