Objective To investigate the quantitation of hepatitis B e antigen (HBeAg) at week 24 in predicting the efficacy of pegylated-interferon alfa-2a (Peg-IFN-α 2a) in HBeAg-positive chronic hepatitis B (CHB) patients at week 48 and to find a useful predictor for treatment efficacy and investigate individualized treatment of antiviral therapy.
Methods Ninety-six HBeAg-positive CHB patients with detectable HBeAg who were treated with Peg-IFN-α 2a were enrolled in this trial. They were categorized into 3 groups according to the changes of HBeAg in week 24: HBeAg decline > 2 log10 group (group A), HBeAg decline between 1 1og10 - 2 log10 (group B), HBeAg decline < 1 log10 group (group C), and group C was randomly distributed into C1 and C2. The patients in group A, group B, and group C1 continued the original therapy and the patients in group C2 were given lamivudine plus Peg-IFN-α 2a for 24 weeks. At week 48, the treatment efficacy and hepatitis B virus covalently closed circular DNA (HBV cccDNA) in liver biopsies were analyzed.
Results At week 48, mean reduction of serum HBV DNA: group A: 5.8 log10 copies/ml, group B: 3.8 log10 copies/ml, group C1: 2.8 log10 copies/ml, group C2: 5.7 log10 copies/ml, the reduction of HBV DNA in group A was greater than groups B and C1 (P < 0.01), that in group C1 was greater than group C2 (P < 0.01), the difference between groups B and C1 had no statistical significance (P = 0.19). Mean reduction of HBeAg: group A: 2.7 log10S/CO, group B: 1.9 log10S/CO, group C1: 0.9 log10S/CO, group C2: 1.5 log10S/CO, the difference among groups A, B and C1 and between groups C1 and C2 were statistically significant (P < 0.01). At week 48, HBV DNA undetectable rate in group A, group B, group C1 and group C2 were 87.5%, 34.5%, 17.4% and 81.9%, respectively, the rate in group A was greater than groups B and C1 (P < 0.01)，that in group C1 was greater than group C2 (P < 0.01). HBeAg seroconversion rate were 75.0%, 24.1%, 13.0% and 22.7%, respectively, that in group A was greater than groups B and C1 (P < 0.01). Group A had lower cccDNA in liver tissue than group B and group C1 (P < 0.01). The difference of HBV cccDNA between groups B and C1 and that between groups C1 and C2 had no statistical significance.
Conclusions HBeAg decline > 2 log10 at week 24 in Peg-IFN-α 2a-treated hepatitis B patients suggested a better efficacy at week 48; HBeAg decline < 2 log10 at week 24 suggests a worse efficacy at week 48, the combined therapy of Peg-IFN-α and lamivudine could improve the clinical responses. The change of quantitative of HBeAg at week 24 may be used as a predictor of treatment effects at week 48.