Immunomodulation of CXCL10 Secretion by Hepatitis C Virus: Could CXCL10 Be a Prognostic Marker of Chronic Hepatitis C?

Abstract

Chemokine (C-X-C motif) ligand (CXCL)10 and other CXCR3 chemokines are involved in the pathogenesis of acute and "chronic hepatitis C virus (HCV) infection" (CHC). Here, we review the scientific literature about HCV and CXCL10. The combination of circulating CXCL10 and single nucleotide polymorphisms (SNPs) in IL-28B can identify patients with acute HCV infection most likely to undergo spontaneous HCV clearance and those in need of early antiviral therapy. In CHC, the HCV and intrahepatic interferon- (IFN-) γ drive a raised CXCL10 expression by sinusoidal endothelium and hepatocytes, thereby inducing the recruitment of CXCR3-expressing T cells into the liver; thus, CXCL10 plays an important role in the development of necroinflammation and fibrosis. Increased CXCL10 was significantly associated with the presence of active vasculitis in HCV-associated cryoglobulinemia, or with autoimmune thyroiditis in CHC. Pretreatment CXCL10 levels are predictive of early virological response and sustained virological response (SVR) to IFN-α and ribavirin and may be useful in the evaluation of candidates for therapy. The occurrence of SNPs adjacent to IL-28B (rs12979860, rs12980275, and rs8099917), and CXCL10 below 150 pg/mL, independently predicted the first phase viral decline and rapid virological response, which in turn independently predicted SVR. Directly acting antiviral agents-mediated clearance of HCV is associated with the loss of intrahepatic immune activation by IFN-α, associated by decreased levels of CXCL10. In conclusion, CXCL10 is an important marker of HCV clearance and successful therapy in CHC patients. Whether CXCL10 is a novel therapeutic target in CHC will be evaluated.

• Authors: Silvia Martina Ferrari, Poupak Fallahi, Ilaria Ruffilli, Giusy Elia, Francesca Ragusa, Sabrina Rosaria Paparo, Armando Patrizio, Valeria Mazzi, Michele Colaci, Dilia Giuggioli, Clodoveo Ferri, Alessandro Antonelli
• Journal: Journal of immunology research (J Immunol Res) Vol. 2019 Pg. 5878960 ( 2019) ISSN: 2314-7156 [Electronic] Egypt
• PMID: 31485460 (Publication Type: Journal Article, Review)

Chemical References

• Antiviral Agents
• CXCR3 protein, human
• Chemokine CXCL10
• interferon-lambda, human
• Interferon-alpha
• Receptors, CXCR3
• Ribavirin
• Interferon-gamma
• Interferons

Topics

• Acute Disease
• Antiviral Agents (therapeutic use)
• Chemokine CXCL10 (blood, genetics)
• Hepatitis C (immunology)
• Hepatitis C, Chronic (diagnosis, drug therapy, immunology)
• Humans
• Immunomodulation
• Interferon-alpha (therapeutic use)
• Interferon-gamma (therapeutic use)
• Interferons (genetics)
• Liver (pathology)
• Polymorphism, Single Nucleotide
• Prognosis
• Receptors, CXCR3 (immunology)
• Ribavirin (therapeutic use)