Sirolimus conversion may suppress viral replication in hepatitis C virus-positive renal transplant candidates

Exp Clin Transplant. 2013 Oct;11(5):408-11. doi: 10.6002/ect.2013.0017.


Objectives: Hepatitis C virus in renal transplant recipients is an independent risk factor for sickness and death. It has been shown that one might limit hepatitis C virus progression in liver transplant recipients with sirolimus-based immunosuppression. The mammalian target of rapamycin is an influential molecule for the anti-hepatitis C virus action of interferon. We report our experience with sirolimus conversion in hepatitis C virus-positive patients with chronic allograft nephropathy regarding hepatic and hematologic effects that might affect its future use.

Materials and methods: Twenty-five patients who had received renal transplants with anti-hepatitis C virus-positive and normal liver function were enrolled. Ten patients had allograft dysfunction because of cyclosporine nephrotoxicity. Sirolimus was initiated at 2 mg/d and adjusted to 6 to 8 ng/mL. Cyclosporine was gradually tapered and then stopped; 15 patients were used as a control group. Sirolimus-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 hepatitis C virus active hepatitis.

Results: After conversion, there was a reduction of hemoglobin and hematocrit. In 1 patient, the immunosuppressive regimen was changed back to cyclosporine owing to anemia and hepatotoxicity leading to prompt return of hematocrit and liver enzymes to their original values. One of 10 antihepatitis C virus-positive patients (10.0%) developed sirolimus-associated hepatotoxicity, compared with 2 patients in the control group (13%). Sirolimus patients showed a significant decrease in the HCV PCR levels from 700 000 to 400 000 IU/mL; P < .001, compared to 680 000 to 660 000 IU/mL in cyclosporine patients; P = NS, with comparable levels of transaminases

Conclusions: Our data suggest that sirolimus has the potential to suppress viral replication in hepatitis C virus-positive renal transplant candidates.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Cyclosporine / adverse effects
  • Drug Substitution
  • Female
  • Hepacivirus / drug effects*
  • Hepacivirus / growth & development
  • Hepatitis C / diagnosis
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Prospective Studies
  • Sirolimus / adverse effects
  • Sirolimus / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Viral Load / drug effects
  • Virus Replication / drug effects*


  • Immunosuppressive Agents
  • Cyclosporine
  • Sirolimus