Brown Robert S, O'Leary Jacqueline G, Reddy K Rajender, Kuo Alexander, Morelli Giuseppe J, Burton James R, Stravitz R Todd, Durand Christine, Di Bisceglie Adrian M, Kwo Paul, Frenette Catherine T, Stewart Thomas G, Nelson David R, Fried Michael W, Terrault Norah A
Weill Cornell Medical College, New York, NY.
Baylor University Medical Center, Dallas, TX.
Liver Transpl. 2016 Jan;22(1):24-33. doi: 10.1002/lt.24366.
Recurrent infection with the hepatitis C virus (HCV) after liver transplantation (LT) is associated with decreased graft and patient survival. Achieving sustained virological response (SVR) with antiviral therapy improves survival. Because interferon (IFN)-based therapy has limited efficacy and is poorly tolerated, there has been rapid transition to IFN-free direct-acting antiviral (DAA) regimens. This article describes the experience with DAAs in the treatment of posttransplant genotype (GT) 1 HCV from a consortium of community and academic centers (Hepatitis C Therapeutic Registry and Research Network [HCV-TARGET]). Twenty-one of the 54 centers contributing to the HCV-TARGET consortium participated in this study. Enrollment criteria included positive posttransplant HCV RNA before treatment, HCV GT 1, and documentation of use of a simeprevir (SMV)/sofosbuvir (SOF) containing DAA regimen. Safety and efficacy were assessed. SVR was defined as undetectable HCV RNA 64 days or later after cessation of treatment. A total of 162 patients enrolled in HCV-TARGET started treatment with SMV+SOF with or without ribavirin (RBV) following LT. The study population included 151 patients treated with these regimens for whom outcomes and safety data were available. The majority of the 151 patients were treated with SOF and SMV alone (n = 119; 79%) or with RBV (n = 32; 21%), The duration of therapy was 12 weeks for most patients, although 15 patients received 24 weeks of treatment. Of all patients receiving SOF/SMV with or without RBV, 133/151 (88%) achieved sustained virological response at 12 weeks after therapy and 11 relapsed (7%). One patient had virological breakthrough (n = 1), and 6 patients were lost to posttreatment follow-up. Serious adverse events occurred in 11.9%; 3 patients (all cirrhotic) died due to aspiration pneumonia, suicide, and multiorgan failure. One experienced LT rejection. IFN-free DAA treatment represents a major improvement over prior IFN-based therapy. Broader application of these and other emerging DAA regimens in the treatment of posttransplant hepatitis C is warranted.
肝移植（LT）后丙型肝炎病毒（HCV）复发感染与移植物和患者生存率降低相关。抗病毒治疗实现持续病毒学应答（SVR）可提高生存率。由于基于干扰素（IFN）的治疗疗效有限且耐受性差，已迅速转向不含IFN的直接抗病毒（DAA）方案。本文描述了社区和学术中心联盟（丙型肝炎治疗注册与研究网络[HCV-TARGET]）使用DAA治疗移植后基因1型（GT 1）HCV的经验。HCV-TARGET联盟的54个中心中有21个参与了本研究。纳入标准包括治疗前移植后HCV RNA阳性、HCV GT 1以及使用含西米普明（SMV）/索磷布韦（SOF）的DAA方案的记录。评估了安全性和疗效。SVR定义为治疗停止64天或更晚后HCV RNA检测不到。共有162例纳入HCV-TARGET的患者在肝移植后开始使用SMV+SOF联合或不联合利巴韦林（RBV）治疗。研究人群包括151例接受这些方案治疗且可获得结局和安全性数据的患者。151例患者中的大多数单独接受SOF和SMV治疗（n = 119；79%）或联合RBV治疗（n = 32；21%），大多数患者的治疗持续时间为12周，尽管有15例患者接受了24周的治疗。在所有接受SOF/SMV联合或不联合RBV治疗的患者中，133/151（88%）在治疗12周后实现了持续病毒学应答，11例复发（7%）。1例出现病毒学突破（n = 1），6例患者失访。严重不良事件发生率为11.9%；3例患者（均为肝硬化患者）因吸入性肺炎、自杀和多器官功能衰竭死亡。1例经历了肝移植排斥反应。不含IFN的DAA治疗是对既往基于IFN治疗的重大改进。有必要在移植后丙型肝炎治疗中更广泛地应用这些及其他新兴的DAA方案。
