Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease
Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease
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DOI：
10.1093/cid/civ897
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发表时间：
2016-02-15
影响因子：
11.8
通讯作者：
Kottilil, Shyamasundaran
中科院分区：
文献类型：
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作者：
Kattakuzhy, Sarah;Wilson, Eleanor;Kottilil, Shyamasundaran
背景。使用联合直接作用抗病毒药物 (DAA) 治疗基因 1 型丙型肝炎病毒 (HCV) 感染 8-24 周可实现高持续病毒学应答 (SVR) 率。我们之前证明，在雷迪帕韦和索磷布韦 (LDV/SOF) 中添加第三种 DAA 可以导致无肝硬化患者的高 SVR 率。在这项研究中，我们调查了类似的治疗方案是否会在晚期肝纤维化患者中产生相同的治愈率。方法。美国国立卫生研究院临床研究中心和相关医疗中心招募了 50 名患者。这里报告了 2014 年 4 月至 2015 年 6 月的入组和随访数据。符合资格的参与者年龄>= 18岁，患有慢性HCV基因1型感染（血清HCV RNA>= 2000 IU/mL），并且患有3-4期肝纤维化。使用逆转录聚合酶链式反应测定法测量 HCV RNA。结果。在接受 LDV、SOF 和 NS3/4A 蛋白酶抑制剂 GS-9451 治疗 6 周的患者中，76%（50 例中的 38 例；95% 置信区间，60%-85%）在治疗结束后 12 周实现了 SVR。初次接受治疗的患者（72%，25 人中的 18 人）和有治疗经验的患者（80%；25 人中的 20 人）之间的治疗效果没有统计学上的显着差异（P=.51）。总体而言，11 名患者 (22%) 出现病毒学复发，1 名患者 (2%) 在治疗后 4 周失访。没有与该方案相关的严重不良事件、停药或死亡。结论。在 LDV/SOF 中添加第三个 DAA 可能会导致中等的 SVR 率，低于在无肝硬化患者中观察到的结果。显着的肝纤维化仍然是短期 DAA 治疗实现 SVR 的障碍。
Background. Treatment of genotype 1 hepatitis C virus (HCV) infection with combination directly acting antivirals (DAA) for 8-24 weeks is associated with high rates of sustained virologic response (SVR). We previously demonstrated that adding a third DAA to ledipasvir and sofosbuvir (LDV/SOF) can result in high SVR rates in patients without cirrhosis. In this study, we investigated whether a similar regimen would yield equivalent rates of cure in patients with advanced liver fibrosis.Methods. Fifty patients were enrolled at the Clinical Research Center of the National Institutes of Health and associated healthcare centers. Enrollment and follow-up data from April 2014 to June 2015 are reported here. Eligible participants were aged >= 18 years, had chronic HCV genotype 1 infection (serum HCV RNA >= 2000 IU/mL), and stage 3-4 liver fibrosis. HCV RNA was measured using a reverse-transcription polymerase chain reaction assay.Results. Of patients treated with LDV, SOF, and the NS3/4A protease inhibitor GS-9451 for 6 weeks, 76% (38 of 50; 95% confidence interval, 60%-85%) had SVR achieved 12 weeks after the end of treatment. There was no statistically significant difference in treatment efficacy between treatment-naive patients (72%, 18 of 25) and those with treatment experience (80%; 20 of 25) (P=.51). Overall, 11 patients (22%) experienced virologic relapse, and 1 (2%) was lost to follow-up at 4 weeks after treatment. No serious adverse events, discontinuations, or deaths were associated with this regimen.Conclusions. Adding a third DAA to LDV/SOF may result in a moderate SVR rate, lower than that observed in patients without cirrhosis. Significant liver fibrosis remains an impediment to achieving SVR with short-duration DAA therapy.