EASL 2013: 恩替 + 干扰素 24周, 恩替120周 V 144周单恩替

StephenW

Abstract 758



ENTECAVIR PLUS PEGINTERFERON ALFA-2A VS. ENTECAVIR ALONE IN THE TREATMENT OF HEPATITIS B E ANTIGEN-POSITIVE CHRONIC HEPATITIS B: AN INTERIM REPORT
     
C.-J. Liu1*, C.-C. Wang2, S.-S. Yang3, C.-W. Su4, L.-Y. Liao5, T.-H. Lee6, W.-L. Chuang7, C.-L. Chen8, R.-N. Chien9, C.-Y. Peng10, C.-M. Lee11, Y.-F. Lee12, J.-H. Kao8, P.-J. Chen8, D.-S. Chen8, Taiwan-LiverNet Consortium (TLC)
1Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei City, 2Department of Internal Medicine, Buddhist Tzu Chi General Hospital Taipei Branch, New Taipei City, 3Cathay General Hospital, 4Taipei Veterans General Hospital, 5Taipei City Hospital, Ren-Ai Branch, Taipei City, 6Far Eastern Memorial Hospital, New Taipei City, 7Kaohsiung Medical University Hospital, Kaohsiung City, 8National Taiwan University College of Medicine and Hospital, Taipei City, 9Keelung Chang Gung Memorial Hospital, Keelung, 10China Medical University Hospital, Taichung City, 11Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 12Academia Sinica, Taipei City, Taiwan R.O.C.. *[email protected]

Background and aims: Peginterferon alfa or nucleos(t)ide analogue monotherapy is the current standard of care for antiviral treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). We aimed to assess the efficacy and safety of peginterferon alfa-2a plus entecavir (ETV) versus ETV alone for compensated HBeAg-positive CHB.
Methods: An open-label, multicenter randomized controlled trial was performed at 10 outpatient hepatology clinics in Taiwan. HBeAg-positive CHB patients were randomized at baseline to receive peginterferon alfa-2a 180mcg/week plus ETV 0.5mg/day for 24 weeks followed by ETV monotherapy for additional 120 weeks (Group A) or ETV alone for 144 weeks (Group B). Post-treatment follow-up was 48 weeks. The primary endpoint was the rate of HBeAg seroconversion at 144 weeks after the start of treatment.
Results: A total of 168 patients (63% male and mean age 39+/-9 years) were enrolled: 84 in each arm. Mean ALT level was 192+/-120 U/L and HBV DNA level was 8.6+/-9 Log10 IU/mL. At week 24, the rate of serum HBV DNA < 1000 copies/mL, ALT normalization, and HBeAg seroconversion in Group A (n=70) versus Group B (n=68) was 80% versus 60%, 47% versus 71%, and 14% versus 7%, respectively. At week 48, the rate of HBeAg seroconversion in Group A (n=65) versus Group B (n=62) was 28% versus 15%. At end of 144-week treatment, the rate of HBV DNA < 1000 copies/mL, ALT normalization, and HBeAg seroconversion in Group A (n=25) versus Group B (n=28) was 92% versus 89%, 92% versus 82%, and 40% versus 39%, respectively. Only 1 patient in Group B dropped out because of intolerable itching sensation. None of the patients in Group A developed peripheral neuropathy or other significant adverse effects.
Conclusions: In HBeAg-positive CHB, 24-week combined peginterferon alfa-2a plus ETV followed by 120-week ETV monotherapy was safe, but resulted in only transient greater efficacy than 144-week ETV monotherapy. No difference in end-of-treatment virologic and serologic response rates was observed between the two treatment arms.


Assigned speakers:
Prof. Chun-Jen Liu, National Taiwan University College of Medicine and Hospital , Taipei City , Taiwan R.O.C.

