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. 2022 Oct 11:13:1025654.
doi: 10.3389/fimmu.2022.1025654. eCollection 2022.

Describing immune factors associated with Hepatitis B surface antigen loss: A nested case-control study of a Chinese sample from Wuwei City

Xiaojie Yuan  1   2 , Ting Fu  1   2 , Lixin Xiao  1   2 , Zhen He  1   2 , Zhaohua Ji  1   2 , Samuel Seery  3 , Wenhua Zhang  4 , Yancheng Ye  5 , Haowei Zhou  1   2 , Xiangyu Kong  1   2 , Shuyuan Zhang  1   2 , Qi Zhou  1   2 , Yulian Lin  1   2 , Wenling Jia  4 , Chunhui Liang  4 , Haitao Tang  4 , Fengmei Wang  4 , Weilu Zhang  1   2 , Zhongjun Shao  1   2
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Describing immune factors associated with Hepatitis B surface antigen loss: A nested case-control study of a Chinese sample from Wuwei City

Xiaojie Yuan et al. Front Immunol. .

Abstract

Background: Hepatitis B surface antigen (HBsAg) loss is considered a functional cure for chronic hepatitis B (CHB), however, several factors influence HBsAg loss.

Methods: 29 CHB patients who had achieved HBsAg loss, were selected and 58 CHB patients with persistent HBsAg were matched, according to gender and age (+/- 3 years). Logistic regression and restricted cubic spline (RCS) modelling were performed.

Results: Multivariate-adjusted logistic regression, based on stepwise selection, showed that baseline HBsAg levels negatively correlated with HBsAg loss (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.98-0.99). Interferon treatment positively related with HBsAg loss (OR = 7.99, 95%CI = 1.62-44.88). After adjusting for age, HBsAg level, ALT level, HBeAg status and interferon treatment, MMP-1 (OR = 0.66, 95%CI = 0.44-0.97), CXCL9 (OR = 0.96, 95%CI = 0.93-0.99) and TNF-R1 (OR = 0.97, 95%CI = 0.94-0.99) baseline levels all negatively correlated with HBsAg loss. Our multivariate-adjusted RCS model showed that baseline CXCL10 was associated with HBsAg loss although the relationship was "U-shaped".

Conclusions: Cytokines such as MMP-1, CXCL9, CXCL10 and TNF-R1 are important factors which influence HBsAg loss. It may be possible to develop a nomogram which intercalates these factors; however, further research should consider immune processes involved in HBsAg loss.

Keywords: HBsAg; MMP-1; TNF-R1; chemokine; interferon.

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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.

Figures

Figure 1
Figure 1
Linear association between HBsAg, cytokines and HBsAg loss using restricted cubic spline with three knots (p5, p50 and p95) (A) HBsAg, adjusting for age, ALT level, HBeAg status and interferon treatment; (B-D) MMP-1, TNF-R1, and CXCL10, adjusting for age, HBsAg level, ALT level, HBeAg status and interferon treatment.
Figure 2
Figure 2
Cytokines comparation between HBsAg consistence and HBsAg loss group (A) TNF-R1 level between HBsAg consistence and HBsAg loss group; (B) Spearman correlation among cytokines. Red, means positive correlation; blue, means negative correlation; *p< 0.05 in Spearman correlation test. (C) Partial least squares discriminant analysis of cytokines.
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