直接抗病毒药物治疗肾移植供者来源性HCV感染的疗效分析  

Therapeutic effect of direct antiviral drugs on donor-derived hepatitis C infection after kidney transplantation

作　　者：陈任杰 昌盛[1] 陈松[1] 刘斌[1] 宫念樵[1] 陈刚[1] 蒋继贫[1] 陈知水[1] 张伟杰[1] Chen RenJie;Chang Sheng;Chen Song;Liu Bin;Gong Nianqiao;Chen Gang;Jiang Jipin;Chen Zhishui;Zhang Weijie(Institute of Organ Transplantation,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Key Laboratory of Organ Transplantation,Ministry of Education,NHC Key Laboratory of Organ Transplantation,Key Laboratory of Organ Transplantation,Chinese Academy of Medical Sciences,Wuhan 430030,Hu Bei,China.)

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所,器官移植教育部重点实验室,国家卫生健康委员会器官移植重点实验室,中国医学科学院器官移植重点实验室,湖北武汉430030

出　　处：《实用器官移植电子杂志》2024年第3期220-224,共5页Practical Journal of Organ Transplantation(Electronic Version)

基　　金：湖北省重点研发计划(2022BCA015)。

摘　　要：目的评估直接抗病毒药物(direct antiviral drugs,DAAs)治疗接受丙型肝炎病毒(hepatitis C virus,HCV)阳性供肾的HCV阴性肾移植受者的安全性及有效性。方法共纳入2018-2023年期间华中科技大学同济医学院附属同济医院器官移植研究所12例患者,其中10例于移植当天立即启动预防性应用DAAs方案,2例于移植后出现肝功能异常及检测出HCV RNA(+)后再予以抗病毒治疗。所有患者均应用12周索非布韦(sofosbuvir,SOF)/维帕他韦(velpatasvir,VEL)口服抗病毒药,并定期复查转氨酶、血肌酐、eGFR、药物浓度及病毒载量等来评估DAAs的疗效和安全性。结果10例预防性用药患者在完成SOF/VEL方案后出现1例治疗失败,检测其基因亚型为3b,其余9例均于停药后12周获得持续性病毒学应答(sustained virological response,SVR12)。初治失败患者在连续两次更换抗病毒方案后最终通过联合利巴韦林(ribavirin,RIB)的方案也实现了SVR12。2例治疗性患者术后1个月时检测到肝功能异常及较高水平病毒载量,立即启动DAAs治疗,在接受治疗后转氨酶水平均能迅速恢复正常并实现SVR12。初治失败患者在使用含利巴韦林抗病毒方案时出现了持续性胆红素升高,所有患者随访期间血肌酐、药物浓度水平均维持稳定。结论HCV阴性受者接受HCV阳性供肾在肾移植术后预防性或治疗性使用DAAs是安全有效的,针对HCV 3b亚型的泛基因型抗病毒方案可能出现治疗失败,初治失败后可选择含利巴韦林的联合抗病毒方案。Objective To assess the safety and efficacy of direct antiviral drugs(DAAs)in hepatitis C virus(HCV)negative recipients undergoing kidney transplantation from HCV IgG(+)/HCV infected renal allografts.Methods A total number of 12 patients were enrolled in the Institute of Organ Transplantation,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from 2018 to 2023,including 10 patients who were preemptively started DAAs regimen immediately after transplantation,and 2 patients who were therapeutically given DAAs regimen after abnormal liver function and detectable viral load.All patients had 12-week oral antiviral regimen of sofosbuvir/velpatasvir(SOF/VEL).Blood transaminase,serum creatinine,eGFR,drug concentration and HCV viral load were regularly reviewed to evaluate the efficacy and safety of DAAs.Results One case of treatment failure occurred after the completion of SOF/VEL therapy in 10 preemptively-treated patients,and the genotype was detected as 3b.The other 9 recipients achieved sustained virological response(SVR)12 weeks after the end of SOF/VEL treatment.After altering the antiviral regimen twice in succession,the patients who failed in the initial treatment ultimately achieved SVR12 with a DAAs combination containing ribavirin(RIB).Abnormal liver function and high HCV viral load were detected in 2 therapeutically treated patients one month after transplantation,the patients had normalized transaminase once SOF/VEL combination was started and achieved SVR12 eventually.The patients who failed to achieve SVR12 showed persistent abnormal bilirubin during the treatment of DAAs containing ribavirin.The serum creatinine and drug concentration of all patients were stable during the follow-up period.Conclusion It is safe and effective for HCV uninfected recipients to receive HCV-positive kidney grafts with DAAs prophylactic or therapeutic therapy.For patients infected with subtype 3b HCV and failed in the initial treatment of pan-genotypic DAAs regime,a combination of SOF/VEL/RIB i

关 键 词：肾移植 慢性丙型肝炎 直接抗病毒药 持续性病毒学应答 复发 

分 类 号：R51[医药卫生—内科学]