In June 2002, a physician reported to the Oregon Department of Human
Services (DHS) a case of acute hepatitis C in a patient who had received a
patellar tendon with bone allograft from a donor approximately 6 weeks before
onset of illness. At the time of the donor's death in October 2000, his serum
had no detectable antibody to hepatitis C virus (anti-HCV). The ensuing investigation
conducted by CDC and DHS confirmed that the donor, although anti-HCV–negative,
was HCV RNA–positive and the probable source of HCV infection for at
least eight organ and tissue recipients. This report summarizes the preliminary
results of the investigation. Although transmission from anti-HCV–negative
tissue donors probably is rare, determining the frequency of transplantations
from such donors and the risk for transmitting HCV to recipients is important
in evaluating whether additional prevention measures are warranted.
The donor was a man in his 40s with a history of hypertension and heavy
alcohol use who died of an intracranial hemorrhage. At the time of death,
he had no signs or symptoms of hepatitis, and his alanine aminotransferase
and aspartate aminotransferase levels were normal. Physical examination revealed
no skin markings indicative of injection-drug use or evidence of liver disease.
A questionnaire administered to the donor's next of kin revealed no history
of injection-drug use or blood transfusion.
At the time of the donor's death, his serum tested negative for anti-HCV
by a second-generation enzyme immunoassay (EIA) (Abbott HCV EIA 2.0, Abbott
Laboratories, Abbott Park, Illinois) and negative for human immunodeficiency
virus (HIV)-1, HIV-2, human T-lymphotropic virus (HTLV) I, HTLV II, hepatitis
B virus, and syphilis. In July 2002, stored, frozen serum obtained premortem
from the donor tested negative for anti-HCV with a third-generation EIA (ORTHO®
HCV Version 3.0 ELISA, Ortho-Clinical Diagnostics, Raritan, New Jersey) but
positive for HCV RNA (AMPLICOR® HCV Test, version 2.0, Roche Molecular
Systems, Branchburg, New Jersey). The donor's HCV genotype was 1a, as determined
from the 300-nucleotide sequence of the nonstructural coding region NS5b.1,2
A case was defined as laboratory-confirmed HCV infection, with a viral
genotype identical to that of the donor, in a recipient not known to have
been infected before transplantation. A definite case was defined as one that
occurred in a recipient who was both anti-HCV– and HCV RNA–negative
before transplantation. A probable case was defined as one that occurred in
a recipient for whom no serum was available before transplantation.
The organ procurement and tissue distribution agencies provided an inventory
of grafts recovered from the donor and the contact information for each health-care
provider or facility that had received grafts. Health-care providers were
contacted to obtain clinical information and to arrange for testing of recipients.
Recipients' post-transplantation and stored pretransplantation sera, when
available, were tested for anti-HCV by EIA 2.0 or 3.0 and for HCV RNA (by
using either AMPLICOR® HCV Test, version 2.0, or HCV RNA DetectR™
PLUS by TMA, Specialty Laboratories, Santa Monica, California). Specimens
positive for anti-HCV by EIA were tested with a supplemental recombinant immunoblot
assay (RIBA®, Chiron Corporation, Emeryville, California). HCV genotype
was determined for all HCV RNA–positive samples.1,2
Of 91 organs and tissues recovered from the donor, 44 were transplanted
into 40 recipients during October 2000–July 2002. Of the remaining 47
grafts, 44 tissues were removed from distribution in July 2002, and two tissues
and one organ had been discarded earlier. Of the 40 recipients, six received
organs, 32 received tissues, and two received corneas. Recipients were located
in 16 states and two foreign countries. All tissues had been treated with
surface chemicals or antimicrobials. Bone grafts also underwent gamma irradiation.
Eight cases were identified among the 40 recipients; all cases were
HCV genotype 1a. Among the six organ recipients, post-transplantation serum
was available for three, and definite cases occurred in all three. Of the
32 tissue recipients, three were known to have been HCV-infected before transplantation,
and test results were not available for another two (one bone and one tendon
with bone recipient). Among the remaining 27 tissue recipients, five probable
cases occurred: in one of two recipients of saphenous vein, in one of three
recipients of tendon, and in all three recipients of tendon with bone (including
the index patient). One other recipient was found to be HCV-infected after
transplantation with genotype 3a. No cases occurred in recipients of skin
(n = two) or irradiated bone (n = 16). Of the two cornea recipients, one was
infected before transplantation. The other recipient was anti-HCV–negative;
however, as of March 27, HCV RNA testing had not been performed.
PR Cieslak, MD, K Hedberg, MD, AR Thomas, MD, MA Kohn, MD, Oregon Dept
of Human Svcs. F Chai, PhD, OV Nainan, PhD, IT Williams, PhD, BP Bell, MD,
Div of Viral Hepatitis, National Center for Infectious Diseases; BD Tugwell,
MD, PR Patel, MD, EIS officers, CDC.
This report describes transmission of HCV by tissues and organs from
a donor whose serum tested anti-HCV–negative at the time of death. However,
stored serum tested subsequently was HCV RNA–positive. The donor was
the probable source of HCV infection for at least eight recipients of organs
or tissues. All cases occurred in recipients of organs or soft tissues; no
infections were found among those who had received skin or irradiated bone.
HCV transmission from tissue donors has been reported infrequently;
the only tissue types reported previously to transmit HCV are nonirradiated
bone and tendon with bone.3- 5 By
contrast, transplanted organs from infected donors are known to carry a high
risk for transmitting HCV.6
At the time of death, the donor probably was in the 8-10 week window
period between infection with HCV and development of a detectable HCV-antibody
response.7 Although available data are limited,
HCV transmission by organ and tissue donors during this period appears to
be uncommon; only one previous report describes HCV transmission from a tissue
donor in whom anti-HCV testing (using a less sensitive first-generation assay)
was negative.3 The frequency of transplantation
from antibody-negative, HCV RNA–positive organ and tissue donors is
not known. However, among voluntary blood donors, whose characteristics probably
differ from those of organ and tissue donors, approximately four per 1,000,000
blood donations are from donors who are anti-HCV–negative and HCV RNA–positive.8
Donor screening is the primary means of preventing transmission of viral
infections from organs and tissues. The Food and Drug Administration (FDA)
and the Health Resources and Services Administration (HRSA) provide regulatory
guidance or oversight for screening of tissue and organ donors. In addition,
organ procurement organizations are required by the Centers for Medicare &
Medicaid Services to ensure that appropriate donor screening tests are performed
by a laboratory certified in accordance with the Clinical Laboratory Improvement
Amendments of 1988. The donor screening process includes medical chart review,
interview of the donor's next of kin, physical assessment, and testing of
donor serum. Guidelines require that organ and tissue donors be tested for
Nucleic acid testing (NAT) to detect HCV RNA among organ and tissue
donors is not performed routinely and has several limitations. Organ viability
declines rapidly as a function of time after donor death. Because NAT often
is not immediately accessible and can require 1-2 days to complete, it might
be impractical in the setting of organ transplantation. By contrast, tissues
often can be stored for months to years before use, allowing ample time for
NAT. However, postmortem serum frequently is the only sample available for
testing from tissue donors. NAT to detect HCV RNA has not been approved by
FDA for use on serum samples obtained postmortem, and the performance of available
assays in this setting has not been evaluated.
Tissue processing methods (e.g., gamma irradiation) might affect the
likelihood of transmission of HCV and other viruses from infected donors.3,9 In this investigation, no cases
occurred in recipients of irradiated bone. Irradiation is not applied routinely
to all tissue types because it can impair tissue structural integrity.
This investigation was initiated by a clinician who suspected allograft-associated
HCV transmission and alerted the state health department. When a new case
of hepatitis C is diagnosed in a recent tissue or organ recipient, health-care
providers should notify local or state health departments promptly so an investigation
can be initiated and, if necessary, tissues can be recalled to prevent further
transmission. Centers performing transplantation should maintain adequate
records of graft recipients to facilitate investigations of allograft-associated
CDC, in collaboration with FDA and HRSA, will determine whether changes
in organ and tissue donor screening guidelines are warranted. Assessing the
performance of available NAT and anti-HCV assays in postmortem specimens would
provide essential information about the period during which donor screening
can be performed reliably. Although transmission from anti-HCV–negative
tissue donors probably is rare, determining the frequency of transplantations
from such donors and the risk for transmitting HCV to recipients will be useful
for evaluating the benefits and limitations of additional prevention measures.
This report is based on information contributed by H Homan, Multnomah
County Health Dept; DN Gilbert, MD, Providence Portland Medical Center and
Oregon Health and Science Univ; C Corless, MD, Oregon Health and Science Univ;
S Kemeny, MD, Providence Portland Medical Center, Portland, Oregon. M Kainer,
MD, Tennessee Dept of Health. W Kuhnert, PhD, Div of Viral Hepatitis; D Jernigan,
MD, Div of Healthcare Quality Promotion, National Center for Infectious Diseases;
K Kiang, MD, K Lofy, MD, EIS officers, CDC.
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