索磷布韦/维帕他韦/伏西瑞韦治疗DAAs经治失败慢性丙型肝炎患者的疗效及安全性分析  

Analysis of the efficacy and safety profile of sofosbuvir/velpatasvir/voxilaprevir in the treatment of patients with chronic hepatitis C with failed DAAs therapy

作　　者：郭艳 赵颂涛 朱研 杨程 李剑萍 张丽华 杨昌明 熊华刚 张冬 田广俊[5] 高碧华[6] 郭莉 夏杰 Guo Yan;Zhao Songtao;Zhu Yan;Yang Cheng;Li Jianping;Zhang Lihua;Yang Changming;Xiong Huagang;Zhang Dong;Tian Guangjun;Gao Bihua;Guo Li;Xia Jie(Department of Infectious Diseases,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing 400038,China;Department of Liver Diseases,Guangzhou Eighth People's Hospital,Guangzhou Medical University,Guangzhou 510440,China;Department Three of Infectious Diseases(Liver Diseases),Dongguan Ninth People's Hospital,Dongguan 523016,China;Department of Liver Diseases,Guiyang Public Health Clinical Center,Guiyang 550004,China;Department of Liver Diseases,Guangdong Provincial Hospital of Chinese Medicine,Zhuhai 519015,China;Department of Infectious Diseases,Beihai People's Hospital of Guangxi Zhuang Autonomous Region,Beihai 536000,China)

机构地区：[1]中国人民解放军陆军军医大学第一附属医院感染病科,重庆400038 [2]广州医科大学附属市八医院肝病科,广州510440 [3]东莞市第九人民医院感染三科(肝病科),东莞523016 [4]贵阳市公共卫生救治中心肝病科,贵阳550004 [5]广东省中医院珠海医院肝病科,珠海519015 [6]广西壮族自治区北海市人民医院感染性疾病科,北海536000

出　　处：《中华肝脏病杂志》2024年第S2期25-30,共6页Chinese Journal of Hepatology

摘　　要：目的探讨索磷布韦/维帕他韦/伏西瑞韦±利巴韦林(SOF/VEL/VOX±RBV)对直接抗病毒药物(DAAs)经治失败的慢性丙型肝炎患者进行挽救治疗的疗效及安全性。方法将2022年1月至2023年12月就诊于重庆、广东、贵州、广西等5家医院的DAAs±RBV治疗失败的慢性丙型肝炎患者纳入该回顾性研究。所有患者既往均接受过一个或多个疗程的DAAs±RBV治疗,随访过程中出现病毒学反弹,采用SOF/VEL/VOX±RBV进行一个疗程的挽救治疗。分析挽救治疗前、治疗后及停药12周的病毒学、生物化学指标,并记录治疗期间药物不良事件。组间数据比较采用t检验或非参数检验。结果共26例DAAs±RBV经治失败的慢性丙型肝炎患者纳入该研究,年龄为(52.9±9.6)岁;21例(80.8%)为男性,16例(61.5%)患者有吸毒史,2例(7.7%)合并人类免疫缺陷病毒感染,14例(53.8%)合并肝硬化。21例(80.8%)患者既往DAAs方案包含SOF/VEL。挽救治疗基线丙型肝炎病毒RNA载量为(5.8±1.6)log 10 IU/ml,16例患者(61.5%)为基因3型。所有患者均完成了为期12周的SOF/VEL/VOX±RBV挽救治疗,在治疗结束时均获得病毒学应答(SVR),完成治疗结束后12周随访的22例患者均获得SVR12,包括基因3型及合并肝硬化患者。治疗结束后丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)复常率分别为94.1%及93.8%,ALT、AST、FIB-4指数、APRI评分均较治疗前明显下降(Z=-3.980、-3.875、-3.461、-3.582,P值均<0.05),aMAP评分较前有所降低;肝癌高风险组患者比例下降(治疗前52.6%与治疗后33.3%),更多患者转为中低风险。治疗期间2例(7.7%)患者出现恶心、腹泻,1例(3.8%)出现头痛,1例(3.8%)出现乏力,均能耐受,未发生严重不良事件、死亡或因不良反应中断治疗。结论SOF/VEL/VOX作为DAAs经治失败慢性丙型肝炎患者的挽救治疗方案安全且有效,尤其是感染基因3型及合并肝硬化的难治人群可从中获益。Objective To explore the efficacy and safety profile of sofosbuvir/velpatasvir/voxilaprevir±ribavirin(SOF/VEL/VOX±RBV)for salvage treatment of chronic hepatitis C patients who have failed direct-acting antivirals(DAAs).Methods Patients with chronic hepatitis C who failed DAAs±RBV treatment and were treated in five hospitals in Chongqing,Guangdong,Guizhou,and Guangxi from January 2022 to December 2023 were included in this retrospective study.One or more courses of DAAs±RBV therapy were evaluated for all patients who had been previously treated.Virological rebound occurrence was observed during the follow-up.SOF/VEL/VOX±RBV was used for one course of salvage treatment.Virological and biochemical indicators were analyzed before salvage therapy,post-treatment,and drug discontinuation at 12 weeks.Adverse drug events were recorded during treatment.Data between groups were compared using t-tests or non-parametric tests.Results A total of 26 cases of chronic hepatitis C who had failed DAAs±RBV were included in this study,with an age of(52.9±9.6)years.Twenty-one cases(80.8%)were male,sixteen(61.5%)had a history of drug abuse,two(7.7%)had combined human immunodeficiency virus infection,and fourteen(53.8%)had combined cirrhosis.The previous DAA regimen of 21 cases(80.8%)included SOF/VEL.The baseline HCV RNA load of salvage treatment was(5.8±1.6)log10 IU/ml,and 16 cases(61.5%)were genotype 3.All patients completed the 12-week SOF/VEL/VOX±RBV salvage treatment and achieved sustained virological response(SVR)at the end of treatment.All 22 cases were followed up for 12 weeks following treatment completion and attained SVR12,including patients with genotype 3 and cirrhosis.Alanine aminotransferase(ALT)and aspartate aminotransferase(AST)had normalized return rates of 94.1%and 93.8%,respectively,following therapy.ALT,AST,FIB-4 index,APRI,and aPMAP scores were significantly lower than those before treatment(Z=−3.980,−3.875,−3.461,−3.582,P<0.05).The proportion of patients in the high-risk group of liver cancer drop

关 键 词：丙型肝炎 治疗 难治型 索磷布韦 维帕他韦 伏西瑞韦 

分 类 号：R51[医药卫生—内科学]