ArticleHepatology international2026
Exploratory analysis of transcriptionally active HBV-host chimeric transcript burden in patients with increasing HBsAg during long-term antiviral therapy.
Article in Hepatology international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND AND
aimsThe longitudinal relationship between transcriptionally active hepatitis B virus (HBV) integration dynamics and serum hepatitis B surface antigen (HBsAg) during long-term antiviral therapy remains unclear.
methodsPatients with HBV-related fibrosis/cirrhosis who underwent at least one liver biopsy at baseline, week 78, or week 260 were enrolled. HBsAg increase was defined as either a ≥5% increase from baseline to week 208 or at least two ≥5% increases between consecutive available visits. A subset of 10 patients with serial liver RNA sequencing underwent integrated clinical, transcriptomic, and histopathological analyses. HBV-host chimeric transcripts were identified using ChimericSeq and verified by BLAST, and intrahepatic HBsAg was assessed by immunohistochemistry.
resultsOverall, 31.8% (99/311) of patients met the criteria for HBsAg increase, while others were classified into the stable/decrease group. Lower baseline HBsAg and higher histologic activity index (HAI) were independently associated with HBsAg increase (both p < 0.05). In the serial-biopsy subset (n = 10), patients in the HBsAg increase group (4/4) showed increased HBV-host chimeric transcript burden at week 260 versus week 78, whereas the six patients in the stable/decrease group showed stable or reduced burden. Intrahepatic HBsAg immunohistochemistry showed persistent clustered cytoplasmic positivity, with transcriptomic analysis indicating downregulation of multiple immune-related pathways in the HBsAg increase group.
conclusionAbout 31.8% of patients had HBsAg increase during antiviral therapy. Baseline HBsAg and HAI were associated with HBsAg increase during antiviral therapy. In the exploratory serial-biopsy subset, patients with HBsAg increase tended to exhibit an increase in transcriptionally active HBV-host chimeric transcript burden and persistent clustered cytoplasmic HBsAg positivity.
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