Gish Robert G, Chang Ting-Tsung, Lai Ching-Lung, de Man Robert A, Gadano Adrian, Llamoso Cyril, Tang Hong
University of California, San Diego School of Medicine, San Diego, CA, USA.
Antivir Ther. 2013;18(5):691-8. doi: 10.3851/IMP2559. Epub 2013 Mar 19.
Entecavir is a potent nucleoside analogue for treating chronic hepatitis B (CHB). Quantitative hepatitis B surface antigen (qHBsAg) levels are predictive of response to interferon-α in CHB treatment; however, the clinical utility of qHBsAg in nucleoside/nucleotide analogue-based CHB therapy is not fully characterized. This study assessed changes in qHBsAg in patients treated with entecavir in the Phase III study ETV-022.
This retrospective post hoc analysis included nucleoside/nucleotide-naive, hepatitis B e antigen (HBeAg)-positive patients receiving entecavir (0.5 mg daily) in ETV-022 who had samples available for qHBsAg analysis through week 48. qHBsAg, HBV DNA and alanine aminotransferase levels were assessed for the overall patient cohort, for cohorts with or without HBeAg loss or HBsAg loss by week 48, and by HBV genotype.
Overall, 95 patients from ETV-022 had available samples for qHBsAg analysis through week 48. In all cohorts, 48 weeks of entecavir therapy resulted in effective HBV DNA suppression. In the overall cohort, qHBsAg declined by -0.92 log10 IU/ml through week 48. The decline in qHBsAg was more pronounced in patients with subsequent HBeAg loss or HBsAg loss, and in patients infected with HBV genotype D or A. On-treatment qHBsAg changes did not correlate with changes in HBV DNA; no on-treatment or baseline factor was found to be predictive of HBeAg loss or HBsAg loss.
Through 48 weeks of entecavir therapy, qHBsAg declined predominantly in those patients who achieved seroclearance of HBeAg or HBsAg. However, unlike with interferon-α-based therapy, early qHBsAg decline was not predictive of serological response at year 1 of entecavir treatment.
恩替卡韦是一种用于治疗慢性乙型肝炎（CHB）的强效核苷类似物。定量乙型肝炎表面抗原（qHBsAg）水平可预测CHB治疗中对α干扰素的反应；然而，qHBsAg在基于核苷/核苷酸类似物的CHB治疗中的临床效用尚未完全明确。本研究评估了在III期研究ETV-022中接受恩替卡韦治疗的患者qHBsAg的变化。
这项回顾性事后分析纳入了ETV-022中初治的、乙型肝炎e抗原（HBeAg）阳性且接受恩替卡韦（每日0.5mg）治疗的患者，这些患者有可用于qHBsAg分析的样本，随访至48周。对整个患者队列、在48周时出现或未出现HBeAg消失或HBsAg消失的队列以及按HBV基因型分组的队列评估qHBsAg、HBV DNA和丙氨酸氨基转移酶水平。
总体而言，ETV-022中有95例患者有可用于qHBsAg分析的样本，随访至48周。在所有队列中，48周的恩替卡韦治疗导致有效的HBV DNA抑制。在整个队列中，至48周时qHBsAg下降了-0.92 log10 IU/ml。在随后出现HBeAg消失或HBsAg消失的患者以及感染HBV基因型D或A的患者中，qHBsAg的下降更为明显。治疗期间qHBsAg的变化与HBV DNA的变化无关；未发现治疗期间或基线因素可预测HBeAg消失或HBsAg消失。
经过48周的恩替卡韦治疗，qHBsAg主要在实现HBeAg或HBsAg血清学清除的患者中下降。然而，与基于α干扰素的治疗不同，恩替卡韦治疗第1年时早期qHBsAg下降并不能预测血清学反应。
