Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negat

StephenW

Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negative patients treated with peginterferon alfa-2a

• Vincent Rijckborst,Bettina E. Hansen,Peter Ferenci,Maurizia R. Brunetto,Fehmi Tabak,
• Yilmaz Cakaloglu,A. Galeota Lanza,Vincenzo Messina,Claudio Iannacone,Benedetta Massetto,
• Loredana Regep,Massimo Colombo,Harry L.A. Janssen
• Pietro Lampertico
  

Received 16 September 2011; received in revised form 18 November 2011; accepted 14 December 2011.  published online 16 January 2012.

Background & AimsIt was recently demonstrated that none of the hepatitis B e antigen (HBeAg)-negative patients without any serum hepatitis B surface antigen (HBsAg) decline and with <2log hepatitis B virus (HBV) DNA decline at week 12 of a 48-week peginterferon alfa-2a (PEG-IFN) treatment course achieved a sustained response (SR). We aimed at validating this stopping rule in two independent trials.
MethodsHBeAg-negative patients receiving 48 or 96weeks of PEG-IFN in the phase III registration trial (N=85) and PegBeLiver study (N=75) were stratified according to the presence of any HBsAg decline and/or 2log HBV DNA decline at week 12. SR was defined as HBV DNA <2000IU/ml and normal alanine aminotransferase 24weeks after treatment.
ResultsThe original PARC trial included 102 patients (genotype A/D/other: 14/81/7), 25 (25%) had an SR. The validation dataset consisted of 160 patients (genotype A/B/C/D/other: 10/18/34/91/7), 57 (36%) achieved an SR. The stopping rule performed well across the two studies (p=0.001) and its negative predictive value [NPV] was 95% in the validation dataset harbouring genotypes A–D. Its performance was best for genotype D. Moreover, among the 34 patients treated for 96weeks, none of the 7 (21%) without HBsAg decline and with <2log HBV DNA decline at week 12 achieved an SR (NPV 100%).
ConclusionsWe confirmed in two independent studies that the combination of HBsAg and HBV DNA levels at week 12 identifies HBeAg-negative patients with a very low chance of SR to either 48 or 96weeks of PEG-IFN therapy.

StephenW

在第12周停止使用聚乙二醇干扰素α-2a治疗HBeAg阴性患者HBsAg和HBV DNA的规则验证

    文森特Rijckborst，贝蒂娜大肠杆菌汉森，得Ferenci，maurizia河Brunetto，fehmi塔巴克

耶尔马兹Cakaloglu, A. Galeota兰扎，蒙特拉墨西拿，劳迪奥Iannacone

benedetta马赛托，loredana Regep，马西莫·科伦坡，哈利洛杉矶Janssenemail地址

彼得罗Lampertico

收到2011年9月16日，在2011年11月18日收到; 2011年12月14日。 2012年1月16日网上公布。


背景与目的

这是最近表明，没有B型肝炎e抗原（HBeAg）阴性患者无任何血清乙型肝炎表面抗原（HBsAg）下降<2log B型肝炎病毒（HBV）DNA的跌幅在12周48周的聚乙二醇干扰素α-2a（PEG-干扰素）治疗过程中实现了持续应答（SR）。我们的目的是验证这两个独立的试验停止规则。
方法

HBeAg阴性患者接受第三阶段的登记试验（n = 85）和PegBeLiver的研究（n = 75），48或PEG干扰素96周的分层根据存在任何HBsAg的下降和/或周2log的HBV DNA下降12。被定义为血清HBV DNA <2000IU/ml和正常的丙氨酸转氨酶24周治疗后的简。
结果

原来的帕洛阿尔托研究中心的试验包括102例患者（基因型的A / D /其他：14/81/7），25（25％），有一个SR。验证数据集包括160例患者（基因型的A / B /C / D/其他：10/18/34/91/7），57（36％）实现的SR。停止规则进行横跨两个研究（P = 0.001）和阴性预测值[净现值]是在验证集窝藏基因型A至D的95％。其表现是最好的D基因型此外，为96周治疗的34例中，没有无HBsAg的下降与<2log 12周时HBV DNA下降7（21％）实现的SR（净现值100％）。
结论

我们在两个独立的研究证实，12周时HBsAg和HBV DNA水平的组合标识与HBeAg阴性患者的SR 48或PEG-干扰素治​​疗96周的机会非常低。

把握当下

e抗原阴性乙肝患者干扰停药原则：
如果3个月长效干扰之后DNA下降小于2次方，并且表面抗原没有下降，那么继续干扰（例如干扰总疗程2年）将收效甚微。