Found programs: National Science and Technology Major Project (No . 2018ZX10302 - 206)
Authors:Zhang Yaqin1 , Ma Zhongrui2 , Qian Yuan3 , Li Junjun4 , Deng Xingli4
Keywords:chronic hepatitis B ; high viral load; nucleoside (acid) drugs; monotherapy; combination therapy; antiviral therapy
DOI:10.19405/j.cnki.issn1000-1492.2025.06.024
〔Abstract〕 To analyze the differential expression profile of miRNAs in amniotic fluid exosomes of fetu- ses with Down syndrome (DS) and provide insights for identifying novel biomarkers for the prenatal diagnosis of DS . Methods Amniotic fluid samples were collected from fetuses with DS and chromosomally normal fetuses . Exo- somes were isolated from the amniotic fluid and subjected to high-throughput sequencing. Differentially expressed miRNAs were identified , and target genes were predicted using TargetScan and miRanda. Target genes located on chromosome 21 were selected , and their biological functions and associated diseases were analyzed using Gene- Cards , HGNC , NCBI Gene , UniProtKB/Swiss-Prot , Ensembl , and OMIM databases . GO and KEGG enrichment analyses were performed to investigate the biological functions of the enriched genes . Results A total of 59 differ- entially expressed miRNAs were identified , including 31 upregulated and 28 downregulated miRNAs . Based on a fold change > 2 and P < 0. 05 , 10 upregulated and 9 downregulated miRNAs with the highest expression levels were combination group was significantly lower than that in the ETV monotherapy group (P < 0. 05) , and was similar to the HBV DNA levels in the TDF , TAF , and TMF groups (P > 0. 05) . At 48 weeks , the HBV DNA levels in the ETV + TDF combination therapy group was significantly lower than those in all monotherapy groups ( P < 0. 05) . The HBV DNA levels in the TDF , TAF , and TMF monotherapy groups were similar (P > 0. 05) . The HBV DNA level in the ETV group was higher than those in the remaining four groups (P < 0. 05) . The HBV DNA suppression rates of the ETV , TDF , TAF , TMF and ETV + TDF groups were 31 . 82% , 51 . 11% , 52. 94% , 56. 00% , and 78. 87% , respectively , the HBV DNA suppression rate in the ETV + TDF combination therapy group was signifi- cantly better than those in all monotherapy groups (P < 0. 05) , the rates of HBV DNA suppression were similar a- mong the TDF , TAF , and TMF groups , and all were superior to that of the ETV monotherapy group (P < 0. 05) . Multivariate analysis revealed that low baseline HBsAg levels (OR = 0. 430 , P = 0. 004) , high baseline ALT levels (OR = 2. 389 , P < 0. 001) , and the combination therapy regimen ( OR = 6. 239 , P < 0. 001) were independent predictors of HBV DNA suppression at 48 weeks of treatment. The reduction in HBsAg levels in the ETV + TDF group was significantly greater than that in the ETV monotherapy group[ (3 . 65 ±0. 85) vs (3 . 88 ±0. 64) , P < 0. 05 ] . The HBsAg clearance rate in the ETV + TDF group was 1 . 41% (1 /71) , while the HBsAg clearance rates in the other groups were all 0% . There were no statistically significant differences in HBeAg seroconversion rates , blood Scr levels , and eGFR levels among the groups (P > 0. 05) . Conclusion For HBeAg-positive chronic hepa- titis B (CHB) patients with high viral load , the combination therapy of ETV and TDF significantly enhances viral suppression compared to monotherapy , without increasing the risk of renal adverse events . This suggests that the combination therapy can be considered a preferred strategy for this specific patient population .