Assigned in sessions:
26.04.2013, 09:00-18:00, Poster Session, P02-07c, Category 07c: Viral Hepatitis B & D: Clinical (therapy, new compounds, resistance), Poster Area

StephenW

背景和目的：聚乙二醇干扰素α或核苷（酸）类似物单药治疗是目前抗病毒治疗乙型肝炎e抗原（HBeAg）阳性的慢性乙型肝炎（CHB）的护理标准。我们的目的是评估疗效和安全性聚乙二醇干扰素α-2a的加替卡韦（ETV）与ETV单独补偿HBeAg阳性CHB。
方法：开放标签，多中心随机对照试验进行了10肝病门诊诊所在台湾。 HBeAg阳性CHB患者随机接受聚乙二醇干扰素α-2a的180mcg/week加ETV 0.5mg/day为24周，随后ETV单药治疗增加120周（A组）或ETV 144周（B组）单独基线。治疗后随访48周。主要终点是在144周开始治疗后HBeAg血清学转换率。
结果：总共有168例患者（63％为男性，平均年龄39 + / -9岁）入选：84在每个手臂。平均ALT水平为192 U / L和HBV DNA水平+ / -120为8.6 + / -9 log10的国际单位/毫升。在第24周，血清HBV DNA <1000拷贝/毫升，ALT复常，HBeAg血清转换组率（N = 70）与B组（N = 68）分别为80％和60％，47％和71％ ，分别为14％与7％。 48周时，HBeAg血清学转换率组（65例）与B组（N = 62）为28％与15％。在144周的治疗结束，率，HBV DNA <1000拷贝/毫升，ALT复常，HBeAg血清转换组（N = 25）与B组（N = 28）为92％，92％和89％与82％，40％与39％，分别为。在B组下降，仅有1例患者因为瘙痒难耐的感觉。没有患者在A组发达的外周神经病变或其他重大不利影响。
结论：HBeAg阳性CHB，联合聚乙二醇干扰素α-2a联合ETV 24周后120周ETV单药治疗是安全的，超过144周ETV单药治疗，但只是暂时的疗效更好。观察到两个治疗组之间在治疗结束病毒学和血清学应答率无差异。

xiangrikui

你好，我大三携带10多年，一个半月前发病，一个月前开始治疗，治疗前转氨酶700，胆红素40多，dna5次方，大三。恩替一个月，1345阳，dna阴，肝功正常。医生建议联合长效干扰素治疗。请问这样做有意义么？还是只服恩替就可？？盼回复。
看完你的帖子后我理解是多此一举？恩替对我效果不错，一个月达到这样我很开心。但是不知道加用佩是不是能更优？
期待您的回复。

StephenW

回复 xiangrikui 的帖子

我不是医生. 根据最新的研究:
如果恩替卡韦治疗不理想，加干扰素，可提高响应（HBeAg血清转换和低HBVDNA）.恩替对你效果不错(dna阴，肝功正常), 我同意没有必要添加干扰素.1年后，如果您还没有变小三 和
你想停止服用恩替卡韦, 你可以考虑加干扰素实现血清转换.

xiangrikui

谢谢

宁静温泉

研究ETV单药治疗，和ETV+干扰素治疗的效果差异。

研究对象：一共168例HBeAg阳性患者，基线ALT平均水平192+/-120 U/L，随机分成两组。A组在前24周时干扰素+ETV，随后120周单用ETV。B组是144周单用ETV。治疗一共持续144周，并随访48周

24周时（A组对B组）：血清HBV DNA <1000拷贝/毫升分别为80％和60％，ALT复常率分别为47％和71％，HBeAg血清转换组率分别为14％与7％。
48周时（A组对B组）：HBeAg血清转换组率分别为28%与15%。
144周时（A组对B组）：血清HBV DNA <1000拷贝/毫升分别为92％和92％，ALT复常率分别为89％和82％，HBeAg血清转换组率分别为40％与39％。

结论：对于HBeAg阳性患者，采用聚乙二醇干扰素联合ETV治疗，相对于用ETV单药治疗，只是暂时性的取得更好疗效。在长期随访中，两组患者的治疗效果相当。

宁静温泉

之前有看到别的研究报告说，当通过核苷类似物治疗达到一定效果时，加用干扰素，可能会取得更好的效果。这两个研究之间粗看似有矛盾，细究则实有差别。读者切不可断章取义，或者就根据这个给自己定治疗计划。

宁静温泉

再加一句：综合目前所看到的文献，似乎干扰素在后期加用效果更好。

StephenW

回复 宁静温泉 的帖子

"再加一句：综合目前所看到的文献，似乎干扰素在后期加用效果更好" - 同意.如何综合是重要的.