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Gastroenterology. 2011 Feb;140(2):676-685.e1. doi: 10.1053/j.gastro.2010.10.048. Epub 2010 Oct 30.

Sporadic reappearance of minute amounts of hepatitis C virus RNA after successful therapy stimulates cellular immune responses.

Author information

1
Immunology Section, NIDDK, National Institutes of Health, DHHS, Bethesda, Maryland 20892-1800, USA.

Abstract

BACKGROUND & AIMS:

Several studies have reported hepatitis C virus (HCV) RNA sequences in the circulation after treatment-induced or spontaneous recovery. We investigated whether the HCV RNA represents persistence of HCV infection or reinfection.

METHODS:

We studied 117 patients who recovered from HCV infection (98 following therapy and 19 spontaneously). A reverse-transcription polymerase chain reaction assay was used to detect the 5'-untranslated region of HCV. T-cell responses were studied by enzyme-linked immunospot for interferon-γ.

RESULTS:

Plasma samples from 15% of treatment-recovered patients and no spontaneously recovered patient tested positive for HCV RNA. Lymphocytes from 3 patients who responded to therapy and 1 who recovered spontaneously tested positive. The frequency of HCV RNA detection in plasma correlated inversely with the time after the end of treatment. Post-treatment HCV 5'-untranslated region sequences matched pretreatment sequences in 85% of cases. T-cell responses were significantly greater at time points with detectable trace amounts of HCV RNA than at time points without detectable HCV RNA (P = .035) and were primarily against nonstructural HCV antigens. The immune hierarchy was preserved over 5 years in patients whose post-treatment HCV RNA sequences matched pretreatment sequences, indicating HCV RNA persistence. An altered immune hierarchy with dominant immune responses, shifting from nonstructural to structural antigens, was observed in a single patient whose post-treatment HCV genotype differed from that of the pretreatment genotype, indicating HCV reinfection.

CONCLUSIONS:

Trace amounts of HCV RNA of pretreatment sequence persisted and reappeared sporadically in the circulation within 8 years after recovery from hepatitis C but not thereafter, indicating that patients are cured of HCV infection. Reappearance of HCV RNA induced HCV-specific T-cell responses.

PMID:
21040725
PMCID:
PMC3399733
DOI:
10.1053/j.gastro.2010.10.048
[Indexed for MEDLINE]
Free PMC Article

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