IL15 polymorphism is associated with advanced fibrosis, inflammation‐related biomarkers and virological response in human immunodeficiency virus/hepatitis C virus coinfection. (14th March 2016)

• Record Type: Journal Article
• Authors: Jiménez‐Sousa, María A.; Berenguer, Juan; Rallón, Norma; Pineda‐Tenor, Daniel; Aldamiz‐Echevarria, Teresa; Soriano, Vicente; García‐Álvarez, Mónica; Vazquez‐Morón, Sonia; Restrepo, Clara; Carrero, Ana; Benito, José M.; Resino, Salvador
• Is Part Of: Liver international. Volume 36:Number 9(2016)
• Page Start: 1258
• Page End: 1266
• Publication Date: 2016-03-14
• Subjects: AIDS -- fibrosis -- hepatitis C virus therapy -- interleukin 15 -- single nucleotide polymorphisms; Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.13079
• Languages: English
• ISSNs: 1478-3223

Abstract

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.