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

Background/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 1,35...

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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: Article
Language:English
Published: Korean Association for the Study of the Liver 2025-04-01
Series:Clinical and Molecular Hepatology
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Online Access:http://e-cmh.org/upload/pdf/cmh-2024-0724.pdf
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author 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
author_facet 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
author_sort Lung-Yi Mak
collection DOAJ
description Background/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.
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spelling doaj-art-34239c7a71b94d26ad461bbb971822d62025-08-20T02:13:19ZengKorean Association for the Study of the LiverClinical and Molecular Hepatology2287-27282287-285X2025-04-0131246047310.3350/cmh.2024.07242127Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parametersLung-Yi Mak0Mark Anderson1Michael Stec2Matthew Shing-Hin Chung3Danny Ka-Ho Wong4Rex Wan-Hin Hui5Wai-Kay Seto6Gavin Cloherty7Man-Fung Yuen8 Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Abbott Laboratories, Abbott Diagnostics Division, Abbott Park, IL, USA Abbott Laboratories, Abbott Diagnostics Division, Abbott Park, IL, USA Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Abbott Laboratories, Abbott Diagnostics Division, Abbott Park, IL, USA Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong KongBackground/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.http://e-cmh.org/upload/pdf/cmh-2024-0724.pdfhbv biomarkerscirrhosisagingnucleoside analogue
spellingShingle 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
Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parameters
Clinical and Molecular Hepatology
hbv biomarkers
cirrhosis
aging
nucleoside analogue
title Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parameters
title_full Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parameters
title_fullStr Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parameters
title_full_unstemmed Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parameters
title_short Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parameters
title_sort longitudinal profile of plasma pregenomic rna in patients with chronic hepatitis b infection on long term nucleoside analogues and its interaction with clinical parameters
topic hbv biomarkers
cirrhosis
aging
nucleoside analogue
url http://e-cmh.org/upload/pdf/cmh-2024-0724.pdf
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