恩替卡韦治疗拉米夫定经治患者的临床观察

目的随着抗病毒药物的广泛应用,核苷（酸）类似物经治患者增多,而经治患者耐药后的治疗仍是临床上的难题。比较拉米夫定（LAM）经治患者在不同病情发展时期改用恩替卡韦（ETV）治疗2年的抗病毒效果。方法选择ETV-050和ETV-056纳入研究患者及部分门诊患者共64例,按照患者在ETV治疗前是否中断LAM治疗分为连续治疗组（29例）和不连续治疗组（35例）,均应用ETV1.0mg/d治疗,比较两组患者血清HBVDNA应答和反弹情况及丙氨酸氨基转移酶（ALT）复常率。结果不连续治疗组病毒应答率显著高于连续治疗组,从治疗第12个月开始,不连续治疗组HBVDNA低于检测下限的比率显著高于连续治疗组,达到65.7%,而连续治疗组的HBVDNA低于检测下限的比率只有31.0%（P〈0.05）。不连续治疗组的ALT复常率较高,病毒反弹率较低,但与连续治疗组比较均无显著差异。结论 LAM经治患者在不同状况下服用ETV治疗存在疗效差异。存在LAM耐药的患者不建议直接换用ETV治疗;LAM经治但未耐药者或曾经LAM耐药而基线无耐药者仍可以选择ETV治疗。

Clinical observation on entecavir for patients with chronic hepatitis B patients with prior exposure to lamivudine

Objective With an extensive application of antiviral drugs,patients previously treated with nucleoside analogue increased.But the therapy was still a tough problem in clinical practice.To compare the two-year antiviral efficacy after swithching after resistance to entecavir in patients with chronic hepatitis B previously treated with lamivudine at different stages between the two groups.Methods Sixty-four patients with chronic hepatitis B from studies of ETV-050 and ETV-056 as well as outpatients of Beijing Ditan Hospital were enrolled.Patients were divided into consecutive treatment group（29 cases）and inconsecutive treatment group（35 cases）according to interrupting lamivudine or not prior to entecavir therapy.All patients were treated with entecavir 1.0 mg/d in order to compare the rates of serum HBV DNA response and breakthrough and ALT normalization between the two groups.Results The viral response rate in inconsecutive treatment group was significantly higher than that in consecutive treatment group.After 12 months treatment,HBV DNA undetectable ratio in inconsecutive treatment group was significantly higher than that in consecutive treatment group（65.7% vs 31.0%,P〈0.05）.ALT normalization rate in inconsecutive treatment group was higher while viral breakthrough rate in inconsecutive treatment group was lower.However,there were no significantly difference compared to consecutive treatment group.Conclusions There was an effective difference in chronic hepatitis B previously treated with lamivudine under different conditions after receiving entecavir therapy.It is not progposed to switch to entecavir therapy directly for chronic hepatitis B patients with resistance to lamivudine.Whereas entecavir therapy still may be an option in patients with chronic hepatitis B previously treated with lamivudine without resistance or previously resistant to lamivudine without resistance at baseline.