Dynamics of Serum Pregenome RNA in Chronic Hepatitis B Patients Receiving 96-Month Nucleos(t)ide Analog Therapy

BackgroundTissue covalently closed circular DNA (cccDNA) can reflect the activity of HBV replication. However, it is impractical to assess intrahepatic cccDNA in every outpatient. Serum pregenome RNA (pgRNA) is transcribed from intrahepatic cccDNA and may reflect the activity of intrahepatic cccDNA....

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Main Authors: Yachao Tao, Menglan Wang, Juan Liao, Xing Cheng, Min He, Dongmei Zhang, Taoyou Zhou, Jie Chen, Enqiang Chen, Hong Tang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2022.787770/full
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author Yachao Tao
Yachao Tao
Menglan Wang
Menglan Wang
Juan Liao
Juan Liao
Xing Cheng
Xing Cheng
Min He
Min He
Dongmei Zhang
Dongmei Zhang
Taoyou Zhou
Taoyou Zhou
Jie Chen
Enqiang Chen
Enqiang Chen
Hong Tang
Hong Tang
author_facet Yachao Tao
Yachao Tao
Menglan Wang
Menglan Wang
Juan Liao
Juan Liao
Xing Cheng
Xing Cheng
Min He
Min He
Dongmei Zhang
Dongmei Zhang
Taoyou Zhou
Taoyou Zhou
Jie Chen
Enqiang Chen
Enqiang Chen
Hong Tang
Hong Tang
author_sort Yachao Tao
collection DOAJ
description BackgroundTissue covalently closed circular DNA (cccDNA) can reflect the activity of HBV replication. However, it is impractical to assess intrahepatic cccDNA in every outpatient. Serum pregenome RNA (pgRNA) is transcribed from intrahepatic cccDNA and may reflect the activity of intrahepatic cccDNA. We explored the dynamics and the potential role of serum pgRNA in patients receiving long-term NAs treatment.MethodsSerum pgRNA, HBV DNA, HBsAg, HBeAg, and ALT levels were quantified, and the relationships between serum pgRNA and these common clinical indicators before and after the treatment were investigated.ResultsSerum pgRNA showed dynamic change during the 96-month NAs therapy, and serum pgRNA levels were positive and detectable in 19 patients with undetectable serum HBV DNA. Serum pgRNA showed strong and positive correlation with serum HBV DNA (r = 0.693, p < 0.001) and serum HBsAg levels (r = 0.621, p < 0.001) at baseline. Patients with HBeAg seroconversion had lower baseline serum pgRNA levels (p = 0.002). The area under the curve (AUC) of baseline serum pgRNA for predicting HBeAg seroconversion was 0.742 (95% CI: 0.606–0.850) with 63.16% sensitivity and 80.56% specificity. The cumulative HBeAg seroconversion rate was higher in patients with low serum pgRNA (p = 0.001).ConclusionSerum pgRNA of low level at baseline or great decline at month 6 may independently predict the high incidence of undetectable serum pgRNA at year 4 following NAs therapy, and the baseline serum pgRNA may serve as a novel predictor for HBeAg seroconversion during NAs therapy.
