血清HBsAg动力学变化对慢性乙型肝炎拉米夫定治疗应答的影响

Serum HBsAg kinetics in predicting the response of chronic hepatitis B patients treated with lamivudine

目的评价慢性乙型肝炎(CHB)患者予拉米夫定(LAM)抗病毒治疗期间血清HBsAg定量水平对治疗应答的影响。方法23例CHB患者予LAM治疗104周,对出现完全应答持续24周以上的患者停药再随访104周,观察持续病毒学应答率。检测基线、LAM治疗24周、52周、76周、104周的血清HBsAg定量水平和血清HBV DNA水平。结果经LAM治疗104周,5例患者出现完全应答24周以上而停药,其在治疗52周、76周和104周的血清HBsAg与基线相比的下降值显著高于未停药组。LAM治疗52周时血清HBsAg下降值ROC曲线下面积为0.806,P<0.05,血清HBsAg下降阈值大于2log10IU/ml时,预测治疗104周出现完全应答的阳性和阴性预测值分别为100%和86%;同时达到停药标准的患者数显著高于下降值小于2logIU/ml的缓慢下降组(P<0.05)和血清HBsAg水平高于基线的升高组(P<0.01),而耐药的发生率低于缓慢下降组和升高组。结论血清HBsAg定量检测可作为CHB患者抗HBV疗效考核指标之一。

Objective To evaluate the role of serum HBsAg kinetics in predicting the response of chronic hepatitis B （CHB） patients treated with lamivudine （LAM）. Methods Twenty-three patients treated with LAM for 104 weeks. Five patients with a complete response more than 24 weeks could discontinue treatment at treatment week 104 and were followed up for 2 years off treatment, 1 patient developed sustained virologic response for 2 years off treatment. Quantitative serum HBsAg levels and serum HBV DNA levels were assessed at baseline,during treatment weeks 24,52, 76 and 104, and during off-treatment follow-up. Results Patients who discontinued treatment had a greater mean reduction from baseline in on-treatment HBsAg levels at weeks 52,76 and 104 than that of continued treatment patients. The receiver operating characteristic curves （ROC） of serum HBsAg levels decline at treatment week 52 from baseline was 0. 806 （P〈0.05） ,the cut-off reduction value of serum HBsAg levels more than 2 log10 IU/ml can be predicted the complete response for the patients treated for 104 weeks, the positive and negative predictive values were 100 Y00 and 86%, respectively;Significantly more patients achieved HBsAg levels declined more than 2 log,, IU/ml from baseline and discontinued treatment at treatment week 52, compared with patients whose serum HBsAg levels declined less than 2 log10 IU/mI（P〈0.05）or even higher than baseline （P〈0. 01 ）, and lower rate of viral resistance observed in patients whose HBsAg levels declined more than 2 log10 IU/ml from baseline. Conclusion Quantitative serum HBsAg levels could be a surrogate marker during the monitoring of the efficacy of HBV treatment.