title: Effect of hepatitis C infection on tacrolimus doses and blood levels in liver transplantation recipients.
abstract: BACKGROUND
  In our cohort of patients with hepatitis-C virus, which is the most common indication for liver transplantation, we have noted higher relative blood levels of tacrolimus compared to patients without hepatitis-C virus.
  
  
  OBJECTIVE
  To verify this observation and determine its clinical significance, we performed a comparison of doses and blood levels of tacrolimus in hepatitis-C virus and non- hepatitis-C virus liver transplantation recipients.
  
  
  METHODS
  Tacrolimus dose and trough level, as well as mean alanine aminotransferase, for all patients transplanted at our center with a deceased donor between 1/1995 and 12/1999 with hepatitis-C virus were recorded at monthly intervals during the first 24 months following transplantation and compared to patients without hepatitis-C virus.
  
  
  RESULTS
  The tacrolimus levels for hepatitis-C virus and non-hepatitis-C virus patients were not significantly different at any of the monthly intervals, except month 9. In addition, the overall mean tacrolimus levels for hepatitis-C virus and non-hepatitis-C virus patients were not significantly different (P = ns). However, the mean tacrolimus dose (mg/kg) was significantly higher for hepatitis-C virus patients at 12, 15, 18, 21 and 24 months, P < 0.01. The total mean tacrolimus dose in hepatitis-C virus patients was lower during year one by 39% (P = 0.018) and by 73% (P = 0.001) during year two. The total difference in cost of tacrolimus (for year one and two) administered to hepatitis-C virus patients was $4920, P = 0.03. The serum alanine aminotransferase was significantly higher in hepatitis-C virus patients at each monthly interval except month 1, P < or = 0.01.
  
  
  CONCLUSIONS
  Liver transplant recipients with hepatitis-C virus require significantly lower oral doses of tacrolimus to achieve the same blood levels compared to non-hepatitis-C virus patients. This difference may result in a significant reduction in the cost of tacrolimus in hepatitis-C virus patients. The most likely explanation for these findings is decreased hepatic clearance of tacrolimus caused by mild hepatic injury from recurrent hepatitis-C virus.
authors.affiliation: Division of Gastroenterology/Hepatology, University of Colorado Health Sciences Center, Denver, CO 80262, USA. james.trotter@uchsc.edu
authors.forename: J F
authors.initials: JF
authors.lastname: Trotter
authors.forename: J C
authors.initials: JC
authors.lastname: Osborne
authors.forename: M
authors.initials: M
authors.lastname: Heller
authors.forename: U
authors.initials: U
authors.lastname: Christians
mesh_terms: D004305:Dose-Response Relationship, Drug; D005260:Female; D006526:Hepatitis C / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus