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

• Published in: Journal of immunology research 2019, Vol.2019 (2019), p.1-11
• Main Authors: Giuggioli, Dilia, Ferri, Clodoveo, Antonelli, Alessandro, Mazzi, Valeria, Patrizio, Armando, Paparo, Sabrina Rosaria, Ragusa, Francesca, Elia, Giusy, Ruffilli, Ilaria, Fallahi, Poupak, Ferrari, Silvia Martina, Colaci, Michele
• Format: Article
• Language: English
• Subjects: Acute Disease; Antiviral agents; Antiviral Agents - therapeutic use; Arthritis; Autoimmune diseases; Chemokine CXCL10 - blood; Chemokine CXCL10 - genetics; Chemokines; Chronic infection; Cryoglobulinemia; CXCL10 protein; CXCR3 protein; Cytokines; Diabetes; Endothelium; Fibroblasts; Fibrosis; Health risk assessment; Hepatitis; Hepatitis C; Hepatitis C - immunology; Hepatitis C, Chronic - diagnosis; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - immunology; Hepatocytes; Hepatology; Humans; Immune clearance; Immunology; Immunomodulation; Infections; Infectious diseases; Interferon; Interferon-alpha - therapeutic use; Interferon-gamma - therapeutic use; Interferons - genetics; Ligands; Liver - pathology; Lymphocytes; Lymphocytes T; Pathogenesis; Polymorphism, Single Nucleotide; Pretreatment; Prognosis; Proteins; Receptors, CXCR3 - immunology; Review; Ribavirin; Ribavirin - therapeutic use; Secretion; Sepsis; Single-nucleotide polymorphism; Therapeutic applications; Thyroiditis; Vasculitis; Viruses; α-Interferon
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2019/5878960

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.