Kinetics of Hepatitis B Surface Antigen Level in Chronic Hepatitis B Patients who Achieved Hepatitis B Surface Antigen Loss during Pegylated Interferon Alpha-2a Treatment

Li, Minghui; Lu, Zhigang; Qu, Xin; Lu, Yao; Shen, Ge; Wu, Shuling; Chang, Min; Liu, Ruyu; Hu, Leiping; Li, Zhenzhen; Hua, Wenhao; Song, Shuangshuang; Xie, Yao

doi:10.4103/0366-6999.200554

Cited by 20 publications

(20 citation statements)

References 34 publications

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“… 5 For the only immune-mediated therapy used today, peg-IFNα, studies are controversial. Some studies show an impact of baseline HBsAg level on response to IFN therapy in CHB patients (response to therapy being higher when baseline HBsAg is low), 10 , 11 while others do not show any correlation. 12 , 13 These discordant observations may be attributed to other confounding factors such as baseline level of HBV DNA and/or pre-existing T cell based immunity.…”

Section: Resultsmentioning

confidence: 99%

A meta-analysis of the antiviral activity of the HBV-specific immunotherapeutic TG1050 confirms its value over a wide range of HBsAg levels in a persistent HBV pre-clinical model

Sansas

Lélu

Evlachev

et al. 2018

Human Vaccines & Immunotherapeutics

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Pre-clinical models mimicking persistent hepatitis B virus (HBV) expression are seldom, do not capture all features of a human chronic infection and due to their complexity, are subject to variability. We report a meta-analysis of seven experiments performed with TG1050, an HBV-targeted immunotherapeutic,1 in an HBV-persistent mouse model based on the transduction of mice by an adeno-associated virus coding for an infectious HBV genome (AAV-HBV). To mimic the clinical diversity seen in HBV chronically infected patients, AAV-HBV transduced mice displaying variable HBsAg levels were treated with TG1050. Overall mean percentages of responder mice, displaying decrease in important clinical parameters i.e. HBV-DNA (viremia) and HBsAg levels, were 52% and 51% in TG1050 treated mice, compared with 8% and 22%, respectively, in untreated mice. No significant impact of HBsAg level at baseline on response to TG1050 treatment was found. TG1050-treated mice displayed a significant shorter Time to Response (decline in viral parameters) with an Hazard Ratio (HR) of 8.3 for viremia and 2.6 for serum HBsAg. The mean predicted decrease for TG1050-treated mice was 0.5 log for viremia and 0.8 log for HBsAg, at the end of mice follow-up, compared to no decrease for viremia and 0.3 log HBsAg decrease for untreated mice. For mice receiving TG1050, a higher decline of circulating viremia and serum HBsAg level over time was detected by interaction term meta-analysis with a significant treatment effect (p = 0.002 and p<0.001 respectively). This meta-analysis confirms the therapeutic value of TG1050, capable of exerting potent antiviral effects in an HBV-persistent model mimicking clinical situations.

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Section: Resultsmentioning

confidence: 99%

A meta-analysis of the antiviral activity of the HBV-specific immunotherapeutic TG1050 confirms its value over a wide range of HBsAg levels in a persistent HBV pre-clinical model

Sansas

Lélu

Evlachev

et al. 2018

Human Vaccines & Immunotherapeutics

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“…In a retrospective study, on‐treatment change in biomarkers at 6 month for qHBsAg, HBcrAg and HBV RNA had AUC of 0.886, 0.589 and 0.586 to predict HBsAg seroconversion 18 . In a study comprising a mixture of HBeAg‐positive and HBeAg‐negative patients the kinetics of HBsAg loss were found to be similar in HBeAg positive or negative patients but those who were HBeAg positive started with higher qHBsAg levels and took longer to achieve HBsAg loss 19 . In a study of HBeAg negative CHB treated with peginterferon ± entecavir, baseline qHBsAg and HBcrAg were predictors of HBsAg loss but week 12 decline in qHBsAg was the strongest predictor with OR 24.3, but decline in HBcrAg at week 12 was not significant.…”

Section: Discussionmentioning

confidence: 98%

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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“…In clinical practice, ALT elevation, which is associated with good response to the therapy,[ 21 ] commonly exist in patients treated with PEG-IFN-α. [ 22 ] Results suggested that the activation of pDC and the elevation IFN-α might contribute to the activation of hepatitis B from IT phase. Results could also explain why the efficacy of IFN therapy is poor in patients in IT phase but good in CHB patients, especially those with high ALT level and severe liver inflammatory in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Association of Cytokines with Alanine Aminotransferase, Hepatitis B Virus Surface Antigen and Hepatitis B Envelope Antigen Levels in Chronic Hepatitis B

Zhang

et al. 2018

Chinese Medical Journal

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Background:Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB).Methods:Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-β1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-β1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis.Results:IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = −0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = −2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ2= 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = −1.419, P = 0.156). The TGF-β1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ2= 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (β= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (β = −0.358, t = −2.308, P = 0.024), HBsAg (β = −0.359, t = −2.288, P = 0.025), and HBeAg contents (β = −0.355, t = −2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (β = −0.459, t = −4.225, P = 0.000; β = −0.616, t = −6.334, P = 0.000; and β = −0.290, t = −2.433, P = 0.018; respectively).Conclusions:IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.

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Kinetics of Hepatitis B Surface Antigen Level in Chronic Hepatitis B Patients who Achieved Hepatitis B Surface Antigen Loss during Pegylated Interferon Alpha-2a Treatment

Cited by 20 publications

References 34 publications

A meta-analysis of the antiviral activity of the HBV-specific immunotherapeutic TG1050 confirms its value over a wide range of HBsAg levels in a persistent HBV pre-clinical model

A meta-analysis of the antiviral activity of the HBV-specific immunotherapeutic TG1050 confirms its value over a wide range of HBsAg levels in a persistent HBV pre-clinical model

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

Association of Cytokines with Alanine Aminotransferase, Hepatitis B Virus Surface Antigen and Hepatitis B Envelope Antigen Levels in Chronic Hepatitis B

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