Factors associated with efficacy of nucleos(t)ide analogues with sequential interferon therapy in HBeAg negative chronic hepatitis B patients

Objective To study the factors associated with efficacy of nucleos(t)ide analogues with sequential interferon in HBeAg negative chronic hepatitis B (CHB) patients. Methods HBeAg negative CHB patients with NA treatment received PEG-IFNα 2a 180 μg subcutaneously once weekly. NA was continually used with PEG-IFN 2a during the first 12 weeks. HBsAg level and HBV DNA load were observed in the sequential pre-treatment (baseline), 12th, 24th, 36th, 48th, 72nd and 96th weeks of sequential therapy in all patients. Results Of the 26 HBeAg negative CHB patients, 6 (23.1%) achieved HBsAg loss/seroconversion. The comparison between HBsAg loss/ seroconversion group and the group not achieved HBsAg loss/ seroconversion showed that the baseline HBsAg level in HBsAg loss/seroconversion group was 2.210 log10IU/ml, was lower than (t=-4.252, P=0.000) HBsAg-positive patients (3.385 log10IU/ml) in the groupp that not achieved HBsAg loss/seroconversion, the difference was statistically significant in HBsAg decreased at 72nd, 96th week in the course of sequential therapy (3.511 vs. 0.723log10IU/ml, 4.291 vs. 0.737 log10IU/ml) (t=6.712, P=0.000, t=13.319; P=0.000, 0.00); the difference was not statistically significant in age, gender and NA therapy time between the two groups; 12 (46.2%) of patients achieved sustained virologic response (SVR), the baseline of HBsAg level was 2.575 log10IU/ml, was less than (t=-4.319, P=0.000) the patients who did not achieve SVR (3.576 log10IU/ml), the difference was statistically significant in HBsAg decrease of each time in the course of sequential therapy between the two groups (0.612 vs. 0.088, 1.192 vs. 0.107, 1.566 vs. 0.167, 1.817 vs. 0.176, 2.424 vs. 0.193, 2.188 vs. 0.014, log10IU/ml) (t=3.109, 4.717, 4.500, 4.544, 5.560, 4.265, P=0.008, 0.010, 0.001, 0.001, 0.000, 0.003), the difference was not statistically significant in gender and NA therapy time, the difference was statistically significant in age (30.8 vs. 39.9 years) ( t=-2.219, P=0.038). Of 9 CHB patients whose baseline HBV DNA were positive, 5 patients (55.6%) had HBV DNA loss after sequential treatment, the patients whose HBV DNA loss with HBsAg decreased at 12th week in the course of sequential therapy, but there was no influence in the HBsAg decrease/loss after 12th week, the difference was not statistically significant in age, gender, NA therapy time, HBsAg and HBsAg decrease in the course of sequential therapy between HBV DNA-negative and HBV DNA-positive groups. Conclusions To HBeAg-negative CHB, patients with low baseline HBsAg (2 log10 IU/ml level) and significantly lower HBsAg decrease early were more likely to receive SVR. Among them, prolonged interferon therapy is easier to achieve HBsAg loss/seroconversion. Key words: Hepatitis B, chronic; Interferon α-2a; Nucleoside (acid) analogues; Hepatitis B surface antigen