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

Yachao Tao; Menglan Wang; Juan Liao; Xing Cheng; Min He; Dongmei Zhang; Taoyou Zhou; Jie Chen; Enqiang Chen; Hong Tang

doi:10.3389/fmed.2022.787770

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

Front Med (Lausanne). 2022 Feb 28:9:787770. doi: 10.3389/fmed.2022.787770. eCollection 2022.

Authors

Yachao Tao^{1

2}, Menglan Wang^{1

2}, Juan Liao^{1

2}, Xing Cheng^{1

2}, Min He^{1

2}, Dongmei Zhang^{1

2}, Taoyou Zhou^{1

2}, Jie Chen³, Enqiang Chen^{1

2}, Hong Tang^{1

2}

Affiliations

¹ Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.
² Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.
³ Shanghai RenDu Biotechnology Co. Ltd, Shanghai, China.

Abstract

Background: Tissue 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.

Methods: Serum 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.

Results: Serum 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).

Conclusion: Serum 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.

Keywords: HBV DNA; chronic hepatitis B; hepatitis B e antigen seroconversion; nucleos(t)ide analogs; pregenome RNA.