Nucleic Acid Testing to Detect HBV Infection in Blood Donors

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http://www.nejm.org/doi/full/10.1056/NEJMoa1007644?query=TOC

Original Article

Nucleic Acid Testing to Detect HBV Infection in Blood Donors

L. Stramer, Ph.D., Ulrike Wend, Candotti, Ph.D., A. ,

B.A., F. Blaine Hollinger, M.D., Y. Dodd, Ph.D., Jean-Pierre Allain, M.D.,

and Wolfram Gerlich, M.D.

N Engl J Med 2011; 364:236-247January 20, 2011

Background

The detection of hepatitis B virus (HBV) in blood donors is achieved by

screening for hepatitis B surface antigen (HBsAg) and for antibodies against

hepatitis B core antigen (anti-HBc). However, donors who are positive for HBV

DNA are currently not identified during the window period before seroconversion.

The current use of nucleic acid testing for detection of the human

immunodeficiency virus (HIV) and hepatitis C virus (HCV) RNA and HBV DNA in a

single triplex assay may provide additional safety.

Methods

We performed nucleic acid testing on 3.7 million blood donations and further

evaluated those that were HBV DNA–positive but negative for HBsAg and anti-HBc.

We determined the serologic, biochemical, and molecular features of samples that

were found to contain only HBV DNA and performed similar analyses of follow-up

samples and samples from sexual partners of infected donors. Seronegative HIV

and HCV-positive donors were also studied.

Results

We identified 9 donors who were positive for HBV DNA (1 in 410,540 donations),

including 6 samples from donors who had received the HBV vaccine, in whom

subclinical infection had developed and resolved. Of the HBV DNA–positive

donors, 4 probably acquired HBV infection from a chronically infected sexual

partner. Clinically significant liver injury developed in 2 unvaccinated donors.

In 5 of the 6 vaccinated donors, a non-A genotype was identified as the dominant

strain, whereas subgenotype A2 (represented in the HBV vaccine) was the dominant

strain in unvaccinated donors. Of 75 reactive nucleic acid test results

identified in seronegative blood donations, 26 (9 HBV, 15 HCV, and 2 HIV) were

confirmed as positive.

Conclusions

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.

(Funded by the American Red Cross and others.)

Disclosure forms provided by the authors are available with the full text of

this article at NEJM.org.

Source Information

From the Scientific Support Office, American Red Cross, Gaithersburg, MD

(S.L.S., G.A.F.), and the Holland Laboratory, American Red Cross, Rockville, MD

(R.Y.D.); the Institute of Medical Virology, University of Giessen, Giessen,

Germany (U.W., W.G.); the National Health Service Blood and Transplant (D.C.)

and the Department of Haematology, University of Cambridge (J.-P.A.) — both in

Cambridge, United Kingdom; and the Eugene B. Casey Hepatitis Research Center,

Baylor College of Medicine, Houston (F.B.H.).

Address reprint requests to Dr. Stramer at the American Red Cross, Scientific

Support Office, 9315 Gaither Rd., Gaithersburg, MD 20877, or at

stramers@....