Composition of HBsAg is predictive of HBsAg loss during treatment in patients with HBeAg-positive chronic hepatitis B

Pfefferkorn, Maria; Schott, T; Böhm, Stephan; Deichsel, D; Felkel, C; Gerlich, Wolfram H.; Glebe, Dieter; Wat, Cynthia; Pavlovic, Vedran; Heyne, R.; Berg, Thomas

doi:10.1016/j.jhep.2020.08.039

Cited by 42 publications

(47 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…During long-term NUC treatment, the three HBs isoforms tended to remain stable or undergo a decrease over time. This result is in line with a previous study describing the kinetics of the three HBs isoforms during treatment with NUC or IFN-alpha and their correlation with the achievement of HBsAg loss [ 21 ]. Interestingly, this study has highlighted that a strong decline of M-HBs is predictive of HBsAg loss during treatment with NUC or IFN-alpha, supporting the role of this HBs isoform as an early predictor of treatment response [ 21 ].…”

Section: Discussionsupporting

confidence: 92%

“…In particular, recently it has been demonstrated that the composition of the HBsAg significantly changes across the different stages of HBV infection, showing lower proportions of L-HBs and M-HBs in the HBV chronic infection quiescent stage compared to those observed during chronic active hepatitis B [ 20 ]. Additionally, a recent study has also demonstrated that a decrease in L-HBs and M-HBs proportions (prior to total HBsAg decay) during NUC or pegylated interferon alpha (PEG-IFN) treatment can represent an early marker of favorable therapeutic outcome, preceding HBsAg loss [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An Increase in the Levels of Middle Surface Antigen Characterizes Patients Developing HBV-Driven Liver Cancer Despite Prolonged Virological Suppression

et al. 2021

View full text Add to dashboard Cite

Hepatitis B virus (HBV) contains three surface glycoproteins—Large-HBs (L-HBs), Middle-HBs (M-HBs), and Small-HBs (S-HBs), known to contribute to HBV-driven pro-oncogenic properties. Here, we examined the kinetics of HBs-isoforms in virologically-suppressed patients who developed or did not develop hepatocellular carcinoma (HCC). This study enrolled 30 chronically HBV-infected cirrhotic patients under fully-suppressive anti-HBV treatment. Among them, 13 patients developed HCC. Serum samples were collected at enrolment (T0) and at HCC diagnosis or at the last control for non-HCC patients (median (range) follow-up: 38 (12–48) months). Ad-hoc ELISAs were designed to quantify L-HBs, M-HBs and S-HBs (Beacle). At T0, median (IQR) levels of S-HBs, M-HBs and L-HBs were 3140 (457–6995), 220 (31–433) and 0.2 (0–1.7) ng/mL. No significant differences in the fraction of the three HBs-isoforms were noticed between patients who developed or did not develop HCC at T0. On treatment, S-HBs showed a >25% decline or remained stable in a similar proportion of HCC and non-HCC patients (58.3% of HCC- vs. 47.1% of non-HCC patients, p = 0.6; 25% of HCC vs. 29.4% of non-HCC, p = 0.8, respectively). Conversely, M-HBs showed a >25% increase in a higher proportion of HCC compared to non-HCC patients (50% vs. 11.8%, p = 0.02), in line with M-HBs pro-oncogenic role reported in in vitro studies. No difference in L-HBs kinetics was observed in HCC and non-HCC patients. In conclusion, an increase in M-HBs levels characterizes a significant fraction of HCC-patients while under prolonged HBV suppression and stable/reduced total-HBs. The role of M-HBs kinetics in identifying patients at higher HCC risk deserves further investigation.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

An Increase in the Levels of Middle Surface Antigen Characterizes Patients Developing HBV-Driven Liver Cancer Despite Prolonged Virological Suppression

et al. 2021

View full text Add to dashboard Cite

show abstract

“…It is well recognized that, besides affecting the host genome, integration driven HBV envelope expression could significantly affect the course and disease severity of HBV infection by for example rescuing mutant viral genomes and contributing to persistence [12]. It could also affect the composition of HBsAg expression which has been shown to predict treatment outcome in HBe+ patients [33]. Of particular interest, functional HBV integration is also likely to contribute to the course of Hepatitis Delta Virus (HDV) infection by allowing for infectious HDV formation in the absence of HBV replication [34,35].…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Ubiquitous expression of HBsAg from integrated HBV DNA in patients with low viral load

