Impact of direct-acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients.
Impact of direct-acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients.
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DOI：
10.1111/tid.13078
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发表时间：
2019-06
期刊：
影响因子：
--
通讯作者：
Tischer S
中科院分区：
文献类型：
--
作者：
Bixby AL;Fitzgerald L;Leek R;Mellinger J;Sharma P;Tischer S
直接作用抗病毒药物（DAAs）已经改变了肝移植后丙型肝炎病毒（HCV）的管理。在DAA治疗期间，随着HCV的清除，肝脏代谢改善，导致他克莫司浓度降低，可能需要调整剂量。本研究的目的是确定在HCV治疗期间和之后肝移植受者免疫抑制的适当管理。本研究是一项单中心回顾性分析，对71例接受DAAs治疗HCV的肝移植受者进行了分析。主要结局是DAA治疗开始至治疗后12周剂量标准化他克莫司浓度的变化。对数转化剂量标准化他克莫司浓度的平均变化为0.43 ng/mL/mg （95% CI; 0.26-0.60, P < 0.0001）。最大的下降发生在治疗的前4周，之后水平稳定。他克莫司总体平均浓度为4.8 ng/mL（±2.5）。2例（3%）患者发生急性细胞排斥反应，2例（3%）患者发生移植物丢失并死亡。从治疗开始到daa治疗后12周，肝移植受者的剂量标准化他克莫司浓度显著下降。总之，在DAAs治疗期间和之后密切监测他克莫司浓度是必要的，因为可能需要增加剂量以维持治疗浓度以防止移植排斥。
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.
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