Clin Mol Hepatol.
2018 Sep;24(3):302-310. 10.3350/cmh.2017.0074.
Interferon-free treatment for hepatitis C virus infection induces normalization of extrahepatic type I interferon signaling
- Affiliations
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- 1Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea. yoonsk@catholic.ac.kr
- 2Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
- 3Department of Internal Medicine, Makati Medical Center, Manila, Philippines.
- KMID: 2428758
- DOI: http://doi.org/10.3350/cmh.2017.0074
Abstract
- BACKGROUND/AIMS
Hepatitis C virus (HCV) replicates in the peripheral blood mononuclear cells (PBMCs), leading to the production of type I interferons (IFNs). It is well known that the gene expression profile of PBMC is similar to that of the liver. The present study explored the dynamic gene expression profile of PBMCs collected from HCV-infected patients undergoing direct-acting antiviral (DAA) therapy.
METHODS
A prospective cohort comprising 27 patients under DAA therapy was formed. Expression level of IFN-β and its downstream interferon-stimulated genes (ISGs) was measured in PBMCs before and after DAA treatment. Furthermore, immunoblotting was performed to identify the signaling molecules involved in the expression of ISGs.
RESULTS
The pretreatment expression level of interferon-induced protein 44 (IFI44) and C-X-C motif chemokine ligand 10 (CXCL10) correlated with the pretreatment expression level of IFN-β. After DAA treatment, a significant decrease in the expression levels of IFN-β, IFI44, and CXCL10 was observed in the PBMCs. Furthermore, the pretreatment expression level of IFN-β and ISGs correlated with the level of signal transducer and activator of transcription 1 (STAT1) phosphorylation, and DAA treatment abrogated STAT1 phosphorylation.
CONCLUSIONS
Pretreatment activation of IFN-β response is rapidly normalized after DAA treatment. The present study suggests that the decreased type I IFN response by the clearance of HCV might contribute to DAA-induced alleviation of extrahepatic manifestation of chronic HCV infection.
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