Dynamic interplay between CXCL levels in chronic Hepatitis C patients treated by Interferon

Abstract

BackgroundCombined pegylated interferon-α and ribavirin therapy has sustained virological response (SVR) rates of 54% to 61%. Pretreatment predictors of SVR to interferon therapy have not been fully investigated yet. The current study assesses a group of chemokines that may predict treatment response in Egyptian patients with chronic HCV infection.Patients and methodsCXCL5, CXCL9, CXCL11, CXCL12, CXCL 13, CXCL 16 chemokines and E-Cadherin were assayed in 57 chronic HCV patients’ sera using quantitative ELISA plate method. All studied patients were scheduled for combined pegylated interferon alpha and ribavirin therapy (32 patients received pegylated interferon α 2b, and 25 patients received pegylated interferon α 2a). Quantitative hepatitis C virus RNA was done by real time RT-PCR and HCV genotyping by INNOLIPAII.ResultsThere was no significant difference (p > 0.05) in baseline HCV RNA levels between responders and non-responders to interferon. A statistically significant difference in CXCL13 (p = 0.017) and E-Cadherin levels (P = 0.041) was reported between responders and nonresponders at week 12. Significant correlations were found between changes in the CXCL13 levels and CXCL9, CXCL16, E-cadherin levels as well as between changes in E-cadherin levels and both CXCL16 and ALT levels that were maintained during follow up. Also, significant changes have been found in the serum levels of CXCL5, CXCL13, and CXCL16 with time (before pegylated interferon α 2 a and α 2 b therapy, and at weeks 12 and 24) with no significant difference in relation to interferon type and response to treatment.ConclusionSerum levels of CXCL13 and E-Cadherin could be used as surrogate markers to predict response of combined PEG IFN-α/RBV therapy, especially at week 12. However, an extended study including larger number of patients is needed for validation of these findings.Clinical trial NoNCT01758939

Acute and chronic immune biomarker changes during interferon/ribavirin treatment in HIV/HCV co‐infected patients

“…However, in patients with other inflammatory liver diseases, such as alcoholic liver disease, higher levels of ENA‐78 were associated with increased inflammation and worse prognosis of liver disease . In addition, ENA‐78 serum levels were reported to decrease during IFN treatment, consistent with our findings . Thus, ENA‐78 appears to be involved in liver inflammation rather than fibrosis.…”

The Role of Chemokines in Hepatitis C Virus-Mediated Liver Disease

“…Pretreatment CXCL16 level increase significantly during IFN therapy, suggesting that IFN treatment induces the recruitment of CXCR6 positive immune cells [136]. Most effector T cells infiltrating the chronically inflamed human liver express not only high levels of CCR1, CCR5 and CXCR3 but also CXCR6, so that CXCL16 expression is important for efficient T cell homing to the liver.…”

CXCL9, CXCL10 and CXCL11 polymorphisms are associated with sustained virologic response in HIV/HCV-coinfected patients

“…Additionally, serum levels of CXCL10 have been related to HCV treatment response in patients infected with GT1/4, and the combination of CXCL10 levels and IL28B polymorphisms improves the prediction of SVR [9,23]. In contrast to CXCL10, the usefulness of serum CXCL9 and CXCL11 levels as predictive markers of response to HCV treatment are still unclear [10,24,25]. In our study, the association of CXCL9-11 polymorphisms was independently related to SVR since IL28B polymorphisms were included in the multivariate analysis.…”