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目的探讨慢性乙型肝炎(CHB)患者应用核苷(酸)类似物治疗后基因耐药变异的病毒学及血清学变化。方法选择2010年6月至2011年12月北京军区总医院287例CHB患者,按照服用拉米夫定(LAM)、阿德福韦酯(ADV)、替比夫定(LdT)和恩替卡韦(ETV)分为4组。定期检测血清HBV DNA载量与ALT水平,用聚合酶链反应-逆向点杂交法检测血清HBV DNA耐药变异位点。结果 LAM治疗后24个月耐药率为41.9%(31/74);ADV耐药率为7.7%(7/91);LdT耐药率为10.8%(4/37);ETV耐药率较低,为2.3%(2/85)。CHB患者抗病毒基因耐药变异组ALT异常率(27.3%)明显高于未变异组(9.9%),差异有统计学意义(P<0.05);未变异组HBV DNA转阴率(62.6%)明显高于变异组(20.5%),差异有统计学意义(P<0.05)。结论 LAM、ADV、LdT和ETV均会出现不同程度的耐药变异。定期进行基因耐药检测有助于及时调整治疗方案,提高疗效。
Objective To investigate the virological and serological changes of drug resistance mutations in patients with chronic hepatitis B (CHB) treated with nucleotide analogs. Methods A total of 287 CHB patients from Beijing Military Region General Hospital from June 2010 to December 2011 were randomly divided into two groups according to LAM, ADV, LdT and ETV Divided into 4 groups. Serum HBV DNA load and ALT levels were detected regularly, and HBV DNA resistance mutation sites were detected by polymerase chain reaction-reverse dot blot hybridization. Results The resistance rate of 24 months after LAM treatment was 41.9% (31/74). The resistance rate of ADV was 7.7% (7/91) and the resistance rate of LdT was 10.8% (4/37) Low, 2.3% (2/85). The abnormal ALT rate (27.3%) was significantly higher in CHB patients than in non-mutation group (9.9%) (P <0.05). The HBV DNA negative rate (62.6% Was significantly higher than the mutation group (20.5%), the difference was statistically significant (P <0.05). Conclusion LAM, ADV, LdT and ETV all show different degrees of resistance variation. Regular testing of gene resistance will help to timely adjust the treatment plan and improve the curative effect.