Matrix metalloproteases and their tissue inhibitors in non-alcoholic liver fibrosis of human immunodeficiency virus-infected patients

• 作者: Angel-Hugo Montes Eulalia Valle-Garay JoséA Cartón Julio Collazos Tomás Suárez-Zarracina Víctor Asensi
• 来源期刊: 世界病毒学杂志
• 学科: 医学
• 关键词: Human IMMUNODEFICIENCY VIRUS Hepatitis C VIRUS Liver FIBROSIS Transient elastometry NONINVASIVE FIBROSIS markers METALLOPROTEASES Their tissue inhibitors Genetic POLYMORPHISMS
• 年，卷（期）: 2017,（2）
• 页码范围: 36-45
• 页数: 10页
• 分类号: R

摘要

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-αand 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-Δ32),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 kPa.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.