HBeAg阳性慢性乙型肝炎患者基于聚乙二醇干扰素-α 24周应答采用不同治疗方案的疗效及预测因素分析

肝脏 ›› 2016, Vol. 21 ›› Issue (7): 528-531.

HBeAg阳性慢性乙型肝炎患者基于聚乙二醇干扰素-α 24周应答采用不同治疗方案的疗效及预测因素分析

陈璐, 周惠娟, 郭斯敏, 赵刚德, 莫瑞东, 郭清, 汤伟亮, 蔡伟, 王晖, 谢青

200025 上海交通大学医学院附属瑞金医院感染科

收稿日期:2016-02-19 出版日期:2016-07-31 发布日期:2020-07-09
通讯作者: 周惠娟,Email:13621619733@163.com
基金资助:
国家自然科学基金资助项目(81171569);上海市科委优秀学术带头人项目(12XD1403600);国家十二五科技重大专项(2012ZX10002007-002-004、2012ZX10002004-003、2012ZX10002003-003-012、2013ZX10002001-001-004);上海市领军人才资助项目;国家临床重点专科建设项目(感染病学);第四轮上海市公共卫生三年行动计划重点学科建设项目(15GWZK0102)

Efficacy and predictive factors of sequential-combination therapy of Peglyated interferon followed with nucleoside analogues for HBeAg positive chronic hepatitis B patients

CHEN Lu, ZHOU Hui-juan, GUO Si-min, ZHAO Gang-de, MO Rui-dong, GUO Qing, TANG Wei-liang, CAI Wei, WANG Hui, XIE Qing

the Department of Infectious Disease, Shanghai JiaoTong University Medical School Ruijin Hospital, Shanghai 200025, China

Received:2016-02-19 Online:2016-07-31 Published:2020-07-09
Contact: ZHOU Hui-juan, Email:13621619733@163.com

摘要/Abstract

摘要： 目的通过研究HBeAg阳性慢性乙型肝炎初治患者接受聚乙二醇干扰素-α(Peg-IFN-α)24周,根据RGT策略给予不同的治疗方案,分析比较其疗效及预测因素。方法收集87例初治选用足量Peg-IFN-α的HBeAg阳性慢性乙型肝炎患者,24周时根据应答情况接受不同序贯单药或联合治疗,分别为a:有早期应答者继续Peg-IFN-α治疗至48周(n=20);而对于无早期应答者采用3种治疗方案,即b:继续单药Peg-IFN-α治疗至48周(n=17);c:Peg-IFN-α单药延长治疗至96周(n=25);d:在Peg-IFN-α基础上联合恩替卡韦并延长治疗至96周(n=25)。比较分析各组之间的疗效及应答的预测因素。结果治疗结束时,a组较b组,d组较c组HBsAg、HBV DNA下降均有明显增加(P值分别为0.0194、0.041以及0.0008、0.0035)。96周治疗患者(无论单药还是联合)在治疗结束时达到HBsAg≤1000 IU/mL且HBeAg(-)的患者均较b组增加(P=0.0384);治疗结束时d组较c组HBeAg下降增加,对HBeAg消失及血清学转换有一定的作用,但差异无统计学意义;基线HBsAg≥1500 IU/mL的患者,治疗结束后d组较c组DNA转阴率、以及获得HBsAg下降≥2 lg IU/mL且HBV DNA转阴的患者都明显增加(P分别为0.0228和0.0237)。结论对于无早期应答患者,延长干扰素疗程并同时加用核苷类药物可以提高HBsAg及HBV DNA载量下降的幅度。基线HBsAg≥1500 IU/mL的患者,仍可选择联合核苷类药物并延长的治疗方案。

关键词: 肝炎,慢性,乙型, 聚乙二醇干扰素, 恩替卡韦, 乙型肝炎表面抗原, 乙型肝炎e抗原

Abstract: Objective To investigate the efficacy and predictive factors of sequential-combination therapy based on respond guided treatment (RGT) for the Peg-IFN-α treated HBeAg positive chronic hepatitis B (CHB) patients.Methods According to the 24-week treatment results, 87 patients who received Peg-IFN-α as their initial treatment were divided into four groups to receive different treatments. In patients with early response (group a), Peg-IFN-α treatment was extended to 48 weeks. Among patients with non-early response (NER), 20 patients remained on Peg-IFN-α monotherapy for another 24 weeks (group b), 17 received Peg-IFN-α monotherapy up to totally 96 weeks (group c) and 25 received entecavir (ETV) added onging Peg-IFN-α therapy up to totally 96 weeks (group d).Results The reductions of HBsAg and HBV DNA were more obvious in a and d group than those in b and c group, respectively ( a versus b, P=0.0194, 0.041 and d versus c, P= 0.0008, 0.0035). At the endpoint of patients with 96-weeks treatment (group c and d), the rates of HBsAg (less than 1000 IU/mL) and HBeAg loss were significantly higher than those in group B (P=0.0384). Moreover, HBeAg decreased more obviously in group d than that in group c, with no statistically significance in HBeAg loss and seroconversion. Baseline HBsAg level was speculated to be a predictive factor for the efficiency, because patients with HBsAg ≥ 1500 IU/mL achieved more HBV DNA loss and HBeAg decrease in group d than those in group c (P=0.0228 and 0.0237).Conclusion Sequential and combining treatment could make patients achieve more HBsAg and HBV DNA loss, with no significant difference in HBeAg loss or serum conversion. Meanwhile, 96-week Peg-IFN-α monotherapy or sequential Peg-IFN-α plus ETV therapy could lead to more HBeAg loss, and we further demonstrate that the baseline level of HBsAg would be an important predict factor for the efficacy.

Key words: Hepatitis B, Chronic, Peglyated interferon, ETV, HBsAg, HBeAg

陈璐, 周惠娟, 郭斯敏, 赵刚德, 莫瑞东, 郭清, 汤伟亮, 蔡伟, 王晖, 谢青. HBeAg阳性慢性乙型肝炎患者基于聚乙二醇干扰素-α 24周应答采用不同治疗方案的疗效及预测因素分析[J]. 肝脏, 2016, 21(7): 528-531.

CHEN Lu, ZHOU Hui-juan, GUO Si-min, ZHAO Gang-de, MO Rui-dong, GUO Qing, TANG Wei-liang, CAI Wei, WANG Hui, XIE Qing. Efficacy and predictive factors of sequential-combination therapy of Peglyated interferon followed with nucleoside analogues for HBeAg positive chronic hepatitis B patients[J]. Chinese Hepatolgy, 2016, 21(7): 528-531.

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