title: On-treatment quantitative hepatitis B e antigen predicted response to nucleos(t)ide analogues in chronic hepatitis B.
abstract: OBJECTIVE
  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,P= 0.003) as well as its declined value (OR = 2.03,P= 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,P= 0.013) as well as its declined value (OR = 2.02,P= 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.
  
  
  CONCLUSIONS
  The combination of HBeAg level and its declined value at 24-wk may be used as a reference parameter to optimize NAs therapy.
authors.affiliation: 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.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Meng
authors.affiliation: 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.
authors.forename: Zhan-Qing
authors.initials: ZQ
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Shang
authors.affiliation: 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.
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Xue-En
authors.initials: XE
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhuang
keywords: Chronic hepatitis B; Hepatitis B e antigen; Hepatitis B virus DNA; Nucleos(t)ide analogues; Quantitative detection; Response predictor