Induction of operational tolerance in stable liver graft recipients

INTERVENTION: In the intervention group immunosuppression shall be weaned, with reduction of drug doses by half for first 3 years of the study. The control group shall continue full dose immunosuppression. If after three years patients with reduced immune suppression have stable biochemistry then they will be offered a follow up liver biopsy and if that remains compatible with operational tolerance they will be offered the opportunity to stop immune suppression altogether. CONDITION: Liver transplant recipients; immunosuppression; operational tolerance ; Surgery PRIMARY OUTCOME: To determine the proportion of stable liver transplant recipients that develop operational tolerance with physician directed reduction or withdrawal of immunosuppression at a late point after transplantation SECONDARY OUTCOME: 1. To determine whether the acquisition of operational tolerance leads to reduction in morbidity or mortality; 2. To determine whether a two‐step strategy of reduction of immune suppression followed by withdrawal is safe and effective INCLUSION CRITERIA: 1. Age over 40 and regarded as competent to make informed decisions 2. More than 5 years from transplantation 3. No episodes of steroid resistant acute rejection or acute rejection beyond one year post‐transplant 4. Transplantation for non‐auto‐immune liver disease 5. Stable liver biochemistry with an ALT less than 30 IU/L and serum immunoglobulins 6. Prepared to have a liver biopsy prior to entry as well as 1 and 3 years after study entry 7. An adequate liver biopsy with minimal inflammation restricted to the portal tract, at worst minimal fibrosis, without bile duct damage or arteriopathy 8. On monotherapy with a calcineurin inhibitor or Sirolimus 9. Prepared to enter a randomised controlled trial