title: Sirolimus conversion may suppress viral replication in hepatitis C virus-positive renal transplant candidates.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Nephrology, Cairo University, Cairo, Egypt.
authors.forename: Amin
authors.initials: A
authors.lastname: Soliman
authors.forename: Ahmed
authors.initials: A
authors.lastname: Fathy
authors.forename: Sahier
authors.initials: S
authors.lastname: Khashab
authors.forename: Noha
authors.initials: N
authors.lastname: Shaheen
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Soliman
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000009:adverse effects; D057915:Drug Substitution; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000254:growth & development; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus