摘要
目的探讨核苷(酸)类似物(NAs)治疗慢性乙型肝炎(CHB)过程中乙型肝炎病毒(HBV)耐药变异的临床意义。方法对67例耐药位点阳性的CHB患者HBV反转录酶(RT)区与NAs相关的耐药突变进行回顾性分析。结果单用阿德福韦酯(ADV)组耐药变异位点N236T13例,A181V14例,A181T7例,A181S1例。单用拉米夫定(LAM)组主要耐药变异位点M204V/I 11例,其中M204V+L180M7例、M204I4例,次要变异位点L180M7例,A181T1例,L229M/V 3例,Q215H1例,V173L1例,L80I2例,S213T2例,V207M2例。序贯治疗组耐药变异位点有LAM耐药特征的耐药位点为M204V+L180M14例,M204V/I+L180M1例,M204I5例;有ADV耐药特征的耐药位点为A181T/V 9例,N236T6例;有恩替卡韦(ETV)耐药特征的耐药位点为S202G7例,T184A/I 3例。次要耐药位点包括ADV次要耐药位点V214A1例,S85A1例;LAM次要耐药位点L80V/I 2例,A213T3例,L229F/M/W 3例。基因型B和基因型C主要耐药变异位点分布差异无统计学意义(P>0.05)。结论高耐药、低基因屏障药物序贯治疗容易导致多药耐药,LAM耐药患者再序贯ETV治疗容易导致ETV耐药,HBV基因型别对耐药变异位点分布无影响。
Objective To evaluate nucleoside analogues（NAs）resistant gene mutation in hepatitis B virus（HBV）and its further clinical significance in treatment of chronic hepatitis B（CHB）.Methods A total of 67 cases with mutated drug-resistant site at the reverse transcriptase（RT）region in HBV were retrospectively reviewed,and study the relation between the mutation of RT in HBV with the drug-resistance of NAs.Results The main mutated drug-resistant sites after using Adefovir Dipivoxil（ADV）only were N236 T（13 cases）,A181 V（14 cases）,A181 T（7 cases）and A181 S（1 cases）.Those mutated sites after using Lamivudine（LAM）only were M204 V/I（11 cases）,L180 M（7 cases）,A181 T（1 cases）,L229 M/V（3 cases）,Q215 H（1 cases）,V173 L（1 cases）,L80 I（2 cases）,S213 T（2 cases）,V207 M（2 cases）.The main sites after sequential therapy were diverse,the LAM-like sites were M204 V＋L180 M（14 cases）,M204 V/I＋L180 M（1 cases）and M204 I（5 cases）.The ADV-like sites were A181 T/V（9 cases）and N236 T（6 cases）.The Entecavir（ETV）-like sites were S202 G（7 cases）,T184 A/I（3 cases）.The minor sites after sequential therapy were V214 A（1 cases）,L80 V/I（2 cases）,A213 T（3 cases）,S85 A（1 cases）and L229 F/M/W（3 cases）.There was no significant difference in distribution of major drug-resistant mutation on genotype B and genotype C.（P0.05）.Conclusion Sequential therapy of highly resistant and low gene barrier drugs is likely to lead to multidrug.Sequential ETV therapy to LAM-resistant patients with CHB easily leads to ETV resistance.Genotype had no effect on the distribution of major drug-resistant mutation.
作者
何吕富
雷巧
梅洪建
HE Lyufu;LEI Qiao;MEI Hongjian(Department of Gastroenterology;Department of Clinical Laboratory,the 903 Hospital of Jiangyou,Jiangyou,Sichuan 621700,China)
出处
《检验医学与临床》
CAS
2018年第21期3242-3244,3248,共4页
Laboratory Medicine and Clinic
