联合抗病毒对于拉米夫定耐药慢性乙型肝炎的临床意义

Clinical significance of combination therapy for patients resistant to lamivudine with chronic hepatitis B infection

目的通过对应用拉米夫定(LAM)耐药的慢性乙型肝炎患者单药和联合抗病毒治疗效果的比较来了解其临床意义。方法将39例应用拉米夫定并经HBVP基因测序和生化、聚合酶链反应(PCR)证实存在耐药的慢性乙型肝炎患者分为两组,一组加用、另一组换用阿德福韦酯(ADV),通过对两组患者的生化学、病毒学和血清学应答,耐药变异发生情况的观测来比较两组治疗方案的疗效。结果经72周的连续监测,加用ADV在病毒学应答率上优于换用ADV组(P=0.02),但在HBVDNA下降程度,生化学、血清学应答方面差异无统计学意义,而出现明确耐药变异数量上加用ADV组明显少于换用ADV组,组间比较差异存在统计学意义(P=0.03)。结论对于LAM耐药的慢性乙型肝炎患者联合治疗在提高抗病毒应答率和降低耐药率方面优于换用ADV。

Objective To identify the clinical significance between alone and combination therapy for patients resistant to lamivudine（LAM）with chronic hepatitis B.Methods Thirty-nine chronic hepatitis B patients who were identified resistant to LAM by HBV P gene sequencing,biochemical analysis,and polymerase chain reaction（PCR）were separated into 2 groups,one group applied combination therapy with adefovir dipivoxil（ADV）,another replaced with ADV.The therapeutic effect was evaluated by the biochemics response,virology response,serology response,and the resistance mutafacient.Results Through 72 weeks continuous monitoring,virology response in the combination group with ADV was significantly higher than that in alone group（P=0.02）.There was no significant difference between two groups in the mean reduction of HBV DNA from baseline,ALT normalization and HBeAg serocoversion.Fewer cases were identified of resistant mutation in genes in combination-group than that in alone group with ADV（P=0.03）.Conclusion For patients resistant to LAM with chronic hepatitis B,combination therapy with ADV has advantages over alone therapy with ADV in virology response and drug resistance.