Conversion To Sirolimus-based Immunosuppression After Liver Transplantation For Hepatocellular Carcinoma

Background Tumor recurrence after liver transplantation for hepatocellularcarcinoma is associated with a poor prognosis. Immunosuppression is a well-known riskfactor for tumor recurrence after liver transplant. Sirolimus is immunosuppressive agentwith potential application as anticancer.Objective A retrospective review was conducted to determine whether SRL-basedimmunosuppression regimen can decrease the risks of tumor recurrence in patients withhepatocellular carcinoma.Methods We retrospectively analyzed22patients who received a liver transplantfor HCC beyond the standard Milan criteria from June2010to June2011. We comparedthis patients who received CNIs or conversion to sirolimus-based immunosuppressionprotocols after liver transplant. The2treatment groups were compared with respect to thetumor stage by explants and Child’s class. They were converted to sirolimus-basedimmunosuppressive protocol with fast CNIs withdrawal in3days．Sirolimus was initiatedat dosage of2mg once daily, with target levels of5to10ng/mL. Periodic examinations ofarterial pressure, post-transplant diabetes mellitus and neurotoxicity, sirolimus blood levels,liver and renal function tests, triglycerides, cholesterol, blood routine test, the rates ofinfection and reinfection of HBV, the frequencies of biopsy-confirmed acute rejection,recipient recurrent-free survival rate. Recurrent-free survival rate was analyzed using theKaplan-Meier product limit method. Measurement data were evaluated by Student’s t-test.All data were analyzed by SPSS16.0, and P <0.05was considered statistically significant.Result After a median follow-up of12±3mo (range,7-18mo), four patients wererelapsed in SRL group, and eight patients in CNI group were found having HCCrecurrence and metastasis. After a follow-up of18months, recurrence-free survival curveswere computed with the Kaplan-Meier method. It demonstrates that a better HCCrecurrence-free survival in patients with SRL than CNI group(P<0.05). No significantdifferences in the frequencies of acute rejection were observed between the groups.SRL-based immunosuppression regimen would not increase the frequencies of acuterejection. Compared with CNI group, leukopenia and thrombocytopenia have a statisticalsignificance(P<0.05). After sirolimus conversion, the situation of CNIs-relatednephrotoxicity in the three patients experienced a modest improvement. Two patients suffered oral ulcers after conversion to SRL treat and no complication respect to arterialthrombosis were observed.Conclusions These results suggested SRL-based immunosuppressant protocols iswell tolerated and reasonably effective in liver transplant recipients with high risk ofrecurrence of malignancies, mainly when poor prognostic factors are detected duringexamination of the explanted liver: Milan criteria not met or low differentiation grade.Furthermore, it demonstrates that in patients with renal impairment conversion tosirolimus-based immunosuppression regimen could reverse or halt the progression of renalimpairment. The protocol has been proven safe, with an acceptable side-effect profile, andCNIs withdrawal would not cause acute rejection.