Peg-IFNα-2b单药或联合阿德福韦对前C区/BCP区突变慢性乙型肝炎患者疗效比较研究

Comparison of the efficacy of Peg-IFNα-2b combined with adefovir and Peg-IFNα-2b mono-therapy in patients with precore and basal core promoter mutants

目的探讨聚乙二醇干扰素α-2b(Peg-IFNα-2b)单药或联合阿德福韦(ADV)对前C区(PC区)/基本核心启动子区(BCP区)突变慢性乙型肝炎(CHB)患者疗效的差异。方法89例乙肝e抗原(HBe Ag)阳性初治CHB患者,随机接受48周Peg-IFNα-2b+ADV联合治疗或Peg-IFNα-2b单药治疗,并随访24周。每位患者在治疗0、4、8、12、24、36、48、60、72周监测血清乙肝表面抗原(HBs Ag)、HBe Ag、乙肝病毒(HBV)DNA及谷丙转氨酶(ALT)水平。结果 89例患者中,73例(82%)为非野生型(Non-WT)患者,16例(18%)为野生型(WT)患者,基线时WT和Non-WT患者中的单药组和联合组分别在年龄、性别、ALT、HBV DNA、HBe Ag、HBs Ag、基因型构成比、PC/BCP区突变构成比等方面差异无统计学意义。治疗结束时(第48周),Non-WT患者中联合组和单药组HBe Ag血清转换率和联合应答(HBe Ag血清转换+HBV DNA<2 000 IU/ml,并且ALT小于正常值上限)率方面差异无统计学意义。随访结束时(第72周),73例Non-WT患者中,联合组(n=40)和单药组(n=33)HBe Ag血清转换率之比差异无统计学意义(P=0.519),但联合应答率差异之比有统计学意义(35%vs 12%,P=0.028)。结论 PegIFNα-2b联合ADV较Peg-IFNα-2b单药可明显提高PC/BCP区突变HBe Ag阳性CHB患者治疗随访后的联合应答率。

Objective To investigate the efficacy of Peg-IFNα-2b combined with adefovir and Peg-IFNα-2b mono-therapy in patients with precore(PC)and basal core promoter mutants(BCP).Methods Eighty-nine treatment-na ve patients with HBeAg-positive CHB were treated with Peg-IFNα-2b mono-therapy or combined with adefovir for 48 weeks and followed up for 24 weeks.Serum HBsAg,HBeAg,HBV DNA and ALT levels were measured at baseline(week 0),during the treatment period(weeks 4,8,12,24 and 48),and during follow-up period(weeks 60 and 72).Results Of the 89 patients,16(18%)patients showed wild-type virus,73(82%)patients showed the PC/BCP mutants.No significant difference was observed in age,sex,serum ALT level,HBV DNA,HBeAg,HBsAg,genotype and mutation between mono-therapy group and combination therapy group in patients with wild-type virus or mutants.At the end of treatment(week 48),there was no significant difference in HBeAg seroconversion rate or combined response(HBeAg seroconversion+HBV DNA<2 000 IU/ml,and ALT normalization)between the combined therapy group and mono-therapy group in patients with mutants.At the end of follow-up(week 72),the HBeAg seroconversion rate was no significant difference between the combined therapy group and mono-therapy group in patients with mutants(P=0.519).But the combined response rate was significant difference between the two group(35%vs 12%,P=0.028)in patients with mutants.Conclusion HBeAg-positive CHB with PC and/or BCP mutants have a high probability of combined response for Peg-IFNα-2b plus adefovir therapy.