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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.
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.
Afiliação
  • Piermatteo L; Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Alkhatib M; Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
  • D'Anna S; Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Malagnino V; Infectious Disease Unit, University Hospital of Rome Tor Vergata, 00133 Rome, Italy.
  • Bertoli A; Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Andreassi E; Microbiology and Virology Unit, University Hospital of Rome Tor Vergata, 00133 Rome, Italy.
  • Basile E; Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Iuvara A; Microbiology and Virology Unit, University Hospital of Rome Tor Vergata, 00133 Rome, Italy.
  • De Cristofaro M; Microbiology and Virology Unit, University Hospital of Rome Tor Vergata, 00133 Rome, Italy.
  • Cappiello G; Microbiology Unit, "Sandro Pertini" Hospital, 00133 Rome, Italy.
  • Cerva C; Microbiology Unit, "Sandro Pertini" Hospital, 00133 Rome, Italy.
  • Minichini C; Infectious Disease Unit, University Hospital of Rome Tor Vergata, 00133 Rome, Italy.
  • Pisaturo M; Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy.
  • Starace M; Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy.
  • Coppola N; Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy.
  • Fontana C; Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy.
  • Grelli S; Microbiology and Virology Unit, University Hospital of Rome Tor Vergata, 00133 Rome, Italy.
  • Ceccherini-Silberstein F; Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Andreoni M; Microbiology and Virology Unit, University Hospital of Rome Tor Vergata, 00133 Rome, Italy.
  • Gill US; Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Kennedy PTF; Infectious Disease Unit, University Hospital of Rome Tor Vergata, 00133 Rome, Italy.
  • Sarmati L; Barts Liver Centre, Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
  • Salpini R; Barts Liver Centre, Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
  • Svicher V; Infectious Disease Unit, University Hospital of Rome Tor Vergata, 00133 Rome, Italy.
Biomedicines ; 9(10)2021 Sep 29.
Article em En | MEDLINE | ID: mdl-34680469
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article