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Background <p>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.</p> Methods <p>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 &lt; 3,000 and ≥ 3,000 IU/mL strata.</p> Results <p>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 &lt; 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.</p> Conclusions <p>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.</p> Graphical abstract <p></p>

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

  • 期刊论文

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  • 发表日期：

    2026年6月19日

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  • 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

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Graphical abstract