替比夫定序贯聚乙二醇干扰素α治疗HBeAg阳性慢性乙型肝炎部分应答者的疗效

Efficacy of sequential therapy with telbivudine in treatment of HBeAg-positive chronic hepatitis B patients with partial response to pegylated interferon-or therapy

目的探讨干扰素治疗HBeAg阳性慢性乙型肝炎（CHB）患者标准疗程后部分应答序贯替比夫定治疗的疗效。方法连续收集2009年1月至2013年12月接受干扰素治疗（48～60周）疗程结束部分应答的HBeAg阳性CHB患者58例进行回顾性队列研究。根据疗程结束后序贯替比夫定治疗及停药观察分为两组，序贯替比夫定组与停药观察组。比较两组生物化学、病毒学及血清学应答率。据资料不同分别采用X2检验、t检验或非参数检验进行统计学分析。结果共有58例患者纳入本研究，其中序贯替比夫定组31例，停药观察组27例。干扰素疗程结束12、24周时，序贯替比夫定组的HBeAg阴转率显著高于对照组（22．6％对比0、29．0％对比3．7％，P〈0．05）。随访至48周时，序贯替比夫定组的联合应答率为22．6％，明显高于对照组（0），差异有统计学意义（P=0．015）。序贯替比夫定组的31例患者中，有11例患者在服用替比夫定期间出现肌酸激酶升高。两组患者在随访期间均未发现肌肉酸痛、肌炎、周围神经病变、肾功能损害、肝功能失代偿等严重不良反应。结论干扰素治疗部分应答的HBeAg阳性CHB患者，序贯替比夫定治疗可以提高48周的HBeAg血清学阴转率及联合应答率。干扰素治疗结束部分应答的HBeAg阳性CHB患者序贯替比夫定治疗具有安全性。

Objective To investigate the efficacy of sequential therapy with telbivudine in the treatment of HBeAg-positive chronic hepatitis B （CHB） patients with partial response after a standard course of interferon therapy. Methods A retrospective cohort study was performed for 58 HBeAg-positive CHB patients with partial response at the end of interferon therapy （48-60 weeks） from January 2009 to December 2013. According to whether telbivudine was used sequentially or withdrawn at the end of the course of treatment, the patients were divided into telbivudine sequential therapy group and withdrawal group, and the two groups were compared with in terms of biochemical, virological, and serological response rates. The chi-square test, the t-test, and the non-parametric test were used based on data type. Results A total of 58 patients were enrolled in this study, with 31 in the telbivudine sequential therapy group and 27 in the withdrawal group. At 12 and 24 weeks after interferon therapy ended, the telbivudine sequential therapy group had a significantly higher HBeAg clearance rate than the withdrawal group （22.6%/29.0% vs 0%/3.7%, P 〈 0.05）. At week 48 of follow-up, the telbivudine sequential therapy group had a significantly higher combined response rate than the withdrawal group （22.6% vs 0%, P = 0.015）. Among the 31 patients in the telbivudine sequential therapy group, 11 had an increase in creatine kinase during the administration of telbivudine. No patient in either group experienced serious adverse reactions during follow-up, such as muscular soreness, myositis, peripheral neuropathy, renal dysfunction, and liver function decompensation. Conclusion In HBeAg-positive CHB patients with partial response to interferon therapy, sequential therapy with telbivudine can increase serological HBeAg clearance rate and combined response rate at week 48, and it is safe in HBeAg-positive CHB patients achieving partial response at the end of interferon therapy.