Clinical and Molecular Hepatology

"Nucleoside analog"

Research Letter

Non-infectivity of hepatitis B virus under nucleoside analog therapy revealed through auxiliary partial orthotopic liver transplantation: Xiaojie Chen, Guiwen Guan, Lin Wei, Jidong Jia, Xiangmei Chen, Fengmin Lu, Zhijun Zhu; Clin Mol Hepatol 2025;31(3):e263-e267.
Published online May 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.0393

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Editorial

Besifovir: a viable option for long-term disease control in chronic hepatitis B: Editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”: Wai-Kay Seto; Clin Mol Hepatol 2026;32(1):374-376.
Published online March 24, 2025; DOI: https://doi.org/10.3350/cmh.2025.0305

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Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang
Clinical and Molecular Hepatology.2026; 32(1): e55. CrossRef

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Original Article

Viral hepatitis

Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parameters: 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; Clin Mol Hepatol 2025;31(2):460-473.
Published online December 26, 2024; DOI: https://doi.org/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.

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Viruses.2026; 18(4): 424. CrossRef
Reconsidering the role of plasma pgRNA in NUC-treated CHB: Stratified biomarker interpretation and the limits of current assays: Letter to the editor on “Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-
Xu Han, Jun Sun, Yinyan Li
Clinical and Molecular Hepatology.2026; 32(2): e131. CrossRef
Profiles and kinetics of PgRNA and clinical characteristics in pregnant, postpartum, and non-pregnant women with chronic HBV infection
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Virology Journal.2025;[Epub] CrossRef

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Review

Viral hepatitis

Options for the management of antiviral resistance during hepatitis B therapy: reflections on battles over a decade: Hyung Joon Yim, Seong Gyu Hwang; Clin Mol Hepatol 2013;19(3):195-209.
Published online September 30, 2013; DOI: https://doi.org/10.3350/cmh.2013.19.3.195

Abstract
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Although much advancement has been achieved in the treatment of chronic hepatitis B, antiviral resistance is still a challenging issue. Previous generation antiviral agents have already developed resistance in a number of patients, and it is still being used especially in resource limited countries. Once antiviral resistance occurs, it predisposes to subsequent resistance, resulting in multidrug resistance. Therefore, prevention of initial antiviral resistance is the most important strategy, and appropriate choice and modification of therapy would be the cornerstone in avoiding treatment failures. Until now, management of antiviral resistance has been evolving from sequential therapy to combination therapy. In the era of tenofovir, the paradigm shifts again, and we have to decide when to switch and when to combine on the basis of newly emerging clinical data. We expect future eradication of chronic hepatitis B virus infection by proper prevention and optimal management of antiviral resistance.

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