聚乙二醇干扰素联合利巴韦林治疗对基因1b型慢性丙型肝炎患者预存耐药相关替代的差异性分析  

Effect of PEG interferonαcombined with ribavirin on resistance-associated substitutions in patients with chronic hepatitis C of genotype 1b

作　　者：任姗[1] 金怡[1] 柳雅立[1] 鲁俊锋[1] 马丽娜[1] 何智敏[1] 郑燕红[1] 王俊丽[1] 陈新月[1] Ren Shan;Jin Yi;Liu Yali;Lu Junfeng;Ma Lina;He Zhinin;Zheng Yanhong;Wang Junli;Chen Xinyue(International Medical Department,Beijing Youan Hospital,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学附属北京佑安医院肝病综合科,100069

出　　处：《北京医学》2020年第6期479-484,488,共7页Beijing Medical Journal

基　　金：“十三五”国家科技重大专项(2017ZX10202201,2017ZX10201021-001-008);北京市属医院科研培育计划(PX2017022);首都医科大学重点实验室开放研究课题(2-03-02-BJYAH2016002)。

摘　　要：目的探索聚乙二醇干扰素-α(PEG interferonα,PEG IFN-α)联合利巴韦林(ribavirin,RBV)治疗对基因1b型慢性丙型肝炎(chronic hepatitis C,CHC)患者直接抗病毒药物(directly acting antiviral,DAA)的预存耐药相关替代(resistance-associated substitutions,RAS)的影响。方法选取2010年7月至2015年11月首都医科大学附属北京佑安医院收治的310例基因1b型CHC患者,均予以PR方案,依据是否获得持续病毒学应答(sustained virology response,SVR)分为SVR组与非SVR组。提取患者基线以及治疗失败时的HCV RNA,聚合酶链反应(polymerase chain reaction,PCR)扩增并测序HCV NS3/4A、NS5A、NS5B区基因,进行DAA相关RAS差异性比较。结果SVR组184例,非SVR组126例。基线NS3/4A区82.5%存在DAA相关RAS,S122为38.8%,Q80L为0.7%;基线NS5A区44.5%检测到RAS,Y93H为6.3%,L31M为2.9%;基线NS5B区88.3%检测到RAS,S282为0.7%,L159F为5.0%。SVR组与非SVR组基线RAS发生率的差异均无统计学意义(P>0.05)。PR治疗失败后部分患者关键位点RAS,如L31M、Y93H出现增加,但差异无统计学意义,π检验以及Tajima’s D检测均未观察到特殊的进化模式。结论基因1b型CHC患者中存在DAA相关RAS,这些突变大多为低度耐药突变,其对PR治疗疗效无影响,且未观察到IFN的选择压力对RAS的变化造成影响。Objective To explore the effect of PEG interferonα(PEG IFN-α)combined with ribavirin(RBV)on resistance-associated substitutions(RAS)in patients with chronic hepatitis C(CHC)of genotype 1 b.Methods A total of 310 patients with CHC of genotype 1 b who were admitted to Beijing Youan Hospital from July 2010 to November 2015 were collected.All the patients were given PR(PEG IFN-αcombined with RBV)regimen.According to whether they received sustained virology response(SVR),the patients were divided into SVR group and Non-SVR group.HCV RNA of patients at baseline and in the case of treatment failure was extracted.HCV NS3/4 A,NS5 A and NS5 B region genes were amplified and sequenced by PCR,and differences of directly acting antiviral(DAA)-related RASs were compared.Results There were 184 patients in SVR group and 126 in Non-SVR group.There was DAAs-related RASs in 82.5%of baseline NS3/4 A region:S122 was38.8%and Q80 L was 0.7%.RASs was detected in 44.5%of NS5 A area at baseline:Y93 H was 6.3%,L31 M was 2.9%.In the baseline NS5 B region,88.3%detected RASs:0.7%of S282 and 5.0%of L159 F.There was no statistically significant difference in the incidence of baseline RASs between SVR group and Non-SVR group(P>0.05).After the failure of PR treatment,RASs such as L31 M and Y93 H,showed an increase in some patients,but the statistical difference was not significant.No special evolutionary pattern was observed in the test ofπor Tajima’s D test.Conclusions DAAs-related RASs exist in CHC patients of genotype 1 b,and most of these mutations are low-resistance,which have no effect on the efficacy of PR therapy,and no effect of IFN selection pressure on RASs was observed.

关 键 词：慢性丙型肝炎 抗病毒药 抗药性 病毒 干扰素 利巴韦林 

分 类 号：R512.63[医药卫生—内科学]