核苷(酸)类似物治疗慢性乙型肝炎患者HBV基因耐药变异影响因素分析  

Factors affecting HBV gene mutations in chronic HBV-infected patients receiving nucleos(t)ide analogue therapy

作　　者：赵攀[1] 戴久增[1] 柳芳芳[1] 姚增涛[1] 李乐[1] 辛绍杰[1] 徐东平[1] 

机构地区：[1]解放军第三〇二医院肝衰竭诊疗与研究中心,北京100039

出　　处：《传染病信息》2013年第2期93-95,130,共4页Infectious Disease Information

基　　金：国家自然基金面上项目(81171617)

摘　　要：目的研究核苷(酸)类似物抗HBV治疗中病毒聚合酶基因区耐药突变的相关因素。方法从我院行HBV聚合酶基因区序列测定的患者中,选择持续单一或联合应用核苷(酸)类似物治疗的慢性乙型肝炎(乙肝)和乙肝肝硬化患者,分析其宿主、病毒和药物等对HBV基因耐药变异的影响,包括性别、年龄、诊断、HBV基因型、HBeAg、HBVDNA水平、ALT、AST、TBIL及药物(包括拉米夫定、阿德福韦酯、恩替卡韦、拉米夫定┼阿德福韦酯联合治疗)。结果分析结果显示,年龄、血清HBVDNA水平、HBeAg(-)和核苷(酸)类似物种类是影响病毒聚合酶基因区突变的相关因素。结论年龄>40岁且HBeAg(-)的血清高病毒载量的慢性乙肝患者,在临床上病毒耐药发生率较高。对于核苷(酸)初治的慢性乙肝患者,恩替卡韦单药治疗与拉米夫定┼阿德福韦酯联合治疗耐药发生率相似,显著低于拉米夫定单药和阿德福韦酯单药治疗。Objective To evaluate the factors affecting drug-resistant mutations in HBV reverse-transcriptase gene in HBV infected patients receiving nucleos（t）ide analogue therapy. Methods Among HBV-infected patients with HBV reverse-transcriptase gene analyzed by a high-sensitive direct PCR sequencing assay, patients with chronic hepatitis B （CHB） and HBV-related cirrhosis who received nucleos（t）ide analogue monotherapy or combination therapy were enrolled in this study. Factors of the host, the virus or drugs, including sex, age, diagnosis, HBV genotype, HBeAg status, serum levels of HBV DNA, ALT, AST and TBIL and nucleos（t）- ide analogue therapy （lamivudine, adefovir dipivoxil, entecavir and combination of lamivudine and adefovir dipivoxil） were analyzed. Results Statistical analysis showed that age, serum HBV DNA level, HBeAg status and the kinds of nueleos （t）ide analogues were correlated with viral mutations in the reverse-transcriptase gene. Conclusions HBV drug-resistant mutations occur more frequently in older CHB patients （〉40 years of age） with HBeAg negative and high serum HBV DNA level. For nucleos （t）ide-naYve CHB patients, the rate of drug resistance associated with entecavir monotherapy is similar to that with combination therapy of lami- vudine and adefovir dipivoxil, significantly lower than the rates of drug resistance associated with lamivudine or adefovir dipivoxil monotherapy.

关 键 词：核苷类 肝炎 乙型 慢性 突变 

分 类 号：R342.1[医药卫生—基础医学]