Published online Dec 8, 2016. doi: 10.4254/wjh.v8.i34.1511
Peer-review started: August 13, 2016
First decision: September 13, 2016
Revised: September 26, 2016
Accepted: October 22, 2016
Article in press: October 24, 2016
Published online: December 8, 2016
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.
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.
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.
The combination of HBeAg level and its declined value at 24-wk may be used as a reference parameter to optimize NAs therapy.
Core tip: Few studies have systematically evaluated quantitative hepatitis B surface antigen, hepatitis B e antigen (HBeAg), hepatitis B core antibody, hepatitis B virus DNA and alanine aminotransferase for predicting treatment response to nucleos(t)ide analogues (NAs) in HBeAg-positive chronic hepatitis B (CHB). In this study, on-treatment HBeAg level as well as its declined value at 24-wk were identified to be the best predictors not only for 96-wk virological response (VR) but also for HBeAg seroconversion (SC). The combination of HBeAg level and its decline at 24-wk strongly predicted 96-wk VR and HBeAg SC with the AUROC of 0.923 and 0.928, respectively. Thus monitoring an early on-treatment HBeAg level and its decline may help to optimize NAs therapy for CHB patients.