AASLD 2011:Response to peginterferon alfa-2a in HBeAg-negative CHB: baseline and

StephenW

Response to peginterferon alfa-2a in HBeAg-negative CHB: baseline and on-treatment kinetics of HBsAg serum levels vary according to HBV genotype
M. R. Brunetto1; P. Marcellin2; B. Cherubini1; C. Yurdaydin3; P. Farci4; S. J. Hadziyannis5; V. Rothe6; L. Regep7; H. Kapprell8; F. Bonino1
1. General Medicine 2 - Digestive and Liver Disease, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
2. Service d’Hepatologie and Centre de Recherches Biologiques Beaujon , University of Paris, Clichy, France.
3. Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
4. Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
5. Department of Medicine and Hepatology, Henry Dunant Hospital, Athens, Greece.
6. IST GmbH, Mannheim, Germany.
7. F. Hoffmann-La Roche, Basel, Switzerland.
8. ABBOTT GmbH & CO KG, Wiesbaden, Germany.


HBsAg levels during peginterferon alfa-2a (PEG-IFNα-2a) therapy are associated with post-treatment response; different HBsAg kinetic patterns were observed. The influence of HBV genotype on on-treatment HBsAg kinetics and end of treatment levels in patients with 5 yrs post-treatment follow-up was assessed. Methods: HBeAg-negative patients who had received PEG-IFNα-2a±lamivudine in the phase 3 study, followed up for 5 yrs post-treatment and with available HBsAg data were analyzed. HBsAg kinetics in responders (HBV DNA<2000 IU/mL 5 yrs post-treatment) and nonresponders (NR, HBV DNA>2000 IU/mL 5 yrs post-treatment) and by genotype are described (patients with HBsAg at baseline and wks 12, 24 and 48). ROC analysis determined HBsAg levels associated with sustained response, NR or relapse (HBV DNA<2000 IU/mL at wk 48, >2000 IU/mL 5 yrs post-treatment) in patients with HBsAg levels at baseline and wk 48 (genotype A: n=13; B: n=64; C: n=91; D: n=31).Results: Baseline HBsAg levels were highest in genotype A (15002 vs 4138, 2648 and 5910 IU/mL for genotypes B, C and D; P<0.0001 for the global comparison). The greatest difference in HBsAg kinetics between responders and NR was at wks 12–24 in genotype A and wks 0–12 in genotypes B and D (table). The difference was minimal in genotype C. In genotypes A and B the difference resulted from the HBsAg decline in responders while the difference in genotype D resulted from the HBsAg increase in NR. As the patterns of on-treatment HBsAg decline varied between genotypes it was not possible to find a single on-treatment predictive rule at a single time point. Applying genotype-specific cut-offs at week 48 gave high positive predictive values (PPV). In genotype A, 100% (3/3) of responders had HBsAg≤400 IU/mL vs 10% (1/10) of NR/relapsers. In genotype B, 100% (7/7) of responders had HBsAg≤50 IU/mL vs 14% (8/57) of NR/relapsers. In genotype C, 41% (11/27) of responders had HBsAg≤50 IU/mL vs 6% (4/64) of NR/relapsers. In genotype D, 60% (6/10) of responders had HBsAg≤1000 IU/mL vs 9.5% (2/21) of NR/relapsers. Conclusion: As on-treatment HBsAg kinetics vary between genotypes, it is not possible to identify a single threshold associated with high PPVs in all genotypes. On the contrary, genotype-specific thresholds should be considered as they are associated with high PPVs.

