HBsAg水平可指导干扰素治疗慢性乙肝

[AASLD 2012]血清HBsAg水平可指导干扰素治疗慢性乙肝
2012年美国肝病研究学会（AASLD）第63届年会上，荷兰鹿特丹伊拉斯谟大学医学院的803例患者的汇总分析表明，HBsAg水平可以很好的预测HBeAg阳性慢性乙肝患者的PEG-IFN应答。不论哪种HBV基因型患者，24周时若HBsAg>20,000IU/mL均是停药的指征。

该分析来自3项全球性随机临床试验(Peginterferon alfa-2a phase 3， Neptune and HBV 99-01)，共纳入803例HBeAg 阳性患者基因型囊括了A-D型，应用PEG-IFN±拉米夫定治疗1年。对基于HBsAg水平较基线期无下降的停药原则与12周时HBsAg < 1500IU/mL 或24周时> 20 000 IU/mL预测高或低应答率的预测原则进行了比较。

患者主要为亚洲人(n = 580，72%）或高加索人 (n = 188，23%)，HBV基因型A/B/C/D所占比例分别为13/25/48/14%。182 (23%)例患者获得应答(治疗6个月HBeAg消失，HBV DNA < 2，000 IU/mL），HBsAg 消失率为39 (5%)。12周或24周HBsAg < 1 500 IU/mL的患者获得的应答率分别为45和46%。12周时，HBsAg水平无下降的患者的应答率为14%，而HBsAg> 20，000 IU/mL的患者的应答率为6%，但是不同基因型间的应答率有差异。基于12周时 HBsAg水平无下降的停药原则更适用于HBV基因型A (NPV 88%）或 D（NPV 98%）的患者，而HBsAg > 20，000 IU/mL可更好地明确基因型B (NPV 92%)或C (NPV 99%)的患者无应答。24周时，几乎所有的HBsAg > 20，000 IU/mL患者未能获得应答，不论是哪种基因型 (NPV 98%)。停药原则很适合于PEG-IFN单药治疗时（n = 465)。

研究论文摘要：

Response-guided peginterferon therapy in HBeAg-positive chronic hepatitis B using serum hepatitis B surface antigen levels: a pooled analysis of 803 patients

Background. On-treatment hepatitis B surface antigen (HBsAg) levels may predict response to peginterferon (PEG-IFN) therapy in chronic hepatitis B (CHB).

Methods. 803 HBeAg-positive patients treated with PEG-IFN ± lamivudine for one year in 3 global randomized studies (Peginterferon alfa-2a phase 3, Neptune and HBV 99-01) infected with HBV genotypes A through D were enrolled. A stopping-rule based on absence of a decline from baseline was compared to a prediction-rule that uses HBsAg levels of <1500IU/mL and >20,000IU/mL at week 12 or 24 to identify patients with high and low probabilities of response.

Results. Patients were predominantly Asian (n=580, 72%) or Caucasian (n=188, 23%) and harboured HBV genotypes A/B/C/D in 13/25/48/14%. Response (HBeAg loss with HBV DNA<2,000 IU/mL at 6 months post-treatment) was achieved in 182(23%) and HBsAg loss in 39 (5%). Patients with an HBsAg level<1,500IU/mL at week 12 or 24 achieved response in 45 and46%. At week 12, patients without HBsAg decline achieved a response in 14%, compared to 6% of patients with HBsAg>20,000IU/mL, but performance varied across HBV genotype. A
stopping-rule based on absence of a decline at week 12 was superior for patients infected with genotypes A (NPV 88%) or D (NPV 98%), while an HBsAg level >20,000 IU/mL better identified non-responders with genotypes B (NPV 92%) or C (NPV 99%). At week 24, nearly all patients with HBsAg >20,000 IU/mL failed to achieve a response, irrespective of HBV genotype (NPV 98%). The performance of the proposed stopping-rules in patients treated with peginterferon monotherapy (n=465) was excellent (figure).

Conclusions. On-treatment HBsAg level is a strong predictor of response to PEG-IFN in HBeAg-positive CHB. Discontinuation is indicated in all patients with an HBsAg level >20,000 IU/mL at treatment week 24, irrespective of HBV genotype.