Published online Feb 27, 2021. doi: 10.4254/wjh.v13.i2.218
Peer-review started: October 2, 2020
First decision: December 3, 2020
Revised: December 14, 2020
Accepted: December 28, 2020
Article in press: December 28, 2020
Published online: February 27, 2021
Matrix metalloproteinases (MMPs) maintain the homeostasis between fibrogenesis and fibrolytic processes in the liver. Few studies on the production and activity of liver MMPs and fibrosis progression have been performed in humans.
The correct determination of liver fibrosis stages is imperative for making the diagnosis and implementing therapeutic decisions. At present, there is no evidence of the production and activity of MMP-2, MMP-7 or MMP-9 or their correlation with fibrosis progression in serum samples from patients with liver diseases.
In the present prospective, cross-sectional, multicenter study, we assessed the production, activity and regulation of matrix metalloproteinases in liver fibrosis stages in chronic hepatitis C (CHC).
We selected CHC patients from the Hospital General de México, “Dr. Eduardo Liceaga,” the Universidad Autónoma de Nuevo Leon and the Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán.” Patients were categorized in fibrosis grades through FibroTest®and/or FibroScan®(F0, F1, F2, F3 or F4). Serum concentrations of MMP-2, -7 and -9 were determined. Differences were validated by the Kruskal-Wallis and Mann-Whitney U tests. Area under the receiver operating characteristic curve was calculated in fibrosis degrees. Proteolytic activity was validated by chromogenic and enzymatic assays and serum concentration, and the regulation of tissue inhibitor of metalloproteinases-1 was tested in fibrosis progression.
We compared 119 CHC patients with 119 healthy subjects. MMP-2, -7 and -9 concentrations were higher in the patients with CHC than in the control subjects. No differences between the serum concentrations of MMP-2 and MMP-9 were found, but MMP-7 showed differential regulation in accordance with fibrosis stages as well as an acceptable receiver operating characteristic (0.705), in advanced fibrosis (F4). Collagenolytic MMP activity was maintained in F0 and F1 but decreased significantly in F2, F3 and F4. Gelatin activity was not observed in any stage of fibrosis. The concentration of tissue inhibitor of metalloproteinases-1 was lower in F2 and F4 compared with F0, F1 and healthy subjects. Inactive MMPs were found in the serum of the CHC patients.
Elevated concentrations of inactive MMPs were present in the serum of CHC patients, reflecting the impossibility to restrain liver fibrosis progression. MMPs could be used in the diagnosis of liver fibrosis and the treatment for its reversal in CHC.
Given that MMP-2, -7 and -9 have not been simultaneously evaluated in the serum from liver fibrosis patients, MMPs could be used to improve the currently available diagnostic methods and as therapeutic targets. They could also be used as a monitoring tool in treatment-experienced patients that continue to present with liver fibrosis and develop cirrhosis and/or hepatocellular carcinoma.