Conditions: Hepatitis C Hepatitis C, Chronic Nonimmune Nonviral Causes of Liver Failure
Keywords: hepatitis hepatitis C HCV liver liver disease liver transplant liver transplantation transplant hepatic hepatic transplantation immunosuppression rejection
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 275
Healthy volunteers: no

Brief summary:
In order to prevent organ rejection, patients receiving liver transplants currently require life-long treatment with immune system-suppressing medications to prevent the rejection of the transplanted liver. However, these medications can cause long-term side effects, such as infection, kidney problems, diabetes, and cancer. In patients infected with hepatitis C virus (HCV), these medications may increase the risk of HCV infection in the transplanted liver. The purpose of this study is to determine whether a slow withdrawal of immune system-suppressing medications is safe in two groups of subjects: those who receive a liver transplant due to HCV, and those who receive a liver transplant due to non-immune, non-viral causes of liver failure. The study will also look at whether slow withdrawal will help reduce the long-term side effects of immune system-suppressing medications and decrease the chance for HCV infection of the new liver in transplant patients with HCV.

Detailed description:
This is a prospective multicenter, open-label, randomized trial in which individuals with liver failure due to hepatitis C or to nonimmune nonviral causes undergo liver transplantation and receive immunosuppression with a calcineurin inhibitor and corticosteroids. Corticosteroids are tapered in the 3 months after transplantation and the calcineurin inhibitor is continued. Participants are regularly assessed for evidence of allograft rejection. One year after transplantation, participants eligible for withdrawal are randomly assigned in a 4 to 1 ratio to immunosuppression withdrawal or to maintenance. Participants assigned to withdrawal undergo a scheduled taper over approximately 1 year.

Arms:
arm 1: Subjects may randomize to this group at 12 to 24 months after transplantation. This is followed by tapered withdrawal of calcineurin inhibitor-based immunosuppression therapy over the course of 1 year. arm 2: Liver transplant, followed by maintenance doses of continuous calcineurin inhibitor-based immunosuppression therapy.

Interventions: intervention 1: calcineurin inhibitor-based immunosuppression intervention 2: liver transplant intervention 3: corticosteroids intervention 4: immunosuppression withdrawal
Intervention descriptions: intervention 1: May be cyclosporine, mycophenolate mofetil, or tacrolimus intervention 2: Occurs at study entry intervention 3: 3-month course of corticosteroids intervention 4: One year after transplantation, participants eligible for withdrawal are randomly assigned in a 4 to 1 ratio to immunosuppression withdrawal or to maintenance.

Protocol document: