【作者】 贾伟；

【导师】 王磊；

【作者基本信息】 山东大学 ， 内科学， 2012， 硕士

【摘要】 背景：乙型肝炎病毒(HBV)耐药突变可在慢性HBV感染患者自身特异性免疫反应压力下发生,并在核苷(酸)类似物治疗过程中出现。以往多数研究结果,显示未经核苷(酸)类似物抗病毒治疗的慢性HBV感染患者体内存在着不同程度的HBV自然耐药突变株。目的：本研究的目的在于采用不同的方法检测并分析未经核苷(酸)类似物治疗慢性HBV感染患者体内自然突变株的存在情况。方法：收集门诊及住院患者共计104例,均为未经任何核苷(酸)类似物治疗的慢性乙型肝炎患者(CHB)和乙型肝炎肝硬化(LC-B)等慢性HBV感染患者,其中42例采用焦磷酸测序法检测耐药突变,62人采用PCR产物直接测序法检测耐药突变。结果：在焦磷酸测序组42例患者中,共检出3例(7.14%)自然耐药突变株,其中2例为原发性耐药突变(均为rtA181T)、1例为补偿性耐药突变(rtV173L)。在PCR产物直接测序法组的62例患者中,共检出6例(9.68%)自然耐药突变株,1例为原发性耐药突变(rtM2.04I变)、5例为补偿性耐药突变(2例rtV207L、2例rtS213T、1例N238T)。经统计学分析,两种检测方法、性别、疾病状态、年龄、谷丙转氨酶水平、谷草转氨酶水平、血清HBV-DNA载量、HBeAg量均与HBV自然耐药突变的出现没有明显相关。结论：自然发生的HBV耐药突变株,包括原发性耐药突变株和补偿性耐药突变株,可以存在于慢性HBV感染患者体内。但是耐药突变株的出现频率较低。是否对慢性HBV感染患者在核苷(酸)类似物治疗前进行耐药突变株的检测,还需要进一步研究。更多还原

【Abstract】 Background:Hepatitis B virus (HBV) variants may either emerge in patients with chronic HBV infected patients as a result of positive selection pressure exerted by specific immune response, or during therapy with nucleostide analogues. Naturally occurring HBV variants with primary antiviral resistance are rarely observed.But some reports show that patients with chronic HBV infected patients are natural resistance to nucleostide analogues.Aim:The aim of this study was to use2different methods to analyze HBV variants with natural resistance to nucleostide analogues currently used as therapy for chronic HBV infected patients.Methods:A total of104cases (42cases in group A of Pyrosequencing and62cases in group B of fluorescent PCR)used different methods for detection and did not receive the treatment of nucleos(t)ide analogues ever.Their serum mutations were detected by microcosmic nucleic acid and cross-nucleic acid quantitative determination,Results:Among42patients in group A without receiving the treatment of nucleos(t)ide analogues, spontaneous HBV variants were detected in3subjects(2181mutants and1173mutant). Among62patients in group B spontaneous HBV variants were detected in6subjects(2207mutants,2213mutants,1204mutant and1238mutant).HBV variants account for7.14%、9.68%in each group. Gender, the state of disease, age, ALT, AST, serum HBV-DNA load were not associated with spontaneous HBV mutation.Conclusion:Spontaneous HBV variants (primary drug resistance mutation and compensatory mutation)exist in chronic hepatitis B patients. But the frequence of these variants are low and the meaning of these still need to be investigated.更多还原