Clinical significance of elevated serum interferon‐ inducible protein‐10 levels in hepatitis C virus carriers with persistently normal serum transaminase levels

Abstract

The aim of this study was to assess the immunological profile in hepatitis C virus carriers with persistently normal serum transaminase levels. Forty-two serum HCV RNA positive patients with persistently normal serum transaminase levels (22 natural 'asymptomatic HCV carriers' and 20 biochemical responders to IFN therapy) and 23 complete responders to IFN therapy were enrolled. The HCV genotypes and serum HCV RNA levels were determined before IFN therapy in treatment responders, and at entry in the others. The serum levels of IFN-inducible protein-10 (IP-10) (a protein mainly induced by IFN-gamma), interleukin (IL)-10, and IL-4 were measured in all patients while the serum transaminase levels were normal. The serum transaminase levels and platelet counts were then monitored for the next 4 years and the changes in liver fibrosis were assessed. The serum levels of IP-10 in infected and biochemically normal patients were significantly higher than the levels in complete responders to therapy, whereas the serum levels of IL-10 and IL-4 did not vary significantly among the different groups. During the 4-year follow-up period, 10/20 (50%) biochemical responders and 12/22 (55%) asymptomatic carriers had an elevation of the serum transaminase levels. A significant (P=0.0370) increase in platelet count after 4 years and improvement in liver fibrosis were noted in treatment responders but not in infected patients. The weak but significant residual immune response as reflected by the increased serum IP-10 level may underlie the outcome of HCV carriers with persistently normal serum transaminase levels.

Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus

“…Furthermore, in human HCV infection, CXCL10 and CXCL9 were shown to be specifically up-regulated on hepatic sinusoidal endothelium [6]. Additionally, CXCL10 plasma levels were mentioned as a marker of HCV disease activity [19,20]. Our results regarding CXCL10 expression in plasma are in accordance with these publications.…”

“…This chemokine has been reported to be associated with disease inflammatory activity [19,20]. We detected significantly higher levels of this chemokine in the plasma of HCVinfected patients relative to controls, regardless of the level of fibrosis (p X 0.001) (Fig.…”

“…Our data regarding CXCL12, CXCL10 and CCL21 suggest that such combinatorial assessments may be indicative of disease activity and fibrosis development. A similar approach regarding an association between high plasma levels of CXCL10 and response to therapy in HCV patients has also been reported [19,20].…”

Fas Ligand Is Responsible for CXCR3 Chemokine Induction in CD4+ T Cell-Dependent Liver Damage

“…The mRNA levels of IP-10, Mig, and ITAC are increased in liver tissues derived from chronic HCV patients and the levels of enhanced expression of these chemokines correlated with severity of liver disease (34 -36). The serum levels of IP-10 can also serve as a marker for the effectiveness of IFN-␣ and ribavirin treatment as the levels of IP-10 dramatically decrease in chronic HCV patients who respond to therapy (37). Additionally, the pretreatment levels of the CXCR3 ligands may have an effect on the outcome of HCV treatment, where increased levels of these chemokines before treatment corresponds with treatment failure (38).…”

Plasmacytoid Dendritic Cell Recruitment by Immobilized CXCR3 Ligands

“…We asked whether soluble CXCR3Ls can affect the TEM induced by immobilized chemokines. This is a relevant question because under pathologic conditions CXCR3Ls can be present in the circulation (33,34). pDCs were pretreated with CXCL9, CXCL10, or CXCL11 before placing them over EC monolayers presenting immobilized CXCL10.…”