Journal article
Detection of Hepatitis B Virus-Host Junction Sequences in Urine of Infected Patients
Hepatology communications, v 5(10), pp 1649-1659
Oct 2021
PMID: 34558837
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Integrated hepatitis B virus (HBV) DNA, found in more than 85% of HBV-associated hepatocellular carcinomas (HBV-HCCs), can play a significant role in HBV-related liver disease progression. HBV-host junction sequences (HBV-JSs), created through integration events, have been used to determine HBV-HCC clonality. Here, we investigate the feasibility of analyzing HBV integration in a noninvasive urine liquid biopsy. Using an HBV-targeted next-generation sequencing (NGS) assay, we first identified HBV-JSs in eight HBV-HCC tissues and designed short-amplicon junction-specific polymerase chain reaction assays to detect HBV-JSs in matched urine. We detected and validated tissue-derived junctions in five of eight matched urine samples. Next, we screened 32 urine samples collected from 25 patients infected with HBV (5 with hepatitis, 10 with cirrhosis, 4 with HCC, and 6 post-HCC). Encouragingly, all 32 urine samples contained HBV-JSs detectable by HBV-targeted NGS. Of the 712 total HBV-JSs detected in urine, 351 were in gene-coding regions, 11 of which, including TERT (telomerase reverse transcriptase), had previously been reported as recurrent integration sites in HCC tissue and were found only in the urine patients with cirrhosis or HCC. The integration breakpoints of HBV DNA detected in urine were found predominantly (~70%) at a previously identified integration hotspot, HBV DR1-2 (down-regulator of transcription 1-2). Conclusion: HBV viral-host junction DNA can be detected in urine of patients infected with HBV. This study demonstrates the potential for a noninvasive urine liquid biopsy of integrated HBV DNA to monitor patients infected with HBV for HBV-associated liver diseases and the efficacy of antiviral therapy.
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Details
- Title
- Detection of Hepatitis B Virus-Host Junction Sequences in Urine of Infected Patients
- Creators
- Selena Y Lin - JBS Science (United States)Yih-Ping Su - The Baruch S. Blumberg Research InstituteDoylestownPAUSAEvan R Trauger - JBS Science (United States)Benjamin P Song - JBS Science (United States)Emilie G C Thompson - The Baruch S. Blumberg Research InstituteDoylestownPAUSAMalcolm C Hoffman - JBS Science (United States)Ting-Tsung Chang - Department of Internal MedicineNational Cheng Kung University Hospital, College of MedicineTainanTaiwan, Republic of ChinaYih-Jyh Lin - Department of SurgeryNational Cheng Kung University Hospital, College of MedicineTainanTaiwan, Republic of ChinaYu-Lan Kao - The Baruch S. Blumberg Research InstituteDoylestownPAUSAYixiao Cui - Baruch S. Blumberg InstituteHie-Won Hann - Liver Disease Prevention CenterDivision of Gastroenterology and HepatologyThomas Jefferson University HospitalPhiladelphiaPAUSAGrace Park - Thomas Jefferson University HospitalFwu-Shan Shieh - JBS Science (United States)Wei Song - JBS Science (United States)Ying-Hsiu Su - The Baruch S. Blumberg Research InstituteDoylestownPAUSA
- Publication Details
- Hepatology communications, v 5(10), pp 1649-1659
- Publisher
- Wiley
- Grant note
- R43 CA165312 / NCI NIH HHS R43 CA192507 / NCI NIH HHS R43 AI167169 / NIAID NIH HHS R44 CA165312 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000688276100001
- Scopus ID
- 2-s2.0-85113375776
- Other Identifier
- 991021463450304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Gastroenterology & Hepatology