Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parameters

• Published in: Clinical and molecular hepatology Vol. 31; no. 2; pp. 460 - 473
• Main Authors: Lung-yi Mak, Mark Anderson, Michael Stec, Matthew Shing-hin Chung, Danny Ka-ho Wong, Rex Wan-hin Hui, Wai-kay Seto, Gavin Cloherty, Man-fung Yuen
• Format: Journal Article
• Language: Korean
• Published: 대한간학회 01.04.2025
• Subjects: Aging; Cirrhosis; HBV biomarkers; Nucleoside analogue; Aging; Cirrhosis; Nucleoside analogue; HBV biomarkers
• ISSN: 2287-2728
• DOI: 10.3350/cmh.2024.0724

Backgrounds/Aims: Plasma pregenomic hepatitis B virus RNA (pgRNA) is a novel biomarker in chronic hepatitis B infection (CHB). We aimed to describe the longitudinal profile of pgRNA and factors influencing its levels in CHB patients on nucleoside analogue (NUC). Methods: Serial plasma samples from 1,354 CHB patients started on first-line NUC were evaluated. Time of NUC initiation was taken as baseline (year 0), followed by 1-year, 3-year and 5-year of NUC therapy. pgRNA was measured by Research Use Only RealTime HBV RNA v2.0 (0.2 mL) (Abbott Diagnostics) with lower limit of detection of 0.8 log U/mL (~20 copies/mL). Results: Among 1,354 subjects (median age at baseline 49.8 [interquartile range, IQR 40.2-57.3]) years, 65.2% male, 16.1% hepatitis B e antigen (HBeAg)-positive, 28.6% cirrhotic), baseline median HBV RNA was 3.68 (IQR 2.42-5.19) log U/mL. Upon NUC therapy, median pgRNA levels were 2.45 (IQR 1.82-3.62), 2.23 (IQR 1.67-3.05) and 2.14 (IQR 1.48-2.86) log U/mL at 1, 3 and 5 years, respectively, with the corresponding log U/mL reductions of 0.82, 1.20 and 1.54. Undetectable/ unquantifiable pgRNA was achieved in 13.5%, 15.9% and 20.1% of patients at 1, 3 and 5 years, respectively. Older age, male sex, HBeAg-negativity and high PAGE-B score were associated with lower pgRNA. Conclusions: Plasma pgRNA declines are modest under NUC therapy, with only 16.3% achieving RNA undetectability after 5 years of first-line NUC indicating cccDNA silencing has not been achieved in the majority of patients. Clinical characteristics should be taken into consideration when interpreting the plasma pgRNA level. (Clin Mol Hepatol 2025;31:460-473)