Background: Direct acting antivirals (DAA) have transformed hepatitis C virus (HCV) management post-liver transplant (LT). As HCV clears, hepatic metabolism improves, resulting in decreased tacrolimus (TAC) levels that may require dose adjustments.

Methods: This study was a single-center retrospective review of post-LT recipients treated for HCV with DAA from 7/2014-3/2017. Patients were excluded if prescribed concomitant ritonavir, interferon, or cyclosporine, did not complete therapy, or had HIV. Primary outcome: difference in dose-normalized TAC level from start to 12 weeks post-DAA. Secondary outcomes: rates of dose adjustments, sustained virologic response (SVR), 1-yr mortality, and 1-yr acute cellular rejection (ACR).

Results: 94 patients screened; 71 patients met inclusion criteria. See Table 1 for baseline demographics. From start of DAA therapy to 12 weeks post therapy, the mean change in dose-normalized TAC levels was -2.5 (+ 5) ng/mL, p=0.01. (see Figure 1). The steepest drop in dose-normalized TAC levels occurred in the first 4 weeks of treatment, after which levels stabilized. The overall mean TAC level was 4.8 ng/mL (+2.5) with a mean of 1 dose change per patient. 70 patients (99%) achieved SVR, 2 patients (3%) had ACR, 2 patients (3%) had graft loss and 2 patients (3%) died.

Conclusions: From start of treatment to 12 weeks post-DAA, LT recipients on DAAs experienced a decrease in dose-normalized TAC levels. Close monitoring of TAC levels, is warranted and TAC dose increases may be indicated.

CITATION INFORMATION: Bixby A., Fitzgerald L., Leek R., Mellinger J., Tischer S. Impact of Direct Acting Antivirals of Hepatitis C Virus Therapy on Tacrolimus Dosing Post-Liver Transplant Am J Transplant. 2017;17 (suppl 3).

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