An optimized mode of interferon intermittent therapy help improve HBsAg disappearance in chronic hepatitis B patients

Minghui Li, Si Xie, Xiaoyue Bi, Fangfang Sun, Zhan Zeng, Wen Deng, Tingting Jiang, Yanjie Lin, Liu Yang, Yao Lu, Lu Zhang, Wei Yi, Yao Xie, Minghui Li, Si Xie, Xiaoyue Bi, Fangfang Sun, Zhan Zeng, Wen Deng, Tingting Jiang, Yanjie Lin, Liu Yang, Yao Lu, Lu Zhang, Wei Yi, Yao Xie

Abstract

Background: To investigate the effect of intermittent interferon therapy mode on the disappearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) patients.

Methods: This is a retrospective cohort study in CHB patients who were suspended from pegylated interferon α (PEG-IFNα) therapy due to a plateau in HBsAg decline during the initial treatment period, and resumed interferon therapy after an interval of 3-6 months. Patients received entecavir or tenofovir during the interval period. Hepatitis B virus (HBV) virological and serological indexes, clinical biochemical indexes, and blood routine tests were performed at the baseline and every 3 months during follow-up of initial interferon treatment. A functional cure was analyzed as a primary outcome.

Results: A total of 304 patients treated with intermittent PEG-IFNα were included in the statistical analysis, including 215 men and 89 women, aged 37.97 ± 8.53 years, and 73 hepatitis B e antigen (HBeAg)-negative and 231 HBeAg positive patients. In total 59 patients (19.41%) achieved HBsAg disappearance through the initial, intermittent, and retreatment of PEG-IFNα treatment, of whom 43 patients (14.14%) achieved HBsAg seroconversion. Early HBsAg response to initial treatment was significantly associated with HBsAg response at 12 and 24 weeks of retreatment. After the intermission period, the incidence of HBsAg disappearance in patients with early HBsAg response in the retreatment period was 43.87%. The baseline HBsAg and 12-week HBsAg response in the retreatment period had higher predictive value than the initial treatment HBsAg response.

Conclusion: The initial, intermittent, and retreatment mode of interferon can help to improve the HBsAg disappearance rate in CHB patients.

Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT04028856].

Keywords: HBV; HBsAg; clinical cure; interferon; intermittent therapy.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer, BF, declared a shared parent affiliation with several authors, ZZ, YnL, ML, and YX, to the handling editor at the time of review.

Copyright © 2022 Li, Xie, Bi, Sun, Zeng, Deng, Jiang, Lin, Yang, Lu, Zhang, Yi and Xie.

Figures

FIGURE 1
FIGURE 1
Patient treatment and observation procedures.
FIGURE 2
FIGURE 2
Patient enrollment process.
FIGURE 3
FIGURE 3
Dynamic changes of HBsAg levels during treatment. There was HBsAg plateau in groups of patients with and without HBsAg loss. Compared with non-HBsAg loss group, HBsAg loss group had a rapid HBsAg decrease at early treatment in the initial and retreatment of PEG-IFNα.
FIGURE 4
FIGURE 4
The HBsAg loss occurred at the time of retreatment (A), and the patients with early HBsAg response had high rates of HBsAg loss by retreatment (B) (G1: Group with early HBsAg response at initial treatment. G2: Group without early HBsAg response at initial treatment. G3: Group with early HBsAg response at retreatment. G4: Group without early HBsAg response at retreatment. G5: Group with early HBsAg response at initial treatment and at retreatment. G6: Group without early HBsAg response initial treatment and at retreatment).

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