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

Abstract

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 α-2a (peg-IFN α-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 × 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.

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 × 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 patients in the add-on group discontinued peg-IFN α-2a due to adverse events. No severe adverse events were noted.

Conclusion: Peg-IFN α-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.

Keywords: Add-on therapy; Chronic hepatitis B; Hepatitis B surface antigen clearance; Hepatitis B surface antigen seroconversion; Nucleos(t)ide analog; Peginterferon α-2a.

Figure 1

Flow diagram of patients enrolled in this study. HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; HBV DNA: Hepatitis B virus-deoxyribonucleic acid; NA: Nucleos(t)ide analog.

Figure 2

Hepatitis B surface antigen clearance rate. A: Per protocol analysis showed that the rate of hepatitis B surface antigen clearance in 48-wk peg-IFN add-on group was significantly higher than monotherapy group at weeks 48 and 72 (^bP < 0.001 vs monotherapy group at week 48; ^dP < 0.001 vs monotherapy group at week 72). Week 0 was defined as the time when the patients were enrolled in this study for patients in the monotherapy group; B: Intention-to-treatment analysis showed that the rate of hepatitis B surface antigen clearance in 48-wk peg-IFN add-on group was significantly higher than the rate in the monotherapy group at weeks 48 and 72 (^bP < 0.001 vs monotherapy group at week 48; ^dP < 0.001 vs monotherapy group at week 72). Week 0 was defined as the time when the patients were enrolled in this study for patients in the monotherapy group. HBsAg: Hepatitis B surface antigen.

Figure 3

Hepatitis B surface antigen seroconversion rate. A: Per protocol analysis showed that the rate of hepatitis B surface antigen seroconversion in 48-wk peg-IFN add-on group was significantly higher than monotherapy group at weeks 48 and 72 (^bP < 0.001 vs monotherapy group at week 48; ^dP < 0.001 vs monotherapy group at week 72). Week 0 was defined as the time when the patients were enrolled in this study for patients in the monotherapy group; B: Intention-to-treatment analysis showed that the rate of hepatitis B surface antigen seroconversion in 48-wk peg-IFN add-on group was significantly higher than rate in monotherapy group at weeks 48 and 72 (^bP < 0.001 vs monotherapy group at week 48; ^dP < 0.001 vs monotherapy group at week 72). Week 0 was defined as the time when the patients were enrolled in this study for patients in the monotherapy group. HBsAg: Hepatitis B surface antigen.

Figure 4

Virological change. A: Dynamics of hepatitis B surface antigen titers (^bP < 0.001 vs monotherapy group for weeks 12, 24, 36, 48 and 72). Data shown are median values of log₁₀ hepatitis B surface antigen and error bars represent 95% confidence interval. B: HBsAg response at week 72.

Figure 5

Change in serum alanine aminotransferase and median serum aspartate transaminase. A: Change in serum alanine aminotransferase (^bP < 0.001 vs monotherapy group for weeks 4, 8, 12, 24, 36 and 48). Data shown are median values of serum alanine aminotransferase and error bars represent 95% confidence interval; B: Change in median serum aspartate transaminase (^bP < 0.001 vs monotherapy group for weeks 4, 8, 12, 24, 36 and 48). Data shown are median values of serum aspartate transaminase and error bars represent 95% confidence interval. HBsAg: Hepatitis B surface antigen; ALT: Alanine aminotransferase; AST: Aspartate transaminase.