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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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 |
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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 |
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