False-positive hepatitis B surface antigen screening test results in patients receiving granulocyte-colony-stimulating factor.

BACKGROUND

Granulocyte-colony-stimulating factor (G-CSF) is used for the mobilization of progenitor cells and granulocytes. False-positive hepatitis B surface antigen (HBsAg) enzyme-linked immunosorbent assays (ELISAs) (NML) from one manufacturer in individuals receiving G-CSF have been observed.

STUDY DESIGN AND METHODS

Sixty-six autologous peripheral blood progenitor cell donors from 1994 were retrospectively reviewed. Donors typically received 5 to 10 micrograms of G-CSF per kg subcutaneously for 5 days before collection. Additional ELISA dilutional studies (1-in-10, 1-in-100, 1-in-1000) with known HBsAg-negative serum were made with G-CSF. Testing was performed by the University of North Carolina, the American Red Cross in Charlotte, NC, or the National American Red Cross, Washington, DC.

RESULTS

Of the 66 patients, none reacted for antibody to hepatitis B core antigen, and 30 (45%) had a positive reaction in the ELISA. Surface antigen positivity was "confirmed" on 6 of the 30 patients by neutralizing ELISA reactivity with an antibody to HBsAg test from the same manufacturer. In all cases, the clinical presentation was not suggestive of hepatitis, and these individuals were not at high risk for hepatitis B. Twenty-seven of the 30 cases were tested with a monoclonal HBsAg ELISA (AUSZYME) from another manufacturer in the peridonation period and did not react. In 1994, 256 autologous whole-blood donors not receiving G-CSF were similarly tested and only 1 (0.4%) had a positive reaction with the second manufacturer's HBsAg ELISA (p < 0.001). Of this group, 41 patients with histories of malignancy were identified, which is comparable to the history of the peripheral blood progenitor cell donors in this study, and none of these blood donors tested positive for HBsAg (p < 0.001). Dilutional studies with G-CSF produced no reactions.

CONCLUSION

The NML HBsAg ELISA studied has an unacceptably high false-positive rate in patients or donors receiving G-CSF. The false reactivity of this assay appears to be an indirect consequence of G-CSF administration, which can also lead to spurious confirmation by the HBsAg neutralization assay from the same manufacturer.