title: Lack of hepatotoxicity upon sirolimus addition to a calcineurin inhibitor-based regimen in hepatitis virus-positive renal transplant recipients.
abstract: BACKGROUND
  We retrospectively analyzed the impact of sirolimus addition (SRL) with a 25% dosing reduction in calcineurin inhibitors on liver function among patients with or without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  
  
  METHODS
  Forty-eight renal transplant recipients (HBsAg-positive, n = 5; anti-HCV-positive, n = 7) with allograft dysfunction (serum creatinine: mean 2.7, median 2.0 mg/dL) and normal liver function were enrolled. The duration of the SRL add-on therapy was 8.0 +/- 3.6 months. SRL trough levels were maintained within 6.5 +/- 3.7 ng/mL. The trough levels of tacrolimus and the 2-hour cyclosporine postdose levels were tapered to 4.6 +/- 1.9 ng/mL (24.6% reduction) and 650 +/- 170 ng/mL (24.3% reduction), respectively. SRL-related hepatitis was defined as a rise in liver transferase or alkaline phosphatase or bilirubin over twice the upper limit of normal. Thirty-six HBsAg-negative and anti-HCV-negative patients served as the controls.
  
  
  RESULTS
  Hepatotoxicity developed in 6 (12.5%) of the 48 patients and in 3 (8.3%) of 36 control subjects. One (20.0%) of five HBsAg-positive patients (P = .959) and two (28.6%) of seven anti-HCV-positive patients (P = .496) developed hepatotoxicity, respectively. Three (25.0%) of the 12 HBsAg-positive or anti-HCV-positive patients developed hepatotoxicity (P = .420).
  
  
  CONCLUSIONS
  Patients with seropositivity of HBsAg or anti-HCV had an insignificantly higher percentage of hepatitis. Use of SRL in the HBV/HCV patients is not contraindicated, but needs monitoring for HBV/HCV activation.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Chung Shan Medical University Hospital, School of Medicine, Chung Shan Medical University, No. 110 Section 1 Chien-Kuo N. Road, Taichung, Taiwan.
authors.forename: H R
authors.initials: HR
authors.lastname: Chang
authors.forename: C-C
authors.initials: CC
authors.lastname: Lin
authors.forename: J-D
authors.initials: JD
authors.lastname: Lian
mesh_terms: D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D006509:Hepatitis B / Q000150:complications; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006526:Hepatitis C / Q000150:complications; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D019259:Lamivudine / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D006514:Hepatitis B Surface Antigens; D007166:Immunosuppressive Agents; D019259:Lamivudine; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus