Published online May 12, 2017. doi: 10.5501/wjv.v6.i2.36
Peer-review started: November 3, 2016
First decision: December 1, 2016
Revised: December 20, 2016
Accepted: February 8, 2017
Article in press: February 13, 2017
Published online: May 12, 2017
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.
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 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. 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.
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.
Certain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosis in HIV-infected patients with/without HCV coinfection.
Core tip: The role of matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) in the development of liver fibrosis is uncertain. We determined some single nucleotide polymorphisms (SNPs), as well as the serum levels of diverse MMPs and TIMPs, in non-alcoholic, human immunodeficiency virus-infected patients with/out hepatitis C virus coinfection, to evaluate their possible relationship with liver fibrosis as assessed by transient elastometry. MMP-2 was independently associated with significant fibrosis. Likewise, MMP-2, TIMP-2 and MMP-9 were independent predictors of transient elastometry values and of other non-invasive tests of fibrosis. No SNP was significantly associated with liver fibrosis. Our findings support the value of these markers in the evaluation of fibrosis.