Author's personal copy Short Communication High plasma fractalkine (CX3CL1) levels are associated with severe liver disease in HIV/HCV co-infected patients with HCV genotype 1 Mónica García-Álvarez a , Juan Berenguer b , María Guzmán-Fulgencio a , Dariela Micheloud a,c , Pilar Catalán d , Mª Ángeles Muñoz-Fernandez e,f , Emilio Álvarez g , Salvador Resino a,⇑ a Laboratory of Molecular Epidemiology of Infectious Diseases, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain b Infectious Diseases-HIV Unit, Hospital General Universitario ‘‘Gregorio Marañón’’, Madrid, Spain c Internal Medicine Department, Hospital General Universitario ‘‘Gregorio Marañón’’, Madrid, Spain d Microbiology Department, Hospital General Universitario ‘‘Gregorio Marañón’’, Madrid, Spain e Molecular Immunobiology Laboratory, Hospital General Universitario ‘‘Gregorio Marañón’’, Madrid, Spain f Human Retrovirology Unit HGUGM-CSIC. Madrid, Spain g Pathology Department, Hospital General Universitario ‘‘Gregorio Marañón’’, Madrid, Spain article info Article history: Received 23 November 2010 Received in revised form 21 February 2011 Accepted 10 March 2011 Available online 3 April 2011 Keywords: Chemokines Hepatitis C HCV genotype 1 HIV/AIDS Fibrosis abstract Background: Inappropriate persistence of chemokines expression in hepatitis C virus (HCV) infection can drive tissue damage, intrahepatic inflammation, and liver cell injury. The aim of study was to study the association of plasma fractalkine (CX3CL1) levels with fibrosis stage and necroinflammatory activity grade of liver biopsies in human immunodeficiency virus (HIV)/HCV co-infected patients with HCV geno- type 1. Methods: We carried out a cross-sectional study on 125 patients. Grading and staging of liver biopsies were carried out by METAVIR score. Plasma CX3CL1 was measured using an immunoassay kit. Results: Patients with advanced fibrosis had higher CX3CL1 levels than those with mild or no fibrosis (p = 0.010); and patients with severe activity grade had higher CX3CL1 levels than those with low activity grade (p = 0.040). Plasma CX3CL1 levels were significantly associated with increased odds of significant fibrosis (odds ratio (OR): 3.47 (95% of confidence interval (95%CI): 1.04; 11.58)), advanced fibrosis (OR: 6.78 (95%CI: 1.70; 26.93)), and moderate necroinflammatory activity grade (OR: 4.09 (95%CI: 1.21; 13.87)). When we analyzed fibrosis stages and activity grades of METAVIR score together, we found a positive significant association of CX3CL1 levels with moderate activity grade/significant fibrosis (OR: 5.49 (95%CI: 1.46; 20.58)) and moderate activity grade/advanced fibrosis (OR: 8.99 (95%CI: 2.06; 39.23)). Conclusion: Plasma CX3CL1 levels were independently associated with several characteristics of severe liver disease in HIV/HCV coinfected patients with HCV-genotype 1, suggesting a role of CX3CL1 in the pathogenesis of HCV infection. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction Chemokines, chemotactic cytokines that attract leukocytes to inflammatory sites, orchestrate the immune response to viruses, including hepatitis C virus (HCV) [1]. However, an inappropriate persistence of chemokine expression in HCV infection can drive tis- sue damage, intrahepatic inflammation, and liver cell injury [1]. Chemokines are involved in fibrosis indirectly by recruiting both inflammatory cells and hepatic stellate cells (HSCs), which both play a central role in fibrogenesis [1,2]. This inflammatory loop is responsible for chronic necroinflammation and the development of fibrosis and cirrhosis [1]. Peripheral (plasma or serum) chemokine levels have been asso- ciated with progressive fibrosis in HCV-monoinfected patients [1] and some chemokines (CXCR3 associated chemokines) were able to predict fibrosis stage in a predominantly white HCV genotype- 1 infected population [3]. HCV-genotype 1 has been associated with higher oxidative damage, inflammation, and activation of the immune system [4,5]. Thus, the HCV genotype could be an- other limiting factor in obtaining significant results between the level of chemokines and fibrosis stage. HIV infection adversely impacts the natural pathology of HCV infection, resulting in higher rates of fibrosis progression, cirrhosis, and end-stage liver disease than for HCV mono-infected patients [6]. Furthermore, HIV infection depends on the exploitation of host cellular machinery for its replication and survival, leading to the 1043-4666/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.cyto.2011.03.001 ⇑ Corresponding author. Address: Laboratory of Molecular Epidemiology of Infectious Diseases, National Centre of Microbiology, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo, Km 2.2, 28220 Majadahonda, Madrid, Spain. Tel.: +34 918 223 266; fax: +34 915 097 946. E-mail address: sresino@isciii.es (S. Resino). Cytokine 54 (2011) 244–248 Contents lists available at ScienceDirect Cytokine journal homepage: www.elsevier.com/locate/issn/10434666