Extract

Background and study aims Continuing immune suppression lifelong following liver transplant has long been held as essential to ensure the best outcome for our patients. However, these immunosuppressive drugs are associated with side effects. These include increased risk of infection, cancer and heart disease. A recent study of UK liver transplants showed that for patients surviving longer than 1 year after transplant the survival rate was half that of the general population. There was no sign that this outcome had improved between 1994 and 2007. These issues have led to a focus on drug weaning strategies, with a view to stopping immune suppression if stable transplant function can be maintained. Early studies have shown this so-called ‘operational tolerance’ is possible in around 20% of patients, although it is believed this could be a lot higher at late time points following transplant. Our aim is to identify: 1. The proportion of stable liver transplant patients that develop operational tolerance with physician-directed reduction or withdrawal of immunosuppression at a late point after transplantation. 2. Whether the development of operational tolerance leads to a reduction in illness and improvement in life expectancy. 3. Whether a two-step strategy of reduction of immune suppression followed by withdrawal is safe and effective. Who can participate? Liver transplant recipients more than 5 years from transplantation. What does the study involve? Participants will be randomly assigned to either the immunosuppression weaning group or the control group. In the immunosuppression weaning group, doses of immunosuppressive drugs will be halved. The control group will continue receiving their current immunosuppression dose. Patients will undergo protocol liver biopsies at time of recruitment, after 1 year and after 3 years. If after 3 years on half-dose immune suppression the patient's liver function tests are stable and liver biopsy satisfactory they will be offered the opportunity to stop immune suppression altogether. It is understandable that they might feel uncomfortable about stopping immune suppression drugs completely and we therefore stress that this aspect of the study is optional. The study will run for 4 years and clinic follow-up will take the same form it does at present. What are the possible benefits and risks of participating? If we are able to successfully stop immune suppression it will mean the participants are not exposed to the potential side effects of the drugs. We expect this to lead to a reduction in illness and longer life expectancy. Clearly, developing rejection on weaning immune suppression is a concern. Reassuringly, previous studies have demonstrated that those patients who fail to become tolerant and develop rejection are not exposed to a higher risk of loss of their transplanted liver or death. Episodes of rejection appear to be mild in most patients and generally settle without requiring high-dose steroids. If they do develop rejection they will be withdrawn from the study and recommenced on their previous treatment. Where is the study run from? Addenbrooke's Hospital Cambridge (lead centre), Queen Elizabeth Hospital Birmingham and King's College Hospital London (UK). When is the study starting and how long is it expected to run for? Recruitment will take place over a 12-month period and it is envisaged that the study will start in January 2013 and will end in December 2018. Who is funding the study? Cambridge University Hospitals NHS Trust (UK). Who is the main contact? Dr Roger McCorry [email protected]

Inclusion criteria

• Liver transplant recipients; immunosuppression; operational tolerance

Links

• ictrp
• isrctn