title: IL15 polymorphism is associated with advanced fibrosis, inflammation-related biomarkers and virological response in human immunodeficiency virus/hepatitis C virus coinfection.
abstract: IL15 is an essential cytokine in both innate and adaptive immune response against hepatitis C virus (HCV) infection. The aim was to analyze whether IL15 rs10833 is associated with liver disease severity and response to pegylated-interferon-alpha plus ribavirin (pegIFN-alpha/RBV) therapy in human immunodeficiency virus (HIV)-/HCV-co-infected patients.
  
  
  
  A retrospective study was performed in 315 patients who started pegIFN-alpha/RBV therapy. Liver fibrosis stage was characterized in 286 patients. IL15 rs10833 and IL28B rs12980275 were genotyped by GoldenGate. The primary outcomes were: (a) advanced liver fibrosis evaluated by liver biopsy (F3-F4) or transient elastography (liver stiffness values ≥9.5 Kpa); (b) sustained virological response (SVR). The secondary outcome variable was the levels of serum biomarkers of inflammation.
  
  
  
  Patients with rs10833 AA genotype had increased odds of having advanced fibrosis (adjusted odds ratio (aOR) = 2.30; P = 0.019), particularly in males (aOR = 2.24; P = 0.040), patients with HCV serum viral load (HCV-RNA) <500 000 IU/ml (aOR = 5.14; P = 0.018) and patients with IL28B rs12980275 AG/GG genotypes (aOR = 2.51; P = 0.046). Moreover, rs10833 AA genotype was significantly associated with higher levels of hepatocyte growth factor (adjusted arithmetic mean ratio (aAMR) = 1.50; P = 0.016), sICAM-1 (aAMR = 1.57; P = 0.025) and sVCAM-1 (aAMR = 1.56; P = 0.007). Finally, patients with rs10833 AA genotype had increased odds of achieving SVR (aOR = 3.12; P = 0.006), particularly in males (aOR = 3.69; P = 0.005), GT1/4 patients (aOR = 3.59; P = 0.006), patients with advanced fibrosis (aOR = 4.64; P = 0.021), HCV-RNA ≥500 000 IU/ml (aOR = 3.92; P = 0.007) and patients with IL28B rs12980275 AG/GG genotype (aOR = 2.98; P = 0.041).
  
  
  
  The presence of IL15 rs10833 AA genotype in HIV-/HCV-co-infected patients was associated with advanced liver fibrosis, inflammation-related biomarkers and increased rates of SVR to pegIFN-alpha/RBV therapy.
authors.affiliation: Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.affiliation: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid, Madrid, Spain.|Hospital Universitario Rey Juan Carlos, Móstoles, Spain.
authors.forename: Norma
authors.initials: N
authors.lastname: Rallón
authors.affiliation: Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.|Servicio de Laboratorio Clínico, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pineda-Tenor
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Aldamiz-Echevarria
authors.affiliation: Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, Spain.|Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
authors.affiliation: Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Álvarez
authors.affiliation: Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Vazquez-Morón
authors.affiliation: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid, Madrid, Spain.|Hospital Universitario Rey Juan Carlos, Móstoles, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Restrepo
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Carrero
authors.affiliation: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid, Madrid, Spain.|Hospital Universitario Rey Juan Carlos, Móstoles, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Benito
authors.affiliation: Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D060085:Coinfection / Q000150:complications / Q000188:drug therapy / Q000821:virology; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D019409:Interleukin-15 / Q000235:genetics*; D007378:Interleukins / Q000235:genetics; D008103:Liver Cirrhosis / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D013030:Spain; D000072230:Sustained Virologic Response; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D007372:Interferons; D019409:Interleukin-15; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C569274:IL15 protein, human
keywords: AIDS; fibrosis; hepatitis C virus therapy; interleukin 15; single nucleotide polymorphisms