Liver Unit, IDIBAPS, CIBEREHD, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Hepatology. 2015 May;61(5):1485-94. doi: 10.1002/hep.27681. Epub 2015 Mar 20.
Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) is associated with accelerated progression of liver disease, frequently leading to graft loss and early death. Existing treatment options for severe recurrent HCV infection are limited by suboptimal efficacy, poor tolerability, and numerous drug interactions. We provided sofosbuvir (SOF) and ribavirin (RBV) on a compassionate-use basis to patients with severe recurrent hepatitis C, including those with fibrosing cholestatic hepatitis (FCH) and decompensated cirrhosis who had a life expectancy of 1 year or less. All patients were to receive 24-48 weeks of SOF plus RBV. Investigators could add pegylated interferon to the regimen at their discretion. Data from the first 104 patients who completed or prematurely discontinued treatment by January 1, 2014 are presented. Of the 104 patients analyzed, 52 had an early severe recurrence (diagnosed <12 months after LT) and 52 had cirrhosis (diagnosed >12 months after LT). Twelve patients who underwent retransplantation were excluded from our efficacy analysis. Of the 92 patients assessed, 54 (59%) achieved sustained virological response (SVR) at 12 weeks after the end of treatment, with a higher rate (73%; 35 of 48) in patients with early severe recurrence. Of the 103 patients assessed for clinical outcome, 59 (57%) reported clinical improvement at the last study visit, 23 (22%) were unchanged, 3 (3%) had a worsened clinical status, and 13 (13%) died. Overall, 123 serious adverse events (SAEs) occurred in 49 patients (47%). SAEs associated with hepatic decompensation were the most frequent, with 26 SAEs occurring in 19 patients (18%).
SOF and RBV provide high rates of SVR in patients with severe recurrent HCV, including patients with early severe recurrence, FCH, and cirrhosis.
肝移植（LT）后丙型肝炎病毒（HCV）复发与肝病进展加速有关，常导致移植物丢失和早期死亡。严重复发性 HCV 感染的现有治疗选择受到疗效不佳、耐受性差和药物相互作用多的限制。我们根据同情用药原则向严重复发性丙型肝炎患者（包括纤维化性胆汁淤积性肝炎（FCH）和失代偿性肝硬化患者）提供索非布韦（SOF）和利巴韦林（RBV），这些患者的预期寿命为 1 年或更短。所有患者均接受 SOF 加 RBV 治疗 24-48 周。研究人员可以自行决定在方案中添加聚乙二醇干扰素。截至 2014 年 1 月 1 日，完成或提前停药的前 104 例患者的数据。在分析的 104 例患者中，52 例有早期严重复发（LT 后 12 个月内诊断），52 例有肝硬化（LT 后 12 个月以上诊断）。12 例接受再次移植的患者被排除在我们的疗效分析之外。在 92 例可评估的患者中，54 例（59%）在治疗结束后 12 周时达到持续病毒学应答（SVR），早期严重复发患者的比例更高（73%，35/48）。在 103 例可评估临床结局的患者中，59 例（57%）在最后一次研究访视时报告临床改善，23 例（22%）无变化，3 例（3%）临床状况恶化，13 例（13%）死亡。总的来说，49 例患者（47%）发生了 123 例严重不良事件（SAE）。与肝功能失代偿相关的 SAE 最常见，19 例患者发生 26 例 SAE（18%）。
SOF 和 RBV 可使严重复发性 HCV 患者（包括早期严重复发、FCH 和肝硬化患者）获得高 SVR 率。
