Evidence of acute primary occult hepatitis B virus infection in an Italian repeat blood donor

BACKGROUND: Preliminary evidence of cases of acute occult hepatitis B virus (HBV) infection (OBI) has been recently reported in the literature. Furthermore, OBI definition has been the object of an international consensus conference. STUDY DESIGN AND METHODS: A case of acute primary OBI was identified and followed up in a repeat female blood donor using a highly sensitive nucleic acid test (NAT; Procleix Ultrio on Tigris, Chiron). Genotyping and sequencing of virus isolates from donor and contact cases were performed. RESULTS: The blood donor never developed detectable hepatitis B surface antigen (HBsAg) until seroconversion to antibody to hepatitis B surface antigen/antibody to hepatitis B core antigen. A very low viral load was observed during the infection course (<50 IU/mL). Donor HBV DNA sequencing consistently showed a CCA deletion leading to amino acid T116 deletion in the small envelope protein (S). Other sequence features showed high homology between donor and contact case, suggesting a sexual transmission. DISCUSSION: The main explanation for HBsAg undetectability relies on the very low level of viremia observed. The single-amino-acid deletion found in the S protein cannot account for HBsAg detection failure, because the capture antibody of the assay used is targeted to a different sequence epitope (aa121-124). Meanwhile, CCA deletion may have impacted the virus replication efficiency since it affects the overlapping reverse transcriptase "finger" domain of the polymerase gene. These findings define this case as an acute primary OBI, confirming the existence of this condition. NAT with high sensitivity is the only screening enabling prevention of HBV transmission by transfusion in such cases.