Role of nucleic acid testing in cadaver organ donor screening: detection of hepatitis C virus RNA in seropositive and seronegative donors

Abstract

Hepatitis C virus (HCV) transmission by both seropositive and seronegative cadaver organ donors has been documented, yet nucleic acid testing is not routinely used to identify active infection in these donors prior to transplantation. Between November 2001 and February 2004, we screened 1445 cadaver organ donors for anti-HCV antibodies with either HCV EIA-2.0 (Abbott Diagnostics, Chicago, IL, USA) and/or Ortho HCV Version 3.0 ELISA (Ortho-Clinical Diagnostics, Raritan, NJ, USA) and confirmed seropositive samples with Chiron RIBA3.0 SIA (Chiron Corporation, Emeryville, CA, USA). Samples with sufficient volume (n = 726) were tested by the VERSANT HCV [transcription-mediated amplification (TMA)] Qualitative assay (Bayer Healthcare LLC, Tarrytown, NY, USA) which can be performed in approximately 5 h. Those with detectable HCV RNA and sufficient volume were quantified by the VERSANT HCV 3.0 (bDNA) Assay (Bayer Healthcare LLC) and/or the HCV RNA TMA Quantitative Assay (n = 23) and genotyped (n = 57). Seventy-seven of 1445 (5.3%) donors were seropositive, reactive by either one or both anti-HCV assays. Fifty-two of 63 (82.5%) of the seropositive samples had detectable HCV RNA and were genotyped. Seventeen of these samples had quantifications ranging from 128,123 to >7,692,307 IU/mL. Six of 663 (0.9%) seronegative samples had detectable HCV RNA. Their quantifications ranged from <9.3 to 1,464,799 IU/mL, and five of these six were successfully genotyped. As HCV RNA was demonstrated in samples from both our seropositive and seronegative cadaver organ donors, we are now incorporating nucleic acid testing into our donor screening/diagnostic algorithm.

Incidence and risk factors for community-acquired hepatitis C infection from birth to 5 years of age in rural Egyptian children

“…Rarely individuals have viraemia with intermittently undetectable levels of HCV antibodies. 23,24 Others reported 0.2–0.9% of anti-HCV-negative organ donors were HCV-RNA-positive in France and the USA, 25,26 and 7 of the 232 mothers in the parent cohort who were HCV-RNA-positive did not have detectable anti-HCV. 10 …”

Transmission of Human Immunodeficiency Virus and Hepatitis C Virus From an Organ Donor to Four Transplant Recipients

“…Existing data suggest that 0.9% of seronegative organ donors have detectable HCV RNA, in part due to the long window period for HCV (31). Further, organs from HCV-infected donors can be safely used in HCV-infected recipients, minimizing the impact of false-positive results on organ availability (32).…”

Regarding unexpected severe and life-threatening donor-transmitted viral infections and use of high-risk behavior donors

“…During the following 3 years, 12 donations (1 per 3.1 million) and 170 donations (1 per 230,000) were found to be negative by antibody test but positive by nucleic acid amplification for HIV‐1 and HCV, respectively 26. In 1 transplant center between November 2001 and February 2004, 1445 organs from deceased donors were screened for anti‐HCV antibodies 27. In 6 (0.9%) of 663 seronegative samples HCV RNA was detected with a viral load 3 to 4 log lower than samples from seropositive donors.…”