Altered expression of MX2 and SAMD4A in PBMCs predicts early treatment responses in HBeAg-positive chronic hepatitis B patients during Peg-IFN-α therapy.

BACKGROUND

Chronic Hepatitis B (CHB) is a major global health concern. This study aimed to evaluate whether myxovirus resistance 2 (MX2) and sterile alpha motif domain containing 4A (SAMD4A) mRNA levels in peripheral blood mononuclear cells (PBMCs) can predict early treatment responses to pegylated interferon-alpha (Peg-IFN-α) in hepatitis B e antigen (HBeAg)-positive CHB patients.

METHODS

This prospective cohort study enrolled HBeAg-positive CHB patients who received Peg-IFN-α for 48 weeks. Patients were classified into virological response (VR; HBV DNA <50 IU/mL at week 48) and non-virological response (NVR) groups, and into serological response (SR; HBeAg seroconversion at week 48) and non-serological response (NSR) groups. MX2 and SAMD4A mRNA levels in PBMCs were measured by quantitative real-time PCR (qRT-PCR) at weeks 0, 12, and 24. Spearman's rank correlation analysis was performed to evaluate the relationships between gene expression levels and declines in HBeAg and HBV DNA. Univariate and multivariate logistic regression analyses were conducted to identify independent predictors of VR and SR, and predictive performance was assessed using receiver operating characteristic (ROC) curves with calculation of the area under the curve (AUC).

RESULTS

At week 48, the VR and SR rates were 64.63% and 39.02%, respectively. Dynamic changes in MX2 and SAMD4A mRNA levels differed significantly between the VR and NVR groups and between the SR and NSR groups. Both MX2 and SAMD4A mRNA levels at weeks 12 and 24 were positively correlated with concurrent reductions in HBeAg and HBV DNA. Notably, early upregulation of both genes at week 12 was significantly associated with subsequent reductions in HBeAg and HBV DNA observed at week 24. Multivariate analysis identified MX2 and SAMD4A as independent predictors of both VR and SR at weeks 12 and 24. At week 24, the AUC values of MX2 were 0.7567 for VR and 0.8421 for SR, while those of SAMD4A were 0.8549 for VR and 0.8717 for SR.

CONCLUSION

MX2 and SAMD4A are important biomarkers for early treatment responses to Peg-IFN-α in HBeAg-positive CHB patients.