索磷布韦/达拉他韦治疗慢性丙型肝炎患者疗效及安全性分析：一项真实世界研究

doi:10.3969/j.issn.1672-5069.2019.03.013

摘要/Abstract

摘要： 目的观察应用索磷布韦/达拉他韦联合或不联合利巴韦林治疗慢性丙型肝炎（CHC）和丙型肝炎肝硬化（LC）患者的疗效和安全性。方法 2016年5月~2017年5月收治的丙型肝炎LC患者129例和CHC患者311例,分别给予索磷布韦/达拉他韦联合利巴韦林或索磷布韦/达拉他韦治疗12周,停药后随访12周。观察停药后12周持续性病毒学应答（SVR12）、生化学应答、肝硬度测量（LSM）和治疗期间不良反应发生情况。结果治疗2周时,LC组血清TBIL、ALT 和AST 水平分别为（18.10±3.46） μmol/L、（32.48±9.97） IU/L和（31.99±6.65） IU/L,显著低于基线时水平【分别为（20.98±28.64） μmol/L、（97.76±106.43） IU/L和（72.47±80.81） IU/L,P<0.05】,CHC组分别为（20.15±3.48） μmol/L、（35.18±18.47） IU/L和（35.05±13.22） IU/L,显著低于基线时水平【分别为（24.07±18.12） μmol/L、（91.42±54.56） IU/L和（81.06±40.45） IU/L,P<0.05】;CHC组血清HCV RNA为（1.83±2.88） lg IU/ml,LC组为（1.67±2.34） lg IU/ml,显著低于基线时水平【分别为（6.12±1.19） lg IU/ml和（5.91±1.17）lg IU/ml,P<0.01】;CHC组LSM为（8.09±0.90）kPa,LC组为（13.32±1.47） kPa,显著低于基线时水平【分别为（11.81±3.33） kPa和（17.56±9.86） kPa,P<0.01】;两组不同基因型感染者SVR均在94%以上;多因素回归分析显示基线肝硬化或复治是不能获得SVR12的高危因素;主要不良反应为乏力和头痛。讨论应用索磷布韦/达拉他韦联合利巴韦林治疗丙型肝炎病毒感染患者可获得极高的SVR12和生化学应答率,显著改善肝纤维化程度,且具有良好的安全性。

关键词: 慢性丙型肝炎, 索磷布韦, 达拉他韦, 直接抗病毒药物, 治疗

Abstract: Objectiv To observe the efficacy and safety of sofosbuvir/daclatasvir in the treatment of patients with chronic hepatitis C （CHC） and hepatitis C cirrhosis （LC）. Methods 311 patients with CHC and 129 patients with LC were recruited in this real-world study in our hospital between May 2016 and May 2017,and they were treated with sofosbuvir/daclatasvir or combination of sofosbuvir/daclatasvir and ribavirin respectively,for 12 weeks. All patients were followed-up for 12 weeks at the end of discontinuation of the regimen. Sustained virological response at the end of 12 weeks（SVR12）,biochemical response,liver stiffness measurement and adverse reactions were observed. Results At the end of two week treatment,serum bilirubin,ALT and AST levels in patients with LC were（18.10±3.46） μmol/L,（32.48±9.97） IU/L and（31.99±6.65） IU/L,significantly lower than （20.98±28.64）μmol/L,（97.76±106.43） IU/L and （72.47±80.81） IU/L at baseline （P<0.05）; serum bilirubin, ALT and AST levels in patients with CHC were （20.15±3.48） μmol/L,（35.18±18.47） IU/L and AST （35.05±13.22） IU/L,significantly lower than （24.07±18.12） μmol/L,（91.42±54.56） IU/L and （81.06±40.45） IU/L at baseline （P<0.05）;serum HCV RNA load in patients with CHC was（1.83±2.88） lg IU/ml,in patients with LC was （1.67±2.34）lg IU/ml,both significantly lower than（6.12±1.19）lg IU/ml and （5.91±1.17） lg IU/ml at baseline （P<0.01）;LSM in patients with CHC was（8.09±0.90） kPa,and in patients with LC was（13.32±1.47） kPa,both significantly lower than （11.81±3.33） kPa and （17.56±9.86） kPa at baseline（P<0.01）;all patients no matter with any HCV genotype infection in both groups got 94% or over of SVR12;Logistic analysis showed that the baseline cirrhosis and relapse patients non-response to PR therapy were the independent risk factors for failed SVR12;the main adverse reactions were fatigue and headache. Conclusion The application of sofosbuvir/daclatasvir regimen in treatment of patients with CHC or hepatitis C cirrhosis might achieve a very high SVR12,biochemical response rate and improved liver fibrosis with a good safety.

Key words: Hepatitis C, Sofosbuvir, Daclatasvir, Direct acting antiviral agents, Treatment

刘立, 李俊义, 杜映荣, 刘春云, 李卫昆, 王辉, 李惠敏, 常丽仙, 祁燕伟. 索磷布韦/达拉他韦治疗慢性丙型肝炎患者疗效及安全性分析：一项真实世界研究[J]. 实用肝脏病杂志, 2019, 22(3): 361-364.

Liu Li，Li Junyi，Du Yingrong. Efficacy and safety of sofosbuvir/daclatasvir in the treatment of patients with chronic hepatitis C and hepatitis C cirrhosis:An real-world study[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(3): 361-364.

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