Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Virol. May 12, 2017; 6(2): 36-45
Published online May 12, 2017. doi: 10.5501/wjv.v6.i2.36
Matrix metalloproteases and their tissue inhibitors in non-alcoholic liver fibrosis of human immunodeficiency virus-infected patients
Julio Collazos, Eulalia Valle-Garay, Tomás Suárez-Zarracina, Angel-Hugo Montes, José A Cartón, Víctor Asensi
Julio Collazos, Infectious Diseases, Hospital de Galdácano, 48960 Vizcaya, Spain
Eulalia Valle-Garay, Angel-Hugo Montes, Biochemistry and Molecular Biology, Hospital Universitario Central de Asturias, Oviedo University School of Medicine, 33006 Oviedo, Spain
Tomás Suárez-Zarracina, José A Cartón, Víctor Asensi, Infectious Diseases, Hospital Universitario Central de Asturias, Oviedo University School of Medicine, 33006 Oviedo, Spain
Author contributions: Collazos J, Suárez-Zarracina T, Cartón JA and Asensi V designed the study and contributed to the data acquisition and selection; Valle-Garay E and Montes AH performed the laboratory determinations and genotypic studies; Collazos J analyzed the data; Collazos J and Asensi V wrote the draft of the initial manuscript; Suárez-Zarracina T, Valle-Garay E, Montes AH and Cartón JA revised the article critically for important intellectual content.
Supported by the Oviedo University research grants, Nos. UNIOV-12-MA-03 and SV-PA-13-ECOEMP-57.
Institutional review board statement: The study was approved by the Principado de Asturias Research Ethic Committee.
Informed consent statement: Given the nature of the study, no formal written approval was necessary, according to our institution’s regulations, being enough a verbal informed consent, which was obtained from all patients.
Conflict-of-interest statement: There is no conflict of interest related to this paper.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Julio Collazos, Infectious Diseases Unit, Hospital de Galdácano, Bº Labeaga s/n, 48960 Vizcaya, Spain. med003033@gmail.com
Telephone: +34-94-6032860 Fax: +34-94-6032867
Received: October 30, 2016
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.

Keywords: Human immunodeficiency virus, Hepatitis C virus, Liver fibrosis, Transient elastometry, Non-invasive fibrosis markers, Metalloproteases, Their tissue inhibitors, Genetic polymorphisms

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.