Matrix metalloproteinases and morphological features in chronic liver diseases

Aim of investigation. To study the relationship of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) with a morphological features of chronic liver diseases (CLD). Materials and methods. 76 patients with CLD of viral or alcoholic etiology aged from 18 to 64 years were examined. Chronic hepatitis was diagnosed in 59 patients, liver cirrhosis (class A according Child-Pugh score) was detected in 17 cases. The control group consisted of 72 practically healthy people. The blood levels of MMP-1, MMP-9, TIMP-1 were determined by enzyme immunoassay, and the ratio of TIMP-1/MMP-1, TIMP-1/MMP-9 was calculated. Results. There was an increase in the concentration of TIMP-1 and MMP-1 in the blood, the ratio of TIMP-1/MMP-9, a decrease in the ratio of TIMP-1/MMP-1 in CLD. In moderate and severe histological activity of CLD the levels of TIMP-1 and MMP-9 were higher, and the ratio of TIMP-1/MMP-9 was lower than in patients with histological activity index values less than 9 points. In patients with liver cirrhosis (fibrosis F4), the maximum values of TIMP-1, TIMP-1/MMP-1 and TIMP-1/MMP-9 were determined, which differed from the corresponding values for fibrosis F0-1 and F2. The blood levels of MMP-9 more than 410 ng/ml predicted severe inflammation in CLD with an accuracy of 82.9 %. The blood levels of TIMP-1 above 624 ng/ml, TIMP-1/MMP-1 more than 37.1, TIMP-1/MMP-9 more than 7.33 had high accuracy (82.9, 80.3, 80.3 %, respectively) in the prediction of liver cirrhosis (fibrosis F4). Conclusion. The imbalance in the matrix metalloproteinase system is associated with the morphological features of CLD and is characterized by hyperexpression of MMP-9 in cases of severe inflammation and increased activity of TIMP-1 in severe stages of liver fibrosis.