Dataset Information

Prediction Model of HBsAg Seroclearance in Patients with Chronic HBV Infection.

ABSTRACT: Background:Prediction of HBsAg seroclearance, defined as the loss of circulating HBsAg with or without development of antibodies for HBsAg in patients with chronic hepatitis B (CHB), is highly difficult and challenging due to its low incidence. This study is aimed at developing and validating a nomogram for prediction of HBsAg loss in CHB patients. Methods:We analyzed a total of 1398 patients with CHB. Two-thirds of the patients were randomly assigned to the training set (n = 918), and one-third were assigned to the validation set (n = 480). Univariate and multivariate analysis by Cox regression analysis was performed using the training set, and the nomogram was constructed. Discrimination and calibration were performed using the training set and validation set. Results:On multivariate analysis of the training set, independent factors for HBsAg loss including BMI, HBeAg status, HBsAg titer (quantitative HBsAg), and baseline hepatitis B virus (HBV) DNA level were incorporated into the nomogram. The HBsAg seroclearance calibration curve showed an optimal agreement between predictions by the nomogram and actual observation. The concordance index (C-index) of nomogram was 0.913, with confirmation in the validation set where the C-index was 0.886. Conclusions:We established and validated a novel nomogram that can individually predict HBsAg seroclearance and non-seroclearance for CHB patients, which is clinically unprecedented. This practical prognostic model may help clinicians in decision-making and design of clinical studies.

SUBMITTER: Cao J

PROVIDER: S-EPMC7443222 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prediction Model of HBsAg Seroclearance in Patients with Chronic HBV Infection.

Cao Jing J Gong Jiao J Tsia Hin Fong Christ-Jonathan CJ Xiao Cuicui C Lin Guoli G Li Xiangyong X Jie Yusheng Y Chong Yutian Y

BioMed research international 20200814

<h4>Background</h4>Prediction of HBsAg seroclearance, defined as the loss of circulating HBsAg with or without development of antibodies for HBsAg in patients with chronic hepatitis B (CHB), is highly difficult and challenging due to its low incidence. This study is aimed at developing and validating a nomogram for prediction of HBsAg loss in CHB patients.<h4>Methods</h4>We analyzed a total of 1398 patients with CHB. Two-thirds of the patients were randomly assigned to the training set (<i>n</i> ...[more]

PMID: 32855968

Similar Datasets

Project description:BACKGROUND:HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. METHODS:This study analyzed 828 chronically HBV-infected European patients exposed to ??1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. RESULTS:At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ??1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P?=?0.002). In genotype-D, the presence of ??1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P?=?0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P?=?0.032). Strong correlation was observed between sP120T and rtM204I/V (P?<?0.001), and their co-presence determined an increased HBV-DNA. At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32-3.10],P?=?0.001). Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties. CONCLUSIONS:Immune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence.

Project description:Background & aimsElimination of chronic HBV/HDV infection remains a major global health challenge. Targeting excessive hepatitis B surface antigen (HBsAg) release may provide an interesting window of opportunity to break immune tolerance and to achieve a functional cure using additional antivirals.MethodsWe evaluated a HBsAg-specific human monoclonal antibody, as part of either a prophylactic or therapeutic strategy, against HBV/HDV infection in cell culture models and in human-liver chimeric mice. To assess prophylactic efficacy, mice were passively immunized prior to infection with HBV or HBV/HDV (coinfection and superinfection setting). Therapeutic efficacy was assessed in HBV and HBV/HDV-coinfected mice receiving 4 weeks of treatment. Viral parameters (HBV DNA, HDV RNA and HBsAg) were assessed in mouse plasma.ResultsThe antibody could effectively prevent HBV/HDV infection in a dose-dependent manner with IC50 values of ∼3.5 ng/ml. Passive immunization showed complete protection of mice from both HBV and HBV/HDV coinfection. Moreover, HDV superinfection was either completely prevented or at least attenuated in HBV-infected mice. Finally, antibody treatment in mice with established HBV/HDV infection resulted in a significant decline in viremia and a concomitant drop in on-treatment HBsAg, with a moderate viral rebound following treatment cessation.ConclusionWe present data on a valuable antibody candidate that could complement other antivirals in strategies aimed at achieving functional cure of chronic HBV and HDV infection.Impact and implicationsPatients chronically infected with HBV may eventually develop liver cancer and are at great risk of being superinfected with HDV, which worsens and accelerates disease progression. Unfortunately, current treatments can rarely eliminate both viruses from chronically infected patients. In this study, we present data on a novel antibody that is able to prevent chronic HBV/HDV infection in a mouse model with a humanized liver. Moreover, antibody treatment of HBV/HDV-infected mice strongly diminishes viral loads during therapy. This antibody is a valuable candidate for further clinical development.

Dataset Information

Prediction Model of HBsAg Seroclearance in Patients with Chronic HBV Infection.

Publications

Prediction Model of HBsAg Seroclearance in Patients with Chronic HBV Infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets