Occupational exposure to hepatitis C virus: early T-cell responses in the absence of seroconversion in a longitudinal cohort study.
Publication/Presentation Date
9-1-2013
Abstract
BACKGROUND: T-cell responses have been described in seronegative patients who test negative for hepatitis C virus (HCV) RNA despite frequent HCV exposure. However, the cross-sectional design of those studies did not clarify whether T cells were indeed induced by low-level HCV exposure without seroconversion or whether they resulted from regular acute infection with subsequent antibody loss.
METHODS: Over a 10-year period, our longitudinal study recruited 72 healthcare workers with documented HCV exposure. We studied viremia and antibody and T-cell responses longitudinally for 6 months.
RESULTS: All healthcare workers remained negative for HCV RNA and antibodies. However, 48% developed proliferative T-cell response and 42% developed responses in interferon-gamma enzyme-linked immunosorbent spot assays, with 29 healthy HCV-unexposed controls used to define assay cutoffs. The response prevalence was associated with the transmission risk score. T-cell responses peaked at week 4 and returned to baseline by week 12 after exposure. They predominantly targeted nonstructural HCV proteins, which are not part of the HCV particle and thus must have been synthesized in infected cells.
CONCLUSIONS: Subclinical transmission of HCV occurs frequently, resulting in infection and synthesis of nonstructural proteins despite undetectable systemic viremia. T-cell responses are more sensitive indicators of this low-level HCV exposure than antibodies.
Volume
208
Issue
6
First Page
1020
Last Page
1025
ISSN
1537-6613
Published In/Presented At
Heller, T., Werner, J. M., Rahman, F., Mizukoshi, E., Sobao, Y., Gordon, A. M., Sheets, A., Sherker, A. H., Kessler, E., Bean, K. S., Herrine, S. K., Stevens, M., Schmitt, J., & Rehermann, B. (2013). Occupational exposure to hepatitis C virus: early T-cell responses in the absence of seroconversion in a longitudinal cohort study. The Journal of infectious diseases, 208(6), 1020–1025. https://doi.org/10.1093/infdis/jit270
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
23801608
Department(s)
Administration and Leadership
Document Type
Article