APASL2013 较新的组合疗法,中期分析乙肝表面抗原动力学

StephenW

Ontreatment HbsAg Kinetics with Newer Combination Therapy in Genotype D, Envelope Antigen Negative Chronic Hepatitis B - Interim Analysis   
  
   
Vadamalainathan Govindasamy, Mohanprasad Virukalpattigopalratnam
Department of Clinical Research, VGM Hospital-Institute of Gastroenterology, Coimbatore, India

Background and aims: HBsAg levels appear to correlate with transcriptionally active cccDNA and HBsAg seroclearance is considered to be the closest to cure in Chronic Hepatitis B and is also associated with a favourable long term outcome. Aim of present study is to assess HBsAg kinetics including HBsAg loss in two combination therapies in HBeAg negative CHB.
Methods: Twenty consecutive patients with HBeAg negative, Genotype D CHB were randomized to two arms. Patients in Arm A received PEG Interferon alpha-2b 1.5mcg/kgbw S/c once weekly along with oral Tenofovir 300mg per day for 48 weeks followed by Tenofovir alone for another 96 weeks. Patients in Arm B received a combination of Telbivudine 600mg with Tenofovir 300mg per day for 144 weeks. Quantification of HBsAg and HBV DNA were performed at baseline and six monthly intervals till 144th Week.
Results: Baseline characteristics were comparable in both the arms. After 48 weeks of treatment, ten patients (100%) in Arm A had undetectable HBV DNA compared to nine pts(90%) in Arm B. ALT normalization was achieved in 10/10 patients in arm A vs 7/10 pts in Arm B. Mean HBsAg decline from baseline was higher in Arm A than Arm B (1.85 vs 0.64 ,p =0.000). No Serious adverse events were noted in either of the groups.
Conclusion: On therapy Decline in HBsAg levels was highest in Interferon therapy arm than Nucleoside analogs arm reinforcing the fact that HBsAg decline is effected more by immune modulation than antiviral effect. The combination of Tenofovir with Peg Interferon has shown greater efficacy in terms of HBV DNA negativity , ALT normalisation as well as reduction in HBsAg levels. However the translation of these positive findings into sustained viral response and HBsAg loss needs to be seen since this is only an interim data.


Assigned speakers:
Dr. Vadamalainathan Govindasamy, VGM Hospital-Institute of Gastroenterology , Coimbatore , India

Assigned in sessions:
07.06.2013, 08:30-17:30, PT-4, HEP B Clinical, Exhibition Hall

StephenW

背景和目的：出现HBsAg水平与cccDNA的转录活性，被认为是乙肝表面抗原转阴是最接近治愈慢性乙型肝炎，也伴随着一个有利的长期结果。本研究的目的是评估乙肝表面抗原包括两个组合治疗HBeAg阴性慢性乙型肝炎的HBsAg消失的动力学。
方法：将20例患者HBeAg阴性，D基因型CHB患者随机分配到两种武器。在ARM患者收到的聚乙二醇干扰素α-2b 1.5mcg/kgbw S / C，每周一次随着每天300毫克口服泰诺福韦泰诺福韦独自另一个96周48周。在B组患者接受替比夫定600毫克的组合为144周泰诺福韦每天300毫克。 HBsAg和HBV DNA定量进行基线和6个月至第144周的间隔。
结果：基线特征在两个武器相媲美。 48周的治疗后，10例患者（100％），在ARM已检测不到HBV DNA相比，9个点（90％）在ARM B. ALT正常化取得了A组与7/10 10/10例在ARM B.平均HBsAg的下降，从基线明显高于臂A比B组（1.85比0.64，P = 0.000）。注意到组无严重不良反应事件。
结论：HBsAg水平Ontherapy下降是最高干扰素治疗臂比核苷类似物臂加强乙肝表面抗原下降的事实，影响抗病毒效果的免疫调制比。泰诺福韦与PEG干扰素结合HBV DNA阴性，ALT正常化，以及降低HBsAg水平方面表现出更大的疗效。但是，这些积极的结果翻译成持续病毒学应答和HBsAg消失需要看到，因为这仅仅是一个临时的数据。