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Differential Hepatitis B Surface Antigen Glycan Isomer Kinetics Between Tenofovir Alafenamide and Entecavir: Hepatocellular Carcinoma Risk Stratification in Hepatitis B e Antigen-Positive Patients.

Created on 29 Jul 2026

Authors

Yuji Kita, Ayato Murata, Hiroki Nago, Masahiro Yamaguchi, Yoko Kato, Rihwa Om, Yuichro Terai, Yuji Ikeda, Sho Sato, Shunsuke Sato, Yuji Shimada, Takuya Genda

Published in

Journal of viral hepatitis. Volume 33. Issue 9. Pages e70218.

Abstract

Nucleos(t)ide analog (NA) therapy suppresses hepatitis B virus (HBV) DNA, but residual hepatocellular carcinoma (HCC) risk persists. O-glycosylated hepatitis B surface antigen glycan isomer (HBsAgGi) uniquely reflects virion burden. We evaluated the impact of tenofovir alafenamide (TAF) versus entecavir (ETV) on 48-week HBsAgGi kinetics and its utility in stratifying HCC risk in 90 NA-naïve patients (ETV: 73; TAF: 17). A favourable response was defined as a reduction or maintenance of low HBsAgGi levels. TAF independently predicted a favourable response compared with ETV (penalised odds ratio 3.60, p = 0.030). A significant interaction occurred between HBeAg status and HBsAgGi response in relation to HCC development (p = 0.038). In HBeAg-positive patients, a poor response was associated with increased HCC risk (hazard ratio 7.34, 95% confidence interval [CI] 1.96-20.35, p = 0.001); however, the exact magnitude warrants cautious interpretation due to wide CIs. This association was absent in HBeAg-negative cases. Adding HBsAgGi response to the aMAP score improved long-term HCC prediction exclusively in the HBeAg-positive cohort. As the assay targets genotype C-specific O-glycosylation, the findings cannot be generalised to genotypes A, B, or D. In conclusion, on-treatment HBsAgGi response is a specific surrogate marker for stratifying residual HCC risk in HBeAg-positive patients, and TAF is more effective than ETV in inducing these favourable kinetics.

PMID:
42522680
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.

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