达拉他韦联合索磷布韦治疗慢性丙型肝炎的真实世界研究  

Real world study of daclatavir combined with sofosbuvir treatment in chronic hepatitis C

作　　者：张春[1] 童陆媛 童照威[1] 王伟洪[1] Zhang Chun;Tong Luyuan;Tong Zhaowei;Wang Weihong(Department of Infectious Diseases,Huzhou Central Hospital,Huzhou City,Zhejiang Province 313000,China)

机构地区：[1]湖州市中心医院感染科,浙江省313000

出　　处：《中华传染病杂志》2019年第12期742-747,共6页Chinese Journal of Infectious Diseases

基　　金：浙江省自然科学基金(LY17H100002)。

摘　　要：目的探讨达拉他韦联合索磷布韦治疗慢性丙型肝炎(chronic hepatitis C,CHC)患者真实世界的疗效和安全性。方法回顾性分析2018年2月至6月在湖州市中心医院接受达拉他韦联合索磷布韦治疗的56例CHC患者,均接受达拉他韦(60 mg/d)联合索磷布韦(400 mg/d)治疗12周,随访24周。分析患者治疗后的病毒学应答以及抗病毒治疗对肝纤维化的影响,采用Sanger法检测非结构蛋白5A(non-structural protein 5A,NS5A)区域突变序列,观察抗病毒治疗的安全性以及不良事件的发生情况。数据采用t检验、Mann-Whitney U检验和卡方检验进行分析。结果达拉他韦联合索磷布韦治疗8周时,所有完成疗程的53例患者的丙型肝炎病毒(hepatitis C virus,HCV)RNA均转阴,12周时持续病毒学应答率为98.1%(52/53)。不同性别,不同球蛋白、胰岛素、三酰甘油、血红蛋白水平的患者HCV RNA转阴速度差异均有统计学意义(χ2=4.47,t=2.51,U=1.98、2.32,t=2.03;均P<0.05)。治疗结束后12周,血清Ⅲ型前胶原、血清Ⅳ型胶原、肝硬度值、天冬氨酸转氨酶与血小板比值指数(aspartate aminotransferase-to-platelet ratio index,APRI)评分、基于4个因素的纤维化指数(fibrosis index based on the four factors,FIB-4)评分有所改善(U=2.03、2.15、2.19、2.12、2.26,均P<0.05)。治疗结束后24周,这一趋势更明显(U=2.09、2.28、2.24、2.33、2.46,均P<0.05)。8例出现Y93H或L31M耐药相关替代突变,治疗2周时8例变异者中HCV RNA转阴2例,无变异者占44.4%(20/45),差异无统计学意义(χ2=1.11,P>0.05)。患者治疗过程中出现头晕,疲劳,恶心、呕吐,心悸,失眠,嗜睡,性功能增强等不良反应。结论达拉他韦联合索磷布韦治疗CHC患者的病毒学应答率高,安全性好,HCV清除后肝纤维化得到改善。Objective To investigate the efficacy and safety of daclatavir combined with sofosbuvir treatment in chronic hepatitis C(CHC)in the real world.Methods A total of 56 CHC patients administrated with daclatavir(60 mg/d)combined with sofosbuvir(400 mg/d)in Huzhou Central Hospital from February to June in 2018 were enrolled.All patients were administrated with daclatavir combined with sofosbuvir for 12 weeks and followed up for 24 weeks.The virological response and the effect of antiviral therapy on hepatic fibrosis were analyzed.Non-structural protein 5A(NS5A)region mutation sequence was detected by Sanger method.Safety and the adverse events were observed.The t test,chi-square test and Mann-Whitney U test were used to analyze the data.Results Hepatitis C virus(HCV)RNA of all patients treated with daclatavir and sofosbuvir was undectable after eight-week treatment.Sustained virological response at 12 weeks post-treatment(SVR12)was 98.1%(52/53).Gender,globulin,insulin,triglyceride and hemoglobin were correlated with virus clearance(χ2=4.47,t=2.51,U=1.98,U=2.32 and t=2.03,respectively,all P<0.05).At 12 weeks of the end of the treatment,serum procollagen typeⅢ,collagen typeⅣ,liver stiffness measurement(LSM)value,aspartate aminotransferase-to-platelet ratio Index(APRI)score and fibrosis index based on the four factors(FIB-4)score were all improved(U=2.03,2.15,2.19,2.12 and 2.26,respectively,all P<0.05).At 24 weeks of the end of treatment,these indexes showed clear improvement(U=2.09,2.28,2.24,2.33 and 2.46,respectively,all P<0.05).Eight patients had Y93H or L31M resistance-related substitution mutations.Two out of eight patients with variants had negative coversion of HCV RNA and 44.4%(20/45)showed no variants after two weeks of treatment.There was no significant difference(χ2=1.11,P>0.05).During the treatment,patients developed dizziness,fatigue,nausea and vomiting,panic,insomnia,sleepiness and sexual function enhancement.Conclusion Daclatavir in combination with sophobuvir shows high virological response and good

关 键 词：肝炎 丙型 慢性 达拉他韦 索磷布韦 真实世界研究 

分 类 号：R51[医药卫生—内科学]