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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
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Analysis of HBV Genome Integration in Patients With HBV-Previously Infected NBNC-HCC
Tomoya Saito1,2, Rigel Suzuki2,3,4, Akhinur Rahman5
1Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Summary
Hepatitis B virus (HBV) genomes integrate into the host genome of Hepatitis B core antibody-positive non-B non-C hepatocellular carcinoma (NBNC-HCC) cases. These integrations, particularly near the TERT gene, may drive NBNC-HCC development, with HBcrAg as a potential noninvasive marker.
Area of Science:
- Hepatology
- Oncology
- Virology
Background:
- Non-B non-C hepatocellular carcinoma (NBNC-HCC) is increasing, with many patients testing positive for Hepatitis B core antibody (HBcAb).
- Previous Hepatitis B virus (HBV) infection is suspected to contribute to NBNC-HCC, but mechanisms remain unclear.
- HBV genome integration into host DNA is a known factor in HBV-related HCC.
Purpose of the Study:
- To investigate HBV genome integration in HBcAb-positive NBNC-HCC.
- To explore how HBV integration contributes to NBNC-HCC development and progression.
- To assess the utility of Hepatitis B core-related antigen (HBcrAg) as a predictive marker.
Main Methods:
- PCR-based HBV detection in NBNC-HCC tissue samples from HBcAb-positive patients.
- Viral DNA-Capture sequencing to identify HBV integration sites.
- Measurement of serum HBcrAg levels to correlate with HBV detection.
Main Results:
- HBV genomes were detected in 19 of 90 HBcAb-positive NBNC-HCC samples.
- HBV integration was observed in 18 samples, with common sites near TERT, KMT2B, and LOC441666.
- TERT mRNA levels were significantly increased in samples with HBV integration near the TERT gene.
Conclusions:
- Identified HBV integration sites in NBNC-HCC mirror those in HBV-related HCC, suggesting a similar role in hepatocarcinogenesis.
- HBV integration may be a key factor in the development of HBcAb-positive NBNC-HCC.
- Serum HBcrAg levels show potential as a noninvasive biomarker for detecting HBV genomes in NBNC-HCC.
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