Published online Apr 7, 2020. doi: 10.3748/wjg.v26.i13.1525
Peer-review started: December 9, 2019
First decision: December 30, 2019
Revised: January 9, 2020
Accepted: March 9, 2020
Article in press: March 9, 2020
Published online: April 7, 2020
Processing time: 120 Days and 0.8 Hours
Nucleos(t)ide analog (NA) has shown limited effectiveness against hepatitis B surface antigen (HBsAg) clearance in chronic hepatitis B (CHB) patients.
Despite promising results with the combination therapy of peginterferon (peg-IFN) and NA, the best combination therapeutic strategy of peg-IFN and NA for the treatment of CHB is still debated. The interim analysis of the NEW SWITCH study showed that patients with baseline HBsAg levels < 1500 IU/mL achieved a higher HBsAg clearance rate than patients with HBsAg > 1500 IU/mL when they switched from NA to 48 wk of peg-IFN α-2α therapy. However, it is not clear what the effects of add-on peginterferon α-2a to an ongoing NA regimen in CHB patients with HBsAg ≤ 1500 IU/mL after over 1 year of NA therapy. Considering the large number of patients who have achieved HBsAg ≤ 1500 IU/mL after long-term NA treatment in our clinic, it is very necessary and significant to explore the efficacy of peg-IFN α add-on treatment in these patients.
This study aimed to evaluate the efficacy and safety of add-on peg-IFN α-2a to an ongoing NA regimen in CHB patients with HBsAg ≤ 1500 IU/mL, hepatitis B e antigen (HBeAg)-negative and hepatitis B virus-deoxyribonucleic acid (HBV DNA) < 1.0 × 102 IU/mL after over 1 year of NA therapy and to analyze independent prediction factors of HBsAg clearance in this population.
In this observational study, 195 CHB patients with HBsAg ≤ 1500 IU/mL, HBeAg-negative (including HBeAg-negative patients or HBeAg-positive patients achieved HBeAg-negative after antiviral treatment with NA) and HBV DNA < 1.0 × 102 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December 2018 at the Second Affiliated Hospital of Xi’an Jiaotong University, China. Patients were given the choice between receiving either peg-IFN α-2a add-on therapy to an ongoing NA regimen (add-on group, n = 91) or continuous NA monotherapy (monotherapy group, n = 104) after being informed of the benefits and risks of the peg-IFN α-2a therapy. Total therapy duration of peg-IFN α-2a was 48 wk. All patients were followed-up to week 72 (24 wk after discontinuation of peg-IFN α-2a). The primary endpoint was the proportion of patients with HBsAg clearance at week 72.
Demographic and baseline characteristics were comparable between the two groups. Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4% (34/91) and 1.9% (2/104) at week 72, respectively. The HBsAg seroconversion rate in the add-on group was 29.7% (27/91) at week 72, and no patients in the monotherapy group achieved HBsAg seroconversion at week 72. The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72 (P < 0.001). Younger patients, lower baseline HBsAg concentration, lower HBsAg concentrations at weeks 12 and 24, greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase ≥ 2 × upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFN α-2a add-on treatment. Regarding the safety of the treatment, 4.4% (4/91) of the patients in the add-on group discontinued peg-IFN α-2a due to adverse events. No severe adverse events were noted in the monotherapy group.
Peg-IFN α as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg ≤ 1500 IU/mL after over 1 year of NA therapy.
Add-on Peg-IFN α to ongoing NA regime in CHB patients with low HBsAg levels and sustained HBV DNA suppression after long-term NA treatment can significantly improve the rates of HBsAg clearance and seroconversion. Some indicators, such as younger patients, lower HBsAg concentrations at baseline, weeks 12 and 24, greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase ≥ 2 × upper limit of normal during the first 12 wk of therapy can serve as predictors of HBsAg clearance in patients with peg-IFN α-2a add-on treatment. peg-IFN α add-on treatment is relatively safe. However,, the long-term efficacy of peg-IFN α add-on treatment needs to be studied.