直接抗病毒药物治疗丙型肝炎失败的影响因素分析  

Influencing factors for direct-acting antiviral therapy failure in treatment of hepatitis C

作　　者：杨宇晴 尚佳 卢诚震 杨松 陈宏宇 潘家莉 韩一凡 席宏丽[1] 亢倩 谭宁 徐小元[1] YANG Yuqing;SHANG Jia;LU Chengzhen;YANG Song;CHEN Hongyu;PAN Jiali;HAN Yifan;XI Hongli;KANG Qian;TAN Ning;XU Xiaoyuan(Department of Infectious Diseases,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院感染疾病科,北京100034

出　　处：《临床肝胆病杂志》2022年第5期1059-1063,共5页Journal of Clinical Hepatology

基　　金：国家科技重大专项课题(2017ZX10302201-004-009,2017ZX10203202-003,2018ZX09201016);北京市科技计划项目(D171100003117005,D161100002716002,D161100002716003)。

摘　　要：目的从基线临床资料和基因测序寻找耐药相关替代突变(RAS)两个方面将抗病毒药物(DAA)治疗结束后HCV RNA复阳患者与DAA治疗成功的HCV感染者进行对比,旨在分析DAA治疗丙型肝炎失败的影响因素。方法纳入2019年11月—2021年10月来自多中心的13例DAA初治失败患者(治疗失败组)并对其复阳血清进行测序,与51例DAA初治成功患者(对照组)的基线临床资料及测序结果进行对比。非正态分布的计量资料组间比较采用Mann-Whitney U检验;计数资料组间比较采用χ^(2)检验,进行单因素和多因素logistic回归分析计算比值比(OR)并分析治疗失败的影响因素。结果12例有完整疗程资料的患者全部于用药结束后1年内复发,男性治疗失败患者的基线TBil、DBil、Cr普遍高于女性(Z值分别为-2.517、-2.440、-2.132,P值分别为0.010、0.010、0.038),年龄在55岁及以下(OR=5.152,95%CI:1.116~23.790,P=0.036)、基因型为3b型(OR=9.726,95%CI:1.325~71.398,P=0.025)的患者治疗失败可能性更高。3种基因片段上的主要RAS发生率在治疗失败和治疗成功组间不同,治疗失败组检测到的共有RAS均未在治疗成功组检测出。结论DAA治疗失败的影响因素有年龄、基因型以及血清病毒基因序列上的RAS种类。Objective To investigate the influencing factors for direct-acting antiviral agent(DAA)therapy failure in the treatment of hepatitis C by comparing baseline clinical data and resistance-associated substitution(RAS)in sequencing data between the patients with HCV RNA reactivation after DAA therapy and the patients with successful DAA treatment.Methods A total of 13 patients from multiple centers who failed DAA therapy from November 2019 to October 2021 were enrolled as treatment failure group,and sequencing was performed for their positive serum samples.A total of 51 patients with successful DAA treatment were enrolled as control group,and baseline clinical data and sequencing results were compared between the treatment failure group and the control group.The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups,and the chi-square test was used for comparison of categorical data between groups;univariate and multivariate logistic regression analyses were performed to calculate odds ratio(OR)and investigate the influencing factors for treatment failure.Results All 12 patients with complete treatment data experienced recurrence within 1 year after the end of medication.The male patients with treatment failure had significantly higher baseline total bilirubin,direct bilirubin,and creatinine than their female counterparts(Z=-2.517,-2.440,and-2.132,P=0.010,0.010,and 0.038),and the patients with an age of≤55 years(OR=5.152,95%confidence interval[CI]:1.116-23.790,P=0.036)or genotype 3b(OR=9.726,95%CI:1.325-71.398,P=0.025)had a higher probability of treatment failure.There were differences in the incidence rates of major RAS mutations on three gene fragments between the treatment failure group and the treatment success group,and the common RAS mutations detected in the treatment failure group were not detected in the treatment success group.Conclusion Age,genotype,and RAS in serum virus gene sequence are influencing factors for DAA treatment failure.

关 键 词：丙型肝炎 抗病毒药 耐药相关替代突变 

分 类 号：R51[医药卫生—内科学]