Development of an NGS-Based Estimation of Integrated HBV DNA in Liver Biopsies and Detection in Liquid Biopsies

IF 6.8 3区医学 Q1 VIROLOGY

Journal of Medical Virology Pub Date : 2025-03-10 DOI:10.1002/jmv.70290

Hsin-Ni Liu, Selena Y. Lin, Ricardo Ramirez, Shin-En Chen, Zachary R. Heimer, Roman Kubas, Fwu-Shan Shieh, Elena S. Kim, Yuanjie Liu, Daryl T. Y. Lau, Ting-Tsung Chang, Haitao Guo, Zhili Wang, Ying-Hsiu Su

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引用次数: 0

Abstract

This study characterized a hepatitis B virus (HBV) hybridization-capture next-generation sequencing (HBV-NGS) assay and applied it to develop a model for estimating the integrated HBV DNA (iDNA) quantity and for HBV genetics liquid biopsy. Using HBV monomers and reconstituted cell line DNA (SNU398, Hep3B, and PLC/PRF/5), the HBV-NGS assay demonstrated high coverage uniformity, reproducibility across HBV genotypes A-D, and 0.1% sensitivity for detecting iDNA. The iDNA sequence and structures from SNU398 and Hep3B are reported. An iDNA estimation model was developed using tissue biopsies from patients with serum viral load < 4 log IU/mL and validated using SNU398 and Hep3B cell line DNA. The assay's utility for HBV genetic liquid biopsy was evaluated using matched plasma-urine samples with HBV DNA levels ranging from high to undetectable. In this pilot study, HBV-JS was detected in all body fluids, regardless of viral load. These findings indicate that the iDNA from patients with negligible or undetectable viral replication can be assessed for iDNA elimination efficacy in drug development. Moreover, a sensitive HBV genetics liquid biopsy can be feasible even for patients with undetectable serum viral load. This study underscores the potential of NGS-based methods to advance HBV management.

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来源期刊

Journal of Medical Virology 医学-病毒学

CiteScore

23.20

自引率

2.40%

发文量

777

审稿时长

1 months

期刊介绍： The Journal of Medical Virology focuses on publishing original scientific papers on both basic and applied research related to viruses that affect humans. The journal publishes reports covering a wide range of topics, including the characterization, diagnosis, epidemiology, immunology, and pathogenesis of human virus infections. It also includes studies on virus morphology, genetics, replication, and interactions with host cells. The intended readership of the journal includes virologists, microbiologists, immunologists, infectious disease specialists, diagnostic laboratory technologists, epidemiologists, hematologists, and cell biologists. The Journal of Medical Virology is indexed and abstracted in various databases, including Abstracts in Anthropology (Sage), CABI, AgBiotech News & Information, National Agricultural Library, Biological Abstracts, Embase, Global Health, Web of Science, Veterinary Bulletin, and others.