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

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• 作者：Vincent Rijckborst¹ ; Bettina E. Hansen¹ ; ² ; Peter Ferenci³ ; Maurizia R. Brunetto⁴ ; Fehmi Tabak⁵ ; Yilmaz Cakaloglu⁶ ; A. Galeota Lanza⁷ ; Vincenzo Messina⁸ ; Claudio Iannacone⁹ ; Benedetta Massetto¹⁰ ; Loredana Regep¹¹ ; Massimo Colombo¹² ; Harry L.A. Janssen¹ ; ^&dagger ; ; ^{h.janssen@erasmusmc.nl} ; Pietro Lampertico¹² ; ^&dagger ;
• 关键词：HBeAg ; hepatitis B e antigen ; CHB ; chronic hepatitis B ; NA ; nucleos(t)ide analogues ; HBV ; hepatitis B virus ; PEG-IFN ; peginterferon ; SR ; sustained response ; HBsAg ; hepatitis B surface antigen ; ALT ; alanine aminotransferase ; ULN ; upper limit of normal ; PCR
• 刊名：Journal of Hepatology
• 出版年：2012
• 期刊代码：162_01688278
• 类别：med
• 出版时间：May, 2012
• 卷：56
• 期：5
• 页码：1006-1011
• 文件大小：782 K

摘要

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lass="h4">Background & Aims

It 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 <2 log 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.

lass="h4">Methods

HBeAg-negative patients receiving 48 or 96 weeks 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 猢? log HBV DNA decline at week 12. SR was defined as HBV DNA <2000 IU/ml and normal alanine aminotransferase 24 weeks after treatment.

lass="h4">Results

The 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 96 weeks, none of the 7 (21%) without HBsAg decline and with <2 log HBV DNA decline at week 12 achieved an SR (NPV 100%).

lass="h4">Conclusions

We 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 96 weeks of PEG-IFN therapy.