Acute HCV: local hepatic gene expression in post-transplantation HCV infection Gene expression profiles will be determined from liver biopsies at organ retrieval, prior to infection by HCV, and at 3, 6 and 12 months after transplantation. Gene changes can therefore be followed in the same patient and between patients; genes levels will be compared to normal liver tissue and to baseline gene expression in HCV-naïve grafts, using statistical methods developed in our lab and at the EBI. Currently 70% of the patients transplanted with HCV in our center are treated for recurrent HCV post-transplantation after evidence of recurrent HCV on liver biopsy, and in these patients quantitative HCV titers are done at 3 or 6 months post-transplantation. Roughly 80% of our patients complete therapy over a 12 month course. Thus, by the end of our 3 year study we will know the response to treatment of between 28-36 patients (we expect a 60% response rate, thus roughly 17-22 responders and 11-14 nonresponders), and eventually will have data on the 42-54 patients expected to complete therapy. With this sample size we can determine which gene subsets are predictive of response to treatment (using the methods noted above). Equally we will be able to relate gene expression to HCV RNA titer in 50-60 patients. By the end of the three year study we will have clinical and genomic data on 72 to 90 patients. Ultimately we will relate gene expression to the development of recurrent cirrhosis, and we anticipate that roughly 18-30 patients will have gone on to this state within 5 years of transplantation. In order to control for the effects of the many confounding factors that could influence hepatic gene expression post-transplantation (eg. acute rejection, immunosuppression) we will perform subgroup analyses using our extensive clinical database. We will compare HCV treatment responders to nonresponders, rejection to no rejection, and different immunosuppressive regimens, in addition to comparing gene expression profiles from acute hepatic HCV to those already determined for chronic HCV. These analyses will allow us to distinguish and describe the effects of acute HCV infection on hepatic gene expression.