Infectivity of Hepatitis B Virus Surface Antigen‐Positive Plasma With Undetectable HBV‐DNA: Can HBsAg Screening Be Discontinued in Egyptian Blood Donors?

Abstract

ABSTRACTHepatitis B Virus (HBV) infectivity data were reviewed and the 50% infectious dose (ID50) was reassessed in different HBsAg‐positive infection stages enabling modelling of transfusion‐transmitted (TT)‐HBV infection risk if HBsAg donor screening was replaced by individual donation nucleic acid amplification technology (ID‐NAT). Quantitative HBsAg and HBV‐DNA assays were performed against international standards to compare the ratio between potential infectious HBV virions and subviral HBsAg particles in Egyptian HBsAg‐positive blood donors as well as in Japanese chimpanzee samples of known infectivity. HBV‐DNA load below the quantification limit of detection was estimated against a reference standard by replicate NAT testing (n = 25). Infectivity of chimpanzee samples collected during ramp‐up and declining viremic phase were tested in a human liver chimeric mice (HLCM) model and compared with published infectivity data from different HBsAg‐positive infection stages. Lowest estimates of ID50 in HBsAg‐positive plasma were 3–6 HBV virions in chimpanzee studies. Infectivity decreased approximately 10‐100‐fold in the declining viremic phase using HLCM. In acute phase samples, HBV to HBsAg particle ratios varied between 1:102–104 but in HBsAg‐positive blood donors this particle ratio reached 1:106–1012 when viral load was below 100 HBV‐DNA copies/mL. Modelled TT‐HBV risk of an HBsAg‐positive/ID‐NAT nonreactive blood transfusion was estimated at 5.5%–27% for components containing 20–200 mL of plasma when assuming an ID50 of 316 (point estimate between 100 and 1000) virions. It cannot be ensured that discontinuation of HBsAg donor screening and reliance on ID‐NAT alone is safe.