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Fluctuation of HCV viral load before seroconversion in a healthy volunteer blood donor
Chyang T Fang1, Leslie H Tobler, Carmen Haesche
1Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross Biomedical Research and Development, 15601 Crabbs Branch Way, Rockville, MD 20855, USA.
Insights
Newly implemented Nucleic Acid Testing (NAT) can detect Hepatitis C Virus (HCV) RNA in blood donations before antibody seroconversion. However, significant viral load fluctuations indicate NAT may not fully prevent HCV transmission.
Area of Science:
- Virology
- Infectious Diseases
- Blood Transfusion Safety
Background:
- Nucleic Acid Testing (NAT) is crucial for detecting infectious agents like Hepatitis C Virus (HCV) during the window period.
- The implementation of NAT aims to enhance blood supply safety by identifying donations made during the preseroconversion period.
Observation:
- A case identified an HCV NAT-positive donation with negative serology and elevated ALT in a 29-year-old female donor.
- The donor's previous donations were seronegative and NAT-negative, despite subsequent seroconversion.
- Significant fluctuations (100- to 1,000-fold) in viral load were observed in serial samples up to 48 days prior to seroconversion.
Findings:
- HCV RNA was detected in a donation prior to seroconversion, with a viral load exceeding 500,000 copies/mL.
- The donor remained seronegative for at least 36 days post-donation.
- The index donation was NAT-positive, but earlier seropositive samples were NAT-negative, highlighting viral load variability.
Implications:
- Dramatic fluctuations in HCV viral load before seroconversion can occur in some individuals.
- Even individual sample NAT testing may not completely eliminate the risk of HCV transmission.
- Further research is needed to understand pre-seroconversion viral dynamics and optimize NAT strategies.
Background:
Newly implemented NAT has been shown to be able to effectively identify HCV-positive blood donated during the preseroconversion period.
Study Design And Methods:
EDTA-plasma pools of 24 donations were tested using an HIV-1/HCV multiplex NAT under an FDA-approved IND application. Samples in a positive pool were retested individually. Positive samples were further tested by two discriminatory assays to determine specific viral reactivity. Upon obtaining informed consent, seronegative donors with positive NAT results were enrolled into a follow-up study for risk factor analysis and laboratory testing.
Results:
A donation by a 29 year old female was identified as HCV NAT-positive with negative serology and an elevated ALT. Her two previous donations, 5 and 12 months earlier, were both seronegative and with normal ALT. Her husband tested positive for HCV RNA. The donor remained seronegative for at least 36 days. The index donation had a viral RNA concentration of >500,000 copies per mL while the first seropositive sample was NAT-negative. Laboratory data on serial follow-up samples showed 100- to 1,000-fold fluctuations in viral load during a period of 48 days prior to seroconversion.
Conclusions:
This case suggests that, at least in some newly infected individuals, the HCV viral load can fluctuate dramatically prior to seroconversion, and that NAT, even on individual samples, will not totally prevent HCV transmission.
