Occult hepatitis B virus infection: implications in transfusion

Vox Sang. 2004 Feb;86(2):83-91. doi: 10.1111/j.0042-9007.2004.00406.x.


Hepatitis B virus (HBV) presents a higher residual risk of transmission by transfusion than hepatitis C virus (HCV) or human immunodeficiency virus (HIV). While most infectious blood units are removed by screening for hepatitis B surface antigen (HBsAg), there is clear evidence that transmission by HBsAg-negative components occurs, in part, during the serologically negative window period, but more so during the late stages of infection. Donations negative for HBsAg, but positive for HBV DNA, with or without the presence of HBV antibodies, correspond to 'occult' HBV infection (OBI). The frequency of OBI depends on the relative sensitivity of both HBsAg and HBV DNA assays. It also depends on the prevalence of HBV infection in the population. OBI may follow recovery from infection, displaying antibody to hepatitis B surface antigen (anti-HBs) and persistent low-level viraemia, escape mutants undetected by the HBsAg assays, or healthy carriage with antibodies to hepatitis B e antigen (anti-HBe) and to hepatitis B core antigen (anti-HBc). Over time, in the latter situation, anti-HBe and, later, anti-HBc may become undetectable. The critical question is whether or not OBI is infectious by transfusion. All forms have been shown to be infectious in immunocompromised individuals, such as organ- or bone marrow-transplant recipients. In immunocompetent recipients, there is no evidence that anti-HBs-containing components (even at low titre) are infectious. Anti-HBc only, with HBV DNA, can be associated with infectivity, as can rare cases of HBV DNA without any serological HBV marker. If HBV nucleic acid amplification technology (NAT) is considered, the OBI viral load would usually be < 500 IU/ml, making testing of plasma pools unsuitable unless the sensitivity of NAT significantly increases by genome enrichment or test improvement.

Publication types

  • Review

MeSH terms

  • Adult
  • Antigenic Variation
  • Child
  • DNA, Viral / blood
  • Disease Transmission, Infectious
  • Hepatitis B / diagnosis
  • Hepatitis B / epidemiology
  • Hepatitis B / prevention & control
  • Hepatitis B / transmission*
  • Hepatitis B Antibodies / blood
  • Hepatitis B Antigens / blood
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B virus / isolation & purification
  • Humans
  • Mass Screening
  • Predictive Value of Tests
  • Prevalence
  • Sensitivity and Specificity
  • Transfusion Reaction*
  • Viremia / diagnosis
  • Virulence


  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Antigens
  • Hepatitis B Surface Antigens