INFECTIVITY OF ORGAN, TISSUE AND CELL TRANSPLANTS IN THE PRESENCE
OF SEROLOGICAL MARKERS OF HEPATITIS B VIRUS
Challine Dominique1, Bouvier-Alias Magali1, Gourlain Karine1, Darthuy Françoise, Rémiré
Jocelyne, Pawlotsky Jean-Michel1
1
Department of Virology and INSERM U635, Hôpital Henri Mondor, Créteil, France
Prevention of hepatitis B virus (HBV) infection through organ, tissue or cell transplantation is
principally based on the exclusion of donors with serological HBV markers. If HBs antigen
(Ag) screening is performed universally, the need for systematically testing donors for antiHBc antibodies (Ab) and anti-HBs Ab is still debated, as well as the utility of HBV DNA
testing to improve viral safety in transplantation. AIMS: To establish the potential infectivity
of organ, tissue or cell grafts by seeking for HBV DNA in the blood of donors with
serological markesr of HBV. METHODS: Among 11,155 organ, tissue and cell donations
systematically tested in our laboratory between May 2000 and May 2004, 626 blood samples
from 520 donors (106 were retested at day 90 after quarantine) were found to have at least one
of three serological HBV markers: HBsAg, anti-HBc Ab, anti-HBs Ab (vaccinated donors
with only anti-HBs Ab were excluded). All samples were tested for the presence of HBV
DNA and HBV DNA was quantified by means of a highly sensitive real-time PCR-based
assay, Cobas TaqMan HBV (Roche Molecular Systems; dynamic range of quantification : 6
to 1.1E8 international Units (IU)/ml, 1 IU/ml = 5.8 Cobas Taqman copies/ml). RESULTS :
N
HBsAg pos
Recovery profile
HBcAb
Other
HBcAb + HBsAb
alone
Brain-dead
organ 199 17/20(85.0%)
0/121
2/53
2/5 (40.0%)
donors
(3.8%)
Living organ donors
13
0/0
0/10
0/3
0/0
Tissue
donors 165
2/2 (100.0%)
0/130
0/33
0/0
(excluding cornea)
Stem cell donors
75
3/5 (60.0%)
0/61
0/9
0/0
Cord blood donors
56
2/2 (100.0%)
0/44
0/10
0/0
Cornea donors
118
1/8 (12.5%)
3/62 (4.8%)
2/21
1/27 (3.7%)
(9.5%)
(i) HBV DNA was detected in most HBsAg-positive donors (mean HBV DNA levels: 3.3, 2.5
and 2.0 log IU/ml, respectively). (ii) HBV DNA was rarely detected in HBsAg-positive
cornea donors, suggesting false positive HBsAg detection. (iii) HBV DNA was never detected
in patients with a recovery profile, except cornea donors. Among the 3 HBV DNA-positive
cornea donors with this profile (HBV DNA: 1.5-3.2 log IU/ml), 2 had detectable HBsAg on
initial determination not confirmed by neutralization. (iv) HBV DNA was detected in a
significant number of donors with anti-HBc Ab only. (v) Two organ donors and one cornea
donor with the 3 HBV markers were HBV DNA positive (mean HBV DNA: 3.5 log IU/ml).
CONCLUSIONS: HBV DNA is detected in most HBsAg-positive organ, tissue and cell
donors, but the level of replication is lower than in patients with chronic hepatitis B. (ii) HBV
DNA can be detected in donors with anti-HBc Ab alone, reinforcing the need for systematic
anti-HBc screening. (iii) HBV DNA is not detected in organ, tissue (except cornea) or cell
donors with both anti-HBc and anti-HBs Ab, emphasizing the utility of systematic anti-HBs
testing. (iv) Cornea donors, often sampled after death, may yield false-positive and falsenegative HBs Ag results. (v) Systematic HBV DNA testing in organ, tissue and cell donors
appears useful to further improve viral safety in transplantation.