Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen ≤ 1500 IU/mL: An observational study

BACKGROUND Nucleos(t)ide analog (NA) has shown limited effectiveness against hepatitis B surface antigen (HBsAg) clearance in chronic hepatitis B (CHB) patients. AIM To evaluate the efficacy and safety of add-on peginterferon alpha-2a (peg-IFN alpha-2a) to an ongoing NA regimen in CHB patients. METHODS In this observational study, 195 CHB patients with HBsAg <= 1500 IU/mL, hepatitis B e antigen (HBeAg)-negative (including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA) and hepatitis B virus-deoxyribonucleic acid < 1.0 x 10(2) 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 alpha-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 alpha-2a therapy. Total therapy duration of peg-IFN alpha-2a was 48 wk. All patients were followed-up to week 72 (24 wk after discontinuation of peg-IFN alpha-2a). The primary endpoint was the proportion of patients with HBsAg clearance at week 72. RESULTS 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 patient 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 x upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFN alpha-2a add-on treatment. Regarding the safety of the treatment, 4.4% (4/91) of patients in the add-on group discontinued peg-IFN alpha-2a due to adverse events. No severe adverse events were noted. CONCLUSION Peg-IFN alpha-2a 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.