     Mean HBsAg change from baseline (log IU/mL)
                Responder     NR
Week    0–12    12–24    0–12    12–24
A(n=12)    0.25    2.10    0.03    0.05
B(n=24)    2.09    2.29    0.04    0.17
C(n=55)    0.13    0.51    0.15    0.35
D(n=26)    0.29    0.58    -0.21    -0.11

StephenW

聚乙二醇干扰素α- 2a的HBeAg阴性CHB：基线和治疗的HBsAg血清动力学响应根据HBV基因型
致辞Brunetto1; P. Marcellin 2; B.凯鲁比尼1，C. Yurdaydin 3，P. Farci 4，律政司司长Hadziyann​​is5;五Rothe 6 L. Regep 7 H. Kapprell 8楼博尼诺1
1。全科医学2 - 消化系统和肝脏疾病，Azienda Ospedaliero Universitaria Pisana，比萨，意大利。
2。服务D' Hepatologie和培训中心Recherches Biologiques Beaujon，克利希，法国巴黎大学。
3。消化内科，安卡拉大学医学院，土耳其安卡拉。
4。 ，卡利亚里，意大利卡利亚里大学医学系。
5。内科和肝病医院，雅典，希腊，亨利杜南。
6。北京时间有限责任公司，德国曼海姆。
7。 F.霍夫曼罗氏，瑞士巴塞尔。
8。雅培GMBH＆CO KG，威斯巴登，德国。


治疗乙肝表面抗原在聚乙二醇干扰素α- 2a（PEG -IFNα- 2a）的水平与治疗后的反应;观察不同的HBsAg的动力学模式。 HBV基因型在5岁后治疗的患者在治疗乙肝表面抗原动力学的影响和治疗水平结束后续评估。方法：HBeAg阴性患者，在第3阶段的研究曾接受PEG -IFNα- 2a的±拉米夫定，随访治疗后的5岁，并与现有的乙肝表面抗原数据进行了分析。应答者HBsAg的动力学（HBV DNA <2000 IU / ml的5岁后治疗）和治疗无效（星期日，HBV DNA> 2000 IU / ml的5岁后治疗）和基因型（乙肝表面抗原在基线和12周的患者，24和48）。 ROC分析确定HBsAg水平与持续应答相关，NR或复发（HBV - DNA <2000 IU /周48毫升，> 2000 IU / mL的5岁后治疗）患者在基线和48周HBsAg水平（A基因型： N = 13，B：N = 64，C：N = 91，D：N = 31），结果：基线HBsAg水平最高，在A基因型（15002 VS 4138，2648和5910 IU /毫升基因型B，C和D，为全球的比较，​​P <0.0001）。在HBsAg的动力学反应和NR之间的最大区别是在12-24周基因型A和基因型B和D（表）0-12周。所不同的是最小的基因型C.在A和B的区别，从应答者HBsAg的下降导致的基因型，而基因型D的区别在NR HBsAg的增加导致。不同基因型之间，作为治疗乙肝表面抗原下降的模式，这是不可能找到一个单一的治疗预测规则，以一个单一的时间点。在48周中的应用基因型具体的削减权衡了较高的阳性预测值（PPV）服务。在A基因型，100％的应答者（3 / 3），乙肝表面抗原≤400国际单位/毫升和10％（1 / 10）上午十时三十分/ relapsers。 B基因型，100％的应答者（7 / 7），乙肝表面抗原≤50 IU / mL的比14％（8 / 57）上午十时三十分/ relapsers。 C基因型，41％的应答者（11/27），乙肝表面抗原≤50 IU /毫升和6％（4 / 64）上午十时三十分/ relapsers。基因型D，60％的应答者（6 / 10），乙肝表面抗原≤1000 IU /毫升和9.5％（2 / 21）上午十时三十分/ relapsers。结论：在治疗乙肝表面抗原动力学之间的基因型不同，它是无法确定一个单一的阈值与所有基因型的高PPVs相关。相反，应考虑基因型特定的阈值，因为它们是与高PPVs关联。

意味着乙肝表面抗原从基线的变化（日志国际单位/毫升）
响应星期日
周0-12 12-24 0-12 12-24
A（N = 12）0.25 2.10 0.03 0.05
乙（N = 24）2.09 2.29 0.04 0.17
C组（n = 55）0.13 0.51 0.15 0.35
D（N = 26）0.29 0.58 -0.21 -0.11