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Impact of direct-acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients.

Authors
  • Bixby, Alexandra L1
  • Fitzgerald, Linda1
  • Leek, Rachael2
  • Mellinger, Jessica3
  • Sharma, Pratima3
  • Tischer, Sarah1
  • 1 Department of Pharmacy, Michigan Medicine, Ann Arbor, Michigan.
  • 2 Department of Pharmacy, Vanderbilt University Medical Center, Nashville, Tennessee.
  • 3 Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan.
Type
Published Article
Journal
Transplant Infectious Disease
Publisher
Wiley (Blackwell Publishing)
Publication Date
Jun 01, 2019
Volume
21
Issue
3
Identifiers
DOI: 10.1111/tid.13078
PMID: 30884055
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Direct-acting antivirals (DAAs) have transformed hepatitis C virus (HCV) management post-liver transplant. As HCV clears during DAA treatment, hepatic metabolism improves, resulting in decreased tacrolimus concentrations that may require dose adjustment. The purpose of this study was to determine appropriate management of immunosuppression in liver transplant recipients during and following treatment of HCV. This study was a single-center retrospective analysis of 71 liver transplant recipients who were treated for HCV with DAAs. The primary outcome was change in dose-normalized tacrolimus concentrations from the start of DAA treatment to 12 weeks following therapy. The mean change in log-transformed dose-normalized tacrolimus concentrations was a reduction of 0.43 ng/mL/mg (95% CI; 0.26-0.60, P < 0.0001). The greatest decrease occurred in the first 4 weeks of treatment, after which levels stabilized. The overall mean tacrolimus concentration was 4.8 ng/mL (±2.5). Two patients (3%) developed acute cellular rejection and two patients (3%) had graft loss and died. From the start of treatment to 12 weeks post-DAA therapy, liver transplant recipients experienced a significant decrease in dose-normalized tacrolimus concentrations. In conclusion, close monitoring of tacrolimus concentrations is warranted during and following treatment with DAAs, as dose increases may be indicated in order to maintain therapeutic concentrations to prevent graft rejection. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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