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. 2023 Dec 31;19(1):2161254.
doi: 10.1080/21645515.2022.2161254. Epub 2023 Jan 22.

The potential effect of HBV vaccination on off-treatment HBsAg reversion after interferon-induced HBsAg clearance

Shaowen Jiang, Minghao Cai, Zhenglan Zhang, Cong Qian, Jiexiao Wang, Ziqiang Li, Qing Guo, Huijuan Zhou, Haiguang Xin, Wei Cai, Hui Wang, Simin Guo, Yan Huang  1 , Qing Xie  1
Affiliations

The potential effect of HBV vaccination on off-treatment HBsAg reversion after interferon-induced HBsAg clearance

Shaowen Jiang et al. Hum Vaccin Immunother. .

Abstract

Off-treatment HBsAg reversion occurs in a considerable number of chronic hepatitis B(CHB) patients after IFN(interferon)-induced HBsAg clearance. HBV vaccination protects the general population against HBV infection. However, it remains unclear whether HBV vaccination could prevent off-treatment HBsAg reversion in CHB patients with HBsAg clearance. CHB patients (n = 199) with HBsAg clearance were included in the current study, comprising spontaneous HBsAg clearance group (n = 51), NA (nucleoside/nucleotide analogues)-induced group (n = 36) and IFN-induced group (n = 112). Log-rank test was performed to compare the cumulative incidences of HBsAg reversion between groups. Cox regression model was used to identify the factors associated with off-treatment HBsAg reversion. The 5-year cumulative incidence of HBsAg reversion in IFN-induced group was significantly higher than that in NA-induced group or spontaneous group (27.6% vs. 3.3% vs. 8.1%, both p < .05). In IFN-induced group, 66.7% of CHB patients received HBV vaccination. The cumulative incidence of HBsAg reversion in individuals with strong responses to HBV vaccination (HBsAb level >100mIU/ml) was significantly lower than that in those with weak responses to HBV vaccination (HBsAb level ≤100mIU/ml) or without HBV vaccination in IFN-induced group (7.7% vs. 58.5% vs. 31.9%, both p < .05). Multivariate Cox regression analysis confirmed strong responses to HBV vaccination were independently associated with a lower cumulative incidence of HBsAg reversion after IFN-induced HBsAg clearance (HR = 0.246, 95%CI: 0.066-0.907, p = .035). HBV vaccination has potential to prevent off-treatment HBsAg reversion in CHB patients after IFN-induced HBsAg clearance via a sufficiently high level of HBsAb, helping clinicians optimize the clinical management of such patients.

Keywords: Chronic hepatitis B; HBV vaccination; HBsAg clearance; HBsAg reversion; functional cure; interferon.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
Flow chart of patient enrollment. Abbreviations: CHB, chronic hepatitis B; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; ICC, intrahepatic cholangiocarcinoma; IFN, interferon; NA, nucleoside/nucleotide analogues; w, weeks.
Figure 2.
Figure 2.
Cumulative incidences of HBsAg reversion according to the different HBsAg clearance methods. Abbreviations: HBsAg, hepatitis B surface antigen; IFN, interferon; NA, nucleoside/nucleotide analogues.
Figure 3.
Figure 3.
HBV vaccination in IFN-induced group. (a) The proportion of the patients with or without HBV vaccination. (b) The proportion of the patients with sequential administration vs. simultaneous administration of IFN and HBV vaccine. (c) The proportion of the patients receiving 1 dose, 2 doses or ≥ 3 doses of HBV vaccine. (d) The proportion of the patients with diverse HBsAb levels following HBV vaccination. (e) The proportion of responders or non-responders to HBV vaccination. (f) The proportion of the patients with weak or strong response to HBV vaccination. Abbreviations: HBV, hepatitis B virus; IFN, interferon.
Figure 4.
Figure 4.
Cumulative incidences of HBsAg reversion in IFN-induced group according to HBV vaccination. (a) The patients without HBV vaccination vs. with HBV vaccination. (b) The patients without HBV vaccination vs. responders to vaccination vs. non-responders to vaccination in the entire IFN-induced group. (c) The patients without HBV vaccination vs. with weak response to vaccination vs. with strong response to vaccination in the entire IFN-induced group. (d) The patients without HBV vaccination vs. with weak response to vaccination vs. with strong response to vaccination in individuals receiving sequential administration of IFN and HBV vaccine. Abbreviations: HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; IFN, interferon.
Figure 5.
Figure 5.
A new decision-making roadmap proposed to evaluate the risk of HBsAg reversion in CHB patients achieving HBsAg clearance by the different methods and to illustrate the application of HBV vaccine in reducing HBsAg reversion. Abbreviations: CHB, chronic hepatitis B; HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; IFN, interferon; NA, nucleoside/nucleotide analogues.
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