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

Abstract

Introduction 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. Methods 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. Results 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. Conclusion 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.

Long-term follow-up of HCV infected kidney transplant recipients receiving direct-acting antiviral agents: a single-center experience in China

“…However, another study observed a significant decrease of trough Tac levels throughout the course of therapy, especially during the first month [14]. Bixby et al [21] also found a great decrease of Tac concentration in the first 4 weeks of DAAs therapy and stable levels thereafter in a liver transplant cohort. Our study reviewed 7 patients with stable trough Tac levels before and after 4 weeks during DAAs therapy, without any dose adjustment, which revealed a different result from part of previous studies.…”

Management and tolerability of glecaprevir‐pibrentasvir pharmacotherapy in hepatitis C viremic heart and lung transplant recipients

“…To date, the majority of clinical data evaluating the impact of DAAs on tacrolimus pharmacotherapy is confined to the liver transplant population. Several of these studies have in fact found transplant recipients required higher doses of tacrolimus to achieve similar levels after completing therapy with DAAs 16,17 . While useful, this information may not apply to recipients of non–liver transplants because it is hypothesized that changes in tacrolimus dose requirements are due to resolution of HCV infection rather than a drug‐drug interaction 18,19 .…”

Safety and efficacy of Sofosbuvir and Velpatasvir in children with active hepatitis C virus infection undergoing haploidentical transplantation

“…Another concern regarding the use of DAA during the course of HCT is the possible interaction with the drugs used for GVHD prophylaxis 15,16 . There is lack of data on the drug‐drug interaction between Sof‐Vel and calcineurin inhibitors or mTOR inhibitors.…”