The Impact of Everolimus Based Immunosuppression in the Evolution of Hepatitis C Fibrosis After Liver Transplantation

Background: Hepatitis C recurrence, which invariably occurs in viremic liver transplant (LT) recipients, associated with accelerated liver fibrosis leading to established graft cirrhosis in 40-20% of patients in 5 years with another 5% experiencing an aggressive form with cirrhosis and graft loss in 1 year. Since treatment after LT has a low efficacy, the overall survival of HCV-infected LT recipients is shorter than that of uninfected LT patients. New immunosuppressive agents such as mTOR inhibitors (Everolimus/Sirolimus) reduce the risk of liver graft rejection, have antifibrotic properties and do not worsen HCV recurrence. Moreover new directly-acting antiviral agents have increased efficacy of interferon-based treatment but their use in LT recipients may be limited by side effects. Hypothesis: Use of individualized immunosuppressive regimen and early personalized anti-viral treatment based on recipient and viral factors would improve outcome of HCV infected liver transplant recipients. Objectives: 1. To evaluate safety and efficacy of two steroid-free immunosuppressive regimens to reduce hepatitis C recurrence associated to fibrosis progression (F≥2 under ISHAK score) at one year post-transplant. 2. To identify viral and recipient factors associated with liver fibrosis progression using ultra-deep pyrosequencing (UDPS).