聚乙二醇化干扰素α-2a（40KD）HBeAg阴性CHB的回应：在处理动

StephenW

Response to peginterferon alfa-2a (40KD) in HBeAg-negative CHB: On-treatment kinetics of HBsAg serum levels vary by HBV genotype

    Maurizia R. Brunetto a, Corresponding author contact information, E-mail the corresponding author,
    Patrick Marcellin b,
    Beatrice Cherubini a,
    Cihan Yurdaydin c,
    Patrizia Farci d,
    Stephanos J. Hadziyannis e,
    Vivien Rothe f,
    Loredana Regep g,
    Ferruccio Bonino h

    a U.O. Epatologia–Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
    b Service d’Hépatologie and Centre de Recherches Biologiques Beaujon, University of Paris, Clichy, France
    c Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey
    d Department of Medical Sciences, University of Cagliari, Cagliari, Italy
    e Department of Medicine and Hepatology, Henry Dunant Hospital and Liver Research Unit of Athens University at Evgenidio Hospital Athens, Greece
    f IST GmbH, Mannheim, Germany
    g F. Hoffmann-La Roche, Basel, Switzerland
    h Cattedra di Gastroenterologia – Università Pisa, Italy

Abstract
Background & aims

We investigated whether HBV genotype influences on-treatment HBsAg kinetics and/or the end-of-treatment HBsAg levels associated with long-term virological response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a ± lamivudine in the Phase III trial.
Methods

All patients (n = 230) who participated in long-term follow-up were included according to the availability of HBsAg levels measurements. Long-term virological response was defined as HBV DNA ⩽10,000 cp/mL (1786 IU/mL) at 5 years post-treatment. Genotype-specific end-of-treatment HBsAg levels associated with long-term virological response (identified by ROC analysis) were assessed in 199 patients with HBsAg measurements available at baseline and end-of-treatment. HBsAg kinetics according to genotype and long-term virological response were investigated in the 117 patients with additional samples available at weeks 12, 24 and 72.
Results

Baseline HBsAg levels were significantly higher for A than B, C and D genotypes (p<0.05). On-treatment HBsAg kinetics varied according to HBV genotype. The difference between responders and non-responders was greatest for genotype A from weeks 12 to 24; for genotypes B and D from baseline to week 12; there was no significant difference over any timeframe for genotype C. High positive predictive values for long-term virological response could be obtained by applying end-of-treatment genotype-specific cut-offs: 75%, 47%, 71% and 75% for genotypes A (<400 IU/mL), B (<50 IU/mL), C (<75 IU/mL) and D (<1000 IU/mL), respectively.
Conclusions

On-treatment HBsAg kinetics vary between HBV genotypes. Genotype-specific monitoring timeframes and end-of-treatment thresholds could ameliorate response-guided treatment of HBeAg-negative chronic hepatitis B.

StephenW

背景与目的

我们研究HBV基因型是否影响对治疗乙肝表面抗原动力学和/或伴有长期的病毒学应答与聚乙二醇干扰素α-2a的±拉米夫定治疗HBeAg阴性慢性乙型肝炎患者的III期临床试验的治疗结束HBsAg水平。
方法

所有患者组（n = 230），参加在长期随访，包括HBsAg水平测量的可用性。长期的病毒学应答定义为HBV DNA⩽10,000 CP /毫升（1786 IU / mL）的治疗后5年。在199例HBsAg的测量基线和治疗结束基因型特异性治疗结束HBsAg水平与长期的病毒学应答（ROC分析确定）进行了评估。 HBsAg的动力学额外的样品，可在12日，24日和72周的117例进行了调查，根据基因型和长期的病毒学应答。
结果

基线HBsAg水平显着高于A比B，C和D基因型（P <0.05）。治疗乙肝表面抗原动力学变化，根据HBV基因型。反应者和无应答者之间的差异是最大的基因型A从12到24周;基因型B和D，从基线到12周，C基因型的高阳性预测值长期也没有显着的差异，在任何时间段内病毒学应答可以得到应用治疗结束基因型特异性切割取舍：75％，47％，71％和75％，基因型A（<400 IU /毫升），B（<50 IU /毫升）， C（<75 IU /毫升）和D（<1000 IU / mL）的分别。
结论

治疗乙肝表面抗原动力学变化之间HBV基因型。特定基因型监测时限和治疗结束阈值可以改善响应引导治疗HBeAg阴性慢性乙型肝炎

咬牙硬挺

感谢分享