Meier

Calabrese

Suslov

et al. 2021

Journal of Hepatology

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

“…An alternative ELISA-based method (HBV NRAg; Beijing Wantai Biological, Beijing, China) has been developed to qualitatively detect the PreS1 antigen and HBcAg, with the former having shown surrogate utility for HBV cccDNA activity and HBV replication [ 90 , 91 ]. Furthermore, the measurement of PreS1, or L-HBsAg, using calibrated ELISA assays, has been described in several studies to be associated with detection of residual serum HBV DNA [ 92 ], differentiation of active and inactive CHB, and prediction of functional cure via L-HBsAg to M-HBsAg ratios [ 93 , 94 ], although L-HBsAg levels differ by HBV genotype [ 95 ] which may confound predictive interpretation in diverse populations. The combined detection of conserved amino acid regions within both antigens [ 96 ], which has been termed ‘nucleic acid-related antigen’ [ 97 ], is performed through a dual sandwich ELISA with antigen specific monoclonal antibodies [ 98 ].…”

Section: Novel Hbv Biomarkersmentioning

confidence: 99%

“…Interestingly, the composition of different surface antigen proteins in HBeAg-positive NA-treated patients could also predict HBsAg loss. Using an assay designed to quantify S-HBsAg, M-HBsAg and L-HBsAg, it was shown that patients who achieved HBsAg seroclearance had significantly lower baseline M-HBsAg levels and rapidly declining M-HBsAg and L-HBsAg concentrations, with M-HBsAg becoming undetectable at month 6 of treatment [ 94 ].…”

Section: Novel Hbv Biomarkersmentioning

confidence: 99%

Novel Biomarkers of Hepatitis B Virus and Their Use in Chronic Hepatitis B Patient Management

Osiowy

2021

Viruses

View full text Add to dashboard Cite

Even though an approved vaccine for hepatitis B virus (HBV) is available and widely used, over 257 million individuals worldwide are living with chronic hepatitis B (CHB) who require monitoring of treatment response, viral activity, and disease progression to reduce their risk of HBV-related liver disease. There is currently a lack of predictive markers to guide clinical management and to allow treatment cessation with reduced risk of viral reactivation. Novel HBV biomarkers are in development in an effort to improve the management of people living with CHB, to predict disease outcomes of CHB, and further understand the natural history of HBV. This review focuses on novel HBV biomarkers and their use in the clinical setting, including the description of and methodology for quantification of serum HBV RNA, hepatitis B core-related antigen (HBcrAg), quantitative hepatitis B surface antigen (qHBsAg), including ultrasensitive HBsAg detection, quantitative anti-hepatitis B core antigen (qAHBc), and detection of HBV nucleic acid-related antigen (HBV-NRAg). The utility of these biomarkers in treatment-naïve and treated CHB patients in several clinical situations is further discussed. Novel HBV biomarkers have been observed to provide critical clinical information and show promise for improving patient management and our understanding of the natural history of HBV.

show abstract

Composition of HBsAg is predictive of HBsAg loss during treatment in patients with HBeAg-positive chronic hepatitis B

Cited by 42 publications

References 25 publications

An Increase in the Levels of Middle Surface Antigen Characterizes Patients Developing HBV-Driven Liver Cancer Despite Prolonged Virological Suppression

An Increase in the Levels of Middle Surface Antigen Characterizes Patients Developing HBV-Driven Liver Cancer Despite Prolonged Virological Suppression

Ubiquitous expression of HBsAg from integrated HBV DNA in patients with low viral load

Novel Biomarkers of Hepatitis B Virus and Their Use in Chronic Hepatitis B Patient Management

Contact Info

Product

Resources

About