Dynamic changes in TREX1 and LGALS9 mRNA levels in PBMCs predict HBsAg clearance and treatment responses to Peg-IFN-α therapy in HBeAg-negative chronic hepatitis B patients

Abstract Objective To investigate whether the mRNA expression levels of three prime repair exonuclease 1 (TREX1) and galectin 9 (LGALS9) in peripheral blood mononuclear cells (PBMCs) are associated with responses to Peg-IFN-α therapy and HBsAg clearance. Methods In this prospective study, HBeAg-negative CHB patients receiving Peg-IFN-α were followed for 48 weeks. Patients were classified as the virological response (VR) and non-virological response (NVR) groups based on the changes in HBsAg levels observed at week 48, and as serological response (SR) and non-serological response (NSR) groups based on whether serum HBsAg loss or seroconversion occurred. TREX1 and LGALS9 mRNA levels in PBMCs were quantified by real-time quantitative PCR. Correlations between TREX1 or LGALS9 mRNA levels and HBsAg reduction were assessed using Spearman’s rank correlation. Univariate and multivariate logistic regression analyses were performed to identify independent factors associated with VR and SR. The diagnostic performance of TREX1 and LGALS9 was assessed by calculating the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Results After the treatment period, the observed VR and SR rates were 48.65% and 32.43%, respectively. Dynamic changes in TREX1 and LGALS9 mRNA levels were significantly different between the VR and NVR groups and between the SR and NSR groups. Both TREX1 and LGALS9 mRNA levels at week 24 were positively correlated with HBsAg reduction, and early induction of these genes at week 12 was associated with subsequent HBsAg decline. Multivariate analyses revealed that TREX1 and LGALS9 mRNA levels at weeks 12 and 24 were independently associated with VR and SR. TREX1 at week 12 demonstrated the highest predictive accuracy for VR (AUC = 0.7295) and SR (AUC = 0.8025), while LGALS9 showed optimal prediction for VR at week 12 (AUC = 0.7412) and for SR at week 24 (AUC = 0.8933). The combination of TREX1 and LGALS9 further improved prediction for VR (AUC = 0.8464) and SR (AUC = 0.9308). Conclusions TREX1 and LGALS9 are important biomarkers for early therapeutic responses to Peg-IFN-α and HBsAg clearance.