time, chronic hepatitis B can led to severe liver disease
including cirrhosis and liver cancer. Although an effective
vaccine is widely available and now part of the routine
childhood immunization series in the U.S., many people remain
U.S. blood donors are screened for hepatitis B surface antigen
(HBsAg) and for antibodies against hepatitis B core antigen
(anti-HBc). People who test positive for anti-HBc are either
currently infected or were infected in the past, cleared
the virus, and now have natural immunity. Individuals with
antibodies against hepatitis B surface antigen (anti-HBs),
but not core antigen, have immunity due to vaccination.
more on HBV testing)
blood donors who test positive for HBsAg and/or anti-HBc
are barred from donating, but it takes some time for a newly
infected person to produce enough antibodies to show up
on the traditional screening test. It is therefore possible
that a recently infected individual could be cleared for
donation during this "window period" before seroconversion,
or antibody detectability.
Stramer from the American Red Cross conducted a study to
evaluate the usefulness of nucleic acid testing, which measures
HBV DNA genetic material and can detect infection sooner.
In particular, they looked at a "triplex" nucleic
acid assay that detects HBV, hepatitis C virus (HCV), and
HIV in a single test.
The investigators performed nucleic acid testing on 3.7
million donated blood samples, with further evaluation of
those that tested HBV DNA positive but negative for HBsAg
and anti-HBc. They determined serological, biochemical,
and molecular features of samples that contained only HBV
DNA, with similar analysis of samples from sexual partners
of infected donors. Individuals who tested positive for
HCV and HIV genetic material but not antibodies were also
75 blood samples were positive for any of the 3 viruses
using nucleic acid testing, but negative for antibodies.
of these were confirmed as positive by follow-up testing:
15 for HCV, 9 for HBV, and 2 for HIV.
analysis identified 9 donors who were positive for HBV
DNA but not the usual screening markers, a rate of 1
in 410,540 donations.
included 6 samples from donors who had received the
HBV vaccine but developed subclinical infection (no
clinical signs or symptoms) that subsequently resolved.
5 of the 6 vaccinated donors had a non-A genotype as
their dominant strain, while subgenotype A2 -- the type
used in the HBV vaccine -- was dominant among unvaccinated
the HBV DNA positive donors, the researchers concluded
that 4 probably acquired HBV from a chronically infected
2 of the unvaccinated HBV DNA positive donors developed
clinically significant liver damage.
on these findings, the study authors concluded, "Triplex
nucleic acid testing detected potentially infectious HBV,
along with HIV and HCV, during the window period before
vaccination appeared to be protective, with a breakthrough
subclinical infection occurring with non-A2 HBV subgenotypes
and causing clinically inconsequential outcomes," they
study also provided further evidence of long-term harm for
people with uncontrolled HBV infection, and offered further
support for the benefits of hepatitis B vaccination.
affiliations: Scientific Support Office, American Red Cross,
Gaithersburg, MD; Holland Laboratory, American Red Cross,
Rockville, MD; Institute of Medical Virology, University
of Giessen, Giessen, Germany; National Health Service Blood
and Transplant, Cambridge, UK; Department of Haematology,
University of Cambridge, Cambridge, UK; Eugene B. Casey
Hepatitis Research Center, Baylor College of Medicine, Houston,
Stramer, U Wend, D Candotti, and others. Nucleic Acid Testing
to Detect HBV Infection in Blood Donors. New England Journal
of Medicine 364(3): 236-247 (Abstract).
January 20, 2011.