Combination of interferon and nucleotide analogues might be more effective in inhibiting replication of hepatitis B virus (HBV), thereby alleviating hepatic fibrosis and hepatocyte necrosis. Herein, we explored the impact of co-treatment of entecavir (ETV) and PEG-IFNα-2a on HBV-RNA, IL-21 level, immune function and prognosis in HBeAg-positive patients with low HBsAg level. Patients treated with ETV over 12 months received PEG-IFNα-2a treatment. Serum HBV markers and HBV-DNA were examined at 12, 24 and 48 weeks, and disappearance of HBsAg were measured at 24 weeks as an evaluation index for efficacy. Besides, levels of IL-21, serum albumin, and complement C3 were measured. During follow-up, we found that, HBsAg serological conversion appeared in 6.0% of all patients, with HBsAg disappearance in 18.1% and HBsAg <10 IU/mL in 10.8%. The HBeAg level in non-disappearing group was lower than HBsAg disappearing group (P <0.05) with AUC score of 0.720 for HBsAg suggested by HBeAg conversion rate (P <0.05). Of note, HBsAg levels decreased at 12 weeks of treatment (≥0.5 log IU/mL) and HBsAg was prone to disappearance (P <0.05). AUC of HBsAg disappearance predicted by the HBsAg levels at 12 weeks and 24 weeks were 0.810 (95% CI: 0.686–0.935, P = 0.000) and 0.842 (95% CI: 0.736–0.947, P = 0.000) compared with baseline. Combination of ETV and PEG-IFNα-2a resulted in enhancement of serum IL-21 level (210.803±72.477) and reduction of IL-21 expression (157.084±38.697). The IL-21 level was negatively correlated with immune function indicators serum albumin and serum complement C3. HBsAg conversion rate and early HBsAg changes are crucial to prediction of HBsAg disappearance. With ETV achieving great virological response, combination of ETV with PEG-IFNα-2a enhanced HBsAg loss, reducing IL-21 expression, and improving immune function in patients.

Background. Chronic hepatitis B (CHB) is a serious infectious disease which is induced by hepatitis B virus (HBV) infection. This project was conducted to reveal the potential mechanism in CHB development via analyzing the public clinical data. Methods. GSE33857 and GSE110217, obtained from the GEO database, were used for bioinformatics excavation. Briefly, the raw data of GSE33857 and GSE110217 were analyzed with the GEO2R, and then the expressed matrix files were generated. The matrix files was visualized as heat map with R software. The targets of the miRNAs were analyzed with the miRDIP database. The functional annotation and pathway enrichment were performed using “clusterProfiler” package in R software. The STRING database was utilized to analyze the interaction of the DEGs, and the PPI and miRNA-mRNA network were established according to the related results. Results. 93 downregulated genes and 17 upregulated genes in GES33857, and 111 downregulated and 40 upregulated genes in GSE110217 were identified as the hub nodes. The targets of the DEGs in the datasets were enriched in PI3K/AKT and MAPK pathways and associated with transcriptional regulation. Moreover, PPI and miRNA-mRNA networks were also established with the DEGs and related targets in the datasets. miR-122-5p, miR-125b-5p, miR-136-5p, miR-194-5p, miR-139-5p, miR-140-5p, miR-181a-5p, and miR-29b-3p were identified as the potential biomarkers in CHB. Conclusion. Eight miRNAs, including miR-122-5p, miR-125b-5p, miR-136-5p, miR-194-5p, miR-139-5p, miR-140-5p, miR-181a-5p, and miR-29b-3p, were identified as the potential biomarkers in CHB, and the PPI and miRNA-mRNA networks were also established.