Trajectories of serum hepatitis B surface antigen kinetics in patients with chronic hepatitis B receiving long‐term nucleos(t)ide analogue therapy

Hsu, Wei‐Fan; Chen, Chuen Fei; Lai, Hsueh Chou; Su, Wen Pang; Lin, Chia Hsin; Chuang, Po‐Heng; Chen, Sheng Hung; Chen, Ching Hsiang; Wang, Hung‐Wei; Huang, Guan-Tarn; Peng, Cheng Yuan

doi:10.1111/liv.13564

Cited by 8 publications

(5 citation statements)

References 28 publications

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“…Specifically, a baseline HBsAg of ≤3 log IU/mL and a reduction in HBsAg during the first year emerged as significant indicators for these outcomes during prolonged NA therapy. These findings align with several previous studies highlighting the importance of baseline HBsAg levels and its first-year decline in predicting functional cure [11,27,32]. Moreover, we emphasize the significance of these markers in achieving low HBsAg levels.…”

Section: Discussionsupporting

confidence: 92%

“…Quantitative HBsAg, which detects Dane particle and sub-viral particles, is known to positively correlate with intrahepatic cccDNA, suggesting that HBsAg kinetics could act as an indicator for HBsAg loss [ 7 ]. Notably, both baseline and 12 month HBsAg levels have been proposed as predictors for HBsAg loss [ 9 , 10 , 11 ]. Despite these findings, the long-term kinetics of HBsAg over 5 years remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Long-Term HBsAg Titer Kinetics with Entecavir/Tenofovir: Implications for Predicting Functional Cure and Low Levels

Lee,

Nam,

Jang

et al. 2024

Diagnostics

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The long-term kinetics of quantitative HBsAg levels in HBV-infected patients treated with entecavir or tenofovir, as well as the role of quantitative HBsAg in predicting functional cure (HBsAg loss) and low HBsAg levels (<2 log IU/mL) remain unclear. Of some 1661 consecutively enrolled patients newly treated with entecavir or tenofovir, we analyzed 852 patients who underwent serial HBsAg level checks every 6–12 months. The primary outcomes included long-term kinetics in HBsAg levels and the rate of functional cure and achieving low HBsAg levels. Over a mean 6.3-year follow-up, the functional cure rate was 2.28% (n = 19), and 12.9% (n = 108) achieved low HBsAg levels. A significant HBsAg level reduction was seen in the first treatment year (p < 0.05), with another stepwise decrease between year 6–7. These trends were pronounced in patients with chronic hepatitis and HBeAg-positivity compared to those with cirrhosis and HBeAg-negativity, respectively. Baseline HBsAg of ≤3 log IU/mL and the first-year HBsAg reduction were key predictors for both functional cure and low HBsAg levels (p < 0.05). In conclusion, our findings elucidate the stepwise reduction in quantitative HBsAg dynamics during high-potency NA therapy (entecavir or tenofovir) along with variations based on different conditions. We also underscore the significance of quantitative HBsAg titer in predicting functional cure and low-HBsAg levels.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Long-Term HBsAg Titer Kinetics with Entecavir/Tenofovir: Implications for Predicting Functional Cure and Low Levels

Lee,

Nam,

Jang

et al. 2024

Diagnostics

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“…The strongest predictors of HBsAg loss was Caucasians with genotype A or D, ≤4 years of infection and qHBsAg >1 log decline at week 24 20 . A study that examined the kinetics of qHBsAg during nucleoside analogue therapy 21 found that HBeAg negative patients with the highest HBsAg loss rates had a 50% reduction in qHBsAg within 12 months and reached < 200 IU/mL. None of our patients were in this rapid responder group, making HBsAg loss due to NA therapy alone less likely.…”

Section: Discussionmentioning

confidence: 99%

Comparative biomarkers for HBsAg loss with antiviral therapy shows dominant influence of quantitative HBsAg (qHBsAg)

Lim

Phyo

Ling

et al. 2020

Aliment Pharmacol Ther

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SummaryBackgroundBiomarkers such as quantitative HBsAg (qHBsAg), quantitative hepatitis B virus (HBV) core‐related antigen (qHBcrAg) and HBV RNA may be useful in predicting HBsAg loss in patients with chronic hepatitis B (CHB) undergoing antiviral therapy.Aim(s)Our study evaluated qHBsAg, HBV RNA and qHBcrAg as a posthoc analysis of a randomized clinical trial of peginterferon±NA to determine their utility in predicting HBsAg loss.MethodsCHB patients who completed therapy with 48weeks peginterferon alpha2b ± nucleoside analogue therapy (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBsAg loss. The predictive ability of qHBsAg, qHBcrAg, HBV RNA and other variables were investigated by univariate and multivariate logistic models for HBeAg‐negative patients by odds ratios, area under the curve (AUC), sensitivity, specificity, and positive and negative likelihood ratios (LR).ResultsHBsAg loss occurred in 15/114(13%) HBeAg‐negative CHB patients who completed 48 weeks of peginterferon. At baseline, qHBsAg was superior to HBcrAg and HBV RNA with AUC 0.916, 0.649 and 0.542, respectively. Using multivariate analysis, the model comprising treatmentarm, age, gender, baseline qHBsAg, HBcrAg and HBV RNA, weeks 4 & 8 qHBsAg had the highest AUC(0.98), but the univariate model with week 8 qHBsAg <70 IU/mL had AUC 0.96. Hence, the contributions of variables other than qHBsAg were marginal. HBV RNA and qHBcrAg were weak predictors of HBsAg loss. Kinetics of the novel markers showed only qHBsAg had a good relationship with HBsAg loss while HBV RNA had a marginal relationship and HBcrAg did not change at all, and none had a good relationship with viral rebound.ConclusionsOn‐treatment biomarker predictors were better than baseline ones, and the best predictor of HBsAg loss at 72 weeks was week 8 qHBsAg <70 IU/mL.

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“…2 A more recent publication from Hsu et al described a 0.09 log 10 IU/ml decline in HBsAg level in HBeAg-negative patients (genotype B and genotype C) after five years of treatment with entecavir. 3 Consequently, the baseline HBsAg levels seen in our predominantly genotype D population, who had not achieved HBsAg loss during NA therapy, may not be out of line with previous experience, as they are unlikely to have changed substantially from when patients started treatment.…”

mentioning

confidence: 74%

Reply to: “Stop-and-watch strategy after cessation of nucleos(t)ide analogue therapy in HBeAg-negative patients”

Berg

Petersen

2018

Journal of Hepatology

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Trajectories of serum hepatitis B surface antigen kinetics in patients with chronic hepatitis B receiving long‐term nucleos(t)ide analogue therapy

Abstract: The trajectory of serum HBsAg levels predicts HBsAg loss in CHB patients receiving long-term NA therapy.

Cited by 8 publications

References 28 publications

Long-Term HBsAg Titer Kinetics with Entecavir/Tenofovir: Implications for Predicting Functional Cure and Low Levels

Long-Term HBsAg Titer Kinetics with Entecavir/Tenofovir: Implications for Predicting Functional Cure and Low Levels

Comparative biomarkers for HBsAg loss with antiviral therapy shows dominant influence of quantitative HBsAg (qHBsAg)

Reply to: “Stop-and-watch strategy after cessation of nucleos(t)ide analogue therapy in HBeAg-negative patients”

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