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.

Plasma IP-10 and IL-6 are linked to Child-Pugh B cirrhosis in patients with advanced HCV-related cirrhosis: a cross-sectional study

“…However, only IP-10 and IL-6 were independently associated with Child-Pugh B cirrhosis (CTP 7-9) with high accuracy. Increased plasma IL-6 and IP-10 levels are related to liver disease severity in HCV-infected patients 11,38 and HIV/HCV-coinfected patients 24 , but in the current study, we found plasma IL-6 and IP-10 levels discriminated with great accuracy the presence of severe cirrhosis with Child-Pugh B (CTP 7-9). The severe cirrhosis seems to be the result of an inflammatory syndrome, which increases the risk of acute-on-chronic liver failure (ACLF) 39 .…”

Investigating Core Signaling Pathways of Hepatitis B Virus Pathogenesis for Biomarkers Identification and Drug Discovery via Systems Biology and Deep Learning Method

“…In contrast, STAT1 promoted apoptosis by inducing the expression of CXCL10 and strengthened the antiviral ability through modulating the expression of GBP1. Amongst these two downstream targets, CXCL10 is a ligand for the receptor CXCR3 involved in chemotaxis, induction of apoptosis, and regulation of cell growth associated with a variety of human diseases including Hepatitis C [ 106 ] and Endotheliitis [ 107 ]. GBP1 is a binding protein which has been shown to provide broad host protection against different pathogen classes through expediting oxidative killing and delivering antimicrobial peptides to autophagolysosomes [ 108 ].…”

Potential Role of CXCL10 in Monitoring Response to Treatment in Leprosy Patients

“…CXCL10 (IP-10) induction may also be mediated by TNF (59). CXCL10 exerts its biological functions via CXCR3, which is expressed by activated T cells (60) through the induction of paracrine and/or autocrine signaling; it has been identified as an important prognostic indicator for various diseases (61)(62)(63)(64). Here, we observed that patients who did not reduce the bacilloscopic index after MDT showed a decrease in CXCL10 (IP-10) sera levels at release, which was not observed in the sera of patients who presented a reduction in bacillary load after 12 doses of MDT; this suggests that higher levels of CXCL-10 are important for the control of bacillary load.…”