Association between IL7R polymorphisms and severe liver disease in HIV/HCV coinfected patients: A cross-sectional study

Abstract

Background: Interleukin-7 (IL-7) is a critical factor for T cell development and for maintaining and restoring homeostasis of mature T cells. Polymorphisms at aα-chain of the IL-7 receptor (IL7R or CD127) gene are related to evolution of HIV-infection, but there are no data concerning the evolution of hepatitis C virus (HCV) infection. The aim of this study was to analyze the association between IL7R polymorphisms and severe liver disease in HCV/HIV coinfected patients. Methods: We performed a cross-sectional study in 220 naïve patients who underwent a liver biopsy. IL7R polymorphisms (rs6897932, rs987106 and rs3194051) were genotyped using the GoldenGate® assay. The outcome variables were: (a) liver biopsy: advanced fibrosis (F≥3), severe activity grade (A3); (b) non-invasive indexes: advanced fibrosis (APRI ≥1.5 and FIB-4 ≥3.25). Logistic regression analysis was used to investigate the association between IL7R polymorphisms and outcome variables. This test gives the differences between groups and the odds ratio (OR) for liver disease. Results: Patients with rs6897932 CC genotype had higher likelihood of having A3 than patients with rs6897932 CT/TT (adjusted odds ratio (aOR)=4.16; p=0.026). Patients with rs987106 TT genotype had higher odds of having F≥3 (aOR=3.09; p=0.009) than rs987106 AA/AT carriers. Finally, patients with rs3194051 AA genotype had higher odds of having severe liver fibrosis (F≥3; APRI ≥1.5, and FIB4 ≥3.25) than patients with rs3194051 AG/GG genotype [aOR=2.73 (p=0.010); aOR=2.52 (p=0.029); and aOR=4.01 (p=0.027); respectively]. The CTA haplotype (comprised of rs6897932, rs987106, and rs3194051) carriers had higher odds of having F≥3 (aOR=1.85; p=0.012), APRI ≥1.5 (aOR=1.94; p=0.023), and FIB4 ≥3.25 (aOR=2.47; p=0.024). Conversely, the CAG haplotype carriers had lower odds of having F≥3 (aOR=0.48; p=0.011), APRI ≥1.5 (aOR=0.48; p=0.029), and FIB4 ≥3.25 (aOR=0.29; p=0.010). Conclusions: The presence of IL7R polymorphisms seems to be related to severe liver disease in HIV/HCV coinfected patients, because patients with unfavorable IL7R genotypes (rs6897932 CC, rs987106 TT, and rs3194051AA) had a worse prognosis of CHC.