Review on immunosuppression in liver transplantation

Table 1 Commonly used immunosuppressive agents in liver transplantation

Agent	Classification	Indications	Dose
Methyl prednisolone (Medrol®), Prednisone or prednisolone[13,16,111]	Corticosteroids	Induction of immunosuppression, treatment of acute cellular rejection, Maintenance of immunosuppression	Variable according to the centers, the etiology of liver disease and history of rejections
Tacrolimus (Prograf®, Astagraf®)[53]	CNI	Maintenance of immunosuppression	Starting 0.1-0.15 mg/kg per day divided every 12 h and adjust to the desired trough level
Cyclosporine (Neoral®, Sandimmune®, Gengraf®)[52,55]	CNI	Maintenance of immunosuppression	Starting 10-15 mg/kg per day divided every 12 h and adjust to the desired (C2) level
Mycophenolate mofetil (Cellcept®, Myfortic®)[60]	Anti-metabolite	Maintenance of immunosuppression, treatment of rejection	Variable doses may be desired in any individual case
Azathioprine (Imuran®)[65]	Anti-metabolite	Maintenance of immunosuppression	Variable, maintenance dose may be 1.5-2.5 mg/kg per day, needs to be adjusted for adverse side effects
Sirolimus (Rapamune®)[48,68,71]	mTORI	Maintenance of immunosuppression, treatment of rejection, special interests for use in malignancies	Usual dosing is a 6 mg (or 3 mg/m2) oral loading, followed by 2 mg/d (or 1 mg/m2 per day) single dose, higher doses may be administered for individual cases1
Everolimus (Afinitor®)[48,69,72]	mTORI	Maintenance of immunosuppression, treatment of rejection, special interests for use in malignancies	Starting at 1 mg oral every twice a day and adjust to a trough level of 3-8 ng/mL1
2Muromonab-CD3 (OKT3)	T cell depleting monoclonal antibody	Induction of immunosuppression, treatment of steroid resistant rejection	Withdrawn from the market because of reduced use, no longer available since 2010
Alemtuzumab (campath-1H®)[44-46]	T cell depleting monoclonal antibody	Induction of immunosuppression	Variable between centers, a single dose of 30 mg may be used in operating room
ATG (Thymoglobulin®, ATGAM®)[27-30]	T cell depleting polyclonal antibody	Induction of immunosuppression, treatment of steroid resistant rejection	Variable between centers, For induction 1.5 mg/kg per day iv for 3 d and for treatment of rejection 1.5 mg/kg per day iv for 5-7 d of thymoglobulin may be used. For ATGAM a higher dose of 15 mg/kg per day is usually used
2Daclizumab (Zenapax®)[23,115]	IL-2Ra, monoclonal antibody	Induction of immunosuppression, treatment of steroid resistant rejection	For induction the first dose of 1 mg/kg is given within 24 h before Tx and 4 more doses are given after Tx with 2 wk intervals Withdrawn from the market because of reduced use, no longer available
Basiliximab (Simulect®)[23,113,114]	IL-2Ra, monoclonal antibody	Induction of immunosuppression, treatment of steroid resistant rejection	For induction a 20 mg iv dose is administered within 2 h prior to reperfusion and another 20 mg on days 4 post Tx

¹Best to be started at least 30 d after transplantation;

²Not manufacturing anymore. CNI: Calcineurin inhibitor; mTORI: Mammalian target of rapamycin inhibitor; iv: Intravenous; IL-2Ra: Interleukin-2 receptor antagonists; Tx: Transplantation.