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. 2023 Feb;43(2):329-339.
doi: 10.1111/liv.15489. Epub 2022 Dec 7.

Lower frequency of MDSCs was significantly related to functional cure in CHB patients treated with peginterferon

Yao Zhang  1 , Jiajia Han  1 , Xueyun Zhang  1 , Fahong Li  1 , Yifei Guo  1 , Jingjing He  1 , Richeng Mao  1 , Haoxiang Zhu  1 , Jie Yu  1 , Yuxian Huang  1 , Feifei Yang  1 , Jiming Zhang  1   2   3
Affiliations

Lower frequency of MDSCs was significantly related to functional cure in CHB patients treated with peginterferon

Yao Zhang et al. Liver Int. 2023 Feb.

Abstract

Background and aims: Myeloid-derived suppressor cells (MDSCs) and CD4+ regulatory T cells (Tregs) expand during chronic hepatitis B virus (HBV) infection and inhibit antiviral immunity. However, the relationship between antiviral effect and the frequencies of those immune suppressive cells after pegylated interferon α-2a (PegIFNα-2a) therapy is not clearly understood. This study aimed to investigate the contribution of monocytic MDSCs (mMDSCs) and CD4+ Tregs to functional cure (HBsAg seroclearance) after PegIFNα-2a therapy and evaluate the effect of PegIFNα-2a therapy on these cells.

Methods: Flow cytometry analysis was performed along with longitudinal immune monitoring of 97 hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) patients receiving PegIFNα-2a weekly for 48 weeks.

Results: The frequencies of mMDSCs and CD4+ Tregs increased in all HBV patients, and they were higher in the HBsAg persistence group than in the HBsAg seroclearance group. A significant decline in the frequency of mMDSCs was found in patients who realized functional cure after PegIFNα-2a treatment. In contrast, the frequency of CD4+ Tregs in both the HBsAg seroclearance and persistence groups significantly increased. Multivariate analyses indicated that the baseline serum HBsAg levels (p < .001) and mMDSCs frequency (p = .027) were independently associated with the HBsAg clearance, and the combined marker (HBsAg plus mMDSCs) displayed the highest specificity (93.1%) than any other markers in predicting HBsAg seroclearance.

Conclusions: These results suggest that a poor response to PegIFNα-2a treatment in CHB patients may be related to the frequencies of immune suppressive cells, while the therapeutic targeting of these cells might be effective in boosting anti-HBV immunity.

Keywords: PegIFNα-2a; chronic hepatitis B; functional cure; monocytic myeloid-derived suppressor cells; regulatory T cells.

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References

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