The anti-HBc-positive/HBsAg-negative status is frequent in HIV-infection and correlates with poor survival. Here, by highly-sensitive assays, we evaluate cryptic HBV replication and factors correlated with its detection in 81 anti-HBc-positive/HBsAg-negative HIV-infected patients. Patients were treated for >12 months with HBV-active modern combined antiretroviral-therapy (cART) and had serum HBV-DNA < 20 IU/mL by commercial Real-Time PCR. Serum HBV-DNA was quantified by droplet digital PCR, serum HBV-RNA by an Abbott research assay, and anti-HBc titer (proposed to infer intrahepatic cccDNA) by Lumipulse/Fujirebio. Cryptic serum HBV-DNA was detected in 29.6% of patients (median (IQR): 4(1-15) IU/mL) and serum HBV-RNA in 3.7% of patients despite HBsAg-negativity and HBV-active cART. Notably, cryptic serum HBV-DNA correlated with an advanced CDC-stage (p = 0.01) and a lower anti-HBs titer (p = 0.05), while serum HBV-RNA correlated with lower nadir CD4+ cell-count (p = 0.01). By analyzing serological HBV-markers, the combination of anti-HBs < 50 mIU/mL (indicating lower immune response) plus anti-HBc > 15COI (reflecting higher HBV replicative activity) was predictive of cryptic serum HBV-DNA (OR: 4.7(1.1-21.7), p = 0.046, PPV = 62.5%, and NPV = 72%). In conclusion, cryptic HBV-replication (not detected by classical assays) characterizes a conspicuous set of anti-HBc-positive HIV-infected patients despite HBsAg-negativity and HBV-active combined antiretroviral therapy (cART). The integration of classical and novel markers may help identify patients with cryptic HBV-replication, thus optimizing the monitoring of anti-HBc-positive/HBsAg-negative HIV-infected patients.

Salpini, R., Malagnino, V., Piermatteo, L., Mulas, T., Alkhatib, M., Scutari, R., et al. (2020). Cryptic HBV replicative activity is frequently revealed in anti-HBC-positive/hbsag-negative patients with HIV infection by highly sensitive molecular assays, and can be predicted by integrating classical and novel serological HBV markers. MICROORGANISMS, 8(11), 1-12 [10.3390/microorganisms8111819].

Cryptic HBV replicative activity is frequently revealed in anti-HBC-positive/hbsag-negative patients with HIV infection by highly sensitive molecular assays, and can be predicted by integrating classical and novel serological HBV markers

Salpini R.;Malagnino V.;Piermatteo L.;Scutari R.;Teti E.;Bertoli A.;Ceccherini-Silberstein F.;Iannetta M.;Andreoni M.;Sarmati L.;Svicher V.
2020-01-01

Abstract

The anti-HBc-positive/HBsAg-negative status is frequent in HIV-infection and correlates with poor survival. Here, by highly-sensitive assays, we evaluate cryptic HBV replication and factors correlated with its detection in 81 anti-HBc-positive/HBsAg-negative HIV-infected patients. Patients were treated for >12 months with HBV-active modern combined antiretroviral-therapy (cART) and had serum HBV-DNA < 20 IU/mL by commercial Real-Time PCR. Serum HBV-DNA was quantified by droplet digital PCR, serum HBV-RNA by an Abbott research assay, and anti-HBc titer (proposed to infer intrahepatic cccDNA) by Lumipulse/Fujirebio. Cryptic serum HBV-DNA was detected in 29.6% of patients (median (IQR): 4(1-15) IU/mL) and serum HBV-RNA in 3.7% of patients despite HBsAg-negativity and HBV-active cART. Notably, cryptic serum HBV-DNA correlated with an advanced CDC-stage (p = 0.01) and a lower anti-HBs titer (p = 0.05), while serum HBV-RNA correlated with lower nadir CD4+ cell-count (p = 0.01). By analyzing serological HBV-markers, the combination of anti-HBs < 50 mIU/mL (indicating lower immune response) plus anti-HBc > 15COI (reflecting higher HBV replicative activity) was predictive of cryptic serum HBV-DNA (OR: 4.7(1.1-21.7), p = 0.046, PPV = 62.5%, and NPV = 72%). In conclusion, cryptic HBV-replication (not detected by classical assays) characterizes a conspicuous set of anti-HBc-positive HIV-infected patients despite HBsAg-negativity and HBV-active combined antiretroviral therapy (cART). The integration of classical and novel markers may help identify patients with cryptic HBV-replication, thus optimizing the monitoring of anti-HBc-positive/HBsAg-negative HIV-infected patients.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/17
English
HBV
HIV
anti-HBc titer
anti-HBs titer
droplet digital PCR
serum HBV-DNA
serum HBV-RNA
Salpini, R., Malagnino, V., Piermatteo, L., Mulas, T., Alkhatib, M., Scutari, R., et al. (2020). Cryptic HBV replicative activity is frequently revealed in anti-HBC-positive/hbsag-negative patients with HIV infection by highly sensitive molecular assays, and can be predicted by integrating classical and novel serological HBV markers. MICROORGANISMS, 8(11), 1-12 [10.3390/microorganisms8111819].
Salpini, R; Malagnino, V; Piermatteo, L; Mulas, T; Alkhatib, M; Scutari, R; Teti, E; Cerva, C; La Rosa, Ky; Brugneti, M; Bertoli, A; Rossi, B; Holzmayer, V; Gersch, J; Kuhns, M; Cloherty, G; Ceccherini-Silberstein, F; Perno, C-; Iannetta, M; Andreoni, M; Sarmati, L; Svicher, V
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/260990
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