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

Medientyp: E-Artikel
Titel: IL15 polymorphism is associated with advanced fibrosis, inflammation‐related biomarkers and virological response in human immunodeficiency virus/hepatitis C virus coinfection
Beteiligte: 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
Erschienen: Wiley, 2016
Erschienen in: Liver International
Sprache: Englisch
DOI: 10.1111/liv.13079
ISSN: 1478-3223; 1478-3231
Schlagwörter: Hepatology
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Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background & Aims</jats:title><jats:p><jats:styled-content style="fixed-case">IL</jats:styled-content>15 is an essential cytokine in both innate and adaptive immune response against hepatitis C virus <jats:styled-content style="fixed-case">(HCV)</jats:styled-content> infection. The aim was to analyze whether <jats:italic>IL15</jats:italic> rs10833 is associated with liver disease severity and response to pegylated‐interferon‐alpha plus ribavirin (peg<jats:styled-content style="fixed-case">IFN</jats:styled-content>‐alpha/<jats:styled-content style="fixed-case">RBV</jats:styled-content>) therapy in human immunodeficiency virus (<jats:styled-content style="fixed-case">HIV</jats:styled-content>)‐/HCV‐co‐infected patients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A retrospective study was performed in 315 patients who started peg<jats:styled-content style="fixed-case">IFN</jats:styled-content>‐alpha/<jats:styled-content style="fixed-case">RBV</jats:styled-content> therapy. Liver fibrosis stage was characterized in 286 patients. <jats:italic>IL15</jats:italic> rs10833 and <jats:italic>IL28B</jats:italic> 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 (<jats:styled-content style="fixed-case">SVR</jats:styled-content>). The secondary outcome variable was the levels of serum biomarkers of inflammation.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Patients with rs10833 <jats:styled-content style="fixed-case">AA</jats:styled-content> genotype had increased odds of having advanced fibrosis (adjusted odds ratio (<jats:styled-content style="fixed-case">aOR</jats:styled-content>) = 2.30; <jats:italic>P</jats:italic> = 0.019), particularly in males (<jats:styled-content style="fixed-case">aOR</jats:styled-content> = 2.24; <jats:italic>P</jats:italic> = 0.040), patients with HCV serum viral load <jats:styled-content style="fixed-case">(HCV</jats:styled-content>‐<jats:styled-content style="fixed-case">RNA)</jats:styled-content> <500 000 <jats:styled-content style="fixed-case">IU</jats:styled-content>/<jats:styled-content style="fixed-case">ml</jats:styled-content> (<jats:styled-content style="fixed-case">aOR</jats:styled-content> = 5.14; <jats:italic>P</jats:italic> = 0.018) and patients with <jats:italic><jats:styled-content style="fixed-case">IL</jats:styled-content>28B</jats:italic> rs12980275 <jats:styled-content style="fixed-case">AG</jats:styled-content>/<jats:styled-content style="fixed-case">GG</jats:styled-content> genotypes (<jats:styled-content style="fixed-case">aOR</jats:styled-content> = 2.51; <jats:italic>P</jats:italic> = 0.046). Moreover, rs10833 <jats:styled-content style="fixed-case">AA</jats:styled-content> genotype was significantly associated with higher levels of hepatocyte growth factor (adjusted arithmetic mean ratio (<jats:styled-content style="fixed-case">aAMR</jats:styled-content>) = 1.50; <jats:italic>P</jats:italic> = 0.016), <jats:styled-content style="fixed-case">sICAM</jats:styled-content>‐1 (<jats:styled-content style="fixed-case">aAMR</jats:styled-content> = 1.57; <jats:italic>P</jats:italic> = 0.025) and <jats:styled-content style="fixed-case">sVCAM</jats:styled-content>‐1 (<jats:styled-content style="fixed-case">aAMR</jats:styled-content> = 1.56; <jats:italic>P</jats:italic> = 0.007). Finally, patients with rs10833 <jats:styled-content style="fixed-case">AA</jats:styled-content> genotype had increased odds of achieving <jats:styled-content style="fixed-case">SVR</jats:styled-content> (<jats:styled-content style="fixed-case">aOR</jats:styled-content> = 3.12; <jats:italic>P</jats:italic> = 0.006), particularly in males (<jats:styled-content style="fixed-case">aOR</jats:styled-content> = 3.69; <jats:italic>P</jats:italic> = 0.005), <jats:styled-content style="fixed-case">GT</jats:styled-content>1/4 patients (<jats:styled-content style="fixed-case">aOR</jats:styled-content> = 3.59; <jats:italic>P</jats:italic> = 0.006), patients with advanced fibrosis (<jats:styled-content style="fixed-case">aOR</jats:styled-content> = 4.64; <jats:italic>P</jats:italic> = 0.021), <jats:styled-content style="fixed-case">HCV</jats:styled-content>‐<jats:styled-content style="fixed-case">RNA</jats:styled-content> ≥500 000 <jats:styled-content style="fixed-case">IU</jats:styled-content>/<jats:styled-content style="fixed-case">ml</jats:styled-content> (<jats:styled-content style="fixed-case">aOR</jats:styled-content> = 3.92; <jats:italic>P</jats:italic> = 0.007) and patients with <jats:italic>IL28B</jats:italic> rs12980275 <jats:styled-content style="fixed-case">AG</jats:styled-content>/<jats:styled-content style="fixed-case">GG</jats:styled-content> genotype (<jats:styled-content style="fixed-case">aOR</jats:styled-content> = 2.98; <jats:italic>P</jats:italic> = 0.041).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The presence of <jats:italic>IL15</jats:italic> rs10833 <jats:styled-content style="fixed-case">AA</jats:styled-content> genotype in <jats:styled-content style="fixed-case">HIV‐</jats:styled-content>/<jats:styled-content style="fixed-case">HCV</jats:styled-content>‐co‐infected patients was associated with advanced liver fibrosis, inflammation‐related biomarkers and increased rates of <jats:styled-content style="fixed-case">SVR</jats:styled-content> to peg<jats:styled-content style="fixed-case">IFN</jats:styled-content>‐alpha/<jats:styled-content style="fixed-case">RBV</jats:styled-content> therapy.</jats:p></jats:sec>

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