Switching From One Type of Anti-rejection Drug (Tacrolimus or Cyclosporine) to Another (Sirolimus) Approximately 90-180 Days After Liver Transplantation

Inclusion Criteria: 1. Adult (18 years or older) patients undergoing liver transplantation at Thomas Jefferson University Hospital. 2. Diagnosed with at least one of the following CNI side effects 90-180 days post transplantation: 1. CNI renal toxicity. Any liver transplant recipient who has elevated creatinine level (greater than 1.4 mg/dl) and impaired creatinine clearance (MDRD) of 40-60 ml/minute or decreased by 15% compared to baseline in the setting of having a therapeutic CNI level, without suspicion of acute or chronic allograft rejection. 2. Hepatic fibrosis on biopsy. Any patient who has fibrosis seen on liver biopsy with LFT's 2 times the upper normal limit. 3. CNI neurologic toxicity. Any patient who has significant neurological side effects from CNIs. This will include the following: seizures not secondary to an epileptogenic focus or any metabolic derangement; alteration of speech ranging from aphasia to slurred speech; inability to be awake and alert. 4. Post transplant diabetes. Any patient who has developed diabetes after transplant and in whom CNIs are thought to be contributing to poor glycemic control. 3. Signed informed consent at approximately 90 -180 days post transplantation. Exclusion Criteria: 1. Invasive/surgical therapy within 2 weeks of the 90-180 day post transplantation conversion. (e.g. patients with T-tubes would not be eligible for the study because the T-tube removal will coincide with the conversion date). 2. Open surgical wound at 90-180 days post transplantation. 3. Acute cellular rejection during the first 90-180 days post transplantation. 4. Re-transplants or multiple-organ transplants. 5. Active infection. 6. Pregnancy. 7. Malignancy within 3 years prior to liver transplantation (except adequately treated basal cell carcinoma). Patients with HCC prior to transplant will not be excluded. 8. Total cholesterol \>300 mg/dl on medical treatment or triglycerides \>150 mg/dl at 90-180 days post transplantation. 9. White blood cell count \<3,000/mm3 or platelet count \<100,000/mm3 at 90-180 days post transplantation. 10. Ascites. 11. Patients on chemotherapy. 12. Urine protein/creatinine ration \> 0.5