Altered expression of ADAR1, N4BP1, and PSME1 in PBMCs correlated with therapeutic outcomes in HBeAg-negative chronic hepatitis B patients treated with Peg-IFN-α

Background and aims: Pegylated interferon alpha (Peg-IFN-α) has the potential for eradicating hepatitis B surface antigen (HBsAg). The aim of our study is to investigate whether the expression levels of adenosine deaminase acting on RNA 1 (ADAR1), NEDD4-binding protein 1 (N4BP1), proteasome activator complex subunit 1 (PSME1) mRNAs in peripheral blood mononuclear cells (PBMCs) of HBeAg-negative chronic hepatitis B virus (HBV) patients are associated with the response to Peg-IFN-α treatment and HBsAg clearance. Methods: In this prospective study, HBeAg-negative chronic HBV patients treated with Peg-IFN-α were followed for 48 weeks. Patients were categorized into the virological response (VR) group and non-virological response (NVR) group based on the observed changes in HBV DNA and HBsAg levels at week 48 of treatment. Additionally, patients were classified into a serological response (SR) group and a non-serological response (NSR) group according to whether serum HBsAg loss or seroconversion occurred. The expression levels of ADAR1, N4BP1, and PSME1 mRNAs in PBMCs were detected by real-time quantitative PCR. The diagnostic performance of ADAR1, N4BP1, and PSME1 was assessed by analyzing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results: After the treatment period, the VR and SR rates were 47.25% and 35.16%, respectively. Dynamic changes in ADAR1, N4BP1, and PSME1 mRNA levels differed significantly between the VR and NVR groups, as well as between the SR and NSR groups. Multivariate analysis revealed that ADAR1 was independently associated with VR and SR at weeks 12 and 24; N4BP1 was independently associated with VR at weeks 12 and 24; PSME1 was independently associated with VR and SR at weeks 12 and 24. At week 24, the AUCs for ADAR1 in predicting VR and SR were 0.9230 and 0.8554. N4BP1 had AUCs of 0.7393 for VR at week 12 and 0.7198 for SR at week 24, while PSME1 had AUCs of 0.7418 for VR and 0.7426 for SR at week 12. Conclusions: ADAR1, N4BP1, and PSME1 are novel biomarkers for early therapeutic response to Peg-IFN-α and HBsAg clearance. Clinical Trial Registration: https://www.medicalresearch.org.cn/login, identifier 2023-311.