应答指导的聚乙二醇干扰素治疗 HBeAg 阳性慢性乙型肝炎患者：一项随机对照研究。
Response-guided peginterferon therapy in patients with HBeAg-positive chronic hepatitis B: A randomized controlled study.
机构信息
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangdong Province, China.
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, Xicheng District, China.
出版信息
J Hepatol. 2016 Oct;65(4):674-682. doi: 10.1016/j.jhep.2016.05.024. Epub 2016 May 26.
BACKGROUND & AIMS: Response-guided therapy has been confirmed to be an effective strategy for the treatment of chronic hepatitis C in the pegylated interferon (PegIFN) era, but no randomized trial utilizing this strategy has been conducted in chronic hepatitis B.
METHODS
In this open-label, multicenter, randomized trial, HBeAg positive patients were treated with PegIFN (180μg/week) for 24weeks. Early responders (HBsAg <1500IU/ml and HBV DNA <10(5)copies/ml at week 24) received PegIFN for a further 24weeks (arm A), while non-early responders were randomized to PegIFN for another 24weeks (arm B), another 72weeks (arm C) or PegIFN for another 72weeks plus adefovir for 36weeks (arm D). The primary endpoint was the change of quantitative HBsAg from baseline to the end of follow-up (EOF).
RESULTS
For non-early responders, 96-week PegIFN monotherapy did not lead to a greater reduction of HBsAg from baseline to EOF, compared with 48-week PegIFN (-0.71 vs. -0.67log10IU/ml, P=0.407). The rate of HBeAg seroconversion with HBV DNA <2000IU/ml at EOF were similar for arms B, C and D (17.9%, 23.9% and 25.0% respectively). For patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24, 38.4% and 37.0% achieved HBeAg seroconversion with HBV DNA <2000IU/ml at EOF respectively.
CONCLUSIONS
Patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24 would benefit from continued PegIFN treatment. Extending the duration of PegIFN with or without adding adefovir did not show superiority over 48weeks PegIFN monotherapy.
LAY SUMMARY
Extending the duration of pegylated interferon (PegIFN) alfa-2a is not recommended in HBeAg positive patients as treatment extension beyond 48weeks did not show convincing benefit. Patients who achieved HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml after 24-week PegIFNα-2a showed satisfactory outcome after the withdrawal of finite PegIFNα-2a treatment.
CLINICAL TRIAL NUMBER
NCT01086085.
背景与目的
在聚乙二醇干扰素（PegIFN）时代，应答指导治疗已被证实是慢性丙型肝炎治疗的有效策略，但在慢性乙型肝炎中尚未开展利用该策略的随机试验。
方法
在这项开放性、多中心、随机试验中，HBeAg 阳性患者接受 PegIFN（180μg/周）治疗 24 周。早期应答者（HBsAg<1500IU/ml 和 HBV DNA<10(5)拷贝/ml 在第 24 周）接受另外 24 周的 PegIFN 治疗（A 组），而非早期应答者随机分为接受 PegIFN 另外 24 周（B 组）、另外 72 周（C 组）或 PegIFN 另外 72 周加阿德福韦酯 36 周（D 组）。主要终点是从基线到随访结束（EOF）时定量 HBsAg 的变化。
结果
对于非早期应答者，与 48 周 PegIFN 相比，96 周 PegIFN 单药治疗并未导致 HBsAg 从基线到 EOF 的更大降低（-0.71 与-0.67log10IU/ml，P=0.407）。EOF 时 HBeAg 血清学转换且 HBV DNA<2000IU/ml 的比率在 B、C 和 D 组相似（分别为 17.9%、23.9%和 25.0%）。对于第 24 周 HBsAg<1500IU/ml 或 HBV DNA<10(5)拷贝/ml 的患者，分别有 38.4%和 37.0%在 EOF 时实现 HBeAg 血清学转换且 HBV DNA<2000IU/ml。
结论
第 24 周 HBsAg<1500IU/ml 或 HBV DNA<10(5)拷贝/ml 的患者将从继续 PegIFN 治疗中获益。延长 PegIFN 时间（联合或不联合阿德福韦酯）并不优于 48 周 PegIFN 单药治疗。
要点总结
不建议 HBeAg 阳性患者延长聚乙二醇干扰素（PegIFN）α-2a 的治疗时间，因为延长至 48 周以上并未显示出令人信服的获益。在接受 24 周 PegIFNα-2a 治疗后 HBsAg<1500IU/ml 或 HBV DNA<10(5)拷贝/ml 的患者在停止有限的 PegIFNα-2a 治疗后获得了满意的疗效。
临床试验注册号
NCT01086085。
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