6 周 Ledipasvir 联合 Sofosbuvir 固定剂量复方制剂治疗急性丙型肝炎病毒基因 1 型单感染患者（HepNet Acute HCV IV）：一项开放标签、单臂、2 期研究。
Ledipasvir plus sofosbuvir fixed-dose combination for 6 weeks in patients with acute hepatitis C virus genotype 1 monoinfection (HepNet Acute HCV IV): an open-label, single-arm, phase 2 study.
机构信息
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; HepNet Study-House, German Liver Foundation, Hannover, Germany.
Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany.
出版信息
Lancet Infect Dis. 2017 Feb;17(2):215-222. doi: 10.1016/S1473-3099(16)30408-X. Epub 2016 Oct 28.
BACKGROUND
Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa is highly effective, but can be associated with frequent side-effects. We investigated the safety and efficacy of an interferon-free regimen for treatment of acute HCV infection.
METHODS
In this prospective, open-label, multicentre, single-arm pilot study, we enrolled adults (≥18 years) with acute HCV genotype 1 monoinfection from ten centres in Germany. Patients were given ledipasvir (90 mg) plus sofosbuvir (400 mg) as a fixed-dose combination tablet once daily for 6 weeks. The primary efficacy outcome was the proportion of patients with sustained virological response (defined as undetectable HCV RNA 12 weeks after the end of treatment; other primary outcomes were safety and tolerability of ledipasvir plus sofosbuvir. The primary analysis population consisted of all patients who received at least one dose of study drug. Safety was also assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, number NCT02309918.
FINDINGS
Between Nov 19, 2014, and Nov 10, 2015, we enrolled 20 patients. Median HCV RNA viral load at baseline was 4·04 log IU/mL (1·71-7·20); 11 patients were infected with HCV genotype 1a and nine patients with genotype 1b. All patients achieved a sustained virological response 12 weeks after the end of treatment (20 [100%] of 20 patients). Treatment was well tolerated; there were no drug-related serious adverse events. Up to 12 weeks after treatment, 22 possible or probable drug-related adverse events were reported. There was one serious adverse event, which was judged unrelated to the study drug; one patient was admitted to hospital for surgery of a ruptured cruciate ligament.
INTERPRETATION
Treatment for 6 weeks with ledipasvir plus sofosbuvir was well tolerated and highly effective in patients with acute HCV genotype 1 monoinfection. Short-duration treatment of acute hepatitis C might prevent the spread of HCV in high-risk populations.
FUNDING
Gilead Sciences, HepNet Study-House/German Liver Foundation, and German Centre for Infection Research (DZIF).
背景
早期使用干扰素 alfa 治疗急性丙型肝炎病毒 (HCV) 感染非常有效，但可能会出现频繁的副作用。我们研究了无干扰素方案治疗急性 HCV 感染的安全性和疗效。
方法
在这项前瞻性、开放性、多中心、单臂试验中，我们从德国的 10 个中心招募了成人（≥18 岁）急性 HCV 基因 1 型单感染患者。患者每日口服一次固定剂量联合片剂（90mg 雷迪帕韦和 400mg 索磷布韦），持续 6 周。主要疗效终点是持续病毒学应答患者的比例（定义为治疗结束后 12 周时 HCV RNA 不可检测；其他主要终点是雷迪帕韦加索磷布韦的安全性和耐受性。主要分析人群为接受至少一剂研究药物的所有患者。在接受至少一剂研究药物的所有患者中也评估了安全性。该试验在 ClinicalTrials.gov 注册，编号为 NCT02309918。
结果
在 2014 年 11 月 19 日至 2015 年 11 月 10 日期间，我们共招募了 20 例患者。基线时 HCV RNA 病毒载量中位数为 4.04 log IU/mL（1.71-7.20）；11 例患者感染 HCV 基因 1a，9 例患者感染基因 1b。所有患者在治疗结束后 12 周时均达到持续病毒学应答（20 例[100%]中的 20 例）。治疗耐受性良好；无药物相关严重不良事件。在治疗结束后 12 周内，报告了 22 例可能或可能与药物相关的不良事件。有 1 例严重不良事件，被判断与研究药物无关；1 例患者因十字韧带破裂接受了医院手术。
结论
雷迪帕韦加索磷布韦治疗 6 周在急性 HCV 基因 1 型单感染患者中耐受性良好且疗效显著。急性丙型肝炎的短疗程治疗可能会阻止 HCV 在高危人群中的传播。
资助
吉利德科学公司、HepNet 研究-德国肝脏基金会和德国感染研究中心（DZIF）。
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