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  • Clinical applications of circulating HBV RNA as a potential surrogate biomarker for intrahepatic cccDNA transcriptional activity

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Clinical applications of circulating HBV RNA as a potential surrogate biomarker for intrahepatic cccDNA transcriptional activity
  1. Xiaoqi Yu1,
  2. Maria Pfefferkorn2,
  3. Florian van Bömmel2,
  4. Xinxin Zhang1,3,
  5. Thomas Berg2
  1. 1 Department of Infectious Diseases, Research Laboratory of Clinical Virology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
  2. 2 Division of Hepatology, Department of Medicine II, University of Leipzig Medical Center, Leipzig, Germany
  3. 3 Clinical Research Center, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
  1. Correspondence to Professor Xinxin Zhang, Department of Infectious Diseases, Research Laboratory of Clinical Virology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China; zhangx{at}shsmu.edu.cn; Prof Thomas Berg, Division of Hepatology, Department of Medicine II, University of Leipzig Medical Center, Leipzig, Germany; thomas.berg{at}medizin.uni-leipzig.de

https://doi.org/10.1136/gutjnl-2023-331217

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    There is a close link between diagnostic and therapeutic approaches. The more precise the biomarker, the more accurately we can predict treatment outcomes. The efficacy of the hepatitis C virus (HCV) RNA biomarker in anticipating both early treatment response and post-treatment cure in HCV infections stands as a prime exemplar. Curing hepatitis B virus (HBV) infection, characterised as the persistent loss of hepatitis B surface antigen (HBsAg) (termed a functional cure), is now a top priority in the management of HBV infection. Despite employing highly sophisticated and efficacious drugs, our progress towards this curative goal has been limited. One possible reason for this could be the suboptimal performance of the cure-defining biomarker—HBsAg. The reality that HBsAg can arise from both covalently closed circular DNA (cccDNA) transcription and integrated DNA adds complexity to the matter and is a likely reason for the therapeutic setbacks. Indeed, strategies aiming to halt transcription from integration differ from those silencing cccDNA. A partial cure, in which cccDNA transcription is silenced but HBsAg derived from integrated HBV DNA persists, increasingly appears to be a viable intermediate step on our path to overcoming HBV. Hence, biomarkers that distinctly discern whether HBsAg originates from cccDNA transcription or integration are paramount.

    Circulating HBV RNA (cirB-RNA) was first described in 1996 in the serum of HBV-infected patients1 and has re-emerged as a research hotspot in the past decade. It is one of the new biomarkers of HBV infection as recommended by the European Association for the Study of the Liver.2 Numerous aspects of cirB-RNA in clinical practice have already been investigated in previous studies. Circulating HBV RNA could cover the ‘blind area’ of HBV DNA and HBsAg in monitoring treatment response and was found to predict HBeAg seroconversion in patients either treated with peginterferon (Peg-IFN)3 or polymerase …

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    Footnotes

    • Twitter @ThomasBerg24

    • Contributors XY and XZ wrote the initial draft of this commentary. MP, FvB and TB critically revised the manuscript and provided meaningful input. MP plotted the figure. All authors approved the final version for submission.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Commissioned; internally peer reviewed.

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