HBeAg阳性慢性乙型肝炎用核苷（酸）类似物治疗部分病毒学应答患者转换聚乙二醇干扰素α-2a治疗的研究

Efficacy of pegylated-interferon α-2a treatment in patients with HBeAg-positive chronic hepatitis B and partial viral response to nucleoside analogue therapy

目的探讨聚乙二醇干扰素（Peg-IFN）α-2a对核苷（酸）类似物在治疗获得部分病毒学应答且HBeAg仍为阳性的慢性乙型肝炎患者的疗效及影响疗效的相关因素。方法对核苷（酸）类似物在治疗中获得部分病毒学应答且HBeAg仍为阳性的慢性乙型肝炎患者进行Peg-IFNα-2a180μg每周皮下注射1次治疗；所有患者采用个性化疗程，对Peg-IFNα-2a治疗期间HBsAg和（或）HBeAg持续下降者则继续治疗。患者入组前及Peg-IFNα-2a治疗期间每3个月检测HBVDNA含量和血清学指标。以Peg-IFNα-2a治疗结束时HBsAg消失或血清学转换为主要疗效评价指标，HBsAg10IU／ml和HBeAg血清学转换为次要疗效评价指标。组间差异采用χ^2检验比较。使用受试者工作特征曲线下面积来评估干扰素治疗前基线血清HBsAg水平对干扰素治疗结束时〈10IU／ml的预测意义。结果共入组并治疗患者81例，核苷（酸）类似物治疗12．0（6．0～24．0）个月。Peg-IFNα-2a治疗19．6（15．5～33．3）个月；8．6%（7例）获得HBsAg消失或血清学转换，除HBsAg消失者外，另有17．3％（14例）达到HBsAg〈10IU／ml。HBeAg消失率为40．7%，HBeAg血清学转换率为38．3％。基线HBsAg〈1500IU／ml预测干扰素治疗结束时HBsAg〈10IU／ml的受试者工作特征曲线下面积=0．747，敏感度和特异度为87．3％和33．3％；阳性预测值和阴性预测值为82．1％和42．8％。结论Peg-IFNα-2a治疗可使经核苷（酸）类似物治疗获得部分病毒应答的HBeAg阳性慢性乙型肝炎的患者获得更高的免疫控制，基线HBsAg水平〈1500IU／ml可预测Peg-IFNα-2a的疗效。

Objective To investigate the efficacy and related factors of pegylated-interferon α-2a （PEG-IFN-2a） trealment in patients with hepatitis B e antigen （HBeAg）-positive chronic hepatitis B （CHB） who achieved partial viral response with nucleoside analogue （NA） therapy. Methods Patients with HBeAg-positive CHB and partial viral response to NAlrealment were administered a PEG-IFN-2a therapy regimen of 180 g subcutaneous injection once weekly for a personalized dttrafion of lime. The existing NA therapy was continued in comb＇marion with the new PEG-IFN-2a treamaent for 12 weeks. Measurements of serum HBV DNA load, hepatitis B surface antigen （HBsAg）, hepatitis B surface antibody （anfi-HBs）, HBeAg and hepatitis B e antibody （anti-HBe） were taken at baseline （prior to addition of the PEGIFN-2a therapy） and every 3 months atterwards. For determining response to trealment, primary efficacy was defined as undetectable HBsAg and seroconversion, and secondary efficacy was defined as HBsAg 〈 10 1U/mL and HBeAg Statistical analysis was carried out using SPSS statistical software. Results A total of 81 consecutive patients with an average of 12.0 months （range： 6.0-24.0 months） of NA therapy were included in the study and received an average of 19.6 months （range： 15.5-33.3 months） of PEG-IFN-2a treamaent. At the end of PEG-IFN-2a therapy, 7 （8.6%） of the patients achieved undetectable HBsAg and seroconversion, and 14 （17.3%） showed HBsAg 〈 10 IU/mL. In addition, 40.7% achieved undetectable HBeAg and seroconversion, a rate that was slightly higher than that （38.3%） seen in Ireamaent-naive patients who received PEG-IFN-2a. Statistical analyses suggest that baseline level of HBsAg at 〈 1500 IU/mL may predict end of PEG-IFN-2a Irealment response for HBsAg 〈 10 IU/mL, as evidenced by the area under the curve measure of 0.747, sensitivity measure of 87.3%, specificity measure of 33.3%, positive predictive value of 82.1% and negative predictive value of 42.8%. Conclusion Patients with HBeAg-positive CHB and partial viral response to NA therapy can achieve undetectable HBsAg and HBeAg seroconversion afl~ switching to PEG-IFN-2a treatment. Baseline HBsAg level may be predictive of response to this therapeutic slrategy.