María A Jiménez-Sousa1, Juan Berenguer2,3, Norma Rallón4,5, Daniel Pineda-Tenor1,6, Teresa Aldamiz-Echevarria2,3, Vicente Soriano7,8, Mónica García-Álvarez1, Sonia Vazquez-Morón1, Clara Restrepo4,5, Ana Carrero2,3, José M Benito4,5, Salvador Resino1. 1. Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. 2. Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain. 3. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. 4. Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid, Madrid, Spain. 5. Hospital Universitario Rey Juan Carlos, Móstoles, Spain. 6. Servicio de Laboratorio Clínico, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain. 7. Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, Spain. 8. Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain.
Abstract
BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND & AIMS:IL15 is an essential cytokine in both innate and adaptive immune response against hepatitis C virus (HCV) infection. The aim was to analyze whether IL15rs10833 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. METHODS: A retrospective study was performed in 315 patients who started pegIFN-alpha/RBV therapy. Liver fibrosis stage was characterized in 286 patients. IL15rs10833 and IL28Brs12980275 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. RESULTS: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 IL28Brs12980275 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 IL28Brs12980275 AG/GG genotype (aOR = 2.98; P = 0.041). CONCLUSIONS: The presence of IL15rs10833 AA genotype in HIV-/HCV-co-infectedpatients was associated with advanced liver fibrosis, inflammation-related biomarkers and increased rates of SVR to pegIFN-alpha/RBV therapy.
Authors: Rebecca T Veenhuis; Jacquie Astemborski; Michael A Chattergoon; Paige Greenwood; Marissa Jarosinski; Richard D Moore; Shruti H Mehta; Andrea L Cox Journal: Clin Infect Dis Date: 2016-12-07 Impact factor: 9.079