Table 5.

Some Principles Underlying Immunosuppression in Liver Allograft Recipients.

Immunosuppressive drugs have significant side-effects and the benefits need to be balanced against the risks - with infection you may lose the patient but with rejection you may lose the graft Immunosuppression will increase the patient's susceptibility to some infections and some cancers and reduce the response to immunisation Tailoring immunosuppression to the individual is an oft stated goal but rarely practiced Therapeutic drug monitoring is necessary for tacrolimus, cyclosporin, sirolimus and everolimus (mTOR inhibitors) and is variably used for mycophenolate. Target levels of immunosuppressive agents will depend on many factors including indication, time after transplant, other immunosuppressive agents, history of rejection, graft function Typical target levels for tacrolimus are 5–8 ng/mL, for cyclosporin 75–120 ng/mL, sirolimus 4–6 ng/mL (all trough whole blood levels) TMPT measurements for those on azathioprine is rarely indicated Trough whole blood levels are a useful guide to immunosuppression: sub-therapeutic levels may be consistent with adequate immunosuppression and high levels may be indicative of the fact that the measured level is not a true trough level. For many of the immunosuppressive drugs, there are several formulations. These are only sometimes interchangeable so pharmacist advice should be taken before switching patients from one brand to another Some data suggest that single once-daily preparations of tacrolimus are associated with better outcomes that twice daily preparations Most units aim to discontinue corticosteroids in the first year although long-term steroids are usually indicated in those transplanted for autoimmune hepatitis and other autoimmune liver diseases and those with a history of recurrent rejection. Clinicians must be prepared to switch regimen in response to the patient's condition: this is rarely done mTORi may be useful in those with some malignancies and a useful alternative to CNI when there is renal failure

TMPT: Thiopurine S-methyltransferase; mTOR: mammalian Target of rapamycin; mTORi: mammalian Target of rapamycin inhibitor; CNI: Calcineurin inhibitor.