• Proportion of participants with progression of hepatitis C-related liver disease, defined as Stage 4 or higher fibrosis on the Ishak scale [ Time Frame: In the 2 years following random assignment ] [ Designated as safety issue: Yes ]
  

• Tolerance induction [ Time Frame: 6 months following immunosuppression withdrawal ] [ Designated as safety issue: No ]
  
• Laboratory tests indicative of successful withdrawal [ Time Frame: 6 months following immunosuppression withdrawal ] [ Designated as safety issue: No ]
  
• Hepatitis C immune response and graft injury [ Time Frame: Random assignment to immunosuppression withdrawal ] [ Designated as safety issue: Yes ]
  
• Definition of rejection profiles from laboratory tests [ Time Frame: Post-immunosuppression withdrawal ] [ Designated as safety issue: No ]
  

More than 60% of liver transplants are done in patients who are infected with HCV. Following organ transplants, immunosuppressive medications are used to prevent the patient's immune system from rejecting the transplanted organ. In general, these antirejection medications are prescribed for the remainder of the transplant recipient's life. However, in patients infected with HCV, these same medications are believed to be associated with a rapid reoccurrence of HCV, which can lead to failure of the transplanted liver, severe hepatitis, cirrhosis, and other serious conditions. This study will evaluate how safe it is to slowly withdraw antirejection medications without the rejection of the transplanted liver in patients with HCV-related liver failure receiving a liver transplant. The study will also determine if the risk for HCV infection in the transplanted liver decreases with this regimen in these patients.

Participants will undergo liver transplantation and receive immunosuppression medications consistent with current standard practices. Study participants will be treated with standard of care antirejection medications after transplant. This includes a 3-month course of corticosteroids and maintenance therapy with one or two antirejection medications (tacrolimus or cyclosporine and/or mycophenolate mofetil). Participants will be tapered off corticosteroids in the first 3 months but will continue maintenance immunosuppression for 1 year. Participants will be regularly monitored for recurrence of hepatitis and for evidence of allograft rejection.

One year after transplantation, participants who meet certain criteria for immunosuppressive withdrawal will be randomly assigned to either the immunosuppression withdrawal group or the control group. Only study participants who are taking one immunosuppressive drug will qualify for the random assignment. Participants assigned to the drug withdrawal group will have their dose of immunosuppressive drug tapered off over the course of 1 year. The control group will be maintained on normal levels of their assigned immunosuppressive drugs. Immunosuppressive drugs will not be provided by this study.

During and after the withdrawal phase, participants will be closely monitored for liver function, signs of rejection, levels of HCV in the blood and liver, and for the response of the immune system to the withdrawal of immunosuppression. Participants will be followed for a minimum of 1 year after the completion of withdrawal, possibly up to 4 years.