Department of Medicine, Division of Gastroenterology, Fondazione IRCCS Ca` Granda Ospedale Maggiore Policlinico, Universita` degli Studi di Milano, Milan, Italy.
Hospital Universitario 12 de Octubre, Sección de Aparato Digestivo, Madrid, Spain.
Gut. 2014 Jul;63(7):1150-8. doi: 10.1136/gutjnl-2013-305667. Epub 2013 Nov 7.
Severe adverse events (AEs) compromise the outcome of direct antiviral agent-based treatment in patients with advanced liver fibrosis due to HCV infection. HEP3002 is an ongoing multinational programme to evaluate safety and efficacy of telaprevir (TVR) plus pegylated-interferon-α (PEG-IFNα) and ribavirin (RBV) in patients with advanced liver fibrosis caused by HCV genotype 1 (HCV-1).
1782 patients with HCV-1 and bridging fibrosis or compensated cirrhosis were prospectively recruited from 16 countries worldwide, and treated with 12 weeks of TVR plus PEG-IFN/RBV, followed by 12 or 36 weeks of PEG-IFN and RBV (PR) alone dependent on virological response to treatment and previous response type.
1587 patients completed 12 weeks of triple therapy and 4 weeks of PR tail (53% cirrhosis, 22% HCV-1a). By week 12, HCV RNA was undetectable in 85% of naives, 88% of relapsers, 80% of partial responders and 72% of null responders. Overall, 931 patients (59%) developed grade 1-4 anaemia (grade 3/4 in 31%), 630 (40%) dose reduced RBV, 332 (21%) received erythropoietin and 157 (10%) were transfused. Age and female gender were the strongest predictors of anaemia. 64 patients (4%) developed a grade 3/4 rash. Discontinuation of TVR due to AEs was necessary in 193 patients (12%). Seven patients died (0.4%, six had cirrhosis).
In compensated patients with advanced fibrosis due to HCV-1, triple therapy with TVR led to satisfactory rates of safety, tolerability and on-treatment virological response with adequate managements of AEs.
由于 HCV 感染，严重不良事件（AE）会影响晚期纤维化患者接受直接抗病毒药物治疗的结果。HEP3002 是一项正在进行的多国计划，旨在评估替拉瑞韦（TVR）联合聚乙二醇干扰素-α（PEG-IFNα）和利巴韦林（RBV）在 HCV 基因 1 型（HCV-1）导致的晚期纤维化患者中的安全性和疗效。
1782 名 HCV-1 伴桥接纤维化或代偿性肝硬化的患者在全球 16 个国家前瞻性入组，并接受 12 周 TVR 联合 PEG-IFN/RBV 治疗，然后根据治疗后的病毒学应答和既往应答类型，单独接受 12 或 36 周 PEG-IFN 和 RBV（PR）治疗。
1587 名患者完成了 12 周的三联治疗和 4 周的 PR 维持治疗（53%为肝硬化，22%为 HCV-1a）。治疗 12 周时，初治患者、复发患者、部分应答患者和无应答患者的 HCV RNA 均不可检测的比例分别为 85%、88%、80%和 72%。总体而言，931 名患者（59%）发生 1-4 级贫血（3/4 级 31%），630 名患者（40%）减少 RBV 剂量，332 名患者（21%）接受了促红细胞生成素治疗，157 名患者（10%）接受了输血。年龄和女性是贫血的最强预测因素。64 名患者（4%）发生 3/4 级皮疹。因 AE 而停用 TVR 的患者有 193 名（12%）。7 名患者死亡（0.4%，均为肝硬化）。
在 HCV-1 导致的代偿性晚期纤维化患者中，TVR 三联疗法安全性、耐受性良好，治疗期间病毒学应答率高，AE 管理得当。
