对阿德福韦酯自然变异耐药与抗病毒后耐药的慢性乙型肝炎患者血清HBV P基因序列比较

Evaluation of adefovir primary resistance and adefovir repulsive mutations of the HBV DNA P gene in chronic hepatitis B patients

目的通过对慢性乙型肝炎(CHB)患者外周血乙型肝炎病毒(HBV)聚合酶RT区序列分析,观察对阿德福韦酯(ADV)自然变异耐药及继发耐药的异同。方法 PCR产物直接测序法检测78例对ADV耐药患者外周血HBV RT区基因序列。其中曾用ADV治疗患者30例(治疗组),未抗病毒治疗48例(未治疗组),并对两组ADV相关耐药变异位点发生频数进行比较。结果未治疗组ADV耐药的主要变异类型为rtA181V/T 10例(20.8%),rtN/H238T/D/S 10例(20.8%)和rtV214A变异13例(27.1%);而治疗组发生的ADV耐药变异主要为rtA181V/T 16例(53.3%),没有发现rtN/H238T/D/S变异,仅发现1例rtV214A变异。结论CHB患者中存在相当严重的ADV自然变异耐药变异,主要变异类型为rtN/H238T/D/S及rtV214A,而抗病毒治疗后该变异位点发生频数反而相对减少。rtA181V/T变异既可以为自然变异也可以由ADV抗病毒治疗而诱发。

Objective To determine if adefovir resistance associated with the HBV DNA P gene in chronic hepatitis B patients （CHB） re- suits from primary or adefovir - induced mutations. Methods Seventy - eight chronic HBV patients were enrolled in the study, including 30 patients who accepted adefovir treatment and 48 patients who refused any type of nucleoside analog （NA） treatment. Serum samples from all participants were genotyped for the HBV DNA P gene by PCR amplification and automated sequencing. Results In the group of untreated patients, the main mutations were rtA181V/T10 （20. 8% ）, rtN/H238T/D/S10 （20. 8% ）, and rtV214A 13 （27. 1% ）. In the group of adefovir -treated patients, the main mutation was rtA181 V/T16 （53.3%） , no rtN/H238T/D/S mutant was detected, and only one patient carried the rtV214A mutant of the HBV RT region. Conclusion CHB patients carry adefovir - resistance mutations that arise spontaneously, as detected in untreated patients. These resistance mutations mainly included rtV214A and rtN/H238T/D/S. However, CHB patients treated with adefovir carried less resistance mutations overall but had a much higher incidence of the rtA181V/T mutation, suggesting that this mutation may be primary or induced by adefovir.