Quantitative Hepatitis B Surface Antigen and Hepatitis B e Antigen Titers in Prediction of Treatment Response to Entecavir
Quantitative Hepatitis B Surface Antigen and Hepatitis B e Antigen Titers in Prediction of Treatment Response to Entecavir
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DOI：
10.1002/hep.24221
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发表时间：
2011-05-01
期刊：
影响因子：
13.5
通讯作者：
Park, Jun Yong
中科院分区：
文献类型：
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作者：
Lee, Jung Min;Ahn, Sang Hoon;Park, Jun Yong
定量乙型肝炎表面抗原（qHBsAg）和定量乙型肝炎e抗原（qHBeAg）滴度正在成为测量病毒载量和预测聚乙二醇化干扰素治疗的病毒学反应（VR）和血清学反应（SR）的有用工具。然而，这些检测在服用恩替卡韦（ETV）患者中的临床应用在很大程度上是未知的。接受ETV治疗2年的慢性乙型肝炎（CHB）初治患者被纳入研究。采用Architect法连续测定qHBsAg和qHBeAg水平。在95例患者中，60.0%的患者乙型肝炎e抗原阳性[HBeAg(1)]，共分析475份样本。基线中位对数乙型肝炎病毒（HBV） DNA、对数qHBsAg和对数qHBeAg值分别为6.73 copies/mL （4.04-9.11 copies/mL）、3.58 IU/mL （1.17-5.10 IU/mL）和1.71 Paul Ehrlich (PE) IU/mL （-0.64 - 2.63 PE IU/mL）。对于预测HBeAg(1)患者的VR(24个月时HBV DNA < 60拷贝/mL)，基线丙氨酸转氨酶（P = 0.013）、HBV DNA （P = 0.040）和qHBsAg水平（P = 0.033）具有显著意义。预测VR时，基线log qHBsAg水平曲线下面积为0.823 (P < 0.001)；截止水平为3.98 IU/mL（非对数标度为9550 IU/mL），灵敏度为86.8%，特异性为78.9%，预测值最高。至于SR（24个月时HBeAg损失），SR(1)组的qHBeAg减少量明显大于SR(2)组。灵敏度和特异性分别为75.0%和89.8%，6个月时下降1.00 PE IU/mL。在接受ETV治疗的HBeAg(1)患者中，HBV DNA和qHBsAg的相关性在6个月时达到顶峰。结论：经ETV治疗后qHBsAg和qHBeAg均显著降低。HBeAg(1)患者的基线qHBsAg水平和治疗期间qHBeAg的下降分别被证明对预测VR和SR非常有用。qHBsAg和qHBeAg的测定可以帮助我们选择合适的策略来管理CHB患者。然而，在抗病毒治疗期间，qHBsAg、qHBeAg和HBV DNA之间的动态相互作用仍有待阐明。(肝脏病学53:1486 2011;1493)
Quantitative hepatitis B surface antigen (qHBsAg) and quantitative hepatitis B e antigen (qHBeAg) titers are emerging as useful tools for measuring viral loads and for predicting the virological response (VR) and serological response (SR) to pegylated interferon therapy. However, the clinical utility of these assays in patients taking entecavir (ETV) is largely unknown. Treatment-naive patients with chronic hepatitis B (CHB) who were taking ETV for 2 years were enrolled. The qHBsAg and qHBeAg levels were serially measured with the Architect assay. From 95 patients, 60.0% of whom were hepatitis B e antigen-positive [ HBeAg(1)], 475 samples were analyzed. The median baseline log hepatitis B virus (HBV) DNA, log qHBsAg, and log qHBeAg values were 6.73 copies/ mL (4.04-9.11 copies/mL), 3.58 IU/ mL (1.17-5.10 IU/mL), and 1.71 Paul Ehrlich (PE) IU/mL (-0.64 to 2.63 PE IU/mL), respectively. For the prediction of VR (HBV DNA < 60 copies/mL at 24 months) in HBeAg(1) patients, baseline alanine aminotransferase (P = 0.013), HBV DNA (P = 0.040), and qHBsAg levels (P = 0.033) were significant. For the prediction of VR, the area under the curve for the baseline log qHBsAg level was 0.823 (P < 0.001); a cutoff level of 3.98 IU/mL (9550 IU/mL on a nonlogarithmic scale) yielded the highest predictive value with a sensitivity of 86.8% and a specificity of 78.9%. As for SR (HBeAg loss at 24 months), the reduction of qHBeAg was significantly greater in the SR(1) group versus the SR(2) group. The sensitivity and specificity were 75.0% and 89.8%, respectively, with a decline of 1.00 PE IU/mL at 6 months. With ETV therapy, the correlation between HBV DNA and qHBsAg peaked at 6 months in HBeAg(1) patients. Conclusion: Both qHBsAg and qHBeAg decreased significantly with ETV therapy. The baseline qHBsAg levels and the on-treatment decline of qHBeAg in HBeAg(1) patients were proven to be highly useful in predicting VR and SR, respectively. The determination of qHBsAg and qHBeAg can help us to select the appropriate strategy for the management of patients with CHB. However, the dynamic interplay between qHBsAg, qHBeAg, and HBV DNA during antiviral therapy remains to be elucidated. (HEPATOLOGY 2011;53:1486-1493)