Chhatwal Jagpreet, Samur Sumeyye, Kues Brian, Ayer Turgay, Roberts Mark S, Kanwal Fasiha, Hur Chin, Donnell Drew Michael S, Chung Raymond T
Massachusetts General Hospital Institute for Technology Assessment, Boston, MA.
Harvard Medical School, Massachusetts General Hospital, Boston, MA.
Hepatology. 2017 Mar;65(3):777-788. doi: 10.1002/hep.28926. Epub 2017 Jan 6.
The availability of oral direct-acting antivirals has altered the hepatitis C virus (HCV) treatment paradigm for both pre-liver transplant (LT) and post-LT patients. There is a perceived trade-off between pre-LT versus post-LT treatment of HCV-treatment may improve liver function but potentially decrease the likelihood of a necessary LT. Our objective was to identify LT-eligible patients with decompensated cirrhosis who would benefit (and not benefit) from pre-LT treatment based on their Model for End-Stage Liver Disease (MELD) scores. We simulated a virtual trial comparing long-term outcomes of pre-LT versus post-LT HCV treatment with oral direct-acting antivirals for patients with MELD scores between 10 and 40. We developed a Markov-based microsimulation model, which simulated the life course of patients on the transplant waiting list and after LT. Simulation of LT integrated data from recent trials of oral direct-acting antivirals (SOLAR 1 and 2), the United Network for Organ Sharing (UNOS), and other studies. The outcomes of the model included life expectancy, 1-year and 5-year patient survival, and mortality. Model-predicted patient survival was validated with UNOS data. We found that, at the national level, treating HCV before LT increased life expectancy if MELD was ≤27 but could decrease life expectancy at higher MELD scores. Depending on the UNOS region, the threshold MELD score to treat HCV pre-LT varied between 23 and 27 and was lower for UNOS regions 3, 10, and 11 and higher for regions 1, 2, 4, 5, 8, and 9. Sensitivity analysis showed that the thresholds were stable.
Our findings suggest that the optimal MELD threshold below which decompensated cirrhosis patients should receive HCV treatment while awaiting LT is between 23 and 27, depending on the UNOS region. (Hepatology 2017;65:777-788).
口服直接抗病毒药物的出现改变了丙型肝炎病毒(HCV)对肝移植前和肝移植后患者的治疗模式。对于HCV的肝移植前与肝移植后治疗,人们认为存在权衡——HCV治疗可能改善肝功能,但可能降低进行必要肝移植的可能性。我们的目标是根据终末期肝病模型(MELD)评分,确定符合肝移植条件的失代偿性肝硬化患者,这些患者会从肝移植前治疗中获益(或无获益)。我们模拟了一项虚拟试验,比较MELD评分在10至40之间的患者接受口服直接抗病毒药物进行肝移植前与肝移植后HCV治疗的长期结局。我们开发了一个基于马尔可夫的微观模拟模型,该模型模拟了移植等待名单上和肝移植后患者的生命历程。肝移植模拟整合了近期口服直接抗病毒药物试验(SOLAR 1和2)、器官共享联合网络(UNOS)及其他研究的数据。模型的结局包括预期寿命、1年和5年患者生存率以及死亡率。模型预测的患者生存率用UNOS数据进行了验证。我们发现,在国家层面,如果MELD≤27,肝移植前治疗HCV可提高预期寿命,但在较高MELD评分时可能降低预期寿命。根据UNOS地区不同,肝移植前治疗HCV的阈值MELD评分在23至27之间变化,UNOS的3、10和11区较低,1、2、4、5、8和9区较高。敏感性分析表明这些阈值是稳定的。
我们的研究结果表明,根据UNOS地区不同,失代偿性肝硬化患者在等待肝移植时应接受HCV治疗的最佳MELD阈值在23至27之间。(《肝脏病学》2017年;65:777 - 788)