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• W2313029207 abstract "Introduction and aim of the work: The presence of hepatitis C virus (HCV) in renal transplant recipients is an independent risk factor for death and graft failure. Limiting hepatitis C virus progression in liver transplant recipients using sirolimus-based immunosuppression was recently demonstrated. The mammalian target of rapamycin (mTOR) is one of the influential molecules for the anti-hepatitis C virus (HCV) action of interferon (IFN). On the other hand, chronic allograft nephropathy (CAN) favored by the use of calcineurin inhibitors (CNI) is one of the main causes of graft loss, whereas sirolimus (SRL) has proven to maintain better graft function with lower rates of CAN. We sought to report our experience with sirolimus conversion among HCV positive patients with chronic allograft nephropathy as regards hepatic and hematologic effects that might impact the drug use. Patients and methods: Twenty five renal transplant recipients with anti-HCV-positivity and normal liver function were enrolled. Ten patients had allograft dysfunction due to CsA nephrotoxicity proved by renal biopsy. SRL was started at 2 mg/d and adjusted to 6 to 8 ng/mL blood levels. CsA was gradually tapered to low levels and eventually stopped. Fifteen patients with hepatitis C positivity on CsA maintenance immunosuppression were used as control group. Creatinine clearance, body weight, ferritin level, hematocrit, hemoglobin, MCV, leucocyte count, platelet count, reticulocyte count, and reticulocyte index were calculated for all patients. All hepatitis C virus positive patients were followed prospectively regarding transaminases, immunosuppressive target levels, and HCV RNA. SRL-related hepatitis was defined as a rise in liver transferases or alkaline phosphatase or bilirubin over twice the upper limit of normal. Viral replication was defined as elevated liver enzymes and increasing viral load and/or biopsy-proven HCV active hepatitis. Results: After conversion, creatinine clearance non significantly rose from a value of 56.67±28.40 to 58.14 ±19.96 ml/min and serum creatinine fell from 2.04±0.4mg/dl to 1.8±0.07mg/dl. Average time on therapy was 24 weeks. There was a considerable reduction of Hb and hematocrit (10±1.15 g/dl before versus 9.25±0.94 after and 33±3% before versus 25.45±3.6% after conversion respectively, (P < 0.01, and < 0.01). In one patient, immunosuppressive regimen was changed back to CsA due to anemia and hepatotoxicity leading to prompt return of hematocrite and liver enzymes to the original value. One of ten anti-HCV-positive patients (10.0%) developed sirolimus associated hepatotoxicity compared to two patients in the control group (13%). Sirolimus patients showed a significant decrease in the HCV PCR levels from 700,000 to 600,000 IU/mL, p< 0.05, compared to 680,000 to 660,000 IU/ml in CsA patients, p=NS with comparable levels of transaminases (45 IU/L for aspartate aminotransferase and 50 IU/L for alanine aminotransferase compared to 49 and 56 IU/L in CyA patients, P=NS). Conclusions: Sirolimus has been shown to be a potent immunosuppressive agent after renal transplantation however, special concern regarding anemia should be evaluated thoroughly in those patients. Our data suggests that sirolimus has the potential to suppress viral replication in HCV positive renal transplant candidates." @default.
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• W2313029207 date "2012-11-01" @default.
• W2313029207 modified "2023-09-26" @default.
• W2313029207 title "Conversion to Sirolimus Has the Potential to Suppress Viral Replication in HCV Positive Renal Transplant Candidates" @default.
• W2313029207 doi "https://doi.org/10.1097/00007890-201211271-00688" @default.
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