Abstract: Objective To investigate the efficacy and predictive factors of sequential-combination therapy based on respond guided treatment (RGT) for the Peg-IFN-α treated HBeAg positive chronic hepatitis B (CHB) patients.Methods According to the 24-week treatment results, 87 patients who received Peg-IFN-α as their initial treatment were divided into four groups to receive different treatments. In patients with early response (group a), Peg-IFN-α treatment was extended to 48 weeks. Among patients with non-early response (NER), 20 patients remained on Peg-IFN-α monotherapy for another 24 weeks (group b), 17 received Peg-IFN-α monotherapy up to totally 96 weeks (group c) and 25 received entecavir (ETV) added onging Peg-IFN-α therapy up to totally 96 weeks (group d).Results The reductions of HBsAg and HBV DNA were more obvious in a and d group than those in b and c group, respectively ( a versus b, P=0.0194, 0.041 and d versus c, P= 0.0008, 0.0035). At the endpoint of patients with 96-weeks treatment (group c and d), the rates of HBsAg (less than 1000 IU/mL) and HBeAg loss were significantly higher than those in group B (P=0.0384). Moreover, HBeAg decreased more obviously in group d than that in group c, with no statistically significance in HBeAg loss and seroconversion. Baseline HBsAg level was speculated to be a predictive factor for the efficiency, because patients with HBsAg ≥ 1500 IU/mL achieved more HBV DNA loss and HBeAg decrease in group d than those in group c (P=0.0228 and 0.0237).Conclusion Sequential and combining treatment could make patients achieve more HBsAg and HBV DNA loss, with no significant difference in HBeAg loss or serum conversion. Meanwhile, 96-week Peg-IFN-α monotherapy or sequential Peg-IFN-α plus ETV therapy could lead to more HBeAg loss, and we further demonstrate that the baseline level of HBsAg would be an important predict factor for the efficacy.

Key words: Hepatitis B, Chronic, Peglyated interferon, ETV, HBsAg, HBeAg