Abstract: Objective To analyze the curative effect of adding peginterferon α-2a to entecavir (ETV) for the treatment of chronic hepatitis B (CHB) patients and to explore the related indexes for the prediction of clinical cure.Methods Patients with CHB who had received ETV for at least one year and achieved HBV DNA negative were selected and treated with ETV in combination with peginterferon α-2a for 48 weeks, or extended the treatment to 72 weeks with a prolonged observation duration of 96 weeks. The HBsAg reduction ratio [(Baseline HBsAg- HBsAg in the Follow-up period of Treatment)/Baseline HBsAg] was calculated as a judgement of treatment efficacy.Results A total of 35 patients were included and divided into two groups, baseline HBeAg positive group (N=18 cases) and baseline HBeAg negative group (N=17 cases). There was no significant difference in baseline parameters between the two groups. Three patients withdrew from the study due to side effects, and 10 patients received interferon for 72 weeks. The HBsAg disappearance rates and HBsAg seroconversion rates of all patients were 1/32 (3.1%) and 0/32 (0) at week 48, 2/32 (6.3%),2/32 (6.3%) at week 72, 3/32 (9.4%),and 2/32 (6.3%) at week 96. At week 48, 72 and 96, the rates of HBsAg<1 IU/mL were 6/32 (18.8%), 8/32 (25.0%) and 6/32 (18.8%), respectively. At week 24, 48, 72 and 96, the medians of the HBsAg reduction ratios were 53.5%, 83.8%, 68.4% and 62.5%, respectively. When compared with the baseline HBeAg positive group, the HBsAg disappearance rate, HBsAg seroconversion rate, HBsAg reduction ratio in the baseline HBeAg negative group were all higher, but without significant difference. The average area under the receiver operating characteristic curve (ROC) for using the HBsAg levels at baseline, Week 24, Week 48 to predict HBsAg clearance, HBsAg<1 IU/mL and HBsAg<10 IU/mL at 48 weeks and 96 weeks was 0.927, which had a high predictive value. According to the analysis of ROC curve coordinates, when the baseline HBsAg was less than 1312 IU/mL, the probability of HBsAg<1 IU/mL at Week 48 and 96 was higher than zero; when the HBsAg level was less than 201 IU/mL at Week 24, the probability of HBsAg<10 IU/mL at Week 48 and HBsAg clearance at Week 96 was higher than zero; when the HBsAg level was less than 7.25 IU/mL at Week 48, the probability of HBsAg clearance at Week 96 was higher than zero. For the preponderant patients with baseline HBsAg<1500 IU/mL, the rate of patients with HBsAg<200 IU/mL at Week 24 was as high as 80%. For patients with baseline HBsAg<1 500 IU/mL and HBsAg<200 IU/mL at Week 24, the HBsAg clearance rates and HBsAg conversion rates were 1/12(8.3%) and 0/12(0) at Week 48, 3/12(25.0%) and 2/12(16.7%) at Week 96 respectively. The rates of patients with HBsAg<1 IU/mL at Week 48 and 96 were all 6/12(50.0%). The HBsAg reduction ratios were as high as 99.6% and 99.2% at Week 48 and 96, respectively.Conclusion No matter HBeAg positive or negative, a combined interferon therapy should be considered in CHB patients treated by entecavir to improve HBsAg serological response rate and even reach the goal of clinical cure. Patients with low HBsAg level (less than 1 500 U/mL) were the advantageous population. HBsAg<200 IU/mL at Week 24 of the combined therapy was a predictive factor for a better HBsAg decline. It is advocated to apply individualized treatment regime to CHB patients formulated by their response in order to achieve a clinical curative effect.

Key words: Chronic hepatitis B, Interferons, Combination therapy, HBsAg reduction ratio, Clinical cure