【摘要】 目的观察阿德福韦酯(adefovir dipivoxil,ADV)单药治疗慢性乙型肝炎(慢乙肝)过程中发生病毒突破的患者乙型肝炎病毒(HBV)P基因区变异发生情况。方法选取51例阿德福韦酯单药治疗(10 mg/d,疗程>12月)发生病毒突破的慢乙肝患者作为研究对象,分别检测随访发现病毒突破时患者的血清ALT、HBV DNA水平,并采用PCR产物直接测序法分析HBV P区基因的变异发生情况。结果51例患者中有37例检测出阿德福韦酯耐药相关变异,且rt181位点变异多于rt236位点(分别为33例和8例,其中两位点联合变异4例,P<0.001)。联合变异患者其血清HBV DNA水平高于单一变异患者[分别为(6.53±0.45)log10拷贝/mL、(5.37±1.08)log10拷贝/mL,P=0.043]。结论在应用阿德福韦酯单药治疗的慢乙肝患者中可筛选出HBV P基因区的相关耐药变异,不同耐药位点患者的HBV DNA水平可有差异。更多还原

【Abstract】 Objective To investigate the mutations in the P gene of hepatitis B virus (HBV) in chronic hepatitis B(CHB) patients who had viral breakthrough during long-term adefovir dipivoxil monotherapy.Methods 51 CHB patients who had viral breakthrough during long-term adefovir dipivoxil(ADV) monotherapy(10 mg/d,duration >12 months) were enrolled in this study.Sera were collected when viral breakthrough was confirmed,and ALT,HBV DNA(real time quantitative PCR),and sequences of partial HBV P gene were determined.Results Mutations related to ADV resistance were found in 37 of 51 CHB patients.The frequency of mutation at rt181 was significantly higher than that at rt236(33 vs 8,P<0.001).Serum HBV DNA load in patients with combination mutations were higher than that with a single mutation when the viral breakthrough occurred(6.53±0.45log10 copies/ml vs 5.37±1.08log10 copies/ml,P=0.043).Conclusions Mutations in HBV P gene can develop during ADV monotherapy in CHB patients.The HBV levels may differ in patients with different mutations.更多还原