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EXPOSURE TO HEPATITIS C VIRUS INDUCES CELLULAR IMMUNE RESPONSES WITHOUT DETECTABLE VIREMIA OR SEROCONVERSION

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  • 1 Egyptian Reference Diagnostic Center, VACSERA, Cairo, Egypt; Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio; Center for Field & Applied Research, Cairo, Egypt; Viral Hepatitis Reference Laboratory, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt; International Health Division, University of Maryland–School of Medicine, Baltimore, Maryland; Istituto di Ricerche di Biologia Molecolare, Pomezia, Rome, Italy; New York Blood Center, New York, New York

Sporadic cases of cell-mediated immunity (CMI) in persons exposed to hepatitis C (HCV) but evidently uninfected have been reported. To further define this, we measured CMI in individuals without evidence of HCV infection, that is, negative for HCV-antibodies (anti-HCV) and RNA, residing in a rural Egyptian community where prevalence of anti-HCV was 24%. Cell-mediated immunity (CMI) measured by interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay, confirmed by intracellular staining using flow cytometry, against HCV peptides was measured in seronegative individuals with high-risk (HR) and low-risk (LR) exposures to HCV. Thirteen of 71 (18.3%) HR subjects but only 1 of 35 (2.9%) LR subjects had detectable CMI (P = 0.032). These data are compatible with the hypothesis that exposures to HCV may lead to development of HCV-specific CMI without anti-HCV and ongoing viral replication. We speculate induced CMI clears HCV sometimes when anti-HCV is not detectable, and HCV-specific CMI is a useful surrogate marker for exposure to HCV.

Author Notes

Reprint requests: G. Thomas Strickland, M.D., Ph.D, D.C.M.T., International Health Division, University of Maryland School of Medicine, 660 West Redwood Street, Suite 100, Howard Hall, Baltimore, MD 21201, Telephone: (410) 706-7550, Fax: (410) 706-8013.
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