Cargando…

HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation

HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, D...

Descripción completa

Detalles Bibliográficos
Autores principales: Piermatteo, Lorenzo, Alkhatib, Mohammad, D’Anna, Stefano, Malagnino, Vincenzo, Bertoli, Ada, Andreassi, Eleonora, Basile, Elisa, Iuvara, Alessandra, De Cristofaro, Maria, Cappiello, Giuseppina, Cerva, Carlotta, Minichini, Carmine, Pisaturo, Mariantonietta, Starace, Mario, Coppola, Nicola, Fontana, Carla, Grelli, Sandro, Ceccherini-Silberstein, Francesca, Andreoni, Massimo, Gill, Upkar S., Kennedy, Patrick T. F., Sarmati, Loredana, Salpini, Romina, Svicher, Valentina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533134/
https://www.ncbi.nlm.nih.gov/pubmed/34680469
http://dx.doi.org/10.3390/biomedicines9101352
_version_ 1784587238479233024
author Piermatteo, Lorenzo
Alkhatib, Mohammad
D’Anna, Stefano
Malagnino, Vincenzo
Bertoli, Ada
Andreassi, Eleonora
Basile, Elisa
Iuvara, Alessandra
De Cristofaro, Maria
Cappiello, Giuseppina
Cerva, Carlotta
Minichini, Carmine
Pisaturo, Mariantonietta
Starace, Mario
Coppola, Nicola
Fontana, Carla
Grelli, Sandro
Ceccherini-Silberstein, Francesca
Andreoni, Massimo
Gill, Upkar S.
Kennedy, Patrick T. F.
Sarmati, Loredana
Salpini, Romina
Svicher, Valentina
author_facet Piermatteo, Lorenzo
Alkhatib, Mohammad
D’Anna, Stefano
Malagnino, Vincenzo
Bertoli, Ada
Andreassi, Eleonora
Basile, Elisa
Iuvara, Alessandra
De Cristofaro, Maria
Cappiello, Giuseppina
Cerva, Carlotta
Minichini, Carmine
Pisaturo, Mariantonietta
Starace, Mario
Coppola, Nicola
Fontana, Carla
Grelli, Sandro
Ceccherini-Silberstein, Francesca
Andreoni, Massimo
Gill, Upkar S.
Kennedy, Patrick T. F.
Sarmati, Loredana
Salpini, Romina
Svicher, Valentina
author_sort Piermatteo, Lorenzo
collection PubMed
description HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for >12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206–1945]PEIU/mL) and declines in chronic hepatitis (481[28–1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = −0.66, p = 0.006) and chronic hepatitis (Rho = −0.35; p = 0.05). Interestingly, qHBeAg strongly and positively correlates with qHBsAg across the study groups, suggesting cccDNA as a major source of both proteins in the setting of HBeAg positivity (with limited contribution of integrated HBV-DNA to HBsAg production). Focusing on 15 patients with HBV-R starting TDF/ETV, virological suppression and HBeAg-loss are achieved in 60% and 53.3%. Notably, the combination of qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL at HBV-R is the only factor predicting no HBeAg loss (HBeAg loss: 0% with vs. 72.7% without qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL, p = 0.03). In conclusion, qHBeAg varies over the natural course of HBV infection, according to the extent of immunological pressure. In the setting of HBV-R, qHBeAg could be useful in predicting the treatment response under immunosuppression.
format Online
Article
Text
id pubmed-8533134
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85331342021-10-23 HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation Piermatteo, Lorenzo Alkhatib, Mohammad D’Anna, Stefano Malagnino, Vincenzo Bertoli, Ada Andreassi, Eleonora Basile, Elisa Iuvara, Alessandra De Cristofaro, Maria Cappiello, Giuseppina Cerva, Carlotta Minichini, Carmine Pisaturo, Mariantonietta Starace, Mario Coppola, Nicola Fontana, Carla Grelli, Sandro Ceccherini-Silberstein, Francesca Andreoni, Massimo Gill, Upkar S. Kennedy, Patrick T. F. Sarmati, Loredana Salpini, Romina Svicher, Valentina Biomedicines Article HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for >12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206–1945]PEIU/mL) and declines in chronic hepatitis (481[28–1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = −0.66, p = 0.006) and chronic hepatitis (Rho = −0.35; p = 0.05). Interestingly, qHBeAg strongly and positively correlates with qHBsAg across the study groups, suggesting cccDNA as a major source of both proteins in the setting of HBeAg positivity (with limited contribution of integrated HBV-DNA to HBsAg production). Focusing on 15 patients with HBV-R starting TDF/ETV, virological suppression and HBeAg-loss are achieved in 60% and 53.3%. Notably, the combination of qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL at HBV-R is the only factor predicting no HBeAg loss (HBeAg loss: 0% with vs. 72.7% without qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL, p = 0.03). In conclusion, qHBeAg varies over the natural course of HBV infection, according to the extent of immunological pressure. In the setting of HBV-R, qHBeAg could be useful in predicting the treatment response under immunosuppression. MDPI 2021-09-29 /pmc/articles/PMC8533134/ /pubmed/34680469 http://dx.doi.org/10.3390/biomedicines9101352 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Piermatteo, Lorenzo
Alkhatib, Mohammad
D’Anna, Stefano
Malagnino, Vincenzo
Bertoli, Ada
Andreassi, Eleonora
Basile, Elisa
Iuvara, Alessandra
De Cristofaro, Maria
Cappiello, Giuseppina
Cerva, Carlotta
Minichini, Carmine
Pisaturo, Mariantonietta
Starace, Mario
Coppola, Nicola
Fontana, Carla
Grelli, Sandro
Ceccherini-Silberstein, Francesca
Andreoni, Massimo
Gill, Upkar S.
Kennedy, Patrick T. F.
Sarmati, Loredana
Salpini, Romina
Svicher, Valentina
HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation
title HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation
title_full HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation
title_fullStr HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation
title_full_unstemmed HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation
title_short HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation
title_sort hbeag levels vary across the different stages of hbv infection according to the extent of immunological pressure and are associated with therapeutic outcome in the setting of immunosuppression-driven hbv reactivation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533134/
https://www.ncbi.nlm.nih.gov/pubmed/34680469
http://dx.doi.org/10.3390/biomedicines9101352
work_keys_str_mv AT piermatteolorenzo hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT alkhatibmohammad hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT dannastefano hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT malagninovincenzo hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT bertoliada hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT andreassieleonora hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT basileelisa hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT iuvaraalessandra hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT decristofaromaria hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT cappiellogiuseppina hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT cervacarlotta hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT minichinicarmine hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT pisaturomariantonietta hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT staracemario hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT coppolanicola hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT fontanacarla hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT grellisandro hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT ceccherinisilbersteinfrancesca hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT andreonimassimo hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT gillupkars hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT kennedypatricktf hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT sarmatiloredana hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT salpiniromina hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation
AT svichervalentina hbeaglevelsvaryacrossthedifferentstagesofhbvinfectionaccordingtotheextentofimmunologicalpressureandareassociatedwiththerapeuticoutcomeinthesettingofimmunosuppressiondrivenhbvreactivation