Multiple HBV transfusion transmissions from undetected occult infections: revising the minimal infectious dose

Hepatitis B remains a global major public health issue and a viral infection transmissible by transfusion. The risk of HBV transfusion transmitted infection has been reduced by the selection of donors; the continuous improvement of serological assays to detect the HBV surface antigen (HBsAg); the implementation of anti-HBc screening for antibodies against the HBV core antigen (anti-HBc) when appropriate according to the epidemiological context and the implementation of viral nucleic acid testing (NAT) as multiplex assays detecting simultaneously HBV, HCV and HIV genomes applied either to pools of plasma samples or, more efficiently, to individual donations. HBV-NAT improved blood safety by reducing the serological window period from 32 to 15 days in donors with acute infectionand by uncovering donors with occult HBV infection. This appears to be a phase of the intrahepatic viral life cycle in which viral replication and gene expression are strongly, but imperfectly controlled by the host immune system and/or related to viral variants, Transmission rate might then be underestimated due to the lack of proper identification of HBV infection in recipients, the absence of recipient pre-transfusion sample to exclude pre-existing infection, the difficulty and reluctance to trace recipients, the lack or limited volume of donor archive samples and undetectable or intermittently detectable HBV-DNA in donors.

This study presenting HBV transmission to nine recipients by blood components from three Slovenian blood donors with occult HBV infectionremaining undetected by highly sensitive NAT allows to reconsider the minimal HBV infectious dose and the NAT sensitivity required to prevent HBV transmission by transfusion.

In the present study, anti-HBs-negative donors with HBV-DNA plasma load <3 IU/mL (<16 copies/mL) transmitted to susceptible recipients non-immune to HBV and transfused with RBC and FFP products containing <320 virions and <3200 virions, respectively. A limitation of the study was that sample volume limitation in donation repository and the insufficient sensitivity of the viral load quantification methods did not permit precise results. However, a method was developed to calculate low-level viral load on the basis of testing multiple replicates of a sample with Ultrio Plus/Elite and derive a viral load by applying the number of positive repeat to a Probit reference curve.

In conclusion, transfusion of FFP and, to a lesser extent, RBC components from donors with occult HBV infectionundetected by the current highly sensitive NAT assays may be at risk of transmitting HBV infection to immunocompetent patients. HBV blood safety could be further improved by either anti-HBc screening, HBV DNA NAT with a limit of detection of 0.8 copies/mL (0.15 IU/mL) or pathogen reduction of blood components. Efficient haemovigilance system and long-term archiving of large volumes of both donors’ and recipients’ plasma samples pre-transfusion are essential to identify and characterize HBV transfusion transmitted infectionin order to limit delays in the therapeutic management of infected patients.


Gut 2018

Multiple HBV transfusion transmissions from undetected occult infections: revising the minimal infectious dose

Daniel Candotti, Sonny Michael Assennato, Syria Laperche, Jean-Pierre Allain, Snezna Levicnik-Stezinar.