Novel fully automated prototype assays for specific detection of phosphorylated and non-phosphorylated Hepatitis B core antigens
Copyright © 2023. Published by Elsevier B.V..
BACKGROUND: Hepatitis B core antigen (HBcAg) has been proposed as a surrogate marker to reflect transcriptional activity of HBV covalently closed circular DNA (cccDNA) during active infections and may be a valuable tool to monitor the efficacy of antiviral therapies. However, HBcAg-specific immunoassays are unavailable, and current assays that measure hepatitis B core-related antigen (HBcrAg) cannot distinguish between HBcAg, HBeAg, and precore (PreC) proteins.
OBJECTIVE: Two fully automated assays were developed to specifically detect phosphorylated HBcAg (P-HBcAg, representing non-HBV DNA-containing particles) and non-phosphorylated HBcAg (representing HBV DNA-containing particles) circulating in HBV infected patients.
STUDY DESIGN: P-HBcAg and HBcAg levels were analyzed in 124 single timepoint patients with active infections, in three longitudinal specimens from patients with acute HBV infections, and in four chronic hepatitis B (CHB) patients on-therapy (TDF - tenofovir disoproxil fumarate, pegIFN - pegylated interferon, NAPs - nucleic acids polymers).
RESULTS: Analyzing acute infections revealed that P-HBcAg and HBcAg levels correlate more closely than HBcrAg to HBV DNA. During antiviral treatment of CHB patients, HBcAg correlates well with HBV DNA and indicates a therapeutic response to the treatment at the beginning of the therapy. In contrast, P-HBcAg tracks more closely to HBV RNA. Importantly, P-HBcAg is detectable several months after HBcAg became undetectable indicating that cccDNA is still transcriptionally active in hepatocytes.
CONCLUSIONS: Overall, the ability to specifically distinguish between the various states of HBcAg (phosphorylated and non-phosphorylated) can provide additional insights for disease staging, drug development, and management of HBV therapies.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:166 |
|---|---|
| Enthalten in: |
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology - 166(2023) vom: 16. Sept., Seite 105529 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Geissler, Rene [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antigen test |
|---|
| Anmerkungen: |
Date Revised 14.08.2023 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1016/j.jcv.2023.105529 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM359077463 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM359077463 | ||
| 003 | DE-627 | ||
| 005 | 20231226080114.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jcv.2023.105529 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1196.xml |
| 035 | |a (DE-627)NLM359077463 | ||
| 035 | |a (NLM)37406597 | ||
| 035 | |a (PII)S1386-6532(23)00152-X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Geissler, Rene |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Novel fully automated prototype assays for specific detection of phosphorylated and non-phosphorylated Hepatitis B core antigens |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 14.08.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2023. Published by Elsevier B.V. | ||
| 520 | |a BACKGROUND: Hepatitis B core antigen (HBcAg) has been proposed as a surrogate marker to reflect transcriptional activity of HBV covalently closed circular DNA (cccDNA) during active infections and may be a valuable tool to monitor the efficacy of antiviral therapies. However, HBcAg-specific immunoassays are unavailable, and current assays that measure hepatitis B core-related antigen (HBcrAg) cannot distinguish between HBcAg, HBeAg, and precore (PreC) proteins | ||
| 520 | |a OBJECTIVE: Two fully automated assays were developed to specifically detect phosphorylated HBcAg (P-HBcAg, representing non-HBV DNA-containing particles) and non-phosphorylated HBcAg (representing HBV DNA-containing particles) circulating in HBV infected patients | ||
| 520 | |a STUDY DESIGN: P-HBcAg and HBcAg levels were analyzed in 124 single timepoint patients with active infections, in three longitudinal specimens from patients with acute HBV infections, and in four chronic hepatitis B (CHB) patients on-therapy (TDF - tenofovir disoproxil fumarate, pegIFN - pegylated interferon, NAPs - nucleic acids polymers) | ||
| 520 | |a RESULTS: Analyzing acute infections revealed that P-HBcAg and HBcAg levels correlate more closely than HBcrAg to HBV DNA. During antiviral treatment of CHB patients, HBcAg correlates well with HBV DNA and indicates a therapeutic response to the treatment at the beginning of the therapy. In contrast, P-HBcAg tracks more closely to HBV RNA. Importantly, P-HBcAg is detectable several months after HBcAg became undetectable indicating that cccDNA is still transcriptionally active in hepatocytes | ||
| 520 | |a CONCLUSIONS: Overall, the ability to specifically distinguish between the various states of HBcAg (phosphorylated and non-phosphorylated) can provide additional insights for disease staging, drug development, and management of HBV therapies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Antigen test | |
| 650 | 4 | |a Antiviral therapy | |
| 650 | 4 | |a Chronic HBV infection | |
| 650 | 4 | |a HBV biomarker | |
| 650 | 4 | |a Hepatitis B treatment | |
| 650 | 4 | |a Infectious disease | |
| 700 | 1 | |a Patel, Megha |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Vaillant, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Xiaoxing |e verfasserin |4 aut | |
| 700 | 1 | |a Cloherty, Gavin |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology |d 1997 |g 166(2023) vom: 16. Sept., Seite 105529 |w (DE-627)NLM097223964 |x 1873-5967 |7 nnns |
| 773 | 1 | 8 | |g volume:166 |g year:2023 |g day:16 |g month:09 |g pages:105529 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jcv.2023.105529 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 166 |j 2023 |b 16 |c 09 |h 105529 | ||