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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 1
Jan.  2023
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Article Contents

Expression levels of HBV pregenomic RNA and hepatitis B core-related antigen in circulating serum and their association with recurrence in chronic hepatitis B patients after withdrawal from nucleos(t)ide analogues

DOI: 10.3969/j.issn.1001-5256.2023.01.009
Research funding:

Special Funds for Municipal School Cooperation of Nanchong (19SXHZ0058)

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  • Corresponding author: MEI Xiaopin, 1124377569@qq.com (ORCID: 0000-0002-5077-1706)
  • Received Date: 2022-10-14
  • Accepted Date: 2022-11-28
  • Published Date: 2023-01-20
  •   Objective  To investigate the expression levels of HBV pregenomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in circulating serum of chronic hepatitis B (CHB) patients after withdrawal from nucleos(t)ide analogues (NUC), as well as the correlation of HBV pgRNA and HBcrAg levels in circulating blood in different periods of time with recurrence in CHB patients after drug withdrawal.  Methods  Among the patients who attended the outpatient service of Affiliated Hospital of North Sichuan Medical College from December 2019 to July 2022, a total of 108 CHB patients who received anti-HBV therapy for at least 5 years and met the criteria for drug withdrawal in 2017 EASL Guidelines were enrolled. According to the time of drug withdrawal, the patients were divided into 4-, 12-, and 24-week groups after drug withdrawal, and according to the presence or absence of recurrence, they were divided into recurrence group and non-recurrence group. Quantitative real-time PCR was used to measure the level of HBV pgRNA in circulating serum of CHB patients; ELISA was used to measure the expression level of HBcrAg in peripheral venous blood; quantitative real-time PCR was used to measure HBV DNA load with high accuracy. The t-test was used for comparison of continuous data between two groups. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Pearson correlation test was used to investigate the correlation between the indices in circulating blood.  Results  For the CHB patients after drug withdrawal, the recurrence rate was 17.1% at 4-12 weeks, cumulative recurrence rate reached 29.3% after 24 weeks of follow-up, the patients with positive HBV DNA alone accounted for 64.3% and 60.0%, respectively, those with positive HBeAg alone accounted for 28.5% and 20.0%, respectively, and those with positive HBV DNA and HBeAg accounted for 7.1% and 20.0%, respectively. The expression levels of HBV pgRNA, HBcrAg, and HBV DNA in circulating serum of CHB patients at 24 weeks after drug withdrawal were significantly higher than those at the time of drug withdrawal and at 4 weeks after drug withdrawal, and there was a significant difference between groups at different time points (all P < 0.05). Compared with the non-recurrence group, the recurrence group had significantly higher expression levels of HBV pgRNA, HBcrAg, and HBV DNA in circulating serum (t=2.549, 8.654, and 27.429, all P < 0.05), and further analysis of the recurrence group showed that the levels of HBV pgRNA, HBcrAg, and HBV DNA in circulating serum at 12-24 weeks were significantly higher than those at 4-12 weeks (all P < 0.05). At the time of drug withdrawal, the recurrence group had significantly higher expression levels of HBV pgRNA and HBcrAg in circulating serum than the non-recurrence group (t=18.561 and 6.152, both P < 0.001). The Pearson correlation analysis showed that in the recurrence group after drug withdrawal, HBV pgRNA and HBcrAg were positively correlated with HBV DNA in circulating serum (r=0.82 and 0.66, both P < 0.001), while no such correlation was observed in the non-recurrence group (r=0.14 and 0.04, both P > 0.05).  Conclusion  The recurrence group had significantly higher expression levels of HBV pgRNA and HBcrAg than the non-recurrence group at the time of drug withdrawal, suggesting that the levels of HBV pgRNA and HBcrAg in the CHB patients of the non-recurrence group at the time of drug withdrawal may be used as the reference thresholds for safe drug withdrawal in CHB patients, and measurement of HBV pgRNA and HBcrAg may be one of the potential reference indicators for the selection of anti-HBV treatment endpoints in the future.

     

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