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聚乙二醇干扰素α联合利巴韦林治疗丙型肝炎失败和复发患者的临床特征及直接抗病毒药物疗效观察
Clinical features of hepatitis C patients with failure or recurrence after treatment with pegylated interferon-α combined with ribavirin and the clinical effect of direct-acting antiviral agents
文章发布日期:2019年09月29日  来源:  作者:张耀弟, 张月荣, 王慧, 等  点击次数:241次  下载次数:45次

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【摘要】: 目的 探讨真实世界中聚乙二醇干扰素α联合利巴韦林的标准方案(PR方案)治疗失败和复发患者的临床特征及不同直接抗病毒药物(DAA)治疗方案对PR治疗失败和复发患者的疗效。方法 回顾性纳入2014年3月- 2018年1月兰州市第一人民医院门诊、住院经标准PR方案治疗失败和复发的慢性丙型肝炎及丙型肝炎相关代偿期肝硬化患者106例,其中男54例,女52例,根据患者PR治疗应答情况分为失败组13例,复发组51例,持续病毒学应答组42例。三组患者行IL-28B基因位点rs12979860和rs8099917检测,基线生化、Cobas HCV RNA、病毒基因分型等检测,比较三组之间的差异。观察PR治疗失败及复发患者接受不同DAA方案的疗效。计数资料组间比较采用χ2检验,计量资料多组间比较采用单因素方差分析。结果 失败组和复发组年龄明显高于应答组,三组比较差异有统计学意义(F=14.05,P<0.001)。失败组病毒基因型以1b型为主,占84.6%,复发组病毒基因型以2a为主,占72.5%,与应答组三组比较差异有统计学意义(χ2=17.269,P=0.002)。失败组基线HCV RNA≥106 IU/L患者所占比例为92.3%,明显高于复发组及应答组,三组比较差异有统计学意义(χ2=10.407,P =0.005),而在性别、肝硬化等方面三组比较,差异均无统计学意义(P值均>0.05)。失败组有100%患者IL-28B rs12979860和92.3%患者rs8099917两个基因位点表达非保护性基因(CT/TT,TG/GG);复发组有84.3%患者IL-28B rs12979860和86.3%患者rs8099917两个基因位点表达非保护性基因(CT/TT,TG/GG),而应答组IL-28B rs12979860位点以CC型为主(85.7%),rs8099917位点以TT型为主(88.1%),三组rs12979860和rs8099917基因多态性构成比比较差异均有统计学意义(χ2值分别为57.263、59.651,P值均<0.001)。以索非布韦为基础的三种DAA方案治疗PR失败及复发患者后,SVR率均为100%。结论 病毒基因分型和IL-28B基因rs12979860和rs8099917位点表达非保护性基因型时是导致PR治疗失败和复发的影响因素。以索非布韦为基础的三种DAA方案治疗PR失败及复发患者均获得100%SVR,不受宿主IL-28B SNP、病毒复制水平等影响,安全性良好。
【Abstract】: Objective To investigate the clinical features of patients with failure or recurrence after treatment with PEG-IFN combined with ribavirin (PR regimen) in the real world and the clinical effect of different direct-acting antiviral agent (DAA) regimens in such patients. Methods A retrospective analysis was performed for the clinical data of 106 patients with chronic hepatitis C or hepatitis C-related compensated liver cirrhosis who attended the outpatient service or were hospitalized in The First Peoples’ s Hospital of Lanzhou from March 2014 to January 2018, and these patients experienced failure or recurrence after the treatment with the standard PR regimen. There were 54 male and 52 female patients. According to the response to PR treatment, the patients were divided into failure group with 13 patients, recurrence group with 51 patients, and sustained virologic response group with 42 patients. All patients underwent IL-28B rs12979860/rs8099917 detection, baseline biochemical examination, Cobas HCV RNA test, and viral genotyping, and these results were compared between groups. The clinical outcomes of patients with failure or recurrence after PR treatment were observed after the treatment with different DAA regimens. The chi-square test was used for comparison of categorical data between groups; a one-way analysis of variance was used for comparison between multiple groups. Results The failure group and the recurrence group had a significantly higher age than the sustained virologic response group (F=14.05, P<0.001). Among the patients in the failure group, 86.4% had viral genotype 1b, while among those in the recurrence group, 72.5% had viral genotype 2a, and there was a significant difference between the three groups (χ2=17.269, P=0.002). Among the patients in the failure group, 92.3% had a baseline HCV RNA level of ≥106 IU/L, and the failure group had a significantly higher proportion of such patients than the recurrence group and the sustained virologic response group (χ2=10.407, P=0.005). There were no significant differences in sex and liver cirrhosis between the three groups (all P>0.05). Among the patients with primary treatment failure, 100% patients had the non-protective genotype of IL-28B rs12979860 CT/TT, and 92.3% had the non-protective genotype of IL-28B rs8099917 TG/GG; among the patients with recurrence, 84.3% patients had the non-protective genotype of IL-28B rs12979860 CT/TT, and 86.3% had the non-protective genotype of IL-28B rs8099917 TG/GG; among the patients in the sustained virologic response group, 85.7% gad genotype CC at IL-28B rs12979860 and 88.1% had genotype TT at IL-28B rs8099917. There were significant differences in the constituent ratios of rs12979860 and rs8099917 gene polymorphisms between the three groups (χ2=57.263 and 59.651, both P<0.001). The patients with failure or recurrence after PR treatment achieved a sustained virologic response rate of 100% after the treatment with three different DAA regimens based on sofosbuvir. Conclusion Viral genotype and non-protective genotypes at IL-28B rs12979860 and rs8099917 are influencing factors for failure and recurrence after PR treatment. The three different DAA regimens based on sofosbuvir achieves a sustained virologic response rate of 100% and has good safety in patients with failure or recurrence after PR treatment, which is not affected by the factors including IL-28B single nucleotide polymorphism and viral replication level in the host.
【关键字】:丙型肝炎, 慢性; 聚乙烯二醇类; 干扰素类; 抗病毒药; 疾病特征; 治疗结果
【Key words】:hepatitis C, chronic; polyethylene glycols; interferons; antiviral agents;disease attributes;treatment outcome
【引证本文】:ZHANG YD, ZHANG YR, WANG H, et al. Clinical features of hepatitis C patients with failure or recurrence after treatment with pegylated interferon-α combined with ribavirin and the clinical effect of direct-acting antiviral agents[J]. J Clin Hepatol, 2019, 35(11): 2456-2460. (in Chinese)
张耀弟, 张月荣, 王慧, 等. 聚乙二醇干扰素α联合利巴韦林治疗丙型肝炎失败和复发患者的临床特征及直接抗病毒药物疗效观察[J]. 临床肝胆病杂志, 2019, 35(11): 2456-2460.

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