Медицинская иммунология (Jan 2017)
EXTRACELLULAR MATRIX CONDITION IN CASE OF HCVASSOCIATED LIVER FIBROSIS
Abstract
Imbalance of the proteolysis/antiproteolysis system is known to be among key components of immunofibrogenesis of liver in cases of chronic hepatitis C. To evaluate these aspects, we studied several factors of liver tissue remodeling in blood serum and local samples from HCV patients associated with liver fibrosis. We determined the levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), MMP-9/TIMP-1 and MMP-9/TIMP-2 complexes. Clinical, laboratory and instrumental examinations have been made for 81 patients with chronic hepatitis C who did not receive antiviral therapy, and 22 healthy volunteers. Extracellular matrix protein (ECM) profile was studied in 103 serum blood samples and 32 liver supernates using ELISA technique. Statistically significant increase of MMP-9 contents (p < 0.05) and its complexes with TIMP-1 (p < 0.05) and TIMP-2 (p < 0.01), as well as low levels of type 1 inhibitor (p < 0.05) were revealed in blood serum of HCV-infected patients, as compared with control group. Protein assays in liver supernates of hepatitis C patients reflecting extracellular matrix state revealed an eight-fold increase in MMP-9/ TIMP-1 complex, as compared with control group (p < 0.05). The values of other proteolytic/antiproteolytic factors proved to be low (p < 0.05). An imbalance in protease contents in blood serum and liver biopsies was revealed, showing differently directed changes. I.e., serum values of MMP-9, TIMP-1 and MMP-9/TIMP-2 during transition of liver fibrosis to cirrhosis (F0 to F4) became decreased (p < 0.05), associated with increased liver concentrations of these proteolytic enzymes (p < 0.05). In summary, we conclude that the data obtained in our study suggest an imbalance of proteolysis/antiproteolysis system leads to a dysregulated liver tissue remodeling in patients with chronic hepatitis C.
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