You have reached the legacy site. Please visit our new site at

Nucleic Acid Testing Identifies Hepatitis B Virus Sooner in Blood Donors

SUMMARY: Use of nucleic acid testing, which directly detects hepatitis B virus (HBV) genetic material in the blood, can identify people with potentially infectious virus earlier than tests that look for anti-HBV antibodies, according to an analysis of nearly 4 million donated blood samples described in the January 20, 2011 New England Journal of Medicine. As expected, people who had been vaccinated against hepatitis B were generally protected, though a few showed evidence of "breakthrough" infection with a virus type not included in the vaccine.

By Liz Highleyman

Over 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 unprotected.

Prospective 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. (For more on HBV testing)

Potential 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.

Susan 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 further analyzed.


Overall, 75 blood samples were positive for any of the 3 viruses using nucleic acid testing, but negative for antibodies.
26 of these were confirmed as positive by follow-up testing: 15 for HCV, 9 for HBV, and 2 for HIV.
The analysis identified 9 donors who were positive for HBV DNA but not the usual screening markers, a rate of 1 in 410,540 donations.
These 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 donors.
Among the HBV DNA positive donors, the researchers concluded that 4 probably acquired HBV from a chronically infected sexual partner.
2 of the unvaccinated HBV DNA positive donors developed clinically significant liver damage.

Based 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 seroconversion."

"HBV vaccination appeared to be protective, with a breakthrough subclinical infection occurring with non-A2 HBV subgenotypes and causing clinically inconsequential outcomes," they added.

The 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.

Investigator 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, TX.


SL 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.























 Google Custom Search
FDA-approved Therapies for Chronic HBV Infection
Baraclude  (entecavir)
  (lamivudine; 3TC)
  (adefovir dipivoxil)
Intron A  (interferon alfa-2b)
Pegasys  (peginterferon alfa-2a)
Viread  (tenofovir)
Tyzeka   (telbivudine)

Experimental Treatments




HBV Articles by Topic

Hepatocellular Carcinoma
Liver Transplantation

Children / Infants / Women
Hepatitis B Clinical Trials
Experimental Treatments
FAQs About Hepatitis
Tests for HBV
Vaccines for HBV