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Interferon-stimulated gene expression and hepatitis C viral dynamics during different interferon regimens.
- Source :
-
Journal of hepatology [J Hepatol] 2003 Sep; Vol. 39 (3), pp. 421-7. - Publication Year :
- 2003
-
Abstract
- Background/aims: To address the molecular mechanism for enhanced antiviral efficacy associated with a frequent dosing of interferon (IFN)-beta.<br />Methods: Serum hepatitis C viral (HCV) dynamics, double-stranded RNA-activated protein kinase (PKR) mRNA and MxA mRNA levels in peripheral blood mononuclear cells (PBMC) were analyzed serially in 140 patients who were randomly assigned to a twice daily (3 MU bid) or once daily (6 MU qd) administration group.<br />Results: In twice daily group, the rate of HCV decline during the second phase was 2-fold greater than in the once daily group (P=0.04). Peak PKR and MxA gene expression levels in the first phase (observed 4 h after a single administration) were 2-fold higher in the once daily group. However, the expression in the second phase was maintained at a significantly higher level in the twice daily group. Initial and peak expression levels were related to initial viral load. Basal expressions in PBMC were significantly correlated with those in the liver tissue (PKR, r=0.81; MxA, r=0.75, respectively, P<0.0001).<br />Conclusions: Our data suggest that elimination of HCV-infected cells is enhanced by twice daily dosing of IFN-beta, and that this enhanced effect is associated with a higher intracellular expression of PKR and MxA during the second phase.
- Subjects :
- Adult
Aged
Drug Administration Schedule
Female
GTP-Binding Proteins genetics
Hepatitis C metabolism
Humans
Intracellular Membranes metabolism
Liver metabolism
Male
Middle Aged
Monocytes metabolism
Myxovirus Resistance Proteins
RNA, Messenger blood
Viral Load
eIF-2 Kinase genetics
Antiviral Agents administration & dosage
Gene Expression drug effects
Hepacivirus drug effects
Hepatitis C drug therapy
Interferon-beta administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 0168-8278
- Volume :
- 39
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 12927929
- Full Text :
- https://doi.org/10.1016/s0168-8278(03)00287-3