Transplanting hepatitis C virus-positive livers into hepatitis C virus-negative patients with preemptive antiviral treatment: A modeling study.
Transplanting hepatitis C virus-positive livers into hepatitis C virus-negative patients with preemptive antiviral treatment: A modeling study.
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DOI：
10.1002/hep.29723
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Chung RT
中科院分区：
文献类型：
--
作者：
Chhatwal J;Samur S;Bethea ED;Ayer T;Kanwal F;Hur C;Roberts MS;Terrault N;Chung RT
根据目前的指南，丙型肝炎病毒（HCV）阳性的肝脏不移植到HCV阴性的受体，因为移植后的不良结果与同种异体移植物HCV感染有关。然而，HCV现在可以在肝移植（LT）后使用直接作用的抗病毒药物（DAA）治愈，成功率>90%;因此，肝移植（LT）等待名单上的HCV阴性患者可能会受益于接受HCV阳性器官的抢先治疗。我们的目的是评估是否以及在哪些HCV阴性患者中接受HCV阳性（即，病毒血症）器官的风险超过了与HCV同种异体移植感染相关的风险。我们开发了一个基于马尔可夫的数学模型，模拟了LT等候名单上HCV阴性患者的虚拟试验，以比较患者的长期结局：1）愿意接受任何（HCV阴性或HCV阳性）肝脏与2）愿意只接受HCV阴性肝脏的患者。接受HCV阳性肝脏的患者预先接受12周的DAA治疗，与接受HCV阴性肝脏的患者相比，移植失败的风险更高。该模型结合了已发表的研究和器官共享联合网络（UNOS）的数据。我们发现，无论HCV状态如何，接受任何肝脏与仅接受HCV阴性肝脏相比，当MELD ≥ 20时，预期寿命增加，并且在MELD 28时获益最高（额外寿命0.172年）。在HCV阳性供体器官率较高的UNOS区域，即区域1、2、3、10和11，临床获益的幅度更大。敏感性分析表明，模型结果是稳健的。将HCV阳性的肝脏移植到HCV阴性的患者中，预先进行DAA治疗可以提高LT等待名单上的患者生存率。我们的分析可以帮助指导临床试验并最大限度地减少患者伤害。
Under current guidelines hepatitis C virus (HCV)-positive livers are not transplanted into HCV-negative recipients because of adverse post-transplant outcomes associated with allograft HCV infection. However, HCV can now be cured post liver transplant (LT) using direct-acting antivirals (DAAs) with >90% success; therefore, HCV-negative patients on the liver transplant (LT) waiting list may benefit from accepting HCV-positive organs with preemptive treatment. Our objective was to evaluate if and in which HCV-negative patients the potential benefit of accepting an HCV-positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov-based mathematical model that simulated a virtual trial of HCV-negative patients on the LT waiting list to compare long-term outcomes in patients: 1) willing to accept any (HCV-negative or HCV-positive) liver versus 2) those willing to accept only HCV-negative livers. Patients receiving HCV-positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV-negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV-negative livers resulted in an increase in life expectancy when MELD was ≥ 20, and the benefit was highest at MELD 28 (0.172 additional life years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV-positive donor organ rates, i.e. Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust. Transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm.
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影响因子：
2.1
作者：
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通讯作者：
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