Hepatitis C Virus Transmission from an Antibody-Negative Organ and Tissue
Donor --- United States, 2000--2002
CDC MMWR Weekly April 4, 2003/52 (13);273-276
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, C
alifornia). 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 forthree, 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.
Reported by: 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 HCVRNA--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 reg
ulatory 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 anti-HCV.
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
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 infections.
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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