IL15 polymorphism is associated with advanced fibrosis, inflammation‐related biomarkers and virological response in human immunodeficiency virus/hepatitis C virus coinfection

Background & Aims IL 15 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 (peg IFN ‐alpha/ RBV ) therapy in human immunodeficiency virus ( HIV )‐/HCV‐co‐infected patients. Methods A retrospective study was performed in 315 patients who started peg IFN ‐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 IL 28B 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), GT 1/4 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 peg IFN ‐alpha/ RBV therapy.