替比夫定治疗慢性乙型肝炎出现病毒变异联用阿德福韦酯治疗的临床观察

目的探讨替比夫定治疗慢性乙型肝炎出现病毒变异后的治疗方案。方法将66例患者随机分为3组,A组单用阿德福韦酯治疗48周;B组采用阿德福韦酯与替比夫定联合治疗12周,后单用阿德福韦酯治疗36周;C组采用阿德福韦酯与替比夫定联合治疗48周。结果①A、B、C 3组治疗12周内ALT水平反弹升高的患者比例分别为27%(6/22),14%(3/22),5%(1/22)(P<0.05);治疗12周、24周3组rtM204 I变异株检测阳性率分别为18%(4/22),5%(1/22),0和5%(1/22),0,0,48周变异株检测阳性率均为0。②治疗48周3组间ALT水平、e抗原阳性患者血清转换率比较均无显著性差异(P均>0.05),C组ALT复常率、HBV DNA转阴率与A组比较有显著性差异(P<0.05),3组的HBV DNA转阴率分别为64%(14/22),77%(17/22),100%(22/22),A组rtN236T、rtA181V+rtN236T变异各1例,B组rtN236T变异1例。结论替比夫定治疗慢性乙型肝炎出现rtM204 I变异后采用与阿德福韦酯联合治疗更安全有效。

Study on combination of adefovir dipivoxil for chronic hepatitis B virus variants associated with telbivudine

Objective It is to approach the therapeutic program of chronic hepatitis B virus variants after telbivudine treatment.MethodsSixty-six patients were randomly divided into three groups: group A of single-use adefovir dipivoxil for 48 weeks;group B with adefovir dipivoxil and telbivudine combination therapy for 12 weeks and a single treatment with adefovir dipivoxil for 36 weeks;group C were treated with adefovir dipivoxil and telbivudine for48 weeks.Results①The rebound rates of elevated ALTlevels in group A,B and C for 12 weeks were 29%(7/22),14%(3/22),5%(1/22) respectively(P<0.05);after 12 weeks,and 24 weeks for treatment,rtM204I mutant positive rate in these groups were 18%(4/22),5%(1/22),0 and 5%(1/22),0,0 respectively,but it was 0 after 48 weeks in all groups.②For 48 weeks of treatment,theALT levels and e antigen seroconversion rates in patients showed no significant difference among the 3 groups(allP>0.05).Compared with group A,ALTnormalization and HBV DNA negative rate in group C was significantly improved(P<0.05).HBV DNA negative conversion rates in 3 groups were 64%(14/22),77%(17/22) and 100%(22/22) respectively.One case with rtN236T and one case with rtA181V +rtN236Tmutation in group A;one case with rtN236Tmutation in Group B.Conclusion It is more safe and effective for the combination therapy with adefovir dipivoxil on Telbivudine treatment of chronic hepatitis B after emergence rtM204I variation.