Two different tests to detect hepatitis C virus (HCV) infection should be used to screen potential organ donors and recipients, researchers recommended in a recent article published in Diagnostic Microbiology & Infectious Disease.
These two screening tests include the conventional method, the HCV antibody test (anti-HCV), and an alternative method that tests for HCV core antigen (HCV-Ag).
Anti-HCV testing is the norm for HCV screening of organ donors before transplantation. However, its main disadvantage is that it doesn’t detect antibodies during the seroconversion window (approximately day 30 to day 70 of infection), noted lead author Rafael Benito, MD, Department of Microbiology, University of Zaragoza, Zaragoza, Spain, and coauthors. Thus, anti-HCV testing can miss infected donors during this early stage of infection.
Other disadvantages to anti-HCV testing: It can’t distinguish between acute, chronic, and past infections; and it can produce false-positive or false-negative results, particularly in immunocompromised individuals.
Compared with anti-HCV, HCV-Ag can be detected earlier and throughout the course of infection, previous research has shown. The HCV-Ag assay detects the HCV antigen from free viral particles and immune complexes.
“HCV antigen is an alternative marker that is detectable during the early phase of the pre-seroconversion window, and in addition, it is not affected by immunological status,” Dr. Benito and coauthors wrote.
For this study, Dr. Benito and colleagues investigated how well the HCV-Ag assay could perform as a screening method for HCV infection in potential organ donors and recipients.
They obtained samples from 315 participants in an organ donor program (mostly for liver transplants), including 81 organ donors, 54 transplant recipients, and 180 transplant candidates. The investigators analyzed all the samples using both anti-HCV and HCV-Ag screening methods. Both types of assay were tested on the same instrument (Abbott ARCHITECT i2000SR immunoassay analyzer), per the manufacturer’s recommendations, to avoid false-positive HCV-Ag results.
Results of the tests showed that anti-HCV was detected in 87 samples (27.62%) and HCV-Ag in 81 samples (25.71%). Concordance between the two assays was 94.29%, the researchers noted.
Discrepancies between assays occurred in 18 cases. In 12 cases, anti-HCV was positive but HCV-Ag was negative. In 6, anti-HCV was negative, but HCV-Ag was positive.
Among the latter group, 5 of the 6 patients had low HCV-Ag levels and a negative viral load. “These results were interpreted as false positives in all cases, perhaps in relation to the patients’ liver disease, and this interpretation was confirmed by patient monitoring,” Dr. Benito and coauthors wrote. “None of the patients was a potential donor, but had they been, they would have been rejected, even though low HCV-Ag levels suggest a false-positive result.”
More research needed
However, the anti-HCV–negative/HCV-Ag–positive profile may not necessarily be a false positive, the researchers cautioned.
“More studies are needed to confirm the significance of this profile, but its existence highlights the importance of being cautious when interpreting low-positive results in the absence of other markers,” they wrote. “Although this profile is unlikely, its detection in an organ donor could be problematic, as it would result in unnecessary rejection.”
Dr. Benito and colleagues affirmed that the HCV-Ag assay, despite its limitations, is useful for HCV screening in transplant programs because it’s fast, easy to use, reliable, and has good sensitivity and specificity.
“The HCV-Ag assay detects HCV infections missed by the anti-HCV assay,” they concluded. “Because of the possibility of discrepancies between HCV-Ag and anti-HCV results, the use of both markers should be contemplated in the screening of organ recipients and donors.”
This study was supported by the Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain. This research did not receive funding from agencies in the public, commercial, or not-for-profit sectors.