索磷布韦/维帕他韦/伏西瑞韦治疗既往直接抗病毒药物治疗失败的慢性丙型肝炎患者的有效性和安全性

朱梦莹; 俞萍; 葛国洪; 马于琪; 傅熙玲; 常家宝

doi:10.12449/JCH241112

索磷布韦/维帕他韦/伏西瑞韦治疗既往直接抗病毒药物治疗失败的慢性丙型肝炎患者的有效性和安全性

DOI: 10.12449/JCH241112

1.
南京中医药大学附属南京医院（南京市第二医院）肝病科，南京 210003
2.
无锡市第五人民医院肝病科，江苏无锡 214011
3.
镇江市第三人民医院肝病科，江苏镇江 212021

伦理学声明：本研究于2023年3月21日经由南京市第二医院伦理委员会审批，批号：2023-LY-kt079。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：常家宝负责研究构思与设计；马于琪、俞萍、葛国洪负责数据采集和分析；朱梦莹撰写文稿；傅熙玲、常家宝负责审阅文稿及定稿。

详细信息

通信作者:
常家宝， chang_jiabao@126.com （ORCID： 0000-0003-3209-4868）

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出版历程
- 收稿日期: 2024-02-22
- 录用日期: 2024-04-16
- 出版日期: 2024-11-25

Efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients with previous direct-acting antiviral agent failure

1.
Department of Hepatology，Nanjing Second Hospital，Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine，Nanjing 210003，China
2.
Department of Hepatology，Wuxi Fifth People’s Hospital，Wuxi，Jiangsu 214011，China
3.
Department of Hepatology，The Third People’s Hospital of Zhenjiang，Zhenjiang，Jiangsu 212021，China

More Information

Corresponding author: CHANG Jiabao， chang_jiabao@126.com （ORCID： 0000-0003-3209-4868）

摘要

摘要: 目的评估真实世界中索磷布韦/维帕他韦/伏西瑞韦（SOF/VEL/VOX）用于既往接受直接抗病毒药物（DAA）治疗失败的慢性丙型肝炎患者的有效性和安全性。方法回顾性研究纳入2020年6月—2023年6月于南京市第二医院、无锡市第五人民医院和镇江市第三人民医院就诊的既往接受DAA抗病毒治疗失败并予以SOF/VEL/VOX（400 mg/100 mg/100 mg/片，1片/d）治疗12周的慢性丙型肝炎患者，观察治疗结束后12周持续病毒学应答（SVR12）情况，并评估生化学指标变化和不良反应发生情况，以评价药物的安全性。计量资料两组间比较采用配对t检验。结果共入组36例患者，非肝硬化27例，代偿期肝硬化9例，既往2次及以上DAA治疗失败4例。2例患者完成治疗后失访，余34例患者（94.4%）达到SVR12。入组的36例患者中，最常见的不良事件为瘙痒、恶心、疲劳和头痛；1例（2.78%）患者出现严重不良事件；未出现导致治疗药物停用或患者死亡的不良事件。结论 SOF/VEL/VOX用于既往接受DAA治疗失败的丙型肝炎患者的挽救性治疗有较高的SVR12，且耐受性和安全性良好。
- 丙型肝炎，慢性 /
- 挽救疗法 /
- 索磷布韦 /
- 维帕他韦 /
- 伏西瑞韦
Abstract: Objective To investigate the efficacy and safety of sofosbuvir/velpatasivr/voxilaprevir （SOF/VEL/VOX） in patients with HCV infection experiencing failure in previous direct-acting antiviral agent （DAA） therapy. Methods A retrospective analysis was performed for the chronic hepatitis C patients who experienced failure in previous DAA antiviral therapy and were treated with SOF/VEL/VOX （400 mg/100 mg/100 mg/tablet， 1 tablet/day） for 12 weeks in Nanjing Second Hospital， Wuxi Fifth People’s Hospital， and The Third People’s Hospital of Zhenjiang from June 2020 to June 2023. Sustained virological response at 12 weeks （SVR12） was observed after the end of treatment， and the changes in biochemical parameters and the incidence rate of adverse reactions were assessed to evaluate drug safety. The paired t-test was used for comparison of continuous data between two groups. Results A total of 36 patients were enrolled， among whom there were 27 non-liver cirrhosis patients and 9 patients with compensated liver cirrhosis， and 4 patients experienced failure in the previous two or more sessions of DAA therapy. Two patients were lost to follow-up after treatment， and the remaining 34 patients （34/36， 94.4%） achieved SVR12. Among the 36 patients enrolled， the most common adverse events were pruritus， nausea， fatigue， and headache， and one patient （2.78%） experienced serious adverse events； there were no adverse events that resulted in the discontinuation of therapeutic agents or the death of patients. Conclusion For chronic hepatitis C patients who experience failure in previous DAA therapy， SOF/VEL/VOX salvage therapy has a relatively high rate of SVR12， with good tolerability and safety.
- Hepatitis C， Chronic /
- Salvage Therapy /
- Sofosbuvir /
- Velpatasvir /
- Voxilaprevir

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图 1 研究入组流程图

注： ITT，意向性；PP，遵循研究方案。

Figure 1. Study flow chart

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表 1 患者基线特征和基因型分布

Table 1. Baseline characteristics and genotype distribution of patients

基线特征	数值
年龄（岁）	51.5±13.2
男［例（%）］	28（77.8）
既往DAA治疗失败次数［例（%）］
1	32（88.9）
≥2	4（11.1）
既往DAA治疗失败方案［例（%）］
EBR/GZR	2（5.6）
LDV/SOF	1（2.8）
SOF+CLP	3（8.3）
SOF/VEL	30（83.3）
DAA挽救治疗方案［例（%）］
SOF/VEL/VOX	31（86.1）
SOF/VEL/VOX+RBV	5（13.9）
糖尿病［例（%）］	3（8.3）
高血压［例（%）］	5（13.9）
肝癌［例（%）］	2（5.6）
酒精性肝病［例（%）］	1（2.8）
HCV RNA（log₁₀IU/mL）	5.7±1.8
HCV基因型［例（%）］
1b	2（5.6）
3b	23（63.9）
6n	3（8.3）
混合基因型	3（8.3）
未知基因型	5（13.9）
注：EBR/GZR，艾尔巴韦/格拉瑞韦；LDV/SOF，来迪派韦/索磷布韦；SOF+CLP，索磷布韦+可洛派韦。

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表 2 治疗前后生化指标变化

Table 2. Changes of biochemical indexes before and after treatment

指标	基线	治疗后12周	t值	P值
ALT（U/L）	63.21±30.33	26.64±7.62	2.86	<0.05
AST（U/L）	49.45±16.55	35.40±11.26	2.34	0.08
总胆红素（μmol/L）	13.72±5.68	18.24±6.27	-1.60	0.18
血小板计数（×10⁹/L）	166.75±46.69	189.42±28.69	-2.89	<0.05
血红蛋白（g/L）	101.52±6.86	103.48±8.02	-2.06	0.11
血肌酐（μmol/L）	78.88±28.35	81.52±26.18	-0.22	0.84
白蛋白（g/L）	33.65±2.89	34.12±1.83	-0.29	0.79

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表 3 SOF/VEL/VOX服药及随访期间的不良事件

Table 3. Adverse events during SOF/VEL/VOX treatment and follow-up

不良事件	例数（%）
任何不良事件	21（58.3）
严重不良事件	1（2.8）
死亡	0（0.0）
≥10%的不良事件
瘙痒	7（19.4）
恶心	5（13.9）
疲劳	4（11.1）
头痛	4（11.1）
3～4级不良事件	3（8.3）
因不良事件导致的治疗中断	0（0.0）

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