目的：评估序贯联合重组人干扰素α1b（IFN-α1b）治疗核苷（酸）类似物（NAs）经治HBeAg阳性CHB患者48周的疗效与安全性。方法159例NAs治疗12～36个月HBV DNA检测不到但未发生血清学应答的HBeAg阳性CHB患者，77例接受序贯联合IFN-α1b治疗48周，82例继续NAs单药治疗48周。基线和治疗期间每12周进行生物化学、病毒学和血清学评估。计量资料采用t检验，计数资料采用χ2检验。结果治疗48周，试验组HBeAg低于检测下限和转换率分别为21.74%和20.29%，对照组HBeAg低于检测下限和转换率分别为5.63%和5.63%，差异有统计学意义（χ2=7.738、6.709， P ＜0.05）。试验组和对照组HBsAg清除率分别为7.25%和0%，差异有统计学意义（χ2=5.335，P＜0.05）。试验组和对照组病毒学反弹率分别为0%和4.22%，差异无统计学意义（χ2=2.979，P ＞0.05）。无论是试验组还是对照组，HBsAg基线水平高的患者（＞2000 IU/ml）的HBeAg血清学转换率高于基线水平低（≤2000 IU/ml）的患者；差异无统计学意义（χ2=2.833、0.147，P ＞0.05）。HBsAg下降幅度与HBeAg下降幅度具有相关性（r=0.606）。NAs基础治疗时间可能对序贯联合干扰素后的HBeAg低于检测下限和转换有一定影响，但无论基础治疗时间长短，序贯联合干扰素均可增加HBeAg应答率。结论序贯联合IFN-α1b有助于提高NAs经治未达满意治疗终点的HBeAg阳性CHB患者的血清学应答率。%Objective To investigate the efifcacy and safety of an extended course (48-week) of sequential interferon alpha-1b therapy for patients with HBeAg positive chronic hepatitis B (CHB) who have poor response to nucleot(s)ide analogue. Methods There were 159 HBeAg positive CHB patients who had completed a 12-24 months of nucleot(s)ide analogues (NAs) monotherapy course, and who had achieved a virological response (HBV DNA<500 copies/ml) but without HBeAg seroconversion were enrolled. The patients were randomly assigned to receive IFN-α1b plus NAs (experimental group, n=77) or continue NAs monotherapy (control group, n=82). Levels of biochemical, virological and serological were measured at baseline and at 12-week intervals throughout the treatment course. Inter-group differences were statistically evaluated by t-test or Chi-squared test. Results At treatment week 48, the experimental group showed signiifcantly higher rate of HBeAg clearance (21.74%vs 7.04%,χ2=7.738, P<0.05) and seroconversion (20.29% vs 7.04%, χ2 = 6.709, P < 0.05). The experimental group also showed higher rate of HBsAg seroconversion (7.25%vs 0,χ2=5.335, P<0.05). The rates of HBV DNA relapse were 0 and 4.22%, but the difference did not reach statistical signiifcance (χ2=2.979, P>0.05). The patients who had higher baseline HBsAg (>2000 IU/ml) showed lower HBeAg seroconversion than the patients who had lower HBsAg (≤2000 IU/ml), but the differences did not reach statistical signiifcance (χ2=2.833 and 0.147, both P>0.05). Sequential plus IFN-α1b could add the rated of HBeAg seroconversion at any time, while it may had relationship between the course of NAs and the rate of HBeAg seroconversion. conclusions For patients with HBeAg-positive CHB who had unsatisfactory response to NAs monotherapy, plus IFN-α1b has higher rate of seroconversion.
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