索非布韦对治疗慢性丙肝及缓解肝脏纤维化的临床研究

Clinical study on sofosbuvir in treatment of chronic hepatitis C and liver fibrosis

目的探讨索非布韦对丙肝患者临床应用的疗效、安全性以及对肝脏纤维化发生发展抑制作用的意义。方法选取2016-11~2017-09初诊于唐都医院普外科未合并肝硬化的慢性丙肝患者80例,采用随机数字法,每组40人分为对照组及观察组,两组间基线资料差异无统计学意义,具有可比性。对照组患者采用皮下注射聚乙二醇干扰素α-2a 180μg/周,口服利巴韦林1 000 mg/d;观察组采用口服索非布韦400 mg/d,口服利巴韦林1 000 mg/d;两组均连续治疗12周。同时选取合并肝硬化代偿期的慢性丙肝患者40例,均采用口服索非布韦400 mg/d,口服利巴韦林1 000 mg/d方案连续12周。于12周、24周时定量分析患者血清中HCV-RNA水平,检测患者病毒学应答情况及持续应答情况;同时统计服药期间患者出现的不良反应;比较血清中Ⅲ型前胶原(PCⅢ)和透明质酸(HA)水平,判断肝脏纤维化水平。结果 12周时对照组病毒学应答率为82.5%,对照组应答率为95.0%,观察组效果明显优于对照组(P<0.01);24周时复查血清HCV-RNA持续阴性率,对照组72.5%,观察组90.0%,观察组依旧优于对照组(P<0.01)。用药24周后,PCⅢ和HA显著下降(P<0.01)。结论索非布韦对慢性丙肝的疗效更佳;相比聚乙二醇干扰素联合利巴韦林,索非布韦发生不良反应明显较少,安全性更高;索非布韦能够有效缓解肝脏纤维化进展。

Objective To explore the curative efficacy,safety of sofosbuvir and its inhibitory effect on liver fibrosis in hepatitis C patients. Methods The chronic hepatitis C patients without liver cirrhosis were selected from November 2016 to September 2017 in the Department of General Surgery of Tangdu Hospital,and randomly divided into control group and observation group. The patients in control group were treated with subcutaneous injection of pegylated interferon alpha-2 a 180 g/week,and oral Leigh Bhave Lin 1 000 mg/d for 12 weeks. The patients in observation group were treated with oral sofosbuvir 400 mg/d and oral Leigh Leigh Bhave Lin 1 000 mg/d for 12 weeks. At the same time,40 chronic hepatitis C patients with decompensated cirrhosis patients were treated with oral sofosbuvir 400 mg/d and Leigh Bhave Lin 1 000 mg/d for 12 weeks. The level of HCV-RNA in serum of patients were analyzed at week 12 and 24 after treatment,the virologic response and sustained response were detected,the adverse reactions were observed during the medication,and the serum procollagen（ PC Ⅲ） and hyaluronic acid（ HA） level were measured to evaluate the level of liver fibrosis. Results There was no statistically significant difference in baseline data between the two groups. After treatment for 12 weeks,the rate of virological response was 82. 5% in control group and 95. 0% in observation group. The curative rate was higher in observation group than in control group（ P〈0. 01）. At week 24,the continuous negative rate of serum HCV-RNA was 72. 5% in control group and 90. 0% in observation group（ P〈0. 01）. At week 24,PCⅢ level and HA level significantly decreased（ P〈0. 01）. Conclusion Compared with pegylated interferon alpha-2 a,sofosbuvir may have better efficacy for chronic hepatitis C with less adverse effect and higher safety. Sofosbuvir can effectively inhibit the progression of liver fibrosis.