Differential intrahepatic integrated HBV DNA patterns between HBeAg-positive and HBeAg-negative chronic hepatitis B

作者：Daryl Lau, Elena S. Kim, Zhili Wang, Wendy C. King, David E. Kleiner, Marc G. Ghany, Amanda S. Hinerman, Yuan‐jie Liu, Raymond T. Chung, Richard K. Sterling, Gavin Cloherty, Selena Y. Lin, Hsin‐Ni Liu, Ying‐Hsiu Su, Haitao Guo · 发表于：Gut · 年份：2026 · DOI：10.1136/gutjnl-2025-337127 · 被引用次数：1 · 研究领域：Hepatitis B Virus Studies、RNA Interference and Gene Delivery、Liver physiology and pathology

BACKGROUND: Hepatitis B surface antigen (HBsAg) can be derived from intrahepatic covalently closed circular DNA (cccDNA) and integrated hepatitis B virus (HBV) DNA (iDNA). OBJECTIVE: We evaluated the cccDNA and iDNA from liver tissues of 24 hepatitis B e antigen (HBeAg)(+) and 32 HBeAg(-) treatment-naïve chronic hepatitis B (CHB) participants in the North American Hepatitis B Research Network. DESIGN: For cccDNA analysis, DNA was heat-denatured and digested by plasmid-safe ATP-dependent DNase to remove relaxed circular DNA and iDNA before real-time polymerase chain reaction. For iDNA detection, total DNA was subjected to HBV hybridisation-targeted next generation sequencing assay for identification of the HBV-host junction sequences. Comparisons of HBV cccDNA and iDNA with other virological biomarkers were assessed. RESULTS: Intrahepatic cccDNA, serum HBV DNA, HBV RNA, hepatitis B core related antigen and quantitative hepatitis B surface antigen were higher in HBeAg(+) CHB. Intrahepatic hepatitis B core antigen staining was present in 87% HBeAg(+) but only 13% HBeAg(-) samples (p<0.0001). HBsAg staining was frequent in over 85% in both groups. 23 (95.8%) HBeAg(+) participants had ≤50% iDNA whereas 25 (78.1%) HBeAg(-) participants had >50% iDNA of total HBV DNA in their livers. For HBeAg(+) CHB, the iDNA integration sites were random with only 15.9% localised to the direct repeat 2 (DR2)-DR1 region. For HBeAg(-) CHB, 52.4% of the iDNA integrations were clustered at DR2-DR1. Mi...