Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, United States.
Division of Gastroenterology and Hepatology, Department of Medicine, University of California at Davis, Davis, CA, United States.
J Hepatol. 2019 Sep;71(3):486-497. doi: 10.1016/j.jhep.2019.04.016. Epub 2019 May 13.
BACKGROUND & AIMS: A comprehensive analysis of changes in symptoms and functioning during and after direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection has not been conducted for patients treated in real-world clinical settings. Therefore, we evaluated patient-reported outcomes (PROs) in a diverse cohort of patients with HCV treated with commonly prescribed DAAs.
PROP UP is a US multicenter observational study of 1,601 patients with HCV treated with DAAs in 2016-2017. PRO data were collected at baseline (T1), early on-treatment (T2), late on-treatment (T3) and 3-months post-treatment (T4). PRO mean change scores were calculated from baseline and a minimally important change (MIC) threshold was set at 5%. Regression analyses investigated patient and treatment characteristics independently associated with PRO changes on-treatment and post-treatment.
Of 1,564 patients, 55% were male, 39% non-white, 47% had cirrhosis. Sofosbuvir/ledipasvir was prescribed to 63%, sofosbuvir/velpatasvir to 21%, grazoprevir/elbasvir to 11%, and paritaprevir/ombitasvir/ritonavir + dasabuvir to 5%. During DAA therapy, mean PRO scores improved slightly in the overall cohort, but did not reach the 5% MIC threshold. Between 21-53% of patients experienced >5% improved PROs while 23-36% experienced >5% worse symptoms. Of 1,410 patients with evaluable sustained virologic response (SVR) data, 95% achieved SVR. Among those with SVR, all mean PRO scores improved, with the 5% MIC threshold met for fatigue, sleep disturbance, and functioning well-being. Regression analyses identified subgroups, defined by age 35-55, baseline mental health issues and a higher number of health comorbidities as predictors of PRO improvements.
In real-world clinical practices, we observed heterogeneous patient experiences during and after DAA treatment. Symptom improvements were more pronounced in younger patients, those with baseline mental health issues and multiple comorbidities.
Patients who received direct-acting antiviral medications for hepatitis C at several liver centers in the US did not generally experience significant changes in baseline symptoms during treatment. We observed a full range of patient experiences with some patients experiencing substantial symptom improvements, yet others experiencing less improvements and some even experiencing a worsening of symptoms. The 1,346 patients who were cured of hepatitis C experienced improvements in fatigue, sleep disturbance, and functional well-being, and trends for improved pain and depression; whereas the 64 who were not cured experienced minimal improvements. Clinicaltrial.gov: NCT02601820.
对于在真实临床环境中接受治疗的慢性丙型肝炎病毒（HCV）感染患者，尚未对直接作用抗病毒（DAA）治疗期间和治疗后的症状和功能变化进行全面分析。因此，我们评估了在接受常用 DAA 治疗的 HCV 患者的多样化队列中患者报告的结局（PROs）。
PROP UP 是一项在美国进行的多中心观察性研究，纳入了 1601 名于 2016-2017 年接受 DAA 治疗的 HCV 患者。在基线（T1）、早期治疗（T2）、晚期治疗（T3）和治疗后 3 个月（T4）采集 PRO 数据。从基线计算 PRO 平均变化评分，并设定最小临床重要变化（MIC）阈值为 5%。回归分析调查了与治疗期间和治疗后 PRO 变化独立相关的患者和治疗特征。
在 1564 名患者中，55%为男性，39%为非白人，47%患有肝硬化。索非布韦/雷迪帕韦被处方给 63%的患者，索非布韦/维帕他韦给 21%，格卡瑞韦/哌仑他韦给 11%，泊沙康唑/奥比他韦/达沙布韦/利托那韦给 5%。在 DAA 治疗期间，整体队列的 PRO 评分略有改善，但未达到 5%的 MIC 阈值。21%-53%的患者经历了 >5%的 PRO 改善，而 23%-36%的患者经历了 >5%的症状恶化。在 1410 名可评估持续病毒学应答（SVR）数据的患者中，95%的患者达到了 SVR。在获得 SVR 的患者中，所有 PRO 评分均有所改善，疲劳、睡眠障碍和功能良好的评分达到了 5%的 MIC 阈值。回归分析确定了年龄在 35-55 岁之间、基线心理健康问题和更多健康合并症的亚组作为 PRO 改善的预测因素。
在真实的临床实践中，我们观察到 DAA 治疗期间和治疗后患者的体验存在异质性。年轻患者、基线心理健康问题和更多合并症的患者症状改善更为明显。
在美国几家肝脏中心接受直接作用抗病毒药物治疗的丙型肝炎患者在治疗期间并未普遍经历明显的基线症状变化。我们观察到患者的体验存在广泛的差异，一些患者的症状有显著改善，而其他患者的改善程度较小，还有一些患者的症状甚至恶化。1346 名被治愈的丙型肝炎患者经历了疲劳、睡眠障碍和功能良好的改善，以及疼痛和抑郁改善的趋势；而 64 名未被治愈的患者仅经历了轻微的改善。Clinicaltrial.gov：NCT02601820。
