HBsAg glycan isomer predicts on-treatment HBsAg decline in low-HBsAg chronic hepatitis B on nucleos(t)ide therapy.

Authors

Daisuke Yokoyama, Goki Suda, Masatsugu Ohara, Takatsugu Tanaka, Shoichi Kitano, Osamu Maehara, Ruixin Deng, Qingjie Fu, Zijian Yang, Naohiro Yasuura, Akimitsu Meno, Risako Kohya, Takashi Kitagataya, Naoki Kawagishi, Masato Nakai, Takuya Sho, Shunsuke Ohnishi, Naoya Sakamoto

Published in

Virology journal. Jun 19, 2026. Epub Jun 19, 2026.

Abstract

Early decline in HBsAg levels during nucleos(t)ide-analog (NA) therapy predicts subsequent HBsAg loss, but stratification tools are limited. We assessed whether a novel baseline HBV biomarker-the HBsAg glycan-isomer (HBsAgGi)-predicts 12-month HBsAg decline.
We retrospectively analysed genotype C chronic hepatitis B patients who initiated entecavir, tenofovir-disoproxil-fumarate, or tenofovir-alafenamide and had serum available for HBsAgGi measurement. Early decliners were defined as those with ≥ 0.10 log10 IU/mL HBsAg reduction after 1 year. Baseline clinical and virological parameters were compared between decliners and non-decliners and within HBsAg < 3,000 and ≥ 3,000 IU/mL strata.
Of 201 screened individuals, 106 had samples for HBsAgGi testing. In this cohort, HBsAg levels continued to fall annually over 5 years in early decliners, whereas non-decliners showed almost no long-term HBsAg reduction. In univariate analyses, higher baseline HBsAg, HBV DNA, HBeAg-positivity, and HBcrAg were associated with 1-year HBsAg decline, whereas HBsAgGi was not; none remained significant in multivariable models. However, among patients with baseline HBsAg < 3,000 IU/mL, HBsAgGi alone differentiated decliners from non-decliners. After adjustment for baseline HBsAg and HBcrAg, lower HBsAgGi remained independently associated with ≥ 0.10 log10 IU/mL HBsAg decline at 1 year. In patients with baseline HBsAg ≥ 3,000 IU/mL, decliners had higher rates of HBeAg positivity and higher baseline HBsAg and HBcrAg. Traditional HBV markers were tightly correlated, whereas HBsAgGi showed only weak-to-modest correlations.
Baseline HBsAgGi adds prognostic value in patients with low HBsAg, identifying those more likely to achieve on-therapy HBsAg decline and potentially informing selection for intensified or combination HBV therapies.

PMID:
42321863
Bibliographic data and abstract were imported from PubMed on 20 Jun 2026.

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