索非布韦联合达卡他韦治疗慢性丙型肝炎:真实世界临床研究

doi:10.3969/j.issn.1672-5069.2020.01.010

摘要/Abstract

摘要： 目的评价直接抗病毒药物(DAAs)索非布韦(SOF)联用达卡他韦(DCV)治疗慢性丙型肝炎(CHC)患者真实世界研究(RWS)的疗效和安全性。方法 2015年9月～2017年9月广州市第八人民医院肝病门诊诊治的CHC患者43例,接受SOF联用DCV治疗12 w,随访12～48 w。结果 43例均完成12 w疗程及停药12 w观察,23例完成停药24 w观察、18例完成停药48 w观察;在治疗2 w、4周 w和12 w时,血清HCV RNA转阴率分别77.0％(33/43)、93.0％(40/43)和100.0％(43/43);在停药12 w时,持续病毒学应答率(SVR12)为100.0%,23例停药24周HCV RNA仍阴性,18例停药48周HCV RNA仍阴性;在治疗2 w、4 w和12 w及停药12 w时,血清ALT水平分别为(28.3±14.4)U /L、(25.4±12.9)U /L、(22.5±9.4)U /L和(21.8±8.6) U /L,显著低于治疗前水平,血清AST水平分别为(25.4±10.4)U /L、(24.7±9.6)U /L、(22.8±7.7)U /L和(22.3±6.5)U /L,也显著低于治疗前水平; 在停药12 w时,血生化学应答率为100.0%,23例停药24 w、18例停药48 w时,肝功能仍持续正常,8例基线估算的肾小球滤过率(eGFR)小于90 ml·min^-1·1.73 m²,治疗期间部分有不同程度的下降(eGFR最低降至60.76 ml·min^-1·1.73 m²),停药后恢复至治疗前水平,未因eGFR下降而需调整用药或停药情况;用药期间发生失眠3例、恶心2例、乏力1例、头痛1例、脱发1例,均发生于治疗的早期,未特殊处理,均自行缓解,无严重不良事件发生。结论采用SOF联合DCV治疗CHC患者可获得极高的SVR12和生化学应答率,且安全性良好。长期疗效仍需观察。

关键词: 慢性丙型肝炎, 索非布韦, 达卡他韦, 真实世界研究, 疗效

Abstract: Objective We conducts a real-world study to investigate the efficacy of combination of sofebuvir (SOF) and daclatasvir (DCV) in the treatment of patients with chronic hepatitis C (CHC). Methods A total of 43 patients with CHC were recruited in this study between September 2015 and September 2017, and all patients were treated with combination of SOF and DCV for 12 weeks. The patients were followed-up for 12 to 48 weeks. Results All the 43 patients completed the 12 week regimen and 12 week followed-up. 23 out of the 43 patients completed 24 week and 18 of them completed 48 week treatment-free followed-up. Serum HCV RNA loss at week 2, 4 and 12 were 77.0% (33/43), 93.0% (40/43), and 100.0% (43/43), respectively, and the SVR12 was 100%; serum HCV RNA kept negative in 23 patients 24 weeks, and in 18 patients 48 weeks after discontinuation of the treatment; serum ALT were (28.3±14.4)U /L, (25.4±12.9)U /L,(22.5±9.4)U /L and (21.8±8.6) U /L at the end of week 2, 4, 12 treatment and at the end of 12 week followed-up, respectively, all significantly lower than(66.0±46.1)U /L at presentation (P <0.01) and serum AST levels were(25.4±10.4)U /L, (24.7±9.6)U /L,(22.8±7.7)U /L and (22.3±6.5)U /L, respectively, also all significantly lower than (51.1±31.7)U /L before treatment (P <0.01); at baseline, estimated glomerular filtration rate (eGFR) was less than 90 ml·min^-1·1.73 m²in 8 patients, a certain declines to 60.76 ml·min^-1·1.73 m² were observed during the anti-viral treatment and all returned to pre-treatment levels after withdrawal of the treatment; there was no dose adjustment during the regimen; the common side effects were insomnia (n=3), nausea(n=2),fatigue(n=1), headache(n=1) and alopecia(n=1), and all the phenomena occurred in the early stage of the treatment and relieved without special treatment. Conclusion The application of combination SOF and DCV in the treatment of patients with CHC might get a short-term satisfactory efficacy, which needs long-term observation.

Key words: Hepatitis C, Sofosbuvi, Daclatasvir, Real-world study, Efficacy

张健珍, 曾春燕, 张春兰, 许敏, 李剑萍, 李慧慧, 关玉娟. 索非布韦联合达卡他韦治疗慢性丙型肝炎:真实世界临床研究[J]. 实用肝脏病杂志, 2020, 23(1): 30-33.

Zhang Jianzhen, Zeng Chunyan, Zhang Chunlan, et al. A real-world study: Efficacy of combination of sofebuvir and daclatasvir in the treatment of patients with chronic hepatitis C[J]. Journal of Practical Hepatology, 2020, 23(1): 30-33.

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