CAJ | 학술논문

目的对我国华南地区184例未行抗病毒治疗的慢性丙型肝炎患者进行NS5B聚合酶抑制剂相关耐药位点检测并分析其特点. 方法根据NS5B区变异位点的特点,将其分成3段扩增.NS5B聚合酶抑制剂相关的耐药位点分析采用自行设计型别特异性引物行巢式PCR,PCR产物纯化后直接测序鉴定,同时对患者的临床资料进行分析.定量资料如人口学指标、生物化学指标、血液学指标、病毒学等指标,参数比较用Student's t检验或ANOVA方差分析,两组间非参数比较用Mann Whitney U检验;分类资料用x 2检验. 结果对核苷类聚合酶抑制剂耐药的变异位点A15G,S96T,S282T主要在HCV 6a型中发生(20/88,22.73％),在HCV 1b型中未发现变异位点;对非核苷类聚合酶抑制剂耐药的变异位点C316N,S365A主要见于HCV 1b型,I482L、V499A主要见于HCV 6a型及HCV 2a型;本研究发现一些新的变异位点如A15S,S365F,S365P,S368A,S368L,这些变异位点能否导致耐药尚待研究. 结论我国慢性丙型肝炎患者对NS5B聚合酶抑制剂存在预存耐药,变异率因HCV基因型而异.不同的基因型可预存不同的耐药,提示使用直接抗病毒药前应常规进行基因检测.
목적 대아국화남지구184례미행항병독치료적만성병형간염환자진행NS5B취합매억제제상관내약위점검측병분석기특점. 방법 근거NS5B구변이위점적특점,장기분성3단확증.NS5B취합매억제제상관적내약위점분석채용자행설계형별특이성인물행소식PCR,PCR산물순화후직접측서감정,동시대환자적림상자료진행분석.정량자료여인구학지표、생물화학지표、혈액학지표、병독학등지표,삼수비교용Student's t검험혹ANOVA방차분석,량조간비삼수비교용Mann Whitney U검험;분류자료용x 2검험. 결과 대핵감류취합매억제제내약적변이위점A15G,S96T,S282T주요재HCV 6a형중발생(20/88,22.73％),재HCV 1b형중미발현변이위점;대비핵감류취합매억제제내약적변이위점C316N,S365A주요견우HCV 1b형,I482L、V499A주요견우HCV 6a형급HCV 2a형;본연구발현일사신적변이위점여A15S,S365F,S365P,S368A,S368L,저사변이위점능부도치내약상대연구. 결론 아국만성병형간염환자대NS5B취합매억제제존재예존내약,변이솔인HCV기인형이이.불동적기인형가예존불동적내약,제시사용직접항병독약전응상규진행기인검측.
Objective To determine the prevalence of mutations in the non-structural protein 5B (NS5B) of the hepatitis C virus (HCV),which are associated with natural resistance to non-nucleoside and nucleoside polymerase inhibitors (PIs),in treatment-naive hepatitis C patients in south China.Methods A nested PCR protocol that amplified three different regions of NS5B was used to detect the naturally occurring drag-resistant substitutions.Direct PCR sequencing was performed to analyze the sequences.Results NS5B mutations known to confer resistance to nucleoside PIs,such as A15G,S96T and S282T,were mainly detected in HCV genotype 6a (20/88,22.73％).Of the NS5B mutations known to confer resistance to non-nucleoside PIs,C316N and S365A were detected in HCV genotype lb (60/60,100％ and 2/60,3.33％,respectively) and I482L and V499A were mainly detected in HCV genotype 2a (9/9,100％ and 4/4,100％,respectively) and HCV genotype 6a (9/9,100％ and 4/4,100％,respectively).Other NS5B mutations found in the study population included A1 5S,S365F,S365P,S368A and S368L;although none of these has been previously shown to confer resistance to PIs.Conclusion Naturally occurring dominant PI resistance mutations in NS5B exist in treatment-na(i)ve hepatitis C patients in south China and may be related to the virus genotype.