Clinical Research Of Conversion Treatment With Sirolimus-based Immunosuppressive Protocol After Liver Transplantation

OBJECTIVETo evalute the efficacy and safety,we retrospectively analyzed the changes of the clinical information after liver transplantation in some orthotopic liver transplant recipients who were converted to the sirolimus-based immunosuppressive protocol(SRL+MMF+Pred).We hope to discover the reasonable regimen and suitably blood concentration of the drug to protect the graft liver effectively and reduce the toxic action largely.METHODSWe retrospectively analyzed 21 liver transplant recipients complicating some risk factors who accepted the treatment of orthotopic liver transplantation from January 2005 to October 2006 They were converted to sirolimus-based immunosuppressive protocol(SRL+MMF+Pred) with fast CNIs withdrawal in 3 days.Sirolimus was titrated to target trough levels of 4～12ng/mL.The recipients were followed up for 6 months post the conversion therapy.The frequencies of acute rejection and graft survival rate were considered as the efficacy indexes.The safety indexes were:recipient survival rate,occurrence of hypertension,glycemia and neurotoxicity;the rates of infection of bacteria and CMV, reinfection of hepatic virus of type B;and the liver function,renal function,blood hemoglobin concentration,leukocyte,platelet.RESULTSIn 6 months postoperatively,the frequencies of acute rejection was 0%.The recipient and graft survival rate at 6-month were same:85.71%.Seven patients(33.33%) were complicated with infection within 6 months,compared with Pre-,the frequencies of infection were not significantly different(P＞0.05).After sirolimus conversion,the situation of CNIs-related hypertension,glycemia and neurotoxicity were improved.GFR improved from(55.43±15.08)uml/L(at conversion) to(87.21±6.92)umol/L(1 months after conversion) and(99.36±7.94)umol/L(6 months after conversion)(P＜0.05);compared with the control group,there were better effects in the trial group(P＜0.05).CONCLUSIONSSirolimus enriches the choice of immunosuppressive protocols after liver transplantation.The study demonstrates that in most patients with renal dysfunction, withdrawal of CNIs and conversion to sirolimus could reverse or halt the progression of renal impairment,and CNIs withdrawal would not cause acute rejection.It is advantageous to the classic CNIs-induced adverse effects such as hypertension,glycemia and neurotoxicity,etc.It could be used in the case of chronic rejection or refractory rejection too.We proposal that the trough level of SRL is maintained at 5～10ng/ml within 3 months after operation and 4～8ng/ml after 3 months.The sirolimus-based immunosuppressive protocol is a new immunosuppressive regimen without causing evident hepatotoxicity and nephrotoxicity.Side effects are rare too.Sirolimus is not appropriate for use as induction, the use of sirolimus is recommended as a "rescue treatment" or a "secondary immunosuppression" for various indications.It could improve the quality of life,graft and patient survival rates,and achieve excellent outcomes with few adverse effects when wisely used in combination with other IS.