摘要
目的评估真实世界中不同直接抗病毒药物(DAAs)方案治疗基因1b型慢性丙型肝炎病毒(hepatitis C virus,HCV)感染患者的疗效及安全性。方法回顾性研究2017年8月至2019年11月于解放军总医院第五医学中心就诊的226例基因1b型慢性HCV感染患者。患者均接受我国已获批上市的DAAs治疗,其中73例采用索磷布韦/维帕他韦±利巴韦林方案,21例采用索磷布韦/莱迪派韦±利巴韦林方案,5例采用索磷布韦联合达拉他韦±利巴韦林方案,11例采用格卡瑞韦/哌仑他韦方案,8例采用艾尔巴韦/格拉瑞韦方案,66例采用奥比帕利联合达塞布韦方案,29例采用阿舒瑞韦联合达拉他韦方案,13例采用达诺瑞韦/利托那韦联合PR方案。记录患者NS5A(L31,Y93)基因耐药相关突变检测结果,以及病毒学、生化学检测资料。通过分析患者病毒学应答情况、生化学应答情况、天冬氨酸氨基转移酶-血小板比率指数(APRI)及不良事件发生情况,评估DAAs的疗效及安全性。结果83例完成耐药相关替代突变(RASs)检测的患者耐药突变率为16.9%。226例患者治疗结束后随访12周持续病毒学应答(SVR12)率为99.6%,丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBil)复常率分别为91.2%、93.4%、94.7%,各方案患者SVR12率,ALT、AST、TBil复常率均无显著差异(P>0.05)。226例患者治疗前APRI为0.54(0.30,1.10),治疗结束时为0.32(0.22,0.61),较基线显著下降(P<0.001)。治疗结束时226例患者不良事件发生率为27.4%,严重不良事件发生率为1.8%,各DAAs方案不良事件发生率无显著差异(P>0.05),但丙型肝炎肝硬化患者不良事件发生率显著高于无肝硬化的慢性丙型肝炎患者。结论DAAs方案治疗基因1b型HCV感染均可实现极高的持续病毒学应答(SVR)率并显著改善患者肝功能,且严重不良事件发生率较低,对提高患者预后有重要意义,但特殊人群的安全性管理仍需重视。
Objective To evaluate the clinical efficiency and safety of different direct-acting antiviral agents(DAAs)against genotype 1 b chronic hepatitis C virus(HCV)infection in the real-world.Methods Totally 226 patients with genotype 1 b chronic HCV infection treated in the Fifth Medical Center of Chinese PLA General Hospital between August 2017 and November 2019 were studied retrospectively.All these patients were treated with DAAs,which had been approved for the market in China.Among them,73 cases were treated with sofosbuvir/velpatasvir±ribavirin,21 cases with sofosbuvir/ledipasvir±ribavirin,5 cases with sofosbuvir+daclatasvir±ribavirin,11 cases with glecaprevir/pibrentasvir,29 cases with asunaprevir+daclatasvir,8 cases with elbasvir+grazoprevir,66 cases with ombitasvir/paritaorevir/ritonavir+dasabuvir,and 13 cases with danoprevir/ritonavir+PR.The results of NS5 A(L31,Y93)resistance associated substitution test and the virological,biochemical data were collected.The efficacy and safety of DAAs were evaluated based on the patients′virological response,biochemical response,aspartate aminotransferase-to-platelet ratio index(APRI)and adverse events.Results The rate of resistance-associated substitution(RAS)was 16.9%among 83 cases.The rate of sustained virological response(SVR12)was 99.6%,while the rates of renormalization of ALT,AST,and TBil were 91.2%,93.4%and 94.7%in226 patients,respectively.There was no significant difference in the SVR12 rate or the renormalization rate of ALT,AST and TBil between different regimens(P>0.05).The APRI index of 226 patients was 0.54(0.30,1.10)at baseline and0.32(0.22,0.61)at the endpoint of treatment.Compared with the baseline,APRI index at the endpoint decreased significantly(P<0.001).At the end of treatment,the incidence of adverse events was 27.4%in 226 patients,while that of serious adverse events was 1.8%.The incidence of adverse events was not significantly different between DAAs schemes(P>0.05),but the incidence of adverse events in patients with liver cirrhosis was significantly higher than that in patients without cirrhosis.Conclusion DAAs treatment of patients with genotype 1 b HCV infection can achieve a high SVR rate and significantly improve the liver function of patients,and the incidence of serious adverse events is low,but the safety management of special populations still deserves attention.
作者
王奕璇
王建军
闫涛
贾晓艳
程勇前
靳雪源
刘红虹
卿松
张晶
付渊洁
刘桃园
何芸娴
李娟
赵平
WANG Yi⁃xuan;WANG Jian⁃jun;YAN Tao;JIA Xiao⁃yan;CHENG Yong⁃qian;JIN Xue⁃yuan;LIU Hong⁃hong;QING Song;ZHANG Jing;FU Yuan⁃jie;LIU Tao⁃yuan;HE Yun⁃xian;LI Juan;ZHAO Ping(Hebei North University,Zhangjiakou,Hebei 075000,China;International Center for Diagnosis and Treatment of Liver Diseases,the Fifth Medical Center,General Hospital of PLA,Beijing 100039,China)
出处
《军事医学》
CAS
北大核心
2020年第7期534-540,共7页
Military Medical Sciences
基金
首都卫生科研发展专项(2014-2-5033)
十三五国家科技重大专项(2017ZX10202202-003-003)
关键词
慢性丙型肝炎
直接抗病毒药物
持续病毒学应答
不良事件
chronic hepatitis C
direct antiviral agents
sustained virological response
adverse events