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spelling doaj.art-6a8c9e8420a1464d92048a0c47bdf1cc2022-12-21T19:29:12ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-02-01910.3389/fmed.2022.787770787770Dynamics of Serum Pregenome RNA in Chronic Hepatitis B Patients Receiving 96-Month Nucleos(t)ide Analog TherapyYachao Tao0Yachao Tao1Menglan Wang2Menglan Wang3Juan Liao4Juan Liao5Xing Cheng6Xing Cheng7Min He8Min He9Dongmei Zhang10Dongmei Zhang11Taoyou Zhou12Taoyou Zhou13Jie Chen14Enqiang Chen15Enqiang Chen16Hong Tang17Hong Tang18Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, ChinaDivision of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, ChinaCenter of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, ChinaDivision of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, ChinaCenter of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, ChinaDivision of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, ChinaCenter of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, ChinaDivision of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, ChinaCenter of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, ChinaDivision of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, ChinaCenter of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, ChinaDivision of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, ChinaCenter of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, ChinaDivision of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, ChinaShanghai RenDu Biotechnology Co. Ltd, Shanghai, ChinaCenter of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, ChinaDivision of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, ChinaCenter of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, ChinaDivision of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, ChinaBackgroundTissue covalently closed circular DNA (cccDNA) can reflect the activity of HBV replication. However, it is impractical to assess intrahepatic cccDNA in every outpatient. Serum pregenome RNA (pgRNA) is transcribed from intrahepatic cccDNA and may reflect the activity of intrahepatic cccDNA. We explored the dynamics and the potential role of serum pgRNA in patients receiving long-term NAs treatment.MethodsSerum pgRNA, HBV DNA, HBsAg, HBeAg, and ALT levels were quantified, and the relationships between serum pgRNA and these common clinical indicators before and after the treatment were investigated.ResultsSerum pgRNA showed dynamic change during the 96-month NAs therapy, and serum pgRNA levels were positive and detectable in 19 patients with undetectable serum HBV DNA. Serum pgRNA showed strong and positive correlation with serum HBV DNA (r = 0.693, p < 0.001) and serum HBsAg levels (r = 0.621, p < 0.001) at baseline. Patients with HBeAg seroconversion had lower baseline serum pgRNA levels (p = 0.002). The area under the curve (AUC) of baseline serum pgRNA for predicting HBeAg seroconversion was 0.742 (95% CI: 0.606–0.850) with 63.16% sensitivity and 80.56% specificity. The cumulative HBeAg seroconversion rate was higher in patients with low serum pgRNA (p = 0.001).ConclusionSerum pgRNA of low level at baseline or great decline at month 6 may independently predict the high incidence of undetectable serum pgRNA at year 4 following NAs therapy, and the baseline serum pgRNA may serve as a novel predictor for HBeAg seroconversion during NAs therapy.https://www.frontiersin.org/articles/10.3389/fmed.2022.787770/fullpregenome RNAchronic hepatitis BHBV DNAhepatitis B e antigen seroconversionnucleos(t)ide analogs
spellingShingle Yachao Tao
Yachao Tao
Menglan Wang
Menglan Wang
Juan Liao
Juan Liao
Xing Cheng
Xing Cheng
Min He
Min He
Dongmei Zhang
Dongmei Zhang
Taoyou Zhou
Taoyou Zhou
Jie Chen
Enqiang Chen
Enqiang Chen
Hong Tang
Hong Tang
Dynamics of Serum Pregenome RNA in Chronic Hepatitis B Patients Receiving 96-Month Nucleos(t)ide Analog Therapy
Frontiers in Medicine
pregenome RNA
chronic hepatitis B
HBV DNA
hepatitis B e antigen seroconversion
nucleos(t)ide analogs
title Dynamics of Serum Pregenome RNA in Chronic Hepatitis B Patients Receiving 96-Month Nucleos(t)ide Analog Therapy
title_full Dynamics of Serum Pregenome RNA in Chronic Hepatitis B Patients Receiving 96-Month Nucleos(t)ide Analog Therapy
title_fullStr Dynamics of Serum Pregenome RNA in Chronic Hepatitis B Patients Receiving 96-Month Nucleos(t)ide Analog Therapy
title_full_unstemmed Dynamics of Serum Pregenome RNA in Chronic Hepatitis B Patients Receiving 96-Month Nucleos(t)ide Analog Therapy
title_short Dynamics of Serum Pregenome RNA in Chronic Hepatitis B Patients Receiving 96-Month Nucleos(t)ide Analog Therapy
title_sort dynamics of serum pregenome rna in chronic hepatitis b patients receiving 96 month nucleos t ide analog therapy
topic pregenome RNA
chronic hepatitis B
HBV DNA
hepatitis B e antigen seroconversion
nucleos(t)ide analogs
url https://www.frontiersin.org/articles/10.3389/fmed.2022.787770/full
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