Matrix metalloproteases and their tissue inhibitors in non-alcoholic liver fibrosis of human immunod

来源 :World Journal of Virology | 被引量 : 0次 | 上传用户:b278651776
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AIM To investigate the relationships among diverse metalloproteases(MMPs) and their tissue inhibitors(TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus(HIV)-infected patients.METHODS Single nucleotide polymorphisms(SNPs) in MMPs, TNF-α and CCR5 genes, and serum levels of MMPs and TIMPs were determined in HIV-infected individuals with/out hepatitis C virus(HCV) coinfection. A total of 158 patients were included, 57 of whom were HCVcoinfected. All patients drank < 50 g ethanol/day. Diverse SNPs(MMP-1-1607 1G/2G, MMP-8-799C/T, MMP-9-1562 C/T, MMP-13-77A/G, TNF-α-308 G/A,CCR5-?32), and serum levels of MMPs(2, 3, 8, 9 and 10) and TIMPs(1, 2 and 4) were assessed. Liver fibrosis was determined by transient elastometry, although other non-invasive markers of fibrosis were also considered. Significant liver fibrosis(F ≥ 2) was defined by a transient elastometry value ≥ 7.1 kP a.RESULTS A total of 34 patients(21.5%) had liver fibrosis ≥ F2. MMP-2 and TIMP-2 serum levels were higher in patients with liver fibrosis ≥ F2(P = 0.02 and P = 0.03, respectively) and correlated positively with transient elastometry values(P = 0.02 and P = 0.0009, respectively), whereas MMP-9 values were negatively correlated with transient elastometry measurements(P = 0.01). Multivariate analyses showed that high levels of MMP-2(OR = 2.397; 95%CI: 1.191-4.827, P = 0.014) were independently associated with liver fibrosis ≥ F2 in the patients as a whole. MMP-2(OR = 7.179; 95%CI: 1.210-42.581, P = 0.03) and male gender(OR = 10.040; 95%CI: 1.621-62.11, P = 0.013) were also independent predictors of fibrosis ≥ F2 in the HCV-infected subgroup. Likewise, MMP-2, TIMP-2 and MMP-9 were independently associated with transient elastometry values and other non-invasive markers of liver fibrosis. None of the six SNPs evaluated had any significant association with liver fibrosis ≥ F2.CONCLUSION Certain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosis in HIVinfected patients with/without HCV coinfection. AIM To investigate the relationships among diverse metalloproteases (MMPs) and their tissue inhibitors (TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus (HIV) -infected patients. METHODS Single nucleotide polymorphisms (SNPs) in MMPs, TNF-a and CCR5 genes, and serum levels of MMPs and TIMPs were determined in HIV-infected individuals with / out hepatitis C virus (HCV) coinfection. A total of 158 patients were included, 57 of whom were HCV coinfected. All patients drank <50 g ethanol / day . Diverse SNPs (MMP-1-1607 1G / 2G, MMP-8-799C / T, MMP-9-1562 C / T, MMP-13-77A / G, TNF- α-308 G / A, CCR5- 32), and serum levels of MMPs (2, 3, 8, 9 and 10) and TIMPs (1, 2 and 4) were assessed. Significant liver fibrosis (F ≥ 2) was defined by a transient elastometry value ≥ 7.1 kP a.RESULTS A total of 34 patients (21.5%) had liver fibrosis ≥ F2. MMP-2 and TIMP-2 serum le vels were higher in patients with liver fibrosis ≥ F2 (P = 0.02 and P = 0.03, respectively) and positively correlated with transient elastometry values ​​(P = 0.02 and P = 0.0009, respectively) Multivariate analyzes showed that high levels of MMP-2 (OR = 2.397; 95% CI: 1.191-4.827, P = 0.014) were independently associated with liver fibrosis ≧ F2 in the patients as a whole. MMP-2 (OR = 7.179; 95% CI: 1.210-42.581, P = 0.03) were also independent predictors of fibrosis> F2 in the HCV-infected subgroup. Likewise, MMP-2, TIMP-2 and MMP-9 were independently associated with transient elastometry values ​​and other non-invasive markers of liver fibrosis. None of the six SNPs had had any significant association with liver fibrosis ≥ F2 .CONCLUSION Certain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosisin HIV infected patients with / without HCV coinfection.
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