Biomedicines (Sep 2021)

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

  • Lorenzo Piermatteo,
  • Mohammad Alkhatib,
  • Stefano D’Anna,
  • Vincenzo Malagnino,
  • Ada Bertoli,
  • Eleonora Andreassi,
  • Elisa Basile,
  • Alessandra Iuvara,
  • Maria De Cristofaro,
  • Giuseppina Cappiello,
  • Carlotta Cerva,
  • Carmine Minichini,
  • Mariantonietta Pisaturo,
  • Mario Starace,
  • Nicola Coppola,
  • Carla Fontana,
  • Sandro Grelli,
  • Francesca Ceccherini-Silberstein,
  • Massimo Andreoni,
  • Upkar S. Gill,
  • Patrick T. F. Kennedy,
  • Loredana Sarmati,
  • Romina Salpini,
  • Valentina Svicher

DOI
https://doi.org/10.3390/biomedicines9101352
Journal volume & issue
Vol. 9, no. 10
p. 1352

Abstract

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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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