治疗期间定量乙肝e抗原可预测慢性乙型肝炎患者对核苷（酸）类似物的反应。
On-treatment quantitative hepatitis B e antigen predicted response to nucleos(t)ide analogues in chronic hepatitis B.
作者信息
Gao Yu-Hua, Meng Qing-Hua, Zhang Zhan-Qing, Zhao Ping, Shang Qing-Hua, Yuan Quan, Li Yao, Deng Juan, Li Tong, Liu Xue-En, Zhuang Hui
机构信息
Yu-Hua Gao, Yao Li, Juan Deng, Tong Li, Xue-En Liu, Hui Zhuang, Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
出版信息
World J Hepatol. 2016 Dec 8;8(34):1511-1520. doi: 10.4254/wjh.v8.i34.1511.
AIM
To investigate potential predictors for treatment response to nucleos(t)ide analogues (NAs) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients.
METHODS
Seventy-six HBeAg-positive CHB patients received 96-wk NAs optimized therapy (lamivudine and adefovir dipivoxil) were studied retrospectively. Serum hepatitis B surface antigen, HBeAg, hepatitis B core antibody, hepatitis B virus (HBV) DNA and alanine aminotransferase levels were quantitatively measured before and during the treatment at 12 and 24 wk. Stepwise logistic regression analyses were performed to identify predictors for treatment response, and areas under the receiver operating characteristic curves (AUROC) of the independent predictors were calculated.
RESULTS
Forty-three CHB patients (56.6%) achieved virological response (VR: HBV DNA ≤ 300 copies/mL) and 15 patients (19.7%) developed HBeAg seroconversion (SC) after the 96-wk NAs treatment. The HBeAg level (OR = 0.45, = 0.003) as well as its declined value (OR = 2.03, = 0.024) at 24-wk independently predicted VR, with the AUROC of 0.788 and 0.736, respectively. The combination of HBeAg titer < 1.3 lg PEIU/mL and its decreased value > 1.6 lg PEIU/mL at 24-wk predicted VR with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of 85%, 100%, 100% and 83%, respectively, and the AUROC increased to 0.923. The HBeAg level (OR = 0.37, = 0.013) as well as its declined value (OR = 2.02, = 0.012) at 24-wk also independently predicted HBeAg SC, with the AUROC of 0.828 and 0.814, respectively. The HBeAg titer < -0.5 lg PEIU/mL combined with its declined value > 2.2 lg PEIU/mL at 24-wk predicted HBeAg SC with a sensitivity, specificity, PPV, NPV of 88%, 98%, 88% and 98%, respectively, and the AUROC reached 0.928.
CONCLUSION
The combination of HBeAg level and its declined value at 24-wk may be used as a reference parameter to optimize NAs therapy.
目的
探讨乙型肝炎e抗原（HBeAg）阳性慢性乙型肝炎（CHB）患者对核苷（酸）类似物（NAs）治疗反应的潜在预测指标。
方法
回顾性研究76例接受96周NAs优化治疗（拉米夫定和阿德福韦酯）的HBeAg阳性CHB患者。在治疗前以及治疗12周和24周时定量检测血清乙肝表面抗原、HBeAg、乙肝核心抗体、乙肝病毒（HBV）DNA和丙氨酸氨基转移酶水平。进行逐步逻辑回归分析以确定治疗反应的预测指标，并计算独立预测指标的受试者工作特征曲线下面积（AUROC）。
结果
96周NAs治疗后，43例CHB患者（56.6%）实现病毒学应答（VR：HBV DNA≤300拷贝/mL），15例患者（19.7%）发生HBeAg血清学转换（SC）。24周时的HBeAg水平（OR = 0.45，P = 0.003）及其下降值（OR = 2.03，P = 0.024）独立预测VR，AUROC分别为0.788和0.736。24周时HBeAg滴度<1.3 lg PEIU/mL及其下降值>1.6 lg PEIU/mL联合预测VR，敏感性、特异性、阳性预测值（PPV）、阴性预测值（NPV）分别为85%、100%、100%和83%，AUROC增至0.923。24周时的HBeAg水平（OR = 0.37，P = 0.013）及其下降值（OR = 2.02，P = 0.012）也独立预测HBeAg SC，AUROC分别为0.828和0.814。24周时HBeAg滴度<-0.5 lg PEIU/mL及其下降值>2.2 lg PEIU/mL联合预测HBeAg SC，敏感性、特异性、PPV、NPV分别为88%、98%、88%和98%，AUROC达0.928。
结论
24周时HBeAg水平及其下降值的联合可作为优化NAs治疗的参考参数。
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