# Novel assay to detect integrated HBV DNA in urine of chronic hepatitis B patients

> **NIH NIH R43** · JBS SCIENCE, INC. · 2022 · $305,372

## Abstract

Novel assay to detect integrated HBV DNA in urine of chronic hepatitis B patients
Hepatitis B virus (HBV) infection is a global public health concern. The CDC estimates that up to 2
million Americans are chronically infected with HBV. HBV infection causes acute and chronic
hepatitis, the latter often leading to severe liver diseases such cirrhosis and HBV-associated
hepatocellular carcinoma (HBV-HCC). HBV-HCC accounts for 50% of HCC cases worldwide. HBV is
a DNA virus, and its partial genome can integrate into a host chromosome. Although HBV DNA
replication can be suppressed effectively by nucleoside analogs, integrated viral DNA and covalently
closed circular HBV DNA (cccDNA) persist in hepatocytes even after prolonged antiviral therapy.
Continuous antiviral treatment is necessary to keep viral replication suppressed due to its
ineffectiveness in eliminating the “remnant” HBV DNA (i.e., integrated HBV DNA and cccDNA) fully.
Currently, the treatment goal is to achieve a functional cure, defined as the clearance of hepatitis B
surface antigen (HBsAg), without definitively eliminating integrated or cccDNA. NO clinical test,
however, is currently capable of identifying this “cured” population. The current thinking is that after
prolonged effective anti-HBV therapy, integrated HBV DNA is the major species of residual HBV DNA
in liver and most HBsAg in HBeAg-negative patients is derived from this DNA. The ability to detect
integrated DNA in patients with chronic hepatitis B is an urgent unmet need. The goal of this
application is to develop a noninvasive urine test that can detect and characterize integrated HBV
DNA, and be used to monitor antiviral treatment efficacy and identify “cured” subjects who can be
taken off the lifelong therapy. In the phase I feasibility study, we will improve our current prototype
HBV-host junction detection assay and develop a computation pipeline, HBVJSeq, for comprehensive
profiling of HBV integration and HBV genetics (Aim 1). In Aim 2, we will perform comparative
analyses to correlate quantitative and qualitative characteristics of integrated DNA in urine and
plasma with the levels of HBsAg and HBV pregenomic RNA (pgRNA) in hepatitis B e-antigen
(HBeAg)-negative patients. Results of these analyses will be used to determine if cell-free integrated
HBV DNA can be developed as a biomarker to identify “cured” patients in HBeAg-negative
populations, warranting a phase II study to bring the test to the clinic for disease management.

## Key facts

- **NIH application ID:** 10384247
- **Project number:** 1R43AI167169-01
- **Recipient organization:** JBS SCIENCE, INC.
- **Principal Investigator:** Selena Lin
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $305,372
- **Award type:** 1
- **Project period:** 2021-12-11 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10384247

## Citation

> US National Institutes of Health, RePORTER application 10384247, Novel assay to detect integrated HBV DNA in urine of chronic hepatitis B patients (1R43AI167169-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10384247. Licensed CC0.

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