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Although chemokines seem to be important in certain inflammatory disorders, little is known about the role of these proteins in chronic hepatitis C.Expression of selected CXC and CC chemokines and their receptors was assessed by immunohistochemistry and flow cytometry in chronic hepatitis C. Tissue samples from normal liver and that of sustained responders were also evaluated. A comparative analysis between the histological grading and the intrahepatic expression level of chemokines was performed.The majority of liver-derived T lymphocytes expressed CXCR3 and CCR5 chemokine receptors, representing high enrichment over levels of CXCR3+ and CCR5+ T cells in blood from chronic hepatitis C. An intense intrahepatic expression of their respective ligands, the CXC chemokine Mig, and RANTES, was detected in the same patients studied, being restricted to the sinusoidal endothelium and to hepatocytes, respectively. A statistically significant association between the intrahepatic chemokine expression level and the inflammatory activity of chronic hepatitis C was found. Of note was the marked expression of both CXCR3 and its ligand Mig on endothelial cells from portal neovessels in chronic hepatitis C.Intrahepatic chemokine signaling could play a key role regulating significant pathological events during chronic hepatitis C, opening new avenues for therapeutic interventions based on chemokine